text:
Number: 0640
Aetna considers allogeneic hematopoietic cell transplantation medically necessary for the treatment of acute lymphocytic leukemia (ALL) when members meet the transplanting institution's selection criteria. In the absence of an institution's selection criteria, Aetna considers allogeneic hematopoietic cell transplantation medically necessary for the treatment of ALL, including primary refractory ALL (i.e., leukemia that does not achieve a complete remission after conventional dose chemotherapy), except for members in refractory relapse, defined as persons in relapse who are unresponsive to 3 or more months of adequate chemotherapy.
Aetna considers non-myeloablative allogeneic hematopoietic cell transplantation, also known as mini-allograft or reduced intensity conditioning transplant, medically necessary for the treatment of ALL for members with no persistent disease who meet all of the selection criteria above. Note: Persons with persistent disease should not be candidates for a mini-allograft transplant.
Aetna considers autologous hematopoietic cell transplantation medically necessary for persons with standard risk ALL where no suitable donor is available.
Aetna considers tandem (also known as sequential) transplants experimental and investigational for the treatment of ALL because their effectiveness for this indication has not been estanlished.
Aetna considers autologous hematopoietic cell transplantation medically necessary for the treatment of acute myelogenous leukemia (AML) when members meet the transplanting institution's selection criteria. In the absence of an institution's selection criteria, Aetna considers autologous hematopoietic cell transplantation medically necessary for the treatment of AML for any indication (e.g., first or second remission or relapsed AML if responsive to intensified induction chemotherapy) except as first-line treatment.
Aetna considers allogeneic hematopoietic cell transplantation (allo-HSCT) (ablative or mini-allograft) medically necessary for the treatment of AML when members meet the transplanting institution's selection criteria. In the absence of an institution's selection criteria, Aetna considers allogeneic hematopoietic cell transplantation for the treatment of AML in any one of the following indications:
Primary refractory AML (i.e., leukemia that does not achieve a complete remission after conventional dose chemotherapy)
Aetna considers a repeat autologous hematopoietic cell transplantation or allogeneic hematopoietic cell transplantation (ablative or mini-allograft) medically necessary for the treatment of AML when members meet the transplanting institution's selection criteria. In the absence of an institution's selection criteria, Aetna considers a repeat autologous or allogeneic hematopoietic cell transplantation (ablative or mini-allograft) medically necessary when the first autologous or allogeneic hematopoietic cell transplantation was unsuccessful due to primary graft failure or failure to engraft or for persons who have relapsed after a prior hematopoietic cell transplantation.
Aetna considers a repeat autologous or allogeneic hematopoietic cell transplantation (ablative or mini-allograft) experimental and investigational for members with persistent or progressive disease because its effectiveness for this indication has not been estanlished.
Aetna considers allogeneic (ablative or non-myeloablative) hematopoietic cell transplantation medically necessary for the treatment of chronic myelo-monocytic leukemia (CMML) and juvenile myelo-monocytic leukemia (JMML) when a matched or haploidentical donor is available.
Aetna considers a repeat allogeneic (ablative or non-myeloablative) hematopoietic cell transplantation due to primary graft failure or failure to engraft medically necessary for the treatment of CMML and JMML.
Aetna considers autologous hematopoietic cell transplantation for the treatment of CMML and JMML experimental and investigational because its effectiveness for these indications has not been established.
Aetna considers allogeneic (ablative or non-myeloablative) hematopoietic cell transplantation medically necessary for T-cell prolymphocytic leukemia.
Aetna considers hematopoietic cell transplantation (allogeneic or autologous) medically necessary as consolidation therapy of acute promyelocytic leukemia in second or subsequent remission.
For hematopoietic cell transplantation for chronic lymphocytic leukemia/small lymphocytic lymphoma, see CPB 0494 - Hematopoietic Cell Transplantation for Non-Hodgkin's Lymphoma.
See also: CPB 0634 - Non-myeloablative Hematopoietic Cell Transplantation (Mini-Allograft/Reduced Intensity Conditioning Transplant), and CPB 0674 - Hematopoietic Cell Transplantation for Chronic Myelogenous Leukemia.Background
Acute Lymphocytic Leukemia:
Acute lymphocytic leukemia (ALL) is a heterogeneous group of malignancies arising from lymphocytic precursors. The heterogeneity is related to whether the malignant clone is derived from a T or B cell as evidenced by the expression of different surface antigens. The different subtypes of ALL are also heterogeneous with respect to response to chemotherapy and to the age distribution (i.e., different subtypes typically occur in either children or adults). Acute lymphocytic leukemia has a bi-modal age distribution with an initial peak at 2 to 3 years, with the incidence again increasing after the age of 50. By definition, ALL primarily affects the bone marrow, but in advanced cases, lymph nodes, liver, spleen and central nervous system (CNS) may be involved. Although the cause of leukemia is not known in most patients, epidemiologic evidence suggests that genetics and environmental factors may play a role in its development. (Franeil et al, 2001)
In the untreated patient, the blood and marrow blast count rises while the granulocyte and platelet count falls accordingly. The most common symptoms and physical findings result from anemia, thrombocytopenia, and neutropenia and include pallor and fatigue, anorexia, petechiae, purpura, bleeding, and infection. Treatment must begin as soon as possible to prevent infection and hemorrhage. It has been proposed that successful treatment of ALL involves the control of bone marrow and systemic disease; it frequently includes the use of systemic combination chemotherapy and CNS preventive therapy. The 4 phases of ALL treatment are as follows: (i) remission induction, (ii) consolidation, (iii) maintenance therapy, and (iv) CNS prophylaxis. The standard remission induction protocol for ALL is the combination of vincristine, prednisone, and an anthracycline. Some regimens also add other drugs, such as asparaginase or cyclophosphamide. The combination of cranial irradiation and intrathecal methotrexate, high-dose systemic methotrexate and intrathecal methotrexate, or intrathecal chemotherapy alone is commonly used for CNS prophylaxis (Scheinber et al, 2001). The average length of treatment of ALL varies between 1.5 and 3 years in the effort to eradicate the leukemic cell population. The greatest number of relapses occurs in the first year after discontinuing chemotherapy (NCI, 2002).
Many studies have attempted to identify ALL patients at high-risk for relapse. The curability of ALL is related to those prognostic factors identified by the peer-reviewed medical literature as follows: (Martin and Gajewski, 2001; NCI, 2002)
Age. In childhood ALL, conventional chemotherapy has been reported to achieve complete remission rates of about 95 % and 80 % can expect to survive 5 years. The remission and long-term survival rates are reported to decline with age. Several studies have correlated age over 35 or 50 years with shorter remission duration and decreased survival rates. It has been reported that approximately 80 to 94 % of adult patients can expect to achieve complete remission rates after conventional chemotherapy and 20 to 40 % can expect to survive 2 years (NCI, 2002; Martin and Gajewski, 2001).
Immunologic subtype. Based on cell surface antigens, ALLs are subdivided according to the corresponding lymphocyte precursor. About 80 % of cases of ALL in children and adults fall into the category of early pre-B cell ALL. Pre-B cell ALL, which lacks the expression of CD10 (also known as the common ALL antigen that is expressed in both B and T cell subtypes), is associated with chromosomal abnormalities, high white count and a poor prognosis. Mature B cell ALL is histologically identical to Burkitt's lymphoma, the only distinction being that ALL involves primarily the bone marrow, while Burkitt's lymphoma involves primarily the lymph nodes. While these entities are recognized as aggressive, their prognosis has improved recently with multi-agent chemotherapeutic regimens. T-cell ALL is seen in about 10 to 15 % of ALL cases in children and adults. T cell ALL is associated with male sex, older age, high white counts, CNS involvement and a mediastinal mass. The lack of expression of CD10 in T-cell ALL is also associated with a poorer prognosis (NCI, 2002).
Cytogenetics. Certain cytogenetic abnormalities are associated with a poor prognosis. The presence of the Philadelphia (Ph) chromosome or its molecular counterpart, the bcr-abl oncogene, is associated with a particularly poor prognosis. The bcr-abl oncogene may be detectable only by pulse-field gel electrophoresis or reverse transcriptase polymerase chain reaction. The presence of the Ph chromosome is more common in adult ALL, occurring in up to 30 % of cases, and thus may be partially responsible for the overall poorer prognosis in adult patients. Two other chromosomal abnormalities with poor prognoses are t(4;11), and t(9;22). In addition, patients with deletion of chromosome 7 or trisomy 8 have been reported to have a lower probability of survival at 5 years compared to patients with a normal karyotype (NCI, 2002). In contrast, hyperdiploidy (i.e., more than 50 chromosomes) is associated with a favorable prognosis in children, but in adults the effect of this abnormality is less clear (Martin and Gajewski, 2001).
Response to induction therapy. Initial chemotherapy promptly achieves a complete remission in most cases. However, a prolonged time to reach complete remission is associated with a poor prognosis in all age groups. Prolonged time to remission can be defined as either requiring 2 cycles of induction therapy, or greater than 4 weeks until complete remission of 5 % leukemic blasts in the bone marrow after 7 to 14 days of induction therapy (Martin and Gajewski, 2001).
Elevated white blood cell count. An elevated white blood count (WBC) is associated with a steadily worse prognosis. Most studies define a WBC of more than 25,000 to 35,000 cells/uL as high-risk (Martin and Gajewski, 2001).
Miscellaneous factors. Other reported poor prognostic features include CNS involvement or extramedullary leukemia, hepatosplenomegaly, and lymphadenopathy (Martin and Gajewski, 2001).
It is considered an important goal in the management of ALL to identify patients that would preferentially benefit from either conventional chemotherapy or intensified therapy such as bone marrow transplant (BMT). Patients with low-risk features have an excellent prognosis and are routinely treated with conventional chemotherapy. In contrast, patients with one or more high-risk features have a poor response to standard chemotherapy. In a large prospective study from Germany, the reported 5-year disease-free survival for adults with one or more high-risk features ranged from 11 % to 33 % (Hoelzer et al, 1988). In many studies, these high-risk patients have been considered for BMT. Bone marrow support can be derived from marrow stem cells harvested from either the bone marrow or peripheral blood from either an allogeneic, autologous or syngeneic (i.e., identical twin) donor.
Retrospective studies evaluating allogeneic transplantation for patients with ALL in first complete remission report higher treatment-related mortality and decreased disease relapse (Horowitz et al, 1991; Oh et al, 1998). These effects appear to offset one another and to counteract any benefit from allogeneic transplantation in first complete remission (Martin and Gajewski, 2001). In the largest prospective (n = 257) multi-center, randomized controlled trial to date (Sebban et al, 1994), adults with ALL in remission and who were younger than age 40 years received allogeneic BMT if a sibling donor was available or were randomly assigned to either ongoing chemotherapy or autologous BMT. There was no advantage to allogeneic BMT for the group of patients with standard-risk ALL. There was significant survival benefit, however, for patients with high-risk ALL (44 % versus 20 %). The long-term survival of patients who received chemotherapy and autologous transplant was identical (NCI, 2002).
The International Bone Marrow Transplant Registry (IBMTR) reported a 38 % disease-free survival in Ph-positive patients in first complete remission receiving human leukocyte antigen (HLA)-matched transplants from sibling donors. These results were similar to those of patients who were refractory to initial induction therapy or who were in second or subsequent remission (Barrett et al, 1992). The Seattle Transplant Group has reported a 49 % disease-free survival at 2 years among 18 Ph-positive patients who received matched unrelated donor transplants (Sierra et al, 1997).
The majority of published studies consider allogeneic BMT a reasonable consideration for all high-risk (e.g., Ph-positive ALL, t(9;22), t(4;11), failure to respond to induction therapy, B-cell lineage with a white blood cell count greater than 30,000/uL) patients of suitable age (Martin and Gajewski, 2001).
Studies report higher relapse rates in recipients of autologous compared with allogeneic transplant (Attal et al, 1995; Blaise et al, 1990 and 1997). Two likely explanations are that (i) allogeneic transplantation is associated with a graft-versus-leukemia effect, and (ii) contamination of the autologous marrow with residual leukemia cells may result in increased disease relapse rates and decrease survival status after autologous BMT (Martin and Gajewski, 2001). The largest prospective study performed to date has found that Ph+ ALL patients receiving allogeneic BMT in first complete remission have better event-free survival and overall survival than similar patients receiving autologous BMT (Goldstone et al, 2001). Therefore, the role of autologous BMT for the treatment of ALL remains uncertain.
Gaynon et al (2006) compared conventional sibling bone marrow transplantation (CBMT), BMT with alternative donor (ABMT), and chemotherapy (CT) for children with ALL and an early first marrow relapse. After informed consent, 214 patients with ALL and early marrow relapse began multi-agent induction therapy. A total of 163 patients with fewer than 25 % marrow blasts and count recovery at the end of induction (second complete remission [CR2]) were allocated by donor availability; and 50 patients with sibling donors were allocated to CBMT. Seventy-two patients were randomly allocated between ABMT and CT while 41 patients refused allocation. Overall, 3-year event free survival from entry is 19 % +/- 3 %. Thirty-two of 50 CBMT patients (64 %) and 19 of 37 ABMT patients (51 %) underwent transplantation in CR2 with 3-year disease-free survival (DFS) of 42 % +/- 7 % and 29 % +/- 7 %. The 3-year DFS is 29 % +/- 7 %, 21 % +/- 7 %, and 27 % +/- 8 % for patients allocated to CBMT, ABMT, and CT, respectively. Contrary to protocol, 12 of 35 patients allocated to CT underwent BMT in CR2. Of these, 5 patients died after BMT and 5 patients relapsed. The authors concluded that over 50 % of patients died, failed re-induction, or relapsed again before 3 months after CR2 (median time to BMT). Intent-to-treat pair-wise comparison of ABMT with CT, CT with CBMT, and CBMT with ABMT yields hazards of 1.2, 1.1, and 0.8 with p values of 0.56, 0.80, and 0.36, respectively. Outcomes remain similar and poor for children with ALL and early marrow relapse. Bone marrow transplantation is not a complete answer to the challenge of ALL and early marrow relapse.
Goldstone and colleagues (2008) prospectively evaluated the role of allogeneic transplantation for adults with ALL and compared autologous transplantation with standard chemotherapy. Patients received 2 phases of induction and, if in remission, were assigned to allogeneic transplantation if they had a compatible sibling donor. Other patients were randomized to chemotherapy for 2.5 years versus an autologous transplantation. A donor versus no-donor analysis showed that Philadelphia chromosome-negative patients with a donor had a 5-year improved overall survival (OS), 53 % versus 45 % (p = 0.01), and the relapse rate was significantly lower (p < or = 0.001). The survival difference was significant in standard-risk patients, but not in high-risk patients with a high non-relapse mortality rate in the high-risk donor group. Patients randomized to chemotherapy had a higher 5-year OS (46 %) than those randomized to autologous transplantation (37 %; p = 0.03). Matched related allogeneic transplantations for ALL in first complete remission provide the most potent anti-leukemic therapy and considerable survival benefit for standard-risk patients. However, the transplantation-related mortality for high-risk older patients was unacceptably high and abrogated the reduction in relapse risk. There is no evidence that a single autologous transplantation can replace consolidation/maintenance in any risk group.
A technology assessment of stem cell transplantation for ALL (IQWiG, 2007) found indirect evidence of prolonged survival from reduced-intensity stem cell transplantation in patients with refractory ALL. The report found, however, that these results are limited by the small number of evaluable patients in clinical studies. The report stated that the relevance of the type of donor remains unclear. The report found no reliable evidence for superiority of non-myeloablative allogeneic stem cell transplantation (compared to myeloablative allogeneic stem cell transplant), or evidence of benefit from in-vitro manipulation of the graft in allogeneic or autologous stem cell transplantation (compared with transplantation without manipulation of the graft). The report also found no additional benefit over chemotherapy of non-myeloablative therapy or autologous transplantation; however, available studies were not designed to evaluate non-inferiority (equivalence) of these types of stem cell transplantation to chemotherapy. The report found, in patients with ALL and their subgroups, no evidence from direct comparative studies of a benefit over chemotherapy of allogeneic stem cell transplantation with an unrelated donor. However, the available literature shows potential benefit, but also harm, from allogeneic stem cell transplantation with an unrelated donor versus chemotherapy for patients with ALL.
Acute Myelogenous Leukemia:
Acute myelogenous leukemia (AML), also known as acute myeloid leukemia and acute non-lymphocytic leukemia, is a clonal disease characterized by the proliferation and accumulation of myeloid progenitor cells in the bone marrow, which ultimately leads to hematopoietic failure. The incidence of AML increases with age, and older patients typically have worse treatment outcomes than do younger patients. In patients with AML, there is an accumulation of leukemic blasts or immature forms in the bone marrow, peripheral blood, and other tissues, with a variable reduction in the production of normal platelets, mature red blood cells, and non-lymphocytic white blood cells (granulocytes, monocytes). The increased production of malignant cells, along with reduction in these mature elements, result in a variety of systemic consequences including anemia, bleeding, as well as increased risks of infection. The prognosis is poor for the majority of AML patients, based on age and/or adverse biologic features. Standard therapy for AML is highly toxic and poorly tolerated, especially in the elderly, for whom few useful therapies exist. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important option for patients with high-risk AML during first complete remission (CR1), as well as for any patient in second or subsequent remission. Use of reduced intensity conditioning transplantations (mini-allograft) has made allo-HSCT for a wider group of individuals (Stone et al, 2004; Stone, 2007; Robak and Wierzbowska, 2009).
Wahlin et al (2009) noted allo-HSCT from an HLA-identical sibling is recommended in standard and poor-risk patients, whereas unrelated donor transplant was reserved for poor-risk patients. Autologous hematopoietic stem cell transplantation (auto-HSCT) is optional for standard or poor-risk patients who are ineligible for allo-HSCT. Jones and Copelan (2009) stated that allo-HSCT provides the most powerful anti-leukemic effect in the treatment of AML. Due to its significant morbidity and mortality, it should be used in CR1 patients whose relapse risk is substantial. Reduced intensity transplantation is safer and extends the application of early transplantation to older patients and those with co-morbidities. In patients with advanced disease, allo-HSCT provides a lower chance for cure, but is often the only curative treatment available.
Edenfield and Gore (1999) noted that allogeneic bone marrow transplantation (allo-BMT) as well as autologous bone marrow transplantation (auto-BMT) have become standard approaches for the management of adults with AML. The indications for transplantation remain controversial as parallel improvements in intensive chemotherapy have resulted in excellent outcomes for many patients. Allo-BMT is the therapy of choice for patients who fail to respond to induction chemotherapy. For those patients in CR1, a policy of intensive post-remission chemotherapy with transplantation upon relapse appears to be optimal. There are no data to support transplantation in CR1, allogeneic or autologous, for those patients with leukemia characterized by favorable cytogenetic abnormalities (i.e., core-binding factor type or t[15;17]), as these patients do well with non-myeloablative strategies. Patients with relapsed disease appear to be best served with allogeneic transplantation from a HLA-matched sibling or one-antigen-mismatched family member, whereas for those patients lacking a related donor, unrelated donor allo-BMT or auto-BMT provides similar long-term overall survival.
Nathan and colleagues (2004) performed a meta-analysis to compare the effectiveness of auto-BMT with that of non-myeloablative chemotherapy alone (or no further treatment) in adults with AML. Eligible studies were identified by searching electronic databases and by examining the reference lists of relevant studies and review articles. Eligible studies were those that prospectively enrolled adults with AML and randomly assigned patients who were in CR1 and who did not have a matched sibling donor to one of the 2 consolidation therapies. Two reviewers independently assessed all studies for relevance and validity. They used a fixed-effects model to calculate the ratio of probabilities for DFS and OS at 48 months or at the nearest recorded assessment point for each study and for all studies combined. All statistical tests were 2-sided. These investigators identified 587 potentially relevant studies, 36 of which were retrieved for detailed evaluation. In the 6 studies eligible for this meta-analysis, a total of 1,044 patients were randomly assigned to receive auto-BMT or non-myeloablative chemotherapy (5 studies) or auto-BMT or no further treatment (1 study). Compared with patients who received chemotherapy or no further treatment, patients who received auto-BMT had a better DFS (ratio of disease-free survival probabilities = 1.24, 95 % confidence interval [CI]: 1.06 to 1.44; p = 0.006) but a similar overall survival (ratio of overall survival probabilities = 1.01, 95 % CI: 0.89 to 1.15; p = 0.86). The authors concluded that these findings do not support the routine use of auto-BMT in adult AML patients in CR1.
Yanada et al (2005) stated that the effectiveness of allo-HSCT from a HLA-identical sibling donor remains controversial for patients with AML in CR1. Because the karyotype identified at diagnosis is the most relevant prognostic factor for AML, it should be possible to assess the effectiveness more accurately on the basis of cytogenetic risk. These researchers carried out a meta-analysis of 5 studies, which employed both natural randomization based on donor availability and intention-to-treat analysis, with OS as an outcome of interest. Meta-regression analysis was then performed to identify the effectiveness for patients stratified into the favorable, intermediate, and poor cytogenetic risk groups. For the entire cohort, there was a statistically significant advantage with allo-HSCT in terms of OS with a summary hazard ratio (HR) of 1.15 (95 % CI: 1.01 to 1.32, p = 0.037) for the random-effect model. Meta-regression analysis showed a significant coefficient of +0.24 for the poor cytogenetic risk group, and -0.25 for the favorable cytogenetic risk group, indicating that the benefit of allo-HSCT was further increased for the former, and lost for the latter. The coefficient for the intermediate cytogenetic risk group was +0.09, and was not statistically significant. The authors concluded that these findings suggested that the effectiveness of allo-HSCT for patients with AML in CR1 depended on cytogenetic risk. The beneficial effect of allo-HSCT was yielded for the poor-risk group, and probably for the intermediate-risk groups, but was absent for the favorable-risk group.
The Dutch-Belgian Hemato-Oncology Cooperative Group and the Swiss Group for Clinical Cancer Research (HOVON-SAKK) collaborative study group (Cornelissen et al, 2007) evaluated outcome of patients with AML in CR1 entered in 3 consecutive studies according to a donor versus no-donor comparison. Between 1987 and 2004, a total of 2,287 patients were entered in these studies of whom 1,032 patients (45 %) without FAB M3 or t(15;17) were in CR1 after 2 cycles of chemotherapy, received consolidation treatment, and were younger than 55 years of age and therefore eligible for allo-HSCT. An HLA-identical sibling donor was available for 326 patients (32 %), whereas 599 patients (58 %) lacked such a donor, and information was not available in 107 patients. Compliance with allo-HSCT was 82 % (268 of 326). Cumulative incidences of relapse were, respectively, 32 % versus 59 % for patients with versus those without a donor (p < 0.001). Despite more treatment-related mortality (TRM) in the donor group (21 % versus 4 %, p < 0.001), DFS appeared significantly better in the donor group (48 % +/- 3 % versus 37 % +/- 2 % in the no-donor group, p < 0.001). Following risk-group analysis, DFS was significantly better for patients with a donor and an intermediate- (p = 0.01) or poor-risk profile (p = 0.003) and also better in patients younger than 40 years of age (p <0 .001). These investigators evaluated their findings and those of the previous MRC, BGMT, and EORTC studies in a meta-analysis, which revealed a significant benefit of 12 % in OS by donor availability for all patients with AML in CR1 without a favorable cytogenetic profile.
Craddock (2008) stated that allo-HSCT represents the most active form of anti-leukemic therapy in AML. Advances in transplant technology and supportive care have resulted in improved outcomes in patients allografted using a myeloablative conditioning regimen. At the same time the use of reduced-intensity conditioning regimens has allowed an immunologically mediated graft-versus-leukaemia effect to be exploited in older patients who were previously ineligible for transplantation on the grounds of age or co-morbidity. This coupled with the increased availability of alternative stem cell sources, in the form of either unrelated or cord blood donations, has established allogeneic transplantation as a key therapeutic strategy in the treatment of both younger and older adults with AML.
Koreth and colleagues (2009) stated that the optimal treatment of AML in CR1 is uncertain. Current consensus, based on cytogenetic risk, recommends myeloablative allo-HSCT for poor-risk but not for good-risk AML. Allogeneic-HSCT, autologous transplantation, and consolidation chemotherapy are considered of equivalent benefit for intermediate-risk AML. These researchers quantified relapse-free survival (RFS) and OS benefit of allo-HSCT for AML in CR1 overall and also for good-, intermediate-, and poor-risk AML. Systematic review and meta-analysis of prospective trials evaluating allo-HSCT versus non-allo-HSCT therapies for AML in CR1 were carried out. These researchers identified 1,712 articles. Prospective trials assigning adult patients with AML in CR1 to undergo allo-HSCT versus non-allo-HSCT treatment(s) based on donor availability and trials reporting RFS and/or OS outcomes on an intention-to-treat, donor versus no-donor basis were identified. Two reviewers independently extracted study characteristics, interventions, and outcomes. Hazard ratios with 95 % CIs were determined. Overall, 24 trials and 6,007 patients were analyzed (5,951 patients in RFS analyses and 5,606 patients in OS analyses); 3,638 patients were analyzed by cytogenetic risk (547, 2,499, and 592 with good-risk, intermediate-risk, and poor-risk AML, respectively). Inter-study heterogeneity was non-significant. Fixed-effects meta-analysis was performed. Compared with non-allo-HSCT, the HR of relapse or death with allo-HSCT for AML in CR1 was 0.80 (95 % CI: 0.74 to 0.86). Significant RFS benefit of allo-HSCT was documented for poor-risk (HR, 0.69; 95 % CI: 0.57 to 0.84) and intermediate-risk AML (HR, 0.76; 95 % CI: 0.68 to 0.85) but not for good-risk AML (HR, 1.06; 95 % CI: 0.80 to 1.42). The HR of death with alloSCT for AML in CR1 was 0.90 (95 % CI: 0.82 to 0.97). Significant OS benefit with allo-HSCT was documented for poor-risk (HR, 0.73; 95 % CI: 0.59 to 0.90) and intermediate-risk AML (HR, 0.83; 95 % CI: 0.74 to 0.93) but not for good-risk AML (HR, 1.07; 95 % CI: 0.83 to 1.38). The authors concluded that compared with non-allo-HSCT therapies, allo-HSCT has significant RFS and OS benefit for intermediate- and poor-risk AML but not for good-risk AML in CR1.
The Italian Society of Hematology and 2 affiliated societies (the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation) commissioned project to an expert panel aimed at developing clinical practice guidelines for the treatment of AML (Morra et al, 2009). After systematic comprehensive literature review, the expert panel formulated recommendations for the management of primary AML (with the exception of acute promyelocytic leukemia) and graded them according to the supporting evidence. When evidence was lacking, consensus-based statements have been added. First-line therapy for all newly diagnosed patients eligible for intensive treatment should include 1 cycle of induction with standard dose cytarabine and an anthracycline. After achieving CR, patients aged less than 60 years should receive consolidation therapy including high-dose cytarabine. Myeloablative allo-HSCT from an HLA-compatible sibling should be performed in CR1: (i) in children with intermediate- to high-risk cytogenetics or who achieved CR1 after the second course of therapy; (ii) in adults less than 40 years with an intermediate-risk; in those aged less than 55 years with either high-risk cytogenetics or who achieved CR1 after the second course of therapy. Stem cell transplantation from an unrelated donor is recommended in CR1 in adults 30 years old or younger, and in children with very high-risk disease lacking a sibling donor. Alternative donor stem cell transplantation is an option in high-risk patients without a matched donor who urgently need transplantation. Patients aged less than 60 years, who either are not candidate for allo-HSCT or lack a donor, are candidates for auto-SCT.
Hartwig and colleagues (2009) noted that for patients with myeloid malignancies who relapse after allo-HSCT, one salvage option is a second allo-HSCT. These researchers retrospectively analyzed outcomes of the second allo-HSCT in 25 patients who received at least 2 allografts from related/unrelated donors due to relapse of acute AML, myelodysplastic syndrome or myelofibrosis after the first allo-HSCT. A minority of the AML/myelodysplastic syndrome patients had reached complete hematological remission before the second allo-HSCT (6/25, 24 %). Reduced conditioning strategies were performed in the majority (n = 23). Complete remission was achieved in all 21 cases with available data after the second allo-HSCT, but relapse was seen in 11/25 patients (44 %). After a median follow-up of 18 months (range of 6 to 47), 8/25 patients (32 %) were still alive, and of those, 6 (24 %) were in stable remission. In 9 cases mortality was associated to relapse, and in 8 cases to transplant-related causes (treatment-related mortality; 8/25, 32 %). The authors concluded that a second allo-HSCT offers the chance of stable remission for some patients relapsing with a myeloid malignancy after a first allo-HSCT, although high treatment-related mortality and relapse rates remain a problem.
A technology assessment of stem cell transplantation for AML (IQWiG, 2007) found evidence from direct comparative studies demonstrated improved survival with non-myeloablative allogeneic stem cell transplantation with a related donor compared to conventional chemotherapy. Indirect comparisons suggest improved OS in both non-myeloablative allogeneic stem cell transplantation with an unrelated donor over conventional chemotherapy in persons with refractory AML. There was also evidence from indirect comparisons suggesting benefit of myeloablative allogeneic stem cell transplantation with an unrelated donor in persons with AML. The assessment found insufficient evidence to draw conclusions about the comparative efficacy of transplants with related donors versus unrelated donors for AML. The assessment found a lack of evidence comparing nonmyeloablative versus myeloablative stem cell transplant in AML. There was also insufficient evidence that in-vitro manipulation of the graft improves outcomes of allogeneic or autologous transplantation in AML.
Acute Promyelocytic Leukemia:
Sanz and Lo-Coco (2011) stated that the advent of all-trans-retinoic acid (ATRA) and its combination with anthracycline-containing chemotherapy have contributed in the past 2 decades to optimize the anti-leukemic effectiveness in acute promyelocytic leukemia (APL), leading to complete remission rates greater than 90 %, virtual absence of resistance, and cure rates of nearly 80 %. Recently reported studies from large cooperative trials have also shown that more rational delivery of treatment and improved outcomes may derive from the use of risk-adapted protocols. In particular, patients at higher risk of relapse (i.e., those presenting with WBC greater than 10 × 10(9)/L) seem to benefit from treatments that include cytarabine in the ATRA-plus-chemotherapy scheme, whereas patients with standard-risk disease can be successfully managed with less-intensive regimens that contain ATRA and anthracycline-based chemotherapy. After the outstanding results with arsenic trioxide (ATO) in the treatment of APL relapse, several experimental trials have been designed to explore the role of ATO in front-line therapy with the aim not only of minimizing the use of chemotherapy but also to reinforce standard ATRA-plus-chemotherapy regimens and additionally improve therapeutic efficacy. The authors noted that auto-HSCT and allo-HSCT can be used as consolidation therapy for APL.
In a review on "The evolving role of stem cell transplantation in acute promyelocytic leukemia", Ramadan and colleagues (2103) stated that there is no role for stem cell transplantation in APL patients in CR1. These investigators noted that auto-HSCT can be recommended for patients with prolonged (greater than 2 years) CR1 who test negative for minimal residual disease (MRD) after 2 cycles of ATO-based therapy, while patients ineligible for HSCT can continue ATO for consolidation and maintenance with close monitoring of MRD. Patients who fail to achieve CR1, those who had short CR1, or those who test positive for MRD after ATO induction and consolidation, should be considered for allo-HSCT if a suitable donor is available.
Holter Chakrabarty and colleagues (2104) identified favored choice of transplantation in patients with APL. These investigators studied 294 patients with APL in CR2 receiving allogeneic (n = 232) or autologous (n = 62) HSCT including 155 with pre-HSCT promyelocytic leukemia protein/retinoic acid receptor-alpha (PML-RAR∝) status (49 % of allogeneic and 66 % of autologous). Patient characteristics and transplantation characteristics, including TRM, OS, and DFS, were collected and analyzed for both uni-variate and multi-variate outcomes. With median follow-up of 115 (allogeneic) and 72 months (autologous), 5-year DFS favored autologous with 63 % (49 % to 75 %), compared with allogeneic at 50 % (44 % to 57 %) (p = 0.10). Overall survival was 75 % (63 % to 85 %) versus 54 % (48 % to 61 %) (p = 0.002), for auto-HSCT and allo-HSCT, respectively. Multi-variate analysis showed significantly worse DFS after allo-HSCT (HR, 1.88; 95 % CI: 1.16 to 3.06; p = 0.011) and age greater than 40 years (HR, 2.30; 95 % CI: 1.44 to 3.67; p = 0.0005). Overall survival was significantly worse after allo-HSCT (HR, 2.66; 95 % CI: 1.52 to 4.65; p = 0.0006); age greater than 40 (HR, 3.29; 95 % CI: 1.95 to 5.54; p < 0.001), and CR1 less than 12 months (HR, 1.56; 95 % CI: 1.07 to 2.26; p = 0.021). Positive pre-HSCT PML-RAR∝ status in 17 of 114 allogeneic and 6 of 41 receiving autologous transplantation did not influence relapse, treatment failure, or survival in either group. The survival advantage for autografting was attributable to increased 3-year TRM: allogeneic 30 %, autologous 2 %, and GVHD. The authors concluded that auto-HSCT yielded superior OS for APL in CR2.
An UpToDate review on "Treatment of relapsed or refractory acute promyelocytic leukemia in adults" (Larson, 2014) states that "The treatment of patients with relapsed (or refractory) acute promyelocytic leukemia (APL) is generally aimed at achieving a second complete molecular remission with plans to proceed to high-dose chemotherapy and hematopoietic cell transplantation (HCT) in those with chemotherapy-sensitive disease. Allogeneic HCT can be considered if a suitable donor is available, but for APL, allogeneic HCT is not clearly better than autologous HCT. For patients who do not achieve RT-PCR [reverse transcription polymerase chain reaction] negativity, allogeneic HCT is the preferred treatment in eligible patients with an available donor".
Chronic Myelo-Monocytic Leukemia and Juvenile Myelo-Monocytic Leukemia:
Chronic myelo-monocytic leukemia (CMML) and juvenile myelo-monocytic leukemia (JMML) are malignancies as a consequence of over-production of monocytes and myelocytes (immature leukocytes) by the bone marrow. Some of these blood stem cells never become mature leukocytes; and these immature leukocytes are known as blasts. Over time, the monocytes, myelocytes, and blasts crowd out the reticulocytes and platelets in the bone marrow leading to infection, anemia, or easy bleeding.
Kroger et al (2002) reported the results of 50 allogeneic transplantations from related (n = 43) or unrelated (n = 7) donors, performed for CMML in 43 European centers. The median age at transplant was 44 years (range of 19 to 61). Eighteen patients had excess blasts ranging from 5 % to 30 % at the time of transplantation. Two graft failures were observed (4 %). Neutrophil (greater than 0.5 x 109/L) and platelet engraftment (greater than 50 x 109/L) was reached after a median of 17 days (range of 11 to 38) and 27 days (range of 11 to 48), respectively. Acute graft-versus-host disease (GVHD grade II to IV was seen in 35 % of patients, while 20 % developed severe-acute GVHD grade III/IV. Twenty-six patients (52 %) died of treatment-related causes. After a median follow-up of 40 months (range of 11 to 110), the 5-year-estimated OS was 21 % (95 % CI: 15 to 27 %) and the 5-year estimated DFS was 18 % (95 % CI: 13 to 23 %). Earlier transplantation in the course of disease, male donor, use of unmanipulated grafts, allogeneic transplantation and occurrence of acute GVHD favored better DFS, but did not reach statistical significance. The 5-year estimated probability of relapse was 49 %. The data showed a trend for a lower relapse probability of acute GVHD grade II to IV (24 % versus 54 %; p = 0.07), and for a higher relapse rate in patients with T cell-depleted grafts (62 % versus 45 %), suggesting a "graft-versus-CMML effect".
Kerbauy and co-workers (2005) evaluated the outcomes of allogeneic HSCT in 43 patients with CMML. Patients were classified according to the French-American-British and World Health Organization classifications, as well as the International Prognostic Scoring System and the M.D. Anderson prognostic score. Co-morbidity scores were assessed by using an HSCT-specific co-morbidity index. Patients were aged 1 to 66 years (median of 48 years). Twenty-one patients received transplants from related donors (18 HLA-identical siblings and 3 HLA-non-identical family members), and 22 received transplants from unrelated donors (18 HLA matched and 4 HLA non-identical). Several busulfan or total body irradiation (TBI)-based conditioning regimens were used. Sustained engraftment was achieved in 41 patients. Eighteen are alive at 1.9 to 14.1 years, for an estimated relapse-free survival of 41 % at 4 years. Ten patients have relapsed, thus leading to a cumulative incidence of 23 % at 4 years. Risk category by International Prognostic Scoring System, World Health Organization, M.D. Anderson prognostic score, or proliferative/dysplastic status had no statistically significant association with outcomes. However, patients with higher co-morbidity scores had worse OS than patients with lower scores (p = 0.01). There was a trend for a higher relapse incidence among patients at higher risk by the M.D. Anderson prognostic score. These findings suggested that patients with few or no co-morbidities and those who undergo transplantation earlier in the disease course have the highest probability of successful outcome after allogeneic HSCT.
Elliott and colleagues (2006) reviewed their experience of allogeneic HSCT and donor lymphocyte infusions (DLI) for adults with CMML. A total of 17 consecutive adults underwent allogeneic HSCT from related (n = 14) or unrelated (n = 3) donors. Median age was 50 years (range of 26 to 60). Seven patients (41 %) demonstrated relapse or persistent disease at a median of 6 months (range of 3 to 55.5). Five patients underwent DLI for morphologic relapse and 1 for mixed donor chimerism. Two patients achieved durable complete remissions of 15 months each. The overall transplant-related mortality was 41 % (n = 7). With a median follow-up of 34.5 months, 3 patients (18 %) currently remain alive and in continuous CR. These findings demonstrated a graft-versus-leukemia effect in CMML, both for allogeneicHSCT and for DLI. However, consistent with reported experience of others, overall outcomes remain less than optimal and unpredictable.
Krishnamurthy et al (2010) reported on single-center results of 18 patients with CMML who have undergone allogeneic HSCT. The median age of patients was 54 years. Seven patients had AML, which had transformed from CMML. Overall, 11 patients received stem cells from an unrelated donor. A total of 15 patients received a T-cell-depleted fludarabine/BU-based reduced-intensity conditioning HSCT. The actuarial 3-year OS, non-relapse mortality (NRM) and relapse incidence for the cohort was 31 +/- 11 %, 31 +/- 14 % and 47 +/- 13 %, respectively. Patients with favorable cytogenetics had a 3-year DFS of 65 +/- 17 %, whereas none of the 7 patients with intermediate-risk or poor-risk cytogenetics survived beyond 2 years (p < 0.01). No patients with favorable risk cytogenetics died from NRM causes, while the 2-year NRM for the intermediate-risk/poor-risk cytogenetics subgroup was 71 +/- 22 % (p < 0.02). In terms of disease status at transplantation, patients who had less than 5 % BM blasts had a 3-year DFS of 46.9 +/- 19 % compared with those with greater than 5% blasts at the time of transplantation (i.e., 20.0 +/- 13 %). Recipient age, type of conditioning regimen or stem cell dose did not have a significant impact on overall outcomes. These findings supported existing evidence that allogeneic HSCT is a feasible therapeutic option for CMML, with the ability to attain long-term remission among patient subgroups.
Cheng et al (2012) performed a literature search and reviewed available data for adult CMML patients undergoing HSCT. The dearth of data that span 2 decades with changing transplant practices prohibited these researchers from performing a formal meta-analysis. However, these investigators elected to present the current status of HSCT in adult CMML patients. The authors concluded that carefully selected CMML patients may have the most benefit from this curative approach.
Woods and associates (2002) reported the first large prospective study of children with myelodysplastic syndrome (MDS) and JMML treated in a uniform fashion on Children's Cancer Group protocol 2891. A total of 90 with JMML, various forms of MDS, or AML with antecedent MDS were treated with a 5-drug induction regimen (standard or intensive timing). Patients achieving remission were allocated to allogeneic BMT if a matched family donor was available. All other patients were randomized between autologous BMT and aggressive non-myeloablative chemotherapy. Results were compared with patients with de novo AML. Patients with JMML and refractory anemia (RA) or RA-excess blasts (RAEB) exhibited high induction failure rates and overall remission of 58 % and 48 %, respectively. Remission rates for patients with RAEB in transformation (RAEB-T) (69 %) or antecedent MDS (81 %) were similar to de novo AML (77 %). Actuarial survival rates at 6 years were as follows: JMML, 31 % +/- 26 %; RA and RAEB, 29 % +/- 16 %; RAEB-T, 30 % +/- 18 %; antecedent MDS, 50 % +/- 25 %; and de novo AML, 45 % +/- 3 %. For patients achieving remission, long-term survivors were found in those receiving either allogeneic BMT or chemotherapy. The presence of monosomy 7 had no additional adverse effect on MDS and JMML. The authors concluded that childhood subtypes of MDS and JMML represent distinct entities with distinct clinical outcomes. Children with a history of MDS who present with AML do well with AML-type therapy. Patients with RA or RAEB respond poorly to AML induction therapy. The optimum treatment for JMML remains unknown.
Baker and colleagues (2004) examined the effectiveness of allogeneic BMT without a TBI conditioning regimen in children with JMML. A total of 8 patients with JMML (n = 6) or monosomy 7 (n = 2) underwent BMT at a median age of 20 months. Donor source included fully matched related (n = 3), mis-matched related (n = 2), or fully matched unrelated (n = 3). The conditioning regimen included busulfan (BU), cyclophosphamide (CY), and etoposide (VP16) (melphalan was substituted for VP16 in 1 patient). The first patient in the series underwent TBI. Graft-versus-host disease prophylaxis was with cyclosporin and methotrexate and in-vivo T-cell depletion (Campath 1 g) for mis-matched and unrelated transplants. Seven and 2 patients, respectively, received chemotherapy and splenectomy before BMT. At a median follow-up of 48 months after BMT, 5 patients remained in remission. The OS rate was 63 % at 5 years. All deaths occurred in patients with refractory disease at the time of BMT. Allogeneic BMT without TBI appears to be effective therapy for JMML and avoids some of the potential late sequelae of TBI in pre-school children.
Korthof et al (2005) noted that JMML is a childhood leukemia for which allogeneic BMT is the only curative therapy. These investigators performed 26 BMTs in 23 children (age of 0.5 to 12.7 years). Conditioning was CY/TBI based (1980 to 1996, n = 14) or BU/CY/melphalan based (1996 to 2001, n = 9). Donors were HLA-identical siblings (n = 11), unrelated volunteers (n = 9) or mis-matched family members (n = 3). A total of 10 patients survive in CR (median follow-up of 6.8 years, range of 3.1 to 22.2 years). Relapse or persistent disease was observed in 8 and 2 patients, respectively. Nine of these patients died, 1 achieved a second remission following acute non-lymphatic leukemia chemotherapy (duration to date 5.3 years). Transplant-related mortality occurred in 4 patients. Overall survival at 5 and 10 years was 43.5 %. Using T-cell-depleted, one-antigen mis-matched unrelated donors was the only significant adverse factor associated with relapse in multi-variate analysis (p = 0.039, HR 4.9). Together with a trend towards less relapse in patients with GVHD and in patients transplanted with matched unrelated donors, this suggested a graft-versus-leukemia effect of allogeneic BMT in JMML.
Locatelli and associates (2005) stated that allogeneic HSCT is the only proven curative therapy for JMML. The European Working Group on Childhood MDS (EWOG-MDS) and the European Blood and Marrow Transplantation (EBMT) Group reported the outcome of 100 children (67 boys and 33 girls) with JMML given unmanipulated HSCT after a preparative regimen including busulfan, cyclophosphamide, and melphalan. Forty-eight and 52 children received transplants from an HLA-identical relative or an unrelated donor (UD), respectively. The source of hematopoietic stem cells was bone marrow, peripheral blood, and cord blood in 79, 14, and 7 children, respectively. Splenectomy had been performed before HSCT in 24 children. The 5-year cumulative incidence of transplantation-related mortality and leukemia recurrence was 13 % and 35 %, respectively. Age older than 4 years predicted an increased risk of disease recurrence. The 5-year probability of event-free survival for children given HSCT from either a relative or a UD was 55 % and 49 %, respectively (p = NS), with median observation time of patients alive being 40 months (range of 6 to 144). In multi-variate analysis, age older than 4 years and female sex predicted poorer outcome. Results of this study compare favorably with previously published reports. Disease recurrence remains the major cause of treatment failure. Outcome of UD-HSCT recipients is comparable to that of children receiving transplants from an HLA-identical sibling.
Loh (2011) stated that JMML is an aggressive myeloid neoplasm of childhood that is clinically characterized by over-production of monocytic cells that can infiltrate organs, including the spleen, liver, gastrointestinal tract, and lung. Juvenile myelo-monocytic leukemia is categorized as an overlap myeloproliferative neoplasms/myelodysplastic syndromes by the World Health Organization and also shares some clinical and molecular features with CMML, a similar disease in adults. While the current standard of care for patients with JMML relies on allogeneic HSCT, relapse is the most frequent cause of treatment failure.
The Lymphoma and Leukemia Society (2009) noted that "Allogeneic stem cell transplantation is the only known curative option for JMML patients. This treatment has been noted to achieve long-term survival in up to 50 % of patients but relapses are known to occur in up to 30 % to 40 % of patients after transplantation. Second transplants have been beneficial for some patients". The Lymphoma and Leukemia Society also noted that "Allogeneic stem cell transplantation has been used to treat and sometimes cure CMML patients".
The National Cancer Institute (2010) noted that "Bone marrow/stem-cell transplantation appears to be the only current treatment that alters the natural history of CMML". Regarding JMML, the NCI (2010) noted that "No consistently effective therapy is available for JMML .... Bone marrow transplantation seems to offer the best chance for a cure".
The National Comprehensive Cancer Network (2010) clinical practice guidelines in myelodysplastic syndromes noted that "Allogeneic HSCT from an HLA-matched sibling donor is a preferred approach for treating a portion of patients with MDS. Standard conditioning is used for relatively younger patients, while the approach using non-myeloablative conditioning is preferable in older individuals".
|CPT Codes / HCPCS Codes / ICD-10 Codes
|Information in the [brackets] below has been added for clarification purposes.  Codes requiring a 7th character are represented by "+":
|ICD-10 codes will become effective as of October 1, 2015:
|CPT codes covered if selection criteria are met:
|Blood-derived hematopoietic cell harvesting for transplantation, per collection; allogeneic [ablative or non-myeloablative]
|Bone marrow harvesting for transplantation; allogeneic
|Hematopoietic progenitor cell (HPC); allogeneic transplantation per donor
|autologous transplantation
|Allogeneic lymphocyte infusions
|HLA typing; A, B or C multiple antigens
|DR/DQ, multiple antigens
|lymphocyte culture, mixed (MCL)
|lymphocyte culture, primed (PLC)
|Other CPT codes related to the CPB:
|38206 - 38215
|Transplant preparation procedures
|86920 - 86923
|Compatibility test each unit
|96401 - 96450
|Chemotherapy administration code range
|HCPCS codes covered if selection criteria are met:
|Bone marrow or blood-derived stem cells (peripheral or umbilical), allogeneic or autologous, harvesting, transplantation, and related complications; including: pheresis and cell preparation/storage; marrow ablative therapy; drugs, supplies, hospitalization with outpatient follow-up; medical/surgical, diagnostic, emergency services, and rehabilitative services; and the number of days of pre- and post-transplant care in the global definition
|ICD-10 codes covered if selection criteria are met:
|Acute lymphoblastic leukemia [ALL]
|Acute myeloblastic leukemia
|Monocytic leukemia [CMML/JMML]
Acute Lymphoblastic Leukemia:
Acute Myelogenous Leukemia:
Chronic Myelo-Monocytic Leukemia and Juvenile Myelo-Monocytic Leukemia:
Acute Promyelocytic Leukemia:


text:
I recently moved to Washington DC. My bike is my primary form of transportation. Once a week or so I find myself travelling to a destination one to five miles from home that I've never been to before. To choose a route I use a hardcopy of the DC Bicycle Map. I try to pick streets that have bike lanes or have low traffic volumes. I pretty much memorize the route I'll take prior to getting on my bike. Sometimes I bring the map along just in case I take a wrong turn or discover a street I wanted to take turns out to be one-way.
I'm very curious to know how others choose their routes, particularly when in unfamiliar territory. Could you share the city you live in and the methods you use to reach new destinations? Thanks.

subset: commoncrawl


text:
Time shows itself all over the body, but most prominently in the eyes, the hands, and the tally marks that appear on your scalp each year. Erase your lines with this Groupon.
Choose from Three Options
- $75 for three microdermabrasion treatments (a $150 value)
- $115 for five microdermabrasion treatments (a $250 value)
- $145 for seven microdermabrasion treatments (a $350 value)
Mantra Medi Spa
Mantra Medi Spa's licensed aestheticians welcome their clients into more than 14 years of skin-fixing experience. Their services range from microdermabrasion treatments that uproot trapped dirt and confetti to laser hair-removal sessions.
100% of 16 customers recommend
"its good and nice service."
"Extremely nice there. Will go back."
"Must get microdermabrasion, skin feels great!"
3939 Mid Rivers Mall Dr.
St. Peters, MO 63376
+16364476800Get Directions


text:
Welcome To ProMark Repair Service, Louisville, Ohio
We would like to welcome you to Promark Repair Service's online store. We are striving to become our area's premier light, medium and heavy duty automotive repair facilities in the Canton, Alliance, Louisville and New Philadelphia areas.
We currently offer mechanical repair, emergency and site maintenance repair services, whether at a job site, the side of the road or even a well pad in the oilfield industry. We also have partnered with Bridgestone, Firestone, BFGoodrich among many other manufacturers to handle our areas need for a reputable tire supplier, no need to ask, if the vehicle has tires, we can supply them! Our massive shop, at a smidge under 16,000 square feet, is equipped with the latest and industry leader of tools and equipment to handle any job, no matter how small or to the most complex. We also offer full fabrication and welding services in house! And if you need a part, we can handle that too!
"One Call Handles it all At PROMARK"
- All Brands
|8:30 a.m.
|5:00 p.m.
|On Call
|On Call


text:
Unisexual rock lizard might be outcompeting its bisexual progenitors in the Caucasus
Version of Record online: 1 SEP 2010
DOI: 10.1111/j.1095-8312.2010.01498.x
© 2010 The Linnean Society of London
Biological Journal of the Linnean Society
Volume 101, Issue 2, pages 447–460, October 2010
Additional Information
How to Cite
TARKHNISHVILI, D., GAVASHELISHVILI, A., AVALIANI, A., MURTSKHVALADZE, M. and MUMLADZE, L. (2010), Unisexual rock lizard might be outcompeting its bisexual progenitors in the Caucasus. Biological Journal of the Linnean Society, 101: 447–460. doi: 10.1111/j.1095-8312.2010.01498.x
Publication History
- Issue online: 20 SEP 2010
- Version of Record online: 1 SEP 2010
- Received 7 March 2010; revised 26 April 2010; accepted for publication 29 April 2010
- Abstract
- Article
- References
- Cited By
- climatic niche;
- competition;
- lizards;
- niche displacement;
- parthenogenesis;
- suitable habitat analysis
We compared the distributions, abundances and ecological requirements of parthenogenetic lizard Darevskia 'dahli' and its bisexual progenitors, D. portschinskii and D. mixta, in Georgia. We developed a regression model relating the species abundances with the distribution of climates. Darevskia portschinskii lives in warmer and drier climates than D. mixta; D. 'dahli' has the intermediate requirements. Temperature is more important than humidity for D. portschinskii, humidity is more important for D. mixta and both temperature and humidity are important for D. 'dahli'. Suitable habitats of all three species overlap broadly; however, the observed ranges partly overlap only for D. 'dahli' and D. portschinskii. The observed abundance of each species, related to its predicted abundance, is lower at the sites with potential competitors. Darevskia 'dahli' occupies a higher proportion of the suitable habitats and has higher abundances than the progenitor species. Competition with D. 'dahli' is an important factor determining current distribution pattern of D. portschinskii and D. mixta. The parthenogen is a stronger competitor than the bisexual breeders and potential advantages of the bisexual reproduction remain unrealized in the given temporal and spatial scale. To explain domination of bisexually breeding lizards on the global scale, considering climate changes in geological timescale is necessary. © 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 101, 447–460.


text:
wastewater disposal Companies in Austria
Jung Pumpen GmbH
based in Steinhagen, GERMANY
For 90 years the name JUNG PUMPEN has stood for reliable and modern drainage technology. To a certain extent JUNG PUMPEN`s success can undoubtedly be attributed to the fact that the company always strives to offer the best possible solution. But another important success factor is its ongoing dialog with partners and customers, because there is no other way for a company ...
Process Wastewater Technologies LLC
based in Rosedale, NORTH CAROLINA (USA)
Process Wastewater Technologies LLC is a leading global manufacturer of products for biological treatment, CSO/SSO, biosolids/sludge handling and municipal wastewater. We revolutionized the storm water and CSO treatment industry in the early 1990s by introducing continuous deflective separation technology to the market. We offer technologies for gross solids and sediment ...
IWA Publishing
based in London, UNITED KINGDOM
IWA Publishing`s vision is to be the leading international membership association for the improvement of urban water management worldwide in an environmentally sustainable way. Specifically, IWA Publishing`s coverage includes all aspects of water supply and treatment, wastewater collection, treatment and disposal and overall management of water quality and quantity ...
CST Wastewater Solutions
based in Roseville, AUSTRALIA
CST Wastewater Solutions P/L (CST) was founded as Contra Shear Technology: a supplier of specialised, patented wastewater screens for the industrial and municipal wastewater markets. Since then, our company has flourished to become a premier provider of innovative wastewater treatment solutions throughout Australia and equipment supplier around the world. CST offers the ...
Wastewater Resources Inc. (WRI)
based in Scottsdale,, ARIZONA (USA)
Wastewater Resources Inc. (WRI) is an original equipment manufacture of wastewater reclamation and advanced treatment systems. Since its inception in 1988, WRI has advocated the continuous reclamation, treatment, and reuse of treated wastewaters to create sustainable water supplies. All of our installed advanced water purification (AWP) plants reclaim, clean, and recycle ...
Jet Inc.
based in Cleveland, OHIO (USA)
Jet is a provider of advanced onsite wastewater treatment systems throughout the world. The Jet residential wastewater treatment plant is the cleaner, lower-odor, lower-maintenance alternative to traditional septic systems. Jet Inc. has designed dependable residential and commercial wastewater treatment systems since 1955, leading the industry with innovative design, ...
SIMPEC S.r.l.
based in Nova Milanese (MB), ITALY
Simpec works in the design, construction, installation and service of industrial water and wastewater treatment plants. Main sector of the company is metal and plastic surface finishing treatments. Simpec works for all the industries that use and consume water in their different production processes. Simpec realizes also plants for landfills (leachate treatment), plants ...
Aeration Industries International (AII)
based in Chaska, MINNESOTA (USA)
Aeration Industries has the expertise and products to provide a full range of wastewater treatment solutions to optimize municipal and industrial wastewater treatment applications, from process water supply to wastewater treatment, sludge management to produced water return. Aeration Industries combines patented technologies with engineering expertise to develop complete ...
GLOBAL Wastewater Treatment Systems, Inc.
based in Grand Island, NEBRASKA (USA)
GLOBAL Wastewater Treatment Systems, Inc. is a leader in the manufacturing and distribution of pre-engineered wastewater treatment systems. Our products are designed according to the latest technology that is available in the United States.
Boydel Wastewater Technologies Inc. - Electrocoagulation
based in Ladysmith, BRITISH COLUMBIA (CANADA)
Welcome to Boydel Companies. Our WaterMiner water scrubbing technology consists of a globally patented hybrid electrocoagulation device and process that has been under in-house development and external validation over the previous 4.5 years. The proprietary Boydel EC reactor is a two stage insitu electrocoagulation-electrolysis design that has no plates, is ...


text:
COLUMBUS, Ohio (AP) - Two protesters were arrested Sunday at the Statehouse after one of them took down the rainbow flag that represents gay rights and burned it, authorities said.
Charles Spingola, 43, and Donald Richardson, 63, were taken into custody during an altercation between the protesters and gay rights advocates, said Lt. John Born of the State Highway Patrol.
Spingola and Richardson were released from the Franklin County jail on bond and are to be arraigned today.
Amarillo Globe-News © 2016. All Rights Reserved. Terms of Service | Privacy Policy / About Our Ads


text:
With all the same features of the original popular design, this Tipperary Sportage 8500 helmet is exceptionally light and comfortable. This riding helmet offers superior impact resistance and a vent system that increases airflow. ASTM F1163-15/SEI Certified.
The Samshield® Shadow Matt® Helmet** combines sophisticated design with superior ventilation. This elegant helmet stays looking like new with its scratch-resistant and durable paint. It has a removable and washable memory foam liner that conforms to your head and doesn't compress so that you stay comfortable. **F1163-04a/SEI Certified.
The Tipperary Sportage 8500 helmet is loaded with all of the same feature that made the original so popular. This is an exceptionally light and comfortable riding helmet. Featuring superior impact resistance and a vent system with increased airflow, this helmet will keep you cool on all of your rides. **ASTM F1163-04a/SEI Certified.
The Charles Owen AYR8 Helmet** uses technologically-advanced materials for the latest technology in thermoregulation for a cool ride. This ventilated helmet has 12 apertures front to rear that help maximize cooling airflow. It has a low-profile design that flatters your face.
This lightweight Troxel® Sport Helmet** keeps riders across disciplines comfortable at a budget-friendly price. Multiple air vents allow cooling airflow and a washable liner helps keep it fresh. **ASTM F1163-15/SEI Certified.
This IRH® Elite Extreme Helmet** keeps the serious rider feeling comfortable and looking stylish. Well ventilated, it has a low profile and is exceptionally lightweight. Air vents keep the head cool, while a padded lining wicks moisture. The adjustable leather harness closes with a clip and has a slot for a ponytail. **ASTM F1163-15/SEI Certified.
This Samshield® Premium Helmet** offers superior comfort by not placing any contact or pressure on the rider's forehead. Sophisticated in style and technical in design, it has a plush liner that conforms to the head and won't compress. **ASTM F1163-15/SEI Certified.
The Charles Owen GR8 Helmet** has a low-profile design and a slightly rounded brim that complements your face. This helmet has a microfiber suede exterior that resists scuffs, a technically-designed outer shell with high-grade polystyrene for impact absorption, and a soft, moisture-wicking Coolmax® lining. **ASTM F1163-04a/SEI certified.
Lightweight and low-profile, this Ovation® Extreme Helmet** has high-flow air vents to help keep your head cool. It's built for a close fit and features an easy adjust dial with extra-strong adjustment teeth. The Coolmax® liner can be removed for washing. **ASTM F1163-15/SEI Certified.
The GPA® Speed Air Evolution Helmet** is designed for intensive riding. Vents on the front, back and sides accelerate air flow for effective cooling. Slim profile visor. Cushioned pad system in back provides extra comfort. Adjustable chin strap with a fast-locking buckle and center comfort pad. **ASTM F1163-04a/SEI Certified.
Low-profile geometry makes this IRH® ATH™ SSV Helmet** polular choice for serious riders. This attractive riding helmet has vents that allow optimal cooling airflow. A rich ultrasuede covering maintains its looks.**ASTM F1163-15/SEI Certified.
The low-profile Charles Owen Wellington Professional Helmet** has a broad brim to keep the sun out of your eyes. The high-quality microfiber suede cover resists fading. An ultra-soft, suede-lined harness covers your nape, while an interior headband cradles your head in comfort. For a classic look, ventilation holes are visible only on the inside. **ASTM F1163-15/SEI Certified.


text:
My Voice ControllerFree
Quick Specs
Total Downloads:18,088
Date Added:Aug. 28, 2014
File Size:641.53KB
Downloads Last Week:41
Product ranking:#13 in Voice Recognition Software
From 5 Hyphen Studios: My Voice Controller software allows you to emulate mouse and keyboard inputs by using voice recognition. Common uses for this software are gaming and assistance for the disabled/injured. I wrote this program to assist me with playing various games including World of Warcraft. Features â?¢ Mapping voice keywords to common tasks; â?¢ Send a single key; â?¢ Send a text phrase; â?¢ Key down/up; â?¢ Mouse button click (Left, right, middle); â?¢ Mouse cursor move, add; â?¢ Mouse cursor position save and load; â?¢ Delays - Useful for keyboard, mouse and macro input; â?¢ Macros - Allows common/long commands to be referenced by a single key word; â?¢ Special voice commands such as repeat last command; â?¢ Push To Talk (PTT); â?¢ Web browser; â?¢ Run external programs; â?¢ Text to Speech (TTS); â?¢ Many more features available. See the profile commands section of this document.
read more +
see all reviews +
read more +
More Products to Consider
- Take an open-source approach to office productivity.View, navigate, and print PDF files.Command applications with voice, dictate e-mails and documen...Transform PDF documents to Excel documents.
- Open, edit, and save files using the new file formats in 200...Convert JPEG, BMP, TIFF, and PNG images to PDF files.Get a comprehensive library of 4,500 sample business letters...Prepare any business documents from 6,000 professionally wri...
- Carry out your writing work while having access to multiple ...Read and write data in different formats.Create your own commands for any software you use.Create invoices and delivery notes for various purposes.
- View Flash multimedia content through your browser.Create, encrypt, and merge PDF files.Create invoices and delivery notes for various purposes.Keep track of how you use your PC.
- Play and organize a variety of audio and video files, as wel...Record mouse clicks with macro and keyboard typings and auto...Convert CSV, TXT, or Excel files to OFX format.Take Google's Chrome browser with you on a USB stick.


text:
The European Film Awards have announced the nominees of this year's European Discovery Award, given to "young and upcoming director for a first full-length feature film." This year's nominees are Steve McQueen's "Hunger," Aida Begic's "Snijeg," Seyfi Teoman's "Tatil Kitabi," and Sergey Dvortsevoy's "Tulpan." The winner will be announced at the 21st annual ceremony, December 6, 2008 in Copenhagen. [Peter Knegt]
By Indiewire | Indiewire September 30, 2008 at 5:30AM


text:
ANALYSIS Why Israel Should Let Foreign Journalists Into Gaza
You want balanced reporting of events? Then it's necessary to ensure the freedom of the press and restrict censorship.
There is a contradiction between Israel completely blocking off access to the Gaza Strip for journalists, and the growing protests of officials in Jerusalem about the way in which many international media representatives are covering the events there. After all, if there is no way for we journalists to get to the points of conflict personally, and hence no chance for us judge the facts with our own eyes, we have no choice but to rely on the reports coming out from victims and witnesses in the Strip. For the most part, they will be are mainly Palestinians or sources close to them. There is no alternative.
You want balanced reporting of events? Then it's necessary to ensure the freedom of the press and restrict censorship. With no possibility of directly checking the veracity of facts, and against the background of the inevitable frustrations that stem from the censorship restrictions, journalists (particularly those from the Western media) will tend, almost by reflex, to adopt the most dramatic versions, the most shocking stories, and the most extreme explanations. The logic behind this is simple: If you hide something from me, that means first and foremost that you want to hide it, and secondly, that you have done something wrong.
Thirty years of experience in areas of confrontation, 20 of them as correspondent for Corriere della Sera in Jerusalem, have taught me to relate with maximum caution to reports about the number of casualties and the dynamics of the events.
I recall the exaggerated data about victims among the Palestinians during the first intifada, the perpetual comparisons between the military repression and the Holocaust, and the baseless reports about civilians dying of hunger during the previous siege of Gaza. Yasser Arafat and Palestinian sources in Beirut and Tunis were grand masters in the dissemination of this kind of disinformation.
The spokesmen for Saddam Hussein in the aftermath of the 1991 Gulf War were the same. They were eager at that time to show us what they claimed as victims of the use of bombs containing depleted uranium, and children suffering from cancer, had not received treatment because of the American-instigated embargo on Iraq. But not one of them spoke to us about the victims of the Iraqi military repression, about the mass graves, about the fact that the hospitals belonging to the Republican Guards were equipped with the necessary appliances and medications.
Some examples
Three episodes from earlier campaigns I covered illustrated for me just how important a free press is in Israel.
The first took place in the Jenin refugee camp in April 2002. Do you remember? The camp was surrounded, and the media was not allowed in. From a distance, one could see pillars of smoke and hear occasional shooting. The Palestinians spoke about 1,500 dead - a toll that later dropped to 500. There were rumors of mass graves, of entire families that had been shot in the streets by Zionist soldiers.
On April 13, I succeeded in crossing through the army barricades on foot and reached the hospital bordering on the refugee camp. I was prepared to see scenes of a bloodbath. Anyone who follows what takes place in the arena of war knows that generally speaking, the ratio of dead to wounded is one to three. That is to say, if there are 500 dead, there will be at least 1,500 wounded. What did I find? Absolutely nothing. The hospital was almost deserted, doctors were playing cards in the emergency room, there were two women in labor and one old man who had had an appendectomy.
In one of the wards I finally saw wounded - 25 people who had been lightly wounded. And the stories they told were indeed heart-rending. "I saw a woman and three children who were shot close by here," one of them told me. Nonetheless, when they were asked for the names of the dead and to show where the bodies were, the responses became evasive. In short, it was all talk and nothing could be verified, nothing was concrete. At the end of that day, I wrote that the death toll was not more than 50 and that most of them were combatants. And indeed, a few weeks later, following a UN investigation, it was reported that there had been 53 dead. The second episode took place in the Church of the Nativity in Bethlehem, at the end of a prolonged siege by the Israeli army in April and May of that same year. On May 10, three hours after the fighting ended, I went to the church with a small group of Italian journalists, with the assistance of Franciscan monks. Here are the opening lines of my dispatch that appeared the following day in the Corriere della Sera: "It is not true that there was systematic desecration of the Christian holy places by Muslim extremists, and it is not true that the Palestinians who were under siege inside lacked food." After a whole month of disinformation, conflicting reports and propaganda, our presence at the site made it possible for us to examine what the actual facts were, especially the second point. Inside the church and in the halls of the Franciscan hostel, there was a plethora of food, as I described it in the article; there were bottles of water, and no one had died of hunger, contrary to the claims of some of the local church spokesmen.
Finally, there was the case of Kafr Qana in southern Lebanon, on July 30, 2006. We the media representatives, who that day were in Tyre in order to follow what was happening in the war, were well aware of the massacre that had taken place at the Unifil base there in the spring of 1996. The reported death toll in that incident stood at 107, victims whose names had been engraved on a memorial stone at the entrance to the village, and whoe were of course mentioned in the ongoing reports filed by all of us.
We arrived at the village during the few hours of hiatus promised by the Israeli army - until 5 P.M., the Israeli army spokesmen made it clear to us. On the way there, in the area where the bombing had taken place, there were heart-rending scenes and the villagers were shocked. The Hezbollah people told us that the death toll in the two families, Shalub and Hashem, was at least 63, and that almost all of them had been children. The entire village was covered with green Islamic flags and yellow Hezbollah flags. But it was from these sites that one of the Hezbollah leaders had acted to get missiles from Syria and Iran, as one of the Unifil heads told us off the record.
Three days later, the director of the hospital in Tyre, Mustafa Jeradiyeh, said in an interview with me: "The total number of dead at Kafr Qana was 27, and 17 of them were children, some of them very small. A day-old baby was one of them. The number of wounded was 18."
I bring up all these details in order to stress the importance attached to having a free press. I well remember how, in 1989, then-prime minister Yitzhak Shamir claimed that had the media not been in the occupied territories, the intifada would have been over within 48 hours. And I know that in Israel, like in many other places in the world, in the West as well, there are people who sympathize with his opinion. With all due respect, I do not. Israel's strength, especially in the Middle East, one often rightly flaunted by its diplomatic representatives, is that it is a democracy. But there is no democracy without a free press, and there is no public debate and no intellectual incentive without it. There is no freedom.
The conclusion is self evident - open up Gaza to the media. Allow us to do our work. Sometimes it will be one sided, most of the time superficial, always not in perfect fashion. But there is no doubt that it is preferable to propaganda, to rumors and to blatant fabrications.
The writer is a journalist for the Italian newspaper Corriere della Sera.
Want to enjoy 'Zen' reading - with no ads and just the article? Subscribe todaySubscribe now


text:
Our Standard and Superior Rooms are refined spaces with simple, understated décor and scenic city or garden views. Relax in a plush armchair with a book or newspaper and a snack from the refreshment center. All rooms offer a dual-line speakerphone, data port, and complimentary High Speed Internet Access for productivity. Refresh in the marble bathroom, and experience deep rest in our signature Westin Heavenly® Bed. Mais >
These spacious accommodations offer floor-to-ceiling windows with panoramic views of the city or garden, plus soothing, upscale décor that includes a plush love seat or chaise lounge for quiet relaxation. Complimentary High Speed Internet Access, data port, and a dual-line speakerphone make productivity easy. Energize in the sleek marble bathroom, and enjoy unmatched rest in the inviting Westin Heavenly® Bed, boasting ten layers of comfort. (366-495 Pés quadrados / 34-46 Metros quadrados) Mais >
Our traditional Japanese-Style Rooms are found in a special guest house, tucked amidst greenery with calming garden views through a floor-to-ceiling window or from the enclosed patio. These sublimely simple tatami rooms are decorated in customary Japanese style throughout, with legless chairs and a tokonoma alcove. A 40-inch flat screen LCD TV provides easy entertainment. The bedroom is appointed with a Heavenly(SM) futon, and the peaceful bathroom features a cedar tub. (334-527 Pés quadrados / 31-49 Metros quadrados) Mais >
These sizeable guest rooms are specially designed for families. Each open layout with city or garden views is furnished with a sofa, armchairs, and 50-inch flat screen LCD TV. Stay connected or productive at an executive work desk with data port and complimentary High Speed Internet Access for work, email, or games. At the end of the day, everyone will sleep soundly in a Westin Heavenly® Bed. Refresh each morning in the sleek marble bathroom. (560 Pés quadrados / 52 Metros quadrados) Mais >
These spacious guest rooms offer soothing garden views for an ideal setting to focus on tasks or rest during downtime. Relax in the plush armchair or wind down with the news on the 42-inch flat screen LCD TV. Ease into work at the desk with data port and complimentary High Speed Internet Access, and sleep soundly in the Westin Heavenly® Bed. Refresh each morning in the sleek marble bathroom. Guests also enjoy Westin Executive Club Lounge access. (388-431 Pés quadrados / 36-40 Metros quadrados) Mais >
Our stylish and understated Junior Suites let you spread out and feel at home amid relaxing views of the city or gardens. Settle into a comfortable living area furnished with plush seating and a 32-inch flat screen LCD TV or complete tasks with complimentary High Speed Internet Access. At the end of the day, retreat to the private bedroom with a Westin Heavenly® Beds and refresh in the sleek marble bathroom. Guests also enjoy Westin Executive Club Lounge access. (549-560 Pés quadrados / 51-52 Metros quadrados) Mais >
Enjoy the upscale comfort and ample space of our Luxury Suites, with remarkable garden views through floor-to-ceiling windows and the furnished balcony. Spread out in the tastefully-furnished living area with a flat screen LCD TV plus a business-ready work desk. At the end of the day, retreat to the private bedroom with its Westin Heavenly® Bed. The spa-like bathroom ensures relaxation with a Jacuzzi tub and separate shower. Guests also enjoy Westin Executive Club Lounge access. (678-915 Pés quadrados / 63-85 Metros quadrados) Mais >
Para explorar a experiência lemeridien.com por completo, será preciso instalar o Flash Player versão 6.39. Clique aqui para fazer o download grátis. Alternativamente, aqui para experimentar a versão não Flash do site lemeridien.com. Divirta-se.


text:
Vladimir Putin Trolls America
Vladimir Putin has decided to troll America with an op-ed in the New York Times. He gets the better of Barack Obama with much of his op-ed, including pointing out that if our rule is we won't touch countries with nukes it is just going to incentivize countries getting nukes. But he ends with this: My working and personal relationship with President Obama is marked | Read More »


text:
Photography: GMWritten by on May 18, 2013
The '14 Corvette will start at $51,995; the convertible at $56,995. The 'Ray has a 6.2L LT1, a new seven-speed trans with Active Rev Matching, a carbon-fiber hood, an aluminum frame that shed 99 pounds over the previous car, and more.
What's your opinion of the new 'Vette?


text:
Media Aashki2 3gp
Below are videos for media aashki2 3gp. You can watch the video related to media aashki2 3gp by hitting the Watch Video link on each video.
Media Aashki2 3gp Results
Watch Aashiqui 2 Best Scenes - youtu.be/95AT64V70XA Share it on Facebook - /Aashiqui2AudioJukebox Presenting full songs of most ... Aashiqui 2 Jukebox Full Songs Aditya Roy Kapur Shraddha Kapoor was published on April 3, 2013


text:
I went once, many years ago........Never again. {{shudder}} :lol:
Printable View
I went once, many years ago........Never again. {{shudder}} :lol:
I like it a lot. I haven't been for quite a while, and honestly I've only seen the "Under New Management" show with Iago and Zazu, but I really enjoyed that one. I grew up with Disney sing-along videos that featured "The Tiki Tiki Tiki Room" and "Let's All Sing Like The Birdies Sing", so even before I'd ever visited one of the parks, it had sort of a special place in my heart. :) Really excited to see the original show now that it's back! It will be brand-new for me, and I know everyone says they prefer the original show better.
Please put me down for a "like". Although we don't visit each time, we have gone quite a bit and I like the nostalgic feel of the place. Takes you back to the 1960's (at least the classic version did)
Tried it for the first time last year.
Would rather sit on IASW for a whole day.
Won't be visiting again this year :D :lol:
I can't believe all the hate for this!
I don't want to know if you hate Carousel if Progress!!
Originally Posted by Johnie, post: 301903
Shall we find out :wink:
We love CoP!
Gives us a chance for a snooze...
Only joking we always do it as we love to sing along!
I'm sort of surprised how many people dislike it too! It was always my understanding that it was widely adored by most Disney fans!
I like it. Not my favorite, but it just doesn't feel like a complete trip to Disney unless we hit the Tiki Room. I really didn't like the updated version, so I'm thrilled that it's back to the older version.
The original Tiki Room at Disneyland was built to be a restaurant and you can still see some vestiges of that. The restaurant idea did no work out though and it was transformed into the attraction that we see today.


text:
~ Read ~
Premiered January, 2013
Follow the romance of Lord Gray & Scarlet Ruby Müller
Lord Ashton Gray (Charlie Woods) is not amused with Scarlet Ruby Müller (Julia Aks). Starting with her street-side marriage proposal, to her habit of sucking on metal rings; from her mysterious Ghost Guardian, to her insane Mining, Minerals and Mayhem party, she is an audacious upstart who is now seeking entrance into his beloved Elements Club.
Scarlet Ruby is no fool. A woman bent on revenge, she knows that Lord Gray's club, a London-based investment group dedicated to scientific endeavors, holds the key to her cherished older brother's death and to the men seeking to take over her family's mining company. As the founder of the Elements Club, what could Lord Gray be hiding?
Segment 01 of The Elements Club series
When the worlds of gemstones and flowers collide, who will emerge victorious in the quest for love and truth?
Segment 02 of The Elements Club series
It took only one look into her eyes, and Lord Edward Gelson, the Viscount of Wesbury, knew his soul was instantly ensnared. But where to find this elusive, masked entertainer with the voice of a spiritual siren, the body of a goddess, and a psyche filled with transparent internal pain? Could the mysterious spirit-stirring entertainer be the aloof, fashion-centered, queen of the racetrack, Master V? Or was his prophetic gifting rebelling by lying to his passionate instinct?
Master V has not let a wife-beating ex-husband, an obsessed fan, or a chauvinist racing owner get the best of her plans to emerge into Society. Determined to keep her heart in check, her goal of building her secret singing career, while publicly racing her prize stallion, are put to the test by the attentions of Lord Wesbury. His achingly sweet, yet daring love notes, his gift of dream interpretation, and his off-beat sense of humor centered on zany animal caricatures, threaten to thaw her heart and breathe life into her bitter soul.
When a public crisis arises, Master V and Lord Wesbury wrestle with the meaning of spiritual destiny and the value of life-long ardor.


text:
change location
We work will all client will all types of budget book your wedding or event with Elegant Weddings Events and Moments by Cindy and...
View Profile »
Our Certified Destination Wedding Specialists guide couples through the planning process and make all of the travel arrangements.The...
Are you looking for a planner who "gets" you, who understands your needs, your style, your personality and your budget concerns?
Belles Memoires provides wedding and event coordination with the highest possible quality services for the most realistic prices. No dream should be forfeited (more)
Create Account
Add Listing
Plan, book and shop for your wedding with inspiration as your guide. Plus, save photos to your favorites!


text:
Drinking freshly extracted vegetable juices is the fastest way to obtain the maximum nutrients necessary to enable the body's self-healing mechanism to restore and maintain optimal health. When the juice is separated from the fiber, most nutrients stay in the juice. Because the fiber is removed, the living nutrients in the juice reach the bloodstream and the cellular level in minutes. And the body benefits from far more living nutrients than you can get from even the best raw whole food diet.
In his book Live Food Juices, Dr. H. E. Kirschner, M.D., explains this:
"...The power to break down the cellular structure of raw vegetables, and assimilate the precious elements they contain, even in the healthiest individual is only fractional, not more than 35%, and in the less healthy, down to 1%. In the form of juice, these same individuals assimilate up to 92% of these elements...It is a well known fact that all foods must become liquid before they can be assimilated."
Other benefits of BeetMax:


text:
Friday, August 08, 2014
2 Comments | Copyright: IANS
Bipasha, who was seen as one of the six key characters in the comic film which wasn't received well, has nothing against the film's co-producers Vashu Bhagnani and Fox Star Studios. But she is glad she took a stand against promoting "Humshakals" when it was required.
She had said she was "extremely disturbed by the end result" of the film and "didn't know how to promote the film with all honesty".
Asked if she will work with Sajid again, Bipasha said here in an interaction: "No, I will never work with him."
"I have nothing against Vashu-ji and Fox Star Studios. They have put in so much money and I respect that. I love Vashu-ji, it's just that I didn't want to come to a podium and lie and look like a fool. I am the worst liar in the world. So I took a stand."
Bipasha says such situations are rare.
"I have been in this industry for way too long. I have worked with many people and nobody has said anything against me. It's rare that you make such a mistake, it's one of those films. I did this film on the basis of trust. Anyone who has seen the film will understand why I didn't promote it.
"I was six minutes into it and I don't know what I was doing in it," she said of the movie, which also stars Ali Khan">Saif Ali Khan, Ram Kapoor, Riteish Deshmukh, Tamannaah and Esha Gupta.
Sarath Kumar experiments with negative role
When I need a new kick, I'll consider direction: Chetan Bhagat
User Comments & RatingsJoin India Forums for free to comment on this story. Have an account already? Use Quick Login to comment.
2 member(s) Liked the above comment :
Orion, pasbarun
Filmmaker Omung Kumar on Wednesday said no scenes featuring Richa ...
Filmmaker duo Sajid-Farhad, who are gearing up for the release of ...
Views : 7253 | Comments : 5
Views : 3755 | Comments : 2
Views : 2673 | Comments : 0
Views : 472 | Comments : 0
Disclaimer: All Logos and Pictures of various Channels, Shows, Artistes, Media Houses, Companies, Brands etc. belong to their respective owners, and are used to merely visually identify the Channels, Shows, Companies, Brands, etc. to the viewer. Incase of any issue please contact the webmaster.
Popular Channels :Star Plus | Zee TV | Sony TV | Colors TV | SAB TV | Life OK
Quick Links :Top 100 TV Celebrities | Top 100 Bollywood Celebs | About Us | Contact Us | Advertise | Forum Index


text:
Ruben Studdard's soulful 'Love IS,' his fourth album and first release since 2006, is out today, May 19 on Hickory Records / 19 Recordings. Entertainment Weekly says Studdard is in "fine voice" with "a romance-themed mix of crafty originals and sturdy covers."
Studdard is wrapping up a tour with the critically acclaimed musical Ain't Misbehavin' and will perform June 13 at New York City's Central Park Summerstage. His music video for "Together" is being played nationwide on BETJ, VH-1 Soul and MTV Hits. Watch "Together" here:
Acclaimed producers Jimmy Jam and Terry Lewis helm "Love IS," while Stargate hold down production for "Together" and "How You Make Me Feel," which, EW opined, "[gives] Ne-Yo a run for his dance-pop money."
The 12-song collection features exceptional versions of Kris Kristofferson's "For The Good Times," Michael Jackson's "I Can't Help It" (penned by Stevie Wonder) and a "totally gorgeous rendition" (EW) of Extreme's "More Than Words."
'Love IS' also contains "A Song For Her," co-written by Ruben for his wife; the deeply romantic "My Love Is A Rock"; and "Footprints In The Sand," a powerful and inspirational album closer.
Ruben Studdard Live:
June 13- New York, NY – Central Park Summerstage (3pm)
'Love IS' Track List:
1). Together
2). More Than Words
3). Song For Her
4). How You Make Me Feel
5). Don't Make 'Em Like U No More
6). I Can't Help It
7). Just Because
8). My Love Is A Rock
9). The Long and Winding Road
10). For the Good Times
11). We Got Love (That's Enough)
12). Footprints in the Sand
Ruben Studdard On MySpace:
-Stay Fly!


text:
Lies, Damn Lies
Begala, Paul, Newsweek
Byline: paul Begala
How the GOP helped Obama win.
At h i s final rally, Barack Obama stood before 20,000 adoring Iowans, just yards from the Des Moines headquarters where his 2008 Children's Crusade began. Something happened. Something we have rarely seen: Obama wept. A few elegant tears slowly descended from his left eye, perhaps in appreciation of the enormity--and the improbability--of what he was about to accomplish. Within 24 hours those tears had turned into dancing. The reelected president was more exuberant, more idealistic, even, than the sober, somber young president-elect of Grant Park 2008. And for good reason.
The economic current against President Obama this year was more like a typhoon than a tide. To put it into perspective, from Truman-era 1948 to Bush-era 2008, America experienced a total of 39 months during which the unemployment rate sat at or over 8 percent. In the 46 months that Barack Obama has been president, we have had 43 months over 8 percent. Median household income for the middle class has dropped by almost $5,000 since 2000. And median net worth-- the total wealth of a middle-class family--dropped by a staggering 40 percent between 2007 and 2010.
Given those economic realities, it Obama wasn't impeached. The fact that he has been reelected is the surest sign that his parents gave him the right name: "Barack," which means "blessed."
How did he do it? Let me count the ways.
The Republicans Helped Him. The strongest Republicans--Jeb Bush, Mitch Daniels, Chris Christie, Marco Rubio, John Thune, Haley Barbour--all took a pass this time. And so Americans looking to replace the president were treated to a clown-car primary in which a new leader emerged every week--each crazier than the last. Romney was the strongest candidate in a weak field, but that's a dubious honor--kind of like being voted the sexiest member of the Supreme Court.
Romney dispatched each rival by outspending him or her by many millions, and by outflanking them on the far right. Let me tell you, when you're attacking Newt Gingrich and Rick Santorum from the right, you are out there. Romney could have run as a moderate. He could have accepted the Bowles-Simpson call for the rich to pay slightly more in taxes. Or opposed 30-round ammo clips for assault weapons. Or stuck with any of his multiple-choice positions on abortion or gay rights.
Instead he ran to the right of George W. Bush, abandoning his support for Bush's sensible comprehensive immigration reform and shamefully attacking Gingrich and Rick Perry for daring to treat undocumented immigrants as human beings.
Romney made a brazen effort to move to the middle in the final weeks of the campaign and it almost worked. If he had run consistently as a Massachusetts moderate, willing to challenge the outdated orthodoxy of the far right, he might be president-elect today.
Fibbing Fails. In his first ad, Mitt Romney quoted Barack Obama saying, "If we keep talking about the economy, we're going to lose." But that was Obama quoting a GOP aide four years ago. The full quote is: "Senator McCain's campaign actually said, and I quote, 'If we keep talking about the economy, we're going to lose.'" From that deceitful ad to his last, disgraceful falsehood that Jeep was transferring production to China, Romney ran a stunningly dishonest campaign. But the leader of the Party of Lincoln should have known you can't fool all of the people all of the time. Romney's Jeep ad backfired, and Obama's support among union members in Ohio--the kind of folks who build those Jeeps in Toledo--far surpassed his 2008 support. Romney may as well have run ads that said, "I think you're stupid," because that's the message voters got.
Conventions Are Still Consequential. Every four years we hear the gripe that conventions don't matter. Baloney. No, there are no smoke-filled rooms in which grizzled pols horse-trade over who the nominee will be: the nominees are chosen by voters. …


text:
|P B ROAD, Chennai, Tamil Nadu, 600007 Furniture
- Evaluations:
3 times viewed 2 times listed
all type of belt conveyor, conveyors, repairing of all type of stone crusher spare parts, rollers conveyor, drum pulley, vibrating screen, perforator, crusher bolts, side plate ... more
... Leaf perforator: Bucculatrix loxophila. ... Cultivars and land races of Africa and Asia Minor, one wild from Southern African. more
Turtle Rock Resort, Southern Oregon Coast RV Park at Gold Beach Oregon - on the Ocean ... Custom built American perforator for varied document and ID marking applications. more
Reprint Author E-mail : firstname.lastname@example.com : Author(s): Lars Steinstraesser; Andrea Rittig; Kai Gevers; Michael Sorkin; Tobias Hirsch; Marco Kesting; Michael ... more
Perforator [Sai Ram Perforators] Perforated Metals [Audhi Lakshmi Engineering Works] ... Plot Promotors [Southern Plot Promoters] Plot Promoters [S.R. Housing Society (Regd.)] more
This was done in a special machine of Edison's invention, called a perforator, consisting of a series of punches operated by a bank of keys--typewriter fashion. more
005184 VIDYADHARAN K T, PALANIAPPAN K (Southern Region, Geological Survey of India, Hyderabad) : Mafic-ultramafic and related rocks of Southern Indian shield-potential target ... more


text:
Hal Leonard Singer's Musical Theatre Anthology Teen's Edition Mezzo-Soprano/Alto/Belter Book/2CD
Sku #H66919000000000
Hal Leonard
Vocal Method Books
- Write a Review
- Seen a Lower Price? Click Here.
45 day price guarantee, 45 day return policy, 100% secure shopping
Songs in authentic versions, chosen especially for teens, with introductory notes about shows and plots; recorded accompaniment CDs are available. The Mezzo-Soprano/Alto edition features 36 songs, including: Castle on a Cloud ∑ Day by Day ∑ Defying Gravity ∑ Freddy, My Love ∑ I Cain't Say No ∑ I Won't Say (I'm in Love) ∑ Mama Who Bore Me ∑ Memory ∑ On My Own ∑ Popular ∑ Sixteen Going on Seventeen ∑ Start of Something New ∑ What It Means to Be a Friend ∑ and more.
- Softcover with CD
- 228 pages
- Size: 12" x 9"
- Editor: Richard Walters