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Chronic lymphocytic leukemia (also called CLL) is a blood and bone marrow disease that usually gets worse slowly. CLL is one of the most common types of leukemia in adults. It often occurs during or after middle age; it rarely occurs in children.
Normally, the body makes blood stem cells (immature cells) that become mature blood cells over time. A blood stem cell may become a myeloid stem cell or a lymphoid stem cell.
A myeloid stem cell becomes one of three types of mature blood cells:
A lymphoid stem cell becomes a lymphoblast cell and then one of three types of lymphocytes (white blood cells):
In CLL, too many blood stem cells become abnormal lymphocytes and do not become healthy white blood cells. The abnormal lymphocytes may also be called leukemia cells. The lymphocytes are not able to fight infection very well. Also, as the number of lymphocytes increases in the blood and bone marrow, there is less room for healthy white blood cells, red blood cells, and platelets. This may cause infection, anemia, and easy bleeding.
This summary is about chronic lymphocytic leukemia. See the following PDQ summaries for more information about leukemia:
Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn't mean that you will not get cancer. Talk with your doctor if you think you may be at risk. Risk factors for CLL include the following:
Usually CLL does not cause any signs or symptoms and is found during a routine blood test. Signs and symptoms may be caused by CLL or by other conditions. Check with your doctor if you have any of the following:
The following tests and procedures may be used:
Treatment options depend on:
The prognosis (chance of recovery) depends on:
Staging is the process used to find out how far the cancer has spread. It is important to know the stage of the disease in order to plan the best treatment. The following tests may be used in the staging process:
In stage 0 chronic lymphocytic leukemia, there are too many lymphocytes in the blood, but there are no other signs or symptoms of leukemia. Stage 0 chronic lymphocytic leukemia is indolent (slow-growing).
In stage I chronic lymphocytic leukemia, there are too many lymphocytes in the blood and the lymph nodes are larger than normal.
In stage II chronic lymphocytic leukemia, there are too many lymphocytes in the blood, the liver or spleen is larger than normal, and the lymph nodes may be larger than normal.
In stage III chronic lymphocytic leukemia, there are too many lymphocytes in the blood and there are too few red blood cells. The lymph nodes, liver, or spleen may be larger than normal.
In stage IV chronic lymphocytic leukemia, there are too many lymphocytes in the blood and too few platelets. The lymph nodes, liver, or spleen may be larger than normal and there may be too few red blood cells.
Refractorychronic lymphocytic leukemia is cancer that does not get better with treatment.
Different types of treatment are available for patients with chronic lymphocytic leukemia. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.
Watchful waiting is closely monitoring a patient's condition without giving any treatment until signs or symptoms appear or change. This is also called observation. During this time, problems caused by the disease, such as infection, are treated.
Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.
Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, or the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.
See Drugs Approved for Chronic Lymphocytic Leukemia for more information.
Splenectomy is surgery to remove the spleen.
Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Monoclonal antibodytherapy and tyrosine kinase inhibitor therapy are types of targeted therapy used in the treatment of chronic lymphocytic leukemia.
Monoclonal antibody therapy is a cancer treatment that uses antibodies made in the laboratory from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances in the body that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells.
Tyrosine kinase inhibitor therapy is a cancer treatment that blocks signals needed for tumors to grow.
This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web site.
Chemotherapy with stem cell transplant is a method of giving chemotherapy and replacing blood-forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient or a donor and are frozen and stored. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body's blood cells.
Biologic therapy is a treatment that uses the patient's immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body's natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.
For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.
Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.
Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.
Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.
Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.
Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.
Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.
Treatment of stage 0 chronic lymphocytic leukemia is usually watchful waiting.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage 0 chronic lymphocytic leukemia. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.
Treatment of stage I, stage II, stage III, and stage IV chronic lymphocytic leukemia may include the following:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia and stage IV chronic lymphocytic leukemia. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.
Treatment of refractorychronic lymphocytic leukemia may include the following:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with refractory chronic lymphocytic leukemia. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.
For more information from the National Cancer Institute about chronic lymphocytic leukemia, see the following:
For general cancer information and other resources from the National Cancer Institute, see the following:
This information is provided by the National Cancer Institute.
This information was last updated on June 9, 2014.
Estimated new cases and deaths from chronic lymphocytic leukemia (CLL) in the United States in 2014:[1]
CLL is a disorder of morphologically mature but
immunologically less mature lymphocytes and is manifested by progressive
accumulation of these cells in the blood, bone marrow, and lymphatic tissues.[2]
In this disorder, lymphocyte counts in the blood are usually greater than or equal to 5,000/mm3 with a characteristic immunophenotype (CD5- and CD23-positive B cells).[3][4]
As assays have become more sensitive for detecting monoclonal B-CLL–like cells in peripheral blood, researchers have detected a monoclonal B-cell lymphocytosis (MBL) in 3% of adults older than 40 years and 6% in adults older than 60 years.[5] Such early detection and diagnosis may falsely suggest improved survival for the group and may unnecessarily worry or result in therapy for some patients who would have remained undiagnosed in their lifetime, a circumstance known in the literature as overdiagnosis or pseudodisease.[6][7]
In two selected series of more than 900 patients followed prospectively for a median of 5 to 7 years, overt CLL requiring chemotherapy occurred in 7% of patients.[5][8] In a database analysis and for up to 77 months before diagnosis, almost all patients with a diagnosis of CLL had prediagnostic B-cell clones that were identified in peripheral blood when available.[4][9]
For patients with progressing CLL, treatment with conventional doses of chemotherapy is not
curative; selected patients treated with allogeneic stem cell transplantation
have achieved prolonged disease-free survival.[10][11][12][13][14] Antileukemic
therapy is frequently unnecessary in uncomplicated early disease.[15] The median survival for all patients ranges from 8 to 12 years in older trials with data from the 1970s through the 1990s.[15][16] There is, however, a large variation in survival among individual patients, ranging from several months to a normal life expectancy. Treatment must be individualized based on the clinical behavior of the disease.[17]
As found in one report, CLL occurs primarily in middle-aged and elderly adults, with increasing
frequency in successive decades of life.[18] The clinical course of this
disease progresses from an indolent lymphocytosis without other evident disease
to one of generalized lymphatic enlargement with concomitant pancytopenia.
Complications of pancytopenia, including hemorrhage and infection, represent a
major cause of death in these patients.[19] Immunological aberrations,
including Coombs-positive hemolytic anemia, immune thrombocytopenia, and
depressed immunoglobulin levels may all complicate the management of CLL.[20]
Prognostic factors that may help predict clinical outcome include cytogenetic
subgroup, immunoglobulin mutational status, ZAP-70, and CD38.[2][21][22][23][24][25][26][27][28][29] (Refer to the Prognostic Factors section in the Stage Information for Chronic Lymphocytic Leukemia section of this summary for more information.) Patients who develop an aggressive high-grade non-Hodgkin lymphoma, usually diffuse large B-cell lymphoma and termed a Richter transformation, have a poor prognosis.[30]
Patients with CLL are also at increased risk for other malignancies, even before therapy.[31]
Confusion with other diseases may be avoided by determination of cell surface
markers. CLL lymphocytes coexpress the B-cell antigens CD19 and CD20 along
with the T-cell antigen CD5.[32] This coexpression only occurs in one other
disease entity, mantle cell lymphoma. CLL B cells express relatively low
levels of surface-membrane immunoglobulin (compared with normal peripheral
blood B cells) and a single light chain (kappa or lambda).[15] CLL is diagnosed
by an absolute increase in lymphocytosis and/or bone marrow infiltration
coupled with the characteristic features of morphology and immunophenotype, which confirm the characteristic clonal population.
The differential diagnosis must exclude hairy cell leukemia and
Waldenström macroglobulinemia. (Refer to the PDQ summaries on Hairy Cell Leukemia and Adult Non-Hodgkin Lymphoma Treatment for more information.) Waldenström
macroglobulinemia has a natural history and therapeutic options similar to CLL,
with the exception of hyperviscosity syndrome associated with macroglobulinemia
as a result of elevated immunoglobulin M. Prolymphocytic leukemia (PLL) is a
rare entity characterized by excessive prolymphocytes in the blood with a
typical phenotype that is positive for CD19, CD20, and surface-membrane
immunoglobulin and negative for CD5. These patients demonstrate splenomegaly
and poor response to low-dose or high-dose chemotherapy.[15][33]
(2-chlorodeoxyadenosine) appears to be an active agent (60% complete remission
rate) for patients with de novo B-cell prolymphocytic leukemia.[34][Level of evidence: 3iiiDiv] Alemtuzumab (campath-1H), an anti-CD52 humanized monoclonal antibody, has been used for 76 patients with T-cell prolymphocytic leukemia after failure of prior chemotherapy (usually pentostatin or cladribine) with a 51% response rate (95% confidence interval, 40%–63%) and median time to progression of 4.5 months (range, 0.1–45.4 months).[35][Level of evidence: 3iiiDiv] These response rates have been confirmed by other investigators.[36] Patients with CLL who show prolymphocytoid transformation
maintain the classic CLL phenotype and have a worse prognosis than PLL
Large granular lymphocyte (LGL) leukemia is characterized by
lymphocytosis with a natural killer cell immunophenotype (CD2, CD16, and CD56)
or a T-cell immunophenotype (CD2, CD3, and CD8).[37][38][39] These patients often
have neutropenia and a history of rheumatoid arthritis. The natural history is
indolent, often marked by anemia and splenomegaly. This condition appears to
fit into the clinical spectrum of Felty syndrome.[40] A characteristic genetic finding in almost 50% of the patients with T-cell LGL involves mutations in the signal transducer and activator of the transcription 3 gene (STAT 3).[41] Therapy includes
low doses of oral cyclophosphamide or methotrexate, cyclosporine, and treatment of
the bacterial infections acquired during severe neutropenia.[37][39][42][43]
Other PDQ summaries containing information about CLL include the following:
American Cancer Society: Cancer Facts and Figures 2014. Atlanta, Ga: American Cancer Society, 2014. Available online. Last accessed May 21, 2014.
Dighiero G, Hamblin TJ: Chronic lymphocytic leukaemia. Lancet 371 (9617): 1017-29, 2008.
Hallek M, Cheson BD, Catovsky D, et al.: Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 111 (12): 5446-56, 2008.
Shanafelt TD, Kay NE, Jenkins G, et al.: B-cell count and survival: differentiating chronic lymphocytic leukemia from monoclonal B-cell lymphocytosis based on clinical outcome. Blood 113 (18): 4188-96, 2009.
Rawstron AC, Bennett FL, O'Connor SJ, et al.: Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia. N Engl J Med 359 (6): 575-83, 2008.
Dighiero G: Monoclonal B-cell lymphocytosis--a frequent premalignant condition. N Engl J Med 359 (6): 638-40, 2008.
Fazi C, Scarfò L, Pecciarini L, et al.: General population low-count CLL-like MBL persists over time without clinical progression, although carrying the same cytogenetic abnormalities of CLL. Blood 118 (25): 6618-25, 2011.
Shanafelt TD, Kay NE, Rabe KG, et al.: Brief report: natural history of individuals with clinically recognized monoclonal B-cell lymphocytosis compared with patients with Rai 0 chronic lymphocytic leukemia. J Clin Oncol 27 (24): 3959-63, 2009.
Landgren O, Albitar M, Ma W, et al.: B-cell clones as early markers for chronic lymphocytic leukemia. N Engl J Med 360 (7): 659-67, 2009.
Ritgen M, Stilgenbauer S, von Neuhoff N, et al.: Graft-versus-leukemia activity may overcome therapeutic resistance of chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene status: implications of minimal residual disease measurement with quantitative PCR. Blood 104 (8): 2600-2, 2004.
Moreno C, Villamor N, Colomer D, et al.: Allogeneic stem-cell transplantation may overcome the adverse prognosis of unmutated VH gene in patients with chronic lymphocytic leukemia. J Clin Oncol 23 (15): 3433-8, 2005.
Khouri IF, Keating MJ, Saliba RM, et al.: Long-term follow-up of patients with CLL treated with allogeneic hematopoietic transplantation. Cytotherapy 4 (3): 217-21, 2002.
Doney KC, Chauncey T, Appelbaum FR, et al.: Allogeneic related donor hematopoietic stem cell transplantation for treatment of chronic lymphocytic leukemia. Bone Marrow Transplant 29 (10): 817-23, 2002.
Pavletic SZ, Khouri IF, Haagenson M, et al.: Unrelated donor marrow transplantation for B-cell chronic lymphocytic leukemia after using myeloablative conditioning: results from the Center for International Blood and Marrow Transplant research. J Clin Oncol 23 (24): 5788-94, 2005.
Rozman C, Montserrat E: Chronic lymphocytic leukemia. N Engl J Med 333 (16): 1052-7, 1995.
Wierda WG, O'Brien S, Wang X, et al.: Prognostic nomogram and index for overall survival in previously untreated patients with chronic lymphocytic leukemia. Blood 109 (11): 4679-85, 2007.
Montserrat E: CLL therapy: progress at last! Blood 105 (1): 2-3, 2005.
Catovsky D, Fooks J, Richards S: Prognostic factors in chronic lymphocytic leukaemia: the importance of age, sex and response to treatment in survival. A report from the MRC CLL 1 trial. MRC Working Party on Leukaemia in Adults. Br J Haematol 72 (2): 141-9, 1989.
Anaissie EJ, Kontoyiannis DP, O'Brien S, et al.: Infections in patients with chronic lymphocytic leukemia treated with fludarabine. Ann Intern Med 129 (7): 559-66, 1998.
Mauro FR, Foa R, Cerretti R, et al.: Autoimmune hemolytic anemia in chronic lymphocytic leukemia: clinical, therapeutic, and prognostic features. Blood 95 (9): 2786-92, 2000.
Döhner H, Stilgenbauer S, Benner A, et al.: Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 343 (26): 1910-6, 2000.
Hamblin TJ, Davis Z, Gardiner A, et al.: Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood 94 (6): 1848-54, 1999.
Damle RN, Wasil T, Fais F, et al.: Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood 94 (6): 1840-7, 1999.
Rosenwald A, Alizadeh AA, Widhopf G, et al.: Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. J Exp Med 194 (11): 1639-47, 2001.
Klein U, Tu Y, Stolovitzky GA, et al.: Gene expression profiling of B cell chronic lymphocytic leukemia reveals a homogeneous phenotype related to memory B cells. J Exp Med 194 (11): 1625-38, 2001.
Orchard JA, Ibbotson RE, Davis Z, et al.: ZAP-70 expression and prognosis in chronic lymphocytic leukaemia. Lancet 363 (9403): 105-11, 2004.
Rassenti LZ, Huynh L, Toy TL, et al.: ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. N Engl J Med 351 (9): 893-901, 2004.
Kröber A, Bloehdorn J, Hafner S, et al.: Additional genetic high-risk features such as 11q deletion, 17p deletion, and V3-21 usage characterize discordance of ZAP-70 and VH mutation status in chronic lymphocytic leukemia. J Clin Oncol 24 (6): 969-75, 2006.
Byrd JC, Gribben JG, Peterson BL, et al.: Select high-risk genetic features predict earlier progression following chemoimmunotherapy with fludarabine and rituximab in chronic lymphocytic leukemia: justification for risk-adapted therapy. J Clin Oncol 24 (3): 437-43, 2006.
Tsimberidou AM, Keating MJ: Richter syndrome: biology, incidence, and therapeutic strategies. Cancer 103 (2): 216-28, 2005.
Tsimberidou AM, Wen S, McLaughlin P, et al.: Other malignancies in chronic lymphocytic leukemia/small lymphocytic lymphoma. J Clin Oncol 27 (6): 904-10, 2009.
DiGiuseppe JA, Borowitz MJ: Clinical utility of flow cytometry in the chronic lymphoid leukemias. Semin Oncol 25 (1): 6-10, 1998.
Melo JV, Catovsky D, Galton DA: The relationship between chronic lymphocytic leukaemia and prolymphocytic leukaemia. I. Clinical and laboratory features of 300 patients and characterization of an intermediate group. Br J Haematol 63 (2): 377-87, 1986.
Saven A, Lee T, Schlutz M, et al.: Major activity of cladribine in patients with de novo B-cell prolymphocytic leukemia. J Clin Oncol 15 (1): 37-43, 1997.
Keating MJ, Cazin B, Coutré S, et al.: Campath-1H treatment of T-cell prolymphocytic leukemia in patients for whom at least one prior chemotherapy regimen has failed. J Clin Oncol 20 (1): 205-13, 2002.
Dearden CE, Matutes E, Catovsky D: Alemtuzumab in T-cell malignancies. Med Oncol 19 (Suppl): S27-32, 2002.
Sokol L, Loughran TP Jr: Large granular lymphocyte leukemia. Oncologist 11 (3): 263-73, 2006.
Semenzato G, Zambello R, Starkebaum G, et al.: The lymphoproliferative disease of granular lymphocytes: updated criteria for diagnosis. Blood 89 (1): 256-60, 1997.
Lamy T, Loughran TP Jr: How I treat LGL leukemia. Blood 117 (10): 2764-74, 2011.
Bowman SJ, Sivakumaran M, Snowden N, et al.: The large granular lymphocyte syndrome with rheumatoid arthritis. Immunogenetic evidence for a broader definition of Felty's syndrome. Arthritis Rheum 37 (9): 1326-30, 1994.
Koskela HL, Eldfors S, Ellonen P, et al.: Somatic STAT3 mutations in large granular lymphocytic leukemia. N Engl J Med 366 (20): 1905-13, 2012.
Loughran TP Jr, Kidd PG, Starkebaum G: Treatment of large granular lymphocyte leukemia with oral low-dose methotrexate. Blood 84 (7): 2164-70, 1994.
Dhodapkar MV, Li CY, Lust JA, et al.: Clinical spectrum of clonal proliferations of T-large granular lymphocytes: a T-cell clonopathy of undetermined significance? Blood 84 (5): 1620-7, 1994.
Staging is useful in chronic lymphocytic leukemia (CLL) to predict prognosis and also to stratify
patients to achieve comparisons for interpreting specific treatment results.
Anemia and thrombocytopenia are the major adverse prognostic variables.
CLL has no standard staging system. The Rai
staging system and the Binet classification are presented below.[1][2] A
National Cancer Institute (NCI)-sponsored working group has formulated standardized guidelines for
criteria related to eligibility, response, and toxic effects to be used in future clinical
trials in CLL.[3]
Stage 0
Stage 0 CLL is characterized by absolute lymphocytosis (>15,000/mm3) without adenopathy, hepatosplenomegaly, anemia, or
Stage I
Stage I CLL is characterized by absolute lymphocytosis with
lymphadenopathy without hepatosplenomegaly, anemia, or thrombocytopenia.
Stage II
Stage II CLL is characterized by absolute lymphocytosis with either
hepatomegaly or splenomegaly with or without lymphadenopathy.
Stage III
Stage III CLL is characterized by absolute lymphocytosis and anemia
(hemoglobin <11 g/dL) with or without lymphadenopathy, hepatomegaly, or
Stage IV
Stage IV CLL is characterized by absolute lymphocytosis and
thrombocytopenia (<100,000/mm3) with or without
lymphadenopathy, hepatomegaly, splenomegaly, or anemia.
Clinical stage A*
Clinical stage A CLL is characterized by no anemia or thrombocytopenia and fewer than three areas of
lymphoid involvement (Rai stages 0, I, and II).
Clinical stage B*
Clinical stage B CLL is characterized by no anemia or thrombocytopenia with three or more areas of
lymphoid involvement (Rai stages I and II).
Clinical stage C
Clinical stage C CLL is characterized by anemia and/or thrombocytopenia regardless of the number of
areas of lymphoid enlargement (Rai stages III and IV).
*Lymphoid areas include cervical, axillary, inguinal, and spleen.
The Binet classification integrates the number of nodal groups involved with
the disease with bone marrow failure. Its major benefit derives from the
recognition of a predominantly splenic form of the disease, which may have a
better prognosis than in the Rai staging, and from recognition that the
presence of anemia or thrombocytopenia has a similar prognosis and does not
merit a separate stage. Neither system separates immune from nonimmune causes
of cytopenia. Patients with thrombocytopenia or anemia or both, which is caused by extensive marrow infiltration and impaired production (Rai III/IV, Binet C)
have a poorer prognosis than patients with immune cytopenias.[4] The
International Workshop on CLL has recommended
integrating the Rai and Binet systems as follows: A(0), A(I), A(II); B(I),
B(II); and C(III), C(IV).[5] The NCI-sponsored working
group has published guidelines for the diagnosis and treatment of CLL in both
clinical trial and general practice settings.[3] Use of these systems allows
comparison of clinical results and establishment of therapeutic guidelines.
Prognostic factors
New prognostic markers are now available to the clinician and investigator.[6][7] The use of these markers to stratify patients in clinical trials, to help assess the need for therapy, and to help select the type of therapy continues to evolve. Prospective trials to verify and establish the role of these prognostic markers are ongoing. No large multivariable analyses exist as yet to test the relative power of these individual prognostic variables.[8] Prognostic indices are under evaluation and will require prospective validation.[9]
Other prognostic factors include:
Rai KR, Sawitsky A, Cronkite EP, et al.: Clinical staging of chronic lymphocytic leukemia. Blood 46 (2): 219-34, 1975.
Binet JL, Auquier A, Dighiero G, et al.: A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer 48 (1): 198-206, 1981.
Moreno C, Hodgson K, Ferrer G, et al.: Autoimmune cytopenia in chronic lymphocytic leukemia: prevalence, clinical associations, and prognostic significance. Blood 116 (23): 4771-6, 2010.
Chronic lymphocytic leukemia: recommendations for diagnosis, staging, and response criteria. International Workshop on Chronic Lymphocytic Leukemia. Ann Intern Med 110 (3): 236-8, 1989.
Developments in the treatment of lymphoproliferative disorders: rising to the new challenges of CLL therapy. A report of a symposium presented during the 48th American Society of Hematology Annual Meeting and Exposition, December 8, 2006, Orlando, Florida. Clin Adv Hematol Oncol 5 (3 Suppl 5): 1-14; quiz 15-6, 2007.
Binet JL, Caligaris-Cappio F, Catovsky D, et al.: Perspectives on the use of new diagnostic tools in the treatment of chronic lymphocytic leukemia. Blood 107 (3): 859-61, 2006.
Shanafelt TD, Jenkins G, Call TG, et al.: Validation of a new prognostic index for patients with chronic lymphocytic leukemia. Cancer 115 (2): 363-72, 2009.
Kharfan-Dabaja MA, Chavez JC, Khorfan KA, et al.: Clinical and therapeutic implications of the mutational status of IgVH in patients with chronic lymphocytic leukemia. Cancer 113 (5): 897-906, 2008.
Crespo M, Bosch F, Villamor N, et al.: ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med 348 (18): 1764-75, 2003.
Grever MR, Lucas DM, Dewald GW, et al.: Comprehensive assessment of genetic and molecular features predicting outcome in patients with chronic lymphocytic leukemia: results from the US Intergroup Phase III Trial E2997. J Clin Oncol 25 (7): 799-804, 2007.
Kröber A, Seiler T, Benner A, et al.: V(H) mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia. Blood 100 (4): 1410-6, 2002.
Shanafelt TD, Witzig TE, Fink SR, et al.: Prospective evaluation of clonal evolution during long-term follow-up of patients with untreated early-stage chronic lymphocytic leukemia. J Clin Oncol 24 (28): 4634-41, 2006.
Catovsky D, Richards S, Matutes E, et al.: Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. Lancet 370 (9583): 230-9, 2007.
Ghia P, Guida G, Stella S, et al.: The pattern of CD38 expression defines a distinct subset of chronic lymphocytic leukemia (CLL) patients at risk of disease progression. Blood 101 (4): 1262-9, 2003.
Montserrat E, Sanchez-Bisono J, Viñolas N, et al.: Lymphocyte doubling time in chronic lymphocytic leukaemia: analysis of its prognostic significance. Br J Haematol 62 (3): 567-75, 1986.
Di Giovanni S, Valentini G, Carducci P, et al.: Beta-2-microglobulin is a reliable tumor marker in chronic lymphocytic leukemia. Acta Haematol 81 (4): 181-5, 1989.
Treatment of chronic lymphocytic leukemia (CLL) ranges from periodic
observation with treatment of infectious, hemorrhagic, or immunologic
complications to a variety of therapeutic options, including steroids,
alkylating agents, purine analogs, combination chemotherapy, monoclonal
antibodies, and transplant options.[1] Because this disease is generally not
curable, occurs in an elderly population, and often progresses slowly, it is
most often treated in a conservative fashion.[1] In asymptomatic patients, treatment may be deferred until the patient becomes symptomatic as the disease progresses. Since the rate of progression may vary from patient to patient, with long periods of stability and sometimes spontaneous regressions, frequent and careful observation is required to monitor the clinical course.[2]
A meta-analysis of randomized
trials showed no survival benefit for immediate versus delayed therapy for
patients with early stage disease, nor for the use of combination regimens
incorporating an anthracycline compared with a single-agent alkylator for
advanced stage disease.[3][Level of evidence: 1iiA] A variety of clinical
factors, including IgVH mutation, chromosomal abnormalities by fluorescent in situ hybridization analysis or cytogenetics, beta-2-microglobulin, and lymphocyte doubling time may be helpful in predicting progression of
Infectious complications in advanced disease are in part a consequence of the
hypogammaglobulinemia and the inability to mount a humoral defense against
bacterial or viral agents. Herpes zoster represents a frequent viral infection
in these patients, but infections with Pneumocystis carinii and Candida
albicans may also occur. The early recognition of infections and the
institution of appropriate therapy are critical to the long-term survival of
these patients. A randomized study of intravenous immunoglobulin (400
mg/kg every 3 weeks for 1 year) in patients with CLL and
hypogammaglobulinemia produced significantly fewer bacterial infections and a
significant delay in onset of first infection during the study period.[4]
There was, however, no effect on survival. Routine chronic administration of
intravenous immunoglobulin is expensive, and the long-term benefit (>1
year) is unproven.[5][6]
Second malignancies and treatment-induced acute leukemias may also occur in a
small percentage of patients.[7] Transformation of CLL to diffuse large cell
lymphoma (Richter syndrome) carries a poor prognosis with a median survival
of less than 1 year, though 20% of the patients may live more than 5 years
after aggressive combination chemotherapy.[8] (Refer to the PDQ summary on
Adult Non-Hodgkin Lymphoma Treatment for more information.)
Autoimmune hemolytic anemia and/or thrombocytopenia can occur in patients with
any stage of CLL.[9] Initial therapy involves corticosteroids with or without
alkylating agents (fludarabine can worsen the hemolytic anemia). It is
frequently advisable to control the autoimmune destruction with
corticosteroids, if possible, prior to administering marrow-suppressive
chemotherapy because such patients may be difficult to transfuse successfully
with either red blood cells or platelets. Alternate therapies include
high-dose immune globulin, rituximab, cyclosporine, azathioprine, splenectomy, and low-dose radiation therapy to
the spleen.[10][11] Tumor lysis syndrome is an uncommon complication (presenting
in 1 out of 300 patients) of chemotherapy for patients with bulky disease.[12]
About 1% of morphologic CLL cases express T-cell markers (CD4 and CD7) and have
clonal rearrangements of their T-cell receptor genes. These patients have a
higher frequency of skin lesions, more variable lymphocyte shape, and shorter
median survival (13 months) with minimal responses to chemotherapy.[13]
Computed tomographic (CT) scans have a very limited role in following patients after completion of treatment; the decision to treat for relapse was determined by CT scan or ultrasound in only 2 of 176 patients in three prospective trials for the German CLL Study Group.[14]
Gribben JG, O'Brien S: Update on therapy of chronic lymphocytic leukemia. J Clin Oncol 29 (5): 544-50, 2011.
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Griffiths H, Brennan V, Lea J, et al.: Crossover study of immunoglobulin replacement therapy in patients with low-grade B-cell tumors. Blood 73 (2): 366-8, 1989.
Weeks JC, Tierney MR, Weinstein MC: Cost effectiveness of prophylactic intravenous immune globulin in chronic lymphocytic leukemia. N Engl J Med 325 (2): 81-6, 1991.
Maddocks-Christianson K, Slager SL, Zent CS, et al.: Risk factors for development of a second lymphoid malignancy in patients with chronic lymphocytic leukaemia. Br J Haematol 139 (3): 398-404, 2007.
Robertson LE, Pugh W, O'Brien S, et al.: Richter's syndrome: a report on 39 patients. J Clin Oncol 11 (10): 1985-9, 1993.
Kaufman M, Limaye SA, Driscoll N, et al.: A combination of rituximab, cyclophosphamide and dexamethasone effectively treats immune cytopenias of chronic lymphocytic leukemia. Leuk Lymphoma 50 (6): 892-9, 2009.
Cheson BD, Frame JN, Vena D, et al.: Tumor lysis syndrome: an uncommon complication of fludarabine therapy of chronic lymphocytic leukemia. J Clin Oncol 16 (7): 2313-20, 1998.
Hoyer JD, Ross CW, Li CY, et al.: True T-cell chronic lymphocytic leukemia: a morphologic and immunophenotypic study of 25 cases. Blood 86 (3): 1163-9, 1995.
Eichhorst BF, Fischer K, Fink AM, et al.: Limited clinical relevance of imaging techniques in the follow-up of patients with advanced chronic lymphocytic leukemia: results of a meta-analysis. Blood 117 (6): 1817-21, 2011.
Because of the indolent nature of stage 0 chronic lymphocytic leukemia (CLL),
treatment is not indicated.[1] The French Cooperative Group on CLL randomly assigned 1,535 patients with previously untreated stage A
disease to receive either chlorambucil or no immediate treatment and found no
survival advantage for immediate treatment with chlorambucil.[2][Level of evidence: 1iiA] A meta-analysis of six trials of immediate versus deferred
therapy with chlorambucil (including the aforementioned trial by the French
Cooperative Group) showed no difference in overall survival at 10
years.[3][Level of evidence: 1iiA] Whether immediate therapy with the
nucleoside analogs or other newer strategies will be superior to a watchful
waiting approach is uncertain.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage 0 chronic lymphocytic leukemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Casper JT: Prognostic features of early chronic lymphocytic leukaemia. International Workshop on CLL. Lancet 2 (8669): 968-9, 1989.
Dighiero G, Maloum K, Desablens B, et al.: Chlorambucil in indolent chronic lymphocytic leukemia. French Cooperative Group on Chronic Lymphocytic Leukemia. N Engl J Med 338 (21): 1506-14, 1998.
Several decades of large, randomized, prospective trials of previously untreated patients have demonstrated statistically significant improvements in response rates, event-free survival (EFS), and progression-free survival (PFS) with comparison of combinations of drugs versus single-agent alkylators,[1][2] but only two trials have shown statistically significant improvement in overall survival (OS).[3][4]
The first trial, a comparison of chlorambucil versus fludarabine, after 15 years of median follow-up, showed improved median OS for patients on the fludarabine regimen at 63 months versus 59 months (P = .04), and an improved percentage of patients were alive at 8 years (31% vs. 19%, P = .04).[3][5][Level of evidence: 1iiA]
The second trial, which had 817 patients, compared FCR (fludarabine + cyclophosphamide + rituximab) versus FC (fludarabine + cyclophosphamide) with a median follow-up of 38 months and showed improved OS at 3 years for the rituximab combination (i.e., 87% vs. 83%, P = .01.[4][Level of evidence: 1iiA] Yet neither fludarabine nor FCR has been compared in a randomized study against watchful waiting in asymptomatic or minimally affected patients.
The improvements in response rates from more intensive regimens have maximized the clearance of minimal residual disease (MRD). In one prospective trial of 493 patients, clearance of MRD was an independent predictor of OS by multivariate analysis.[6] The surrogate endpoint of such clearance of residual disease, while prognostic,[6] has not been shown to improve survival in a randomized prospective trial; the necessary study would take patients who fail to completely clear the marrow with induction therapy and randomly assign them to further alternative treatment versus the same treatment later at relapse, looking at OS as the primary endpoint.[1][2]
The sequencing of the following treatment options cannot be determined from the current set of completed clinical trials. When patients become symptomatic or require treatment, FCR has become the most frequently chosen option outside of a clinical trial, mostly on the basis of the previously described prospective study.[4]
Treatment options:
Note: Standard options are roughly ordered by level of toxic effects, starting with the least toxic options. More recently discovered options are mentioned at the end of the list.
Several randomized trials have compared the purine analogs with chlorambucil;
with cyclophosphamide, doxorubicin, and prednisone; or with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in previously untreated
patients.[5][23][24][25][26] All of these trials showed
higher or equivalent response rates for the purine analog and most showed an improvement in
PFS, with one reaching significance in OS favoring fludarabine.[3][23][24][25][26][27][Level of evidence: 1iiDiii]
A comparison of chlorambucil versus fludarabine, after 15 years' median follow-up, showed patients with improved median OS with fludarabine at 63 versus 59 months (P = .04) and an improved percentage of patients alive at 8 years (31% vs. 19%, P = .04).[3][Level of evidence: 1iiA] All
of the trials demonstrated higher toxic effects with the purine analogs,
especially granulocytopenic infections, herpes infections, autoimmune
hemolytic anemia, and persistent thrombocytopenia.[28]
The increased risk of infection may persist for months or years after treatment with a purine analog.[27][29]
Although empiric evidence is lacking, some investigators recommend prophylaxis with trimethoprim-sulfa during therapy and for 6 to 12 months afterwards to prevent pneumocystis infection. In a similar way, other investigators employ prophylaxis (e.g., acyclovir) for the herpes viruses.[29] Purine analogs cause less hair loss or nausea than combination chemotherapy, including alkylators and anthracyclines.[25]
Bendamustine is a cytotoxic agent with bifunctional properties of an alkylator and a purine analog.[30] In previously treated and untreated patients, bendamustine with rituximab has shown response rates around 70% to 90%.[31][32][Level of evidence: 3iiiDiii]
In a randomized comparison with chlorambucil in 319 previously treated patients, bendamustine showed a better response rate (68% vs. 31%, P < .0001) and PFS (21.6 months vs. 8 months) with a median follow-up of 35 months.[33][Level of evidence: 1iiDiii] The German CLL Study Group is comparing bendamustine plus rituximab versus FCR as first-line therapy in patients with CLL who require therapy.[31]
Lenalidomide is an oral immunomodulatory agent with response rates over 50%, with or without rituximab, for patients with previously treated and untreated disease.[34][35][36][37][38][39][Level of evidence: 3iiiDiv] Prolonged, lower-dose approaches and attention to prevention of tumor lysis syndrome are recommended with this agent.[34][40] Combination therapy and long-term toxicities from using lenalidomide (such as increased myelodysplasia, as seen in myeloma patients) remain undefined for patients with CLL.
A trial of 817 patients comparing FCR versus FC with a median follow-up of 38 months showed improved OS at 3 years for the rituximab combination (87% vs. 83%, P = .01).[4][Level of evidence: 1iiA] FCR has never been compared with watchful waiting up front in asymptomatic or minimally affected patients. The improvements in response rates from more intensive regimens have maximized the clearance of MRD. However, the surrogate endpoint of MRD clearance has not been proven to be a valid surrogate for improved survival in a randomized prospective trial; the necessary study would take patients who fail to completely clear the marrow with induction therapy and randomly assign them to further alternative treatment versus the same treatment later at relapse looking at OS as the primary endpoint.[1][2] A cumulative incidence of 6% to 8 % for myelodysplasia is seen at 5 to 7 years in patients who received fludarabine plus cyclophosphamide, with or without rituximab.[41][42]
Other combination chemotherapy regimens include the following:
A meta-analysis of ten trials comparing combination chemotherapy (before the availability of rituximab) with
chlorambucil alone showed no difference in OS at 5
years.[7][Level of evidence: 1iiA]
In a combination regimen, subcutaneous alemtuzumab plus fludarabine (with or without cyclophosphamide) or intravenous alemtuzumab plus alkylating agents have resulted in excess infectious toxicities and death, with no compensatory improvement in efficacy in phase II trials.[64][65][66][Level of evidence: 3iiiDiv]
Previously-treated patients
In a randomized prospective study, 335 previously treated patients received intravenous alemtuzumab plus fludarabine versus fludarabine alone; with a median follow-up of 30 months, the combination of fludarabine plus intravenous alemtuzumab had better PFS, with a median of 23.7 months versus 16.5 months (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.47–0.80; P = .0003); and better OS, with a median not reached, versus 52.9 months (HR, 0.65; 95% CI, 0.45–0.94; P = .021).[67][Level of evidence: 1iiA] Profound and long-lasting immunosuppression has been seen, which mandates monitoring for reactivation of cytomegalovirus and prophylaxis for pneumocystis and herpes virus infections.[68][69] Antibiotic prophylaxis includes trimethoprim and sulfamethoxazole, itraconazole, and acyclovir (or ganciclovir) for asymptomatic cytomegalovirus viremia.
In a prospective randomized trial, 241 previously untreated patients younger than 66 years with advanced-stage disease received induction therapy with a CHOP-based regimen followed by fludarabine.[77] Complete responders (105 patients) were randomly assigned to undergo autologous stem cell transplantation (ASCT) or observation, while the other 136 patients were randomly assigned to receive dexamethasone, high-dose aracytin, and cisplatin reinduction followed by either ASCT or fludarabine plus cyclophosphamide. Although the 3-year EFS favored ASCT in complete responders, there was no difference in OS in any of the randomized comparisons.[77][Level of evidence: 1iiDi]
Patients with adverse prognostic factors are very likely to die from CLL. These patients are candidates for clinical trials that employ high-dose chemotherapy and immunotherapy with myeloablative or nonmyeloablative allogeneic peripheral stem cell transplantation.[70][71][72][73][74][75][78][79][80][81][82][83][84][85] Although most patients who attain complete remission after ASCT eventually relapse,[76] a survival plateau for allogeneic stem cell support suggests an additional graft-versus-leukemia effect.[85]
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia and stage IV chronic lymphocytic leukemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
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Hallek M, Fischer K, Fingerle-Rowson G, et al.: Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 376 (9747): 1164-74, 2010.
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O'Brien SM, Kantarjian H, Thomas DA, et al.: Rituximab dose-escalation trial in chronic lymphocytic leukemia. J Clin Oncol 19 (8): 2165-70, 2001.
Byrd JC, Murphy T, Howard RS, et al.: Rituximab using a thrice weekly dosing schedule in B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma demonstrates clinical activity and acceptable toxicity. J Clin Oncol 19 (8): 2153-64, 2001.
Hainsworth JD, Litchy S, Barton JH, et al.: Single-agent rituximab as first-line and maintenance treatment for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol 21 (9): 1746-51, 2003.
Castro JE, Sandoval-Sus JD, Bole J, et al.: Rituximab in combination with high-dose methylprednisolone for the treatment of fludarabine refractory high-risk chronic lymphocytic leukemia. Leukemia 22 (11): 2048-53, 2008.
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Wierda WG, Padmanabhan S, Chan GW, et al.: Ofatumumab is active in patients with fludarabine-refractory CLL irrespective of prior rituximab: results from the phase 2 international study. Blood 118 (19): 5126-9, 2011.
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Morrison VA, Rai KR, Peterson BL, et al.: Impact of therapy with chlorambucil, fludarabine, or fludarabine plus chlorambucil on infections in patients with chronic lymphocytic leukemia: Intergroup Study Cancer and Leukemia Group B 9011. J Clin Oncol 19 (16): 3611-21, 2001.
Robak T, Blonski JZ, Gora-Tybor J, et al.: Cladribine alone and in combination with cyclophosphamide or cyclophosphamide plus mitoxantrone in the treatment of progressive chronic lymphocytic leukemia: report of a prospective, multicenter, randomized trial of the Polish Adult Leukemia Group (PALG CLL2). Blood 108 (2): 473-9, 2006.
Robak T, Bloński JZ, Kasznicki M, et al.: Cladribine with prednisone versus chlorambucil with prednisone as first-line therapy in chronic lymphocytic leukemia: report of a prospective, randomized, multicenter trial. Blood 96 (8): 2723-9, 2000.
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Dearden C, Wade R, Else M, et al.: The prognostic significance of a positive direct antiglobulin test in chronic lymphocytic leukemia: a beneficial effect of the combination of fludarabine and cyclophosphamide on the incidence of hemolytic anemia. Blood 111 (4): 1820-6, 2008.
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Khouri IF, Saliba RM, Admirand J, et al.: Graft-versus-leukaemia effect after non-myeloablative haematopoietic transplantation can overcome the unfavourable expression of ZAP-70 in refractory chronic lymphocytic leukaemia. Br J Haematol 137 (4): 355-63, 2007.
Sorror ML, Storer BE, Sandmaier BM, et al.: Five-year follow-up of patients with advanced chronic lymphocytic leukemia treated with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. J Clin Oncol 26 (30): 4912-20, 2008.
Schetelig J, van Biezen A, Brand R, et al.: Allogeneic hematopoietic stem-cell transplantation for chronic lymphocytic leukemia with 17p deletion: a retrospective European Group for Blood and Marrow Transplantation analysis. J Clin Oncol 26 (31): 5094-100, 2008.
Malhotra P, Hogan WJ, Litzow MR, et al.: Long-term outcome of allogeneic stem cell transplantation in chronic lymphocytic leukemia: analysis after a minimum follow-up of 5 years. Leuk Lymphoma 49 (9): 1724-30, 2008.
Dreger P, Döhner H, Ritgen M, et al.: Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial. Blood 116 (14): 2438-47, 2010.
Advani RH, Buggy JJ, Sharman JP, et al.: Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol 31 (1): 88-94, 2013.
Byrd JC, Furman RR, Coutre SE, et al.: Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med 369 (1): 32-42, 2013.
Porter DL, Levine BL, Kalos M, et al.: Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med 365 (8): 725-33, 2011.
Clinical trials are appropriate and should be considered when possible.[1]
In small studies, response rates of more than 40% have been reported for lenalidomide [2][3][4] and flavopiridol.[5][6][Level of evidence: 3iiiDiv] The addition of the Bcl-2 anti-sense oligonucleotide oblimersen to fludarabine/cyclophosphamide improved complete response rates in a randomized study of 241 patients with relapsed disease.[7][Level of evidence: 1iiDiv] Bone marrow and peripheral stem
cell transplantations are under clinical evaluation.[8][9][10][11][12][13][14]
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with refractory chronic lymphocytic leukemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Byrd JC, Rai KR, Sausville EA, et al.: Old and new therapies in chronic lymphocytic leukemia: now is the time for a reassessment of therapeutic goals. Semin Oncol 25 (1): 65-74, 1998.
Andritsos LA, Johnson AJ, Lozanski G, et al.: Higher doses of lenalidomide are associated with unacceptable toxicity including life-threatening tumor flare in patients with chronic lymphocytic leukemia. J Clin Oncol 26 (15): 2519-25, 2008.
Byrd JC, Lin TS, Dalton JT, et al.: Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia. Blood 109 (2): 399-404, 2007.
Lin TS, Ruppert AS, Johnson AJ, et al.: Phase II study of flavopiridol in relapsed chronic lymphocytic leukemia demonstrating high response rates in genetically high-risk disease. J Clin Oncol 27 (35): 6012-8, 2009.
O'Brien S, Moore JO, Boyd TE, et al.: 5-year survival in patients with relapsed or refractory chronic lymphocytic leukemia in a randomized, phase III trial of fludarabine plus cyclophosphamide with or without oblimersen. J Clin Oncol 27 (31): 5208-12, 2009.
Dreger P, Brand R, Milligan D, et al.: Reduced-intensity conditioning lowers treatment-related mortality of allogeneic stem cell transplantation for chronic lymphocytic leukemia: a population-matched analysis. Leukemia 19 (6): 1029-33, 2005.
This information was last updated on April 16, 2014.


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The ideal fleece mittens for your trunk, glove box and garage - or for tucking in your suitcase when you're headed up North. Not typical cheapos that slip and slide off a steering wheel, but a solid pair with supple deerskin palms that really grip and grab. Their lightweight insulation is warm, won't hinder dexterity. Longer wrists stay tucked under sleeves, helping keep

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Crinkle Puff Quilt + Sham, Black
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- Overview
We chose light and airy cotton crinkle voile in vivid hues to create this cozy bedding.
- 100% cotton voile.
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- Sham has an envelope closure.
- Twin-sized quilt fits both standard twin and twin XL dorm mattresses.
- Quilt, sham and insert sold separately.
- Machine wash.
- Imported.
Mix + match our bedding to create your own unique look with our Design Your Own Bed Tool.
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- Twin: 68 x 86"
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We rely on donations we receive from our generous community to ensure that men, women, and children who come to the shelter can get what they need when they are fleeing domestic violence.
Volunteers play a critical role in helping CAPSA to offer a high level of service to our clients. There are many ways that you can help us while becoming an advocate for those in need.
We are dedicated to helping victims of domestic violence and sexual assault in Logan, Utah, and surrounding areas, and providing education in order to prevent violence in our community.
24-Hour Crisis Line:
24 Hours a Day
7 Days a Week
Mailing Address:
P.O. Box 3617
Logan, Utah 84323-3617
Disclaimer: Any information contained in CAPSA's website is intended only for informational purposes, as a reference to identify possible forms of abuse, and a resource for potential victims. The information on these pages is not intended to interpret the law or take the place of legal advice. CAPSA is not an attorney's office and cannot give out legal advice. Call us at 435-753-2500 for more information or for information on finding an attorney.
© 2013 Citizens Against Physical and Sexual Abuse (CAPSA), Logan, Utah | 24-Hour Crisis Line: 435-753-2500


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We've also included a couple places that are having Turkey Eve events tonight.
At this late date, you better call these restaurants before you go.
•The Holiday Inn at the coliseum/IPFW is having a Thanksgiving Day feast 11 a.m.-3 p.m. The family-style buffet will be in the Mastodon Grill Restaurant. On the buffet: turkey, ham, salmon, salads, vegetables, mashed potatoes, whipped sweet potatoes, dressing, macaroni and cheese, gravy, cranberry relish, pumpkin and apple pie, chocolate pecan tarts, and red velvet cake.
The bar will be open, so you can enjoy a mimosa or bloody Mary with your meal, and watch football on one of three large-screen TVs. Cost: $21.95 adults; $18.95 seniors; $10.95 ages 6-12; free ages 5 and younger. For reservations call 482-3800.
•Red River Steakhouse, located in the Marriott Hotel, 305 E. Washington Center Road, is serving a Thanksgiving Day buffet 10:30 a.m.-4 p.m.
The buffet includes chef-carved beef and turkey, shrimp cocktail, ham, salmon, dressing, vegetable medley, mashed potatoes, gravy, breads, salads and desserts, including pies and cakes. Cost: $27.95 adults; $22.95 seniors; $13.95 ages 5-12; and free under 5. Reservations are required: call 484-0411, Ext. 310.
•Don Hall's Triangle Park, 3010 Trier Road. The restaurant is open 11 a.m.-3 p.m. with a special Thanksgiving menu featuring turkey and dressing, cranberry sauce, mashed potatoes, green beans, corn and soup or salad. Children may substitute chicken strips for turkey. Cost: $13.99 for adults, $11.99 for seniors and $5.99 for ages 12 and younger.
Do you prefer beef? You can get a New York strip or filet mignon with bread and two sides for $17.99 adults, $14.99 seniors and $7.99 ages 12 and under.
A steak and lobster meal with two sides is $26.99.
Ham, baked scrod or raspberry-pecan chicken with two sides is $13.99 for adults, $11.99 for seniors and $5.99 for children under 12. Desserts are $2.49 each.
For reservations call 482-4342.
•Don Hall's Guesthouse, 1313 W. Washington Center Road, is serving a Thanksgiving Day Buffet in the grand ballroom 11 a.m.-3 p.m. On the menu: turkey, dressing and gravy; roast beef; Ossian ham; garlic smashed potatoes; broccoli-and-rice casserole; sweet potato casserole; green beans; corn casserole; fresh fruits and vegetables; salad station; cranberry salad; desserts; and coffee, tea and soft drinks. Cost: $18.95 for adults; $7.95 for ages 4-10; and free ages 3 and younger. Call 489-2524, Ext. 413, to make reservations.
Another option at the hotel is in the Guesthouse Grille Restaurant, which will be open for breakfast off the menu 8 a.m.-11a.m. A Thanksgiving Day buffet will be served 11 a.m.-3 p.m. for $15.95 for adults; $7.95 for ages 4-10; and free for ages 3 and under. The menu includes turkey, ham, smashed potatoes, gravy, stuffing, sweet potato casserole, broccoli-rice casserole, green bean casserole, sweet corn casserole, cranberry salad and pies. Guests can order off the dinner menu 11a.m.-6 p.m. The last seating is at 6 p.m. Reservations are recommended; call 489-2524, Ext. 413.
•Liberty Diner, 2929 Goshen Road, will be open 7 a.m.-3 p.m. for breakfast and 10 a.m.-3 p.m. for dinner, and will include a free slice of pumpkin pie with meals.
•The new Teppanyaki Grill Supreme Buffet at 285 Coliseum Blvd. E. will be open 11 a.m.-9:30 p.m.
•Ceruti's Catering is offering a turkey dinner you can pick up the day before Thanksgiving. The cost is $6.95 per person, with a minimum of five orders. The dinner includes sliced roasted turkey with gravy and dressing, redskin smashed potatoes, green beans with bacon and onion, and rolls and butter. Order by Monday. Phone: 207-2000. Pick up at Ceruti's Catering, 6601 Innovation Blvd.
•Bob Evans bills its Farmhouse Feast as a way for families to enjoy a traditional holiday feast without a lot of prep work or cleanup. The heat-and serve meal serves eight and comes with a choice of a whole boneless turkey breast or sliced boneless ham, dressing, mashed potatoes with gravy, corn, green beans with ham, cranberry relish, rolls, a loaf of pumpkin bread and a pumpkin pie with whipped topping all for $74.99. For larger groups, additional servings can be added a la carte. A smaller meal for four costs $44.99. The meals can be ordered online at www.bobevans.com or by calling or visiting any Bob Evans restaurant. Bob Evans restaurants are closed Thanksgiving Day, so the meals will have to be picked up beforehand.
•Richard's Bakery, 1130 N. Wells St., is taking Thanksgiving orders for pies, cakes, cookies and other pastries. Call 424-4012. Hours: 6 a.m.-6 p.m. Monday-Friday and 6 a.m.-1 p.m. Saturdays. Richard's also will be part of the Holly Trolley Shopping Day on Nov. 24.
•Waynedale Bakery, 2610 Lower Huntington Road, is selling pumpkin, pecan, apple, cherry and blueberry pies for $8-$9. Turkey and pumpkin- shaped iced sugar cookies are $8 a dozen. Butterflake rolls are $2.75 a dozen, and pumpkin or Swiss cake rolls are $12 each. Phone: 747-2992.*The Lucky Moose, 622 E. Dupont Road, is hosting its Turkey eve party today with the theme, "eat a shrimp, save a turkey." From 4 to 8 p.m. the restaurant will serve a seafood buffet with royal red shrimp, cold peel and eat shrimp, Cajun shrimp, other seafood items and a crepe station all for $13.13.
Also, The Lucky Moose has added 50 craft brews to its menu and all will be $1 off all day Wednesday.
*Dicky's Wild Hare, 2910 Maplecrest Road, will have $3 well drinks, a $6 pizza buffet and live music starting at 9 p.m. tonight. Cover is a nonperishable item for a food pantry.
Something happening at your eatery? Call Cindy Larson at 461-8284, fax 461-8817, email firstname.lastname@example.com or write Restaurant Notes, C/O The News-Sentinel, PO Box 102, Fort Wayne, IN 46801. This column is the personal opinion of the writer and does not necessarily reflect the views or opinion of The N-S. To read other columns, go to www.news-sentinel.com/section/LARSON.


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As emcee of the Carlsbad Chamber of Commerce's 90th anniversary celebration last Saturday, county Treasurer Dan McAllister announced the winners of three opportunity drawings held during the evening.
That is, until his own name was randomly drawn as winner of a $900 cash prize. "I couldn't take that," McAllister said afterward. So he declined his winning ticket and asked organizers to draw a replacement name. This time, Lori Thomas, a U-T San Diego account manager, won the cash. "Lori, come on down and get my money," said McAllister, who, when wearing his tax collector hat, never turns away dough. The grand prize of $1,923 (the Chamber formed in 1923) went to attendee Tom Ruggiero.
Strange, but true: It was a quirky request. As his health failed, local homebuilder Bob Casey asked his relatives to do him one favor after he died.
Frustrated by an annoying succession of inadequate hearing aids he had been saddled with since his hearing loss began in his early 20s, Casey, at age 84, vowed to get revenge. He urged son Rob Casey, of Jamul, to promise to take his hearing devices and a shotgun into a remote area, "throw 'em up in the air and blast them into the stratosphere."
So Rob recently took a bag containing his late father's hearing aids into San Diego's back country and did just that.
Rob missed the target on the first toss by his son, Cory, but his second shot found its mark, obliterating the ear pieces in a shower of smoke.
Karen Casey is convinced the blast was loud enough for her father to hear up in heaven — even without a hearing aid.
Dream dates: San Diegans Kiptyn Locke and Roberto Martinez, of "The Bachelorette" show fame, are on the auction block, so to speak. They're teaming up to offer an all-day double date to the highest bidder (who is invited to bring a friend) at the Chris4Life charity event April 5 at the SLS Hotel in Beverly Hills.
The date starts with a morning horseback ride in rural San Diego, followed by a picnic, then a trip to a La Jolla beach for surfing or kayaking, ending romantically at dusk by a fire pit on the beach. (Hard Rock Hotel San Diego is adding a one-night vacation package.)
But lest any gal get too excited about the "dream date," it's only fair to note that Roberto Martinez, the former fiancé of "Bachelorette" Ali Fedotowsky, isn't very eligible these days. "Life & Style" magazine reports this week that Martinez, 29, is seriously involved with Playboy playmate Sara Underwood. Oh, and the magazine, in a cover story headlined, "Over Already," also reveals that the romance of the newest "Bachelor" show couple, Sean Lowe and Catherine Giudici, is on the rocks.
Sign of the times: Thursday was declared Tricia Pummill day in San Diego in honor of the retirement of Pummill, a longtime consumer advocate in the S.D. City Attorney's Office. However, as City Attorney Jan Goldsmith handed her the proclamation at her goodbye luncheon, he noted that his signature was missing. Not about to let the moment pass without an editorial comment, Channel 10 TV's senior investigative producer J W August quipped that maybe Goldsmith could ask the mayor to sign it — a veiled reference, of course, to the well-publicized rift between Goldsmith and Bob Filner.
Easter surprise: As San Diegan Joyce Flannery bought her spring truffles at See's Candies, she made a surprise discovery. Some See's sweets — bonbons and fancy chocolate Easter eggs — are still decorated by hand, as the confections were when the company originated in 1921 with Mary See's recipes.
"This is not only 'made in America,'" marvels Flannery, "it is 'handmade in America.'"
email@example.com (619) 293-1518


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COLLEGE STATION, Texas (AP)- Jerrod Johnson threw for 349 yards and two touchdowns and ran for a score to lead Texas A&M to a 41-6 win over New Mexico on Saturday.
Johnson completed 31 of 41 passes, and Cyrus Gray and Christine Michael added touchdown runs for the Aggies (1-0), who piled up 606 yards. The A&M defense showed dramatic improvement from last season, holding New Mexico to 21 rushing yards and sacking Donovan Porterie five times.
Porterie completed 29 of 40 passes for New Mexico (0-1) in his first start since tearing ligaments in his right knee in the fourth game last season and undergoing surgery.
The Lobos played poorly in Mike Locksley's head coaching debut and failed to score a touchdown in their opener for the fourth straight season. The loss also marked New Mexico's 10th straight defeat in Texas.
The Aggies, starting their second year under Mike Sherman, dominated from the start and built a 20-3 halftime lead.
Johnson completed a 42-yard pass to freshman Uzoma Nwachukwu on A&M's first possession and Johnson scrambled for a 16-yard touchdown with 9:52 left in the opening quarter.
Jeff Fuller caught an 18-yard pass from Johnson early in the second quarter, setting up Randy Bullock's 22-yard field goal. Fuller led A&M with 10 catches for 111 yards in the game.
Michael, one of 12 freshmen to play for A&M in the first half, broke two runs over 20 yards on the Aggies' next possession. Michael went out for a rest and Cyrus Gray's 13-yard touchdown run put A&M up 17-0 with 4:44 left in the half.
Demond Dennis fumbled on the Lobos' next play from scrimmage. A&M safety Jordan Pugh recovered and Bullock kicked afield goal for a 20-0 lead.
James Aho kicked a field goal with 13 seconds left in the first half to complete New Mexico's best drive of the game. The Aggies' defense, one of the nation's worst in 2008, held the Lobos to two rushing yards and nine first downs in the first half.
A&M marched 86 yards in 12 plays to start the second half. Johnson went 6-for-6 on the drive and Michael finished it with a 2-yard touchdown run.
Aho matched his career best with a 48-yard field goal later in the third quarter. A&M answered with a 17-play drive, capped by Johnson's 7-yard touchdown pass to Fuller.
Johnson threw a 44-yard touchdown pass to freshman Kenric McNeal with 9:14 left. Tommy Dorman finished the game at quarterback for the Aggies.
Texas A&M has won 24 of its last 26 home openers, though it lost to Arkansas State in Sherman's debut in 2008.


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I've seen these things at WalMart a couple times now. I've been buying the vinyl sheets that go into these machines and it works flawlessly.
Anyone every tried one? I've not done a lot of research on plotters, but I'm looking for a smaller, inexpensive one. I don't want a big thing taking up a corner of my home office.


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HOUSTON - Houston police are searching for the person who broke into a southwest Houston home and shot a man to death.
It all happened around 5 a.m. Sunday in the 4700 block of Beechaven. Houston police responded to reports of a man shot inside of his home.
"They entered the bedroom of the complainant, who is Hispanic male in his 20s. He was shot several times," said HPD Homicide Sgt. Thomas Biggs
The man was transported to the hospital but was later pronounced dead. Local 2 has learned the victim lives with his grandparents, who woke up to the sound of gun shots and feared for their lives.
"When the grandparents responded the pistol was pointed at them as well. Suspect or suspects then fled the scene through the same place they entered," said Sgt. Thomas.
Investigators collected evidence on a nearby vehicle. They believe the suspect may have touched a nearby car.
In the meantime, residents said they're frightened by the shooting death.
"This is very scary to know this is going on in my block," said neighbor Elizabeth Gutierrez.
Gutierrez doesn't know the victim and didn't hear anything, but she said she's worried.
"I have kids, it's scary to think this is going on in my neighborhood. I don't know what happened but this is not right," said Gutierrez.
Investigators said they're trying to determine if the victim knew his attacker. If you have any information about this case, you're asked to call Crime Stoppers at 713-222-TIPS.
Copyright 2013 by Click2Houston.com. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.


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The YEP-201 is made out of finest brass. In combination with the golden lacquer the instrument gets a clear sound which spreads through the whole room and get excellent mixed in ensembles.
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dude, you need to lay off the caffeine at night.This quote is hidden because you are ignoring this member. Show QuoteWARNING: MASSIVE TYLER DERAIL (you knew it was coming....ps, I'm excited about DJ as a bench PG who could maybe start with GH as the scoring 6th man star)
It's like people don't think that other people know about B-ball reference.com or something.
So I asked for all players 6'9" to 7'0" listed as PF or F-C only (not C-F or C) and said that the player's season had to qualify for the MPG leaderboard (not be a leader but meet the requirements for consideration).
All single seasons in the last 3 years, so any players that played all 3 years could make the list 3 times
I sorted by eFG% (adjusted for 3PM FG%) and at #165 of 166 came Tyler's 11-12 season. The only dude listed below that was Ben Wallace's 11-12 season. Tyler also ranked at 144 with his "good" season of 10-11. 09-10 he didn't qualify due to injury (but his FG% sucked so it's just as well).
Some guys WAY up the list from there - Casspi, J Thompson, Taj Gibson, Darrell Arthur, Donte Green, Carl Landry, Harrington, H Warrick...it's a long list.
So what? He's a PF not a scoring specialist. Well just how does he rank in FGA/36 I wonder...
53rd in 10-11 with 14.4 per 36
97th in 11-12 with 12 per 36 (at least it went down a little bit)
So he shoots horrible but takes them like he's not too shabby. Interesting comparison here with JAMES JOHNSON...you know, super elite backup PF Johnson
11-12 nearly identical FGA, 7.2 to 6.7 reb (adv Tyler barely), 45% to 40% shooting (adv James obviously).
Yes, James Johnson in his 11-12 season with Toronto put up basically better total key numbers than Tyler did in 11-12. But Tyler is an elite backup? So now that makes Johnson an elite backup too I guess?
But he's a rebounding machine (pretend you didn't just see the spoiler in the JJ comparison)
Hey, look at that, he comes in at 79th for his 10-11 season with an 8.6 per 36. TIED WITH MCROBERTS own 10-11 season with Indy and his same 8.6. but not quite enough to match Blatche's own 10-11 season of 8.7
Keep in mind that Josh "cost too much" at 3m, whereas Tyler is a great deal at....3m.
Considering the identical stat at rebounding, with Josh leading him in FG%, blocks and obviously assists, why in the F did the Pacers agree to keep paying Tyler (rather than trading) while letting Josh walk for the same money? (cough Bird)
Anyway, Tyler also made the list at 118th with his 11-12 season which is totally awesome. I mean not Jerebko or N Collison or H Warrick or Aminu awesome, but certainly way better than I could do (which I think must be the benchmark we've set for "elite backup PF")*
But his rim defense, he's a tough dude that intimidates in that classic Dale PF way. It must be that because so far it's either "meh" to "suck" which doesn't seem to match elite, but WTF do I know.
Atta boy, tied for 145th...or 158 depending on which end of the ties at 0.4 blocks per 36 you put him at. When Luis Scola blocks as many shots as you do, you might have to consider that a lot of your blocks are either accidents or are being misapplied to you by the stats guys.
Tyler comes in strong for a 2nd showing tied at 162nd to dead last with his 0.2 blk per 36 in 11-12. (why did I look, it only hurts more to see Josh's 10-11 blocks ranked 47th, his 11-12 season didn't have enough PT to qualify)
Near worst in shooting, worst in shot blocking, average at best in rebounding....but hey, slightly better than average in chucking up a shot.
And just when you want to dismiss the stats as misleading, a quick check of his FTA/36 puts him at 12th and 23rd. Funny how the one thing his critics acknowledge he does well is the one way in which he statistically shines.
One more "can you believe they paid Tyler 3m but not Josh" stat check...assists
Josh 10-11 ranks 16th, surrounded by Odom and Garnett
Tyler ranks tied for 144-153 (with Lou of 10-11 PHX) and 159-162.
Thank god for 3 seasons of Ibaka and 1 year of Kantner to keep Tyler from ranking last again. Too bad for Tyler that Ibaka actually dunks his way to 53% shooting and blocks 15-20 times more shots (no, literally)
* most of this section should be read in my best Archer sarcastic voice impersonation.
And I'm sure it just make me a giant d-bag to have this tone, but F anyone that has me up at 2AM researching, linking and verifying all the statistical evidence that any damn Pacers fan should already know. I'm a lot friendlier before I read stuff like "tyler is an elite backup" or "why are people so down on Tyler", as if this numbers are a big secret or surprise.


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A Challenging Remodel
Today, I am happy to post our first report from project manager Dylan Eastman, who shares some behind-the-scenes info about the state of Blog Cabin 2013.
When the house was surveyed, structural challenges, including 2×4 floor joists, 7′ ceilings and variances in floor height, were discovered. The porch, kitchen and mechanical room are also out of current construction code; the decision was made to rebuild rather than repair them.
1. The brother of the selling agent remodeled portions of the home in the early 1990s. A gabled roof was installed over the master bedroom.
2. Flooring is water damaged in areas where wind-driven rain seeped under exterior doors. Termite damage is also evident.
3. Several renovations over the home's 150-year history have resulted in floor level changes.
4. Exterior wood shakes, now interior elements, are clues that both the kitchen and master bedroom were additions.
5. Ship's ladder-style stairs to the second floor, originally a loft/sleeping space coined "the jump", are not to code.
6. A second story existed over the main portion of the house prior to the addition of the space over the dining and birthing rooms. This is evidenced by the short slope of the ceiling paneling.


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The most heavily used area of any library system is its main youth room, and that's certainly true for the Tippecanoe County Public Library system. In 2008, a $136,000 renovation replaced 20-year old carpeting, refurbished restrooms, relocated and expanded the preschool area, increased space for library collections, provided additional computer stations and replaced or refurbished aging and damaged furnishings.
Donors to the Youth Room renovation provided a significant portion of the funding.


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Despite complaints of low flying helicopters over parts of St Keverne parish, councillors have continued their support of RNAS Culdrose.
The issue of aircraft flying over Rosenithon on practise runs over Dean Quarry was an item for discussion by St Keverne parish councillors when they met last Thursday.
Chairman Russell Peters said the council had received complaints from some members of the public, adding: "It isn't the first time we have had this."
However, clerk Grace Hatton passed on a message from Cornwall Councillor Walter Sanger to say that the aircraft had restricted area landing sites at four locations at Dean Quarry.
When the matter previously came before the council members agreed to take no action, due to the benefits that RNAS Culdrose brought to Helston and the Lizard Peninsula.
These included a boost the local economy, plus the essential help given by the search and rescue service.
Councillor David Lambrick said: "I thought we as a council agreed we would allow it to carry on, because of Culdrose. I can't see that as a council we can change that."
Councillor Russell Hocking agreed: "I've said many times before, we pay a very small price for the benefit we receive with Culdrose being in existence. If it went out of existence we would be poverty stricken and unemployment would rise and rise."
He added that he lived on the flight path to Culdrose and described it as "a privilege" to be underneath it because of the advantages being derived from the naval base.
Councillor Anthony Richards questioned what the limit was for helicopters flying over Helston and said: "Why should people in Rosenithon and surrounding dwellings have to be treated as second class citizens if they're flying too low?"
But Mr Lambrick replied: "How do we know it is any different to Helston?"
However, he did not disagree with the council finding out the minimum height aircraft could fly.
It was agreed to write to RNAS Culdrose for that information.


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Baylor tennis teams continue string of top preseason rankings
You may have read recently that Baylor is the only school in the nation to have its football, men's basketball and women's basketball programs ranked in the top 14 nationally. But that doesn't mean BU's other athletic programs are slouches.
Take tennis, for example. The Baylor men are coming off their 11th Big 12 Conference title in 14 years, and their 12th straight Sweet 16 appearance. Not to be outdone, the Baylor women have won nine of the last 11 Big 12 championships and reached the Sweet 16 eight of the last nine years. This year promises similar success, as the women begin their spring schedule tomorrow in Hawai'i and the men follow suit next weekend in Los Angeles.
For the 11th time in 12 years, the Baylor men will open their spring season ranked among the nation's top 10; the Bears came in at No. 8 in this year's preseason ITA rankings, tops in the Big 12. Head coach Matt Knoll's squad is led by three players ranked among the nation's top 20 individuals: sophomore Julian Lenz (ranked No. 2 nationally in singles), senior Patrick Pradella (No. 7) and junior Diego Galeano (No. 18).
The Lady Bears are 19th in the preseason ITA rankings, their ninth straight year in the preseason top 20. Head coach Joey Scrivano's team features only one ranked singles player (sophomore Kiah Generette, No. 38 in the country) and one ranked doubles team (Victoria Kisialeva and Blair Shankle, No. 37), numbers that are likely to improve as the spring progresses.
The two programs also received some good news in December, when it was announced that Baylor will host the 2015 NCAA Tennis Championships. Recent improvements to the Hurd Tennis Center and the addition of the Hawkins Indoor Tennis Center made the honor possible.
Sic 'em, Baylor tennis!


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