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Extracorporeal photopheresis (ECP) is a leukapheresis-based immunomodulatory procedure that involves the following steps:
ECP has been investigated for the treatment of patients with a variety of autoimmune diseases, graft-versus-host disease (GVHD), and cutaneous T-cell lymphoma (CTCL), as well as treatment for and prevention of organ rejection after solid-organ transplant.
Treatment for and Prevention of Organ Rejection after Solid-Organ Transplant
The standard of care for treatment of organ transplant rejection is immunosuppression, with the particular regimen dictated by the organ being transplanted. As organ transplantation success rates have improved, more patients are facing the morbidity and mortality associated with immunosuppressive therapies developed to prevent rejection of the transplanted organ. Immunosuppressive therapies are used to lower the responsiveness of the recipient's immune system, decreasing the chance of rejection. Unfortunately, portions of the immune system responsible for the prevention of viral, fungal, and bacterial infection are also affected. This can, in turn, lead to serious infections, including opportunistic infections.
While first approved for the treatment of CTCL, ECP has more recently been used as a supplement to conventional therapies in the area of transplantation.
Recurrent allograft rejection is defined as having at least two rejection episodes that recurred after standard immunosuppressive therapy.
Reports of the successful use of ECP in human cardiac transplant recipients were published in 1992 and use in other transplant patients followed. Although the specific mechanism of action of ECP is unknown, the reinfusion of treated leukocytes seems to specifically suppress the patient's immune response to the donor organ, while maintaining the body's ability to respond to other antigens. The specificity of ECP to target the immune response to the transplanted organ allows ECP to decrease organ rejection without an increased risk of infection, common with immunosuppressant drugs.
Treatment of Graft-versus-Host Disease (GVHD)
ECP as a treatment of GVHD after a prior allogeneic stem-cell transplant is based on the fact that GVHD is an immunologically mediated disease. GVHD can be categorized into acute disease, occurring within the first 100 days after infusion of allogeneic cells, or chronic disease, which develops some time after 100 days. Acute GVHD is commonly graded from I–IV, ranging from mild disease, which is characterized by a skin rash without involvement of the liver or gut, to grades III and IV, which are characterized by generalized erythroderma, elevated bilirubin levels, or diarrhea. Grade III acute GVHD is considered severe, while grade IV is considered life-threatening. Chronic GVHD typically presents with more diverse symptomatology resembling autoimmune diseases such as progressive systemic sclerosis, systemic lupus erythematosus, or rheumatoid arthritis. Chronic GVHD may affect the mouth, eyes, respiratory tract, musculoskeletal system, and peripheral nerves, as well as the skin, liver, or gut—the usual sites of acute GVHD.
An alternating regimen of cyclosporine and prednisone is commonly used to treat chronic graft-versus-host disease. Other therapies include antithymocyte globulin, corticosteroid monotherapy, and cytotoxic immunosuppressive drugs such as procarbazine, cyclophosphamide, or azathioprine. Therefore, refractory disease is defined as chronic graft-versus-host disease that fails to respond adequately to a trial of any of the above therapies.
Treatment of Cutaneous T-Cell Lymphoma (CTCL)
According to the National Cancer Institute (NCI), CTCL is a neoplasia of malignant T lymphocytes that initially present as skin involvement. CTCL is extremely rare, with an estimated incidence of approximately 0.4 per 100,000 annually but, because most are low-grade malignancies with long survival, the overall prevalence is much higher. Two CTCL variants, mycosis fungoides and the Sezary syndrome, account for approximately 60% and 5% of new cases of CTCL, respectively.
CTCL is included in the Revised European-American Lymphoma classification as a group of low-grade T-cell lymphomas, which should be distinguished from other T-cell lymphomas that involve the skin, such as anaplastic large cell lymphoma, peripheral T-cell lymphoma, adult T-cell leukemia/lymphoma (usually with systemic involvement), or subcutaneous panniculitic T-cell lymphoma. In addition, a number of benign or very indolent conditions can be confused with mycosis fungoides, further complicating diagnosis.
Mycosis fungoides typically progress from an eczematous patch/plaque stage, covering less than 10% of the body surface (T1), to a plaque stage, covering 10% or more of the body surface (T2), and finally to tumors (T3) that frequently undergo necrotic ulceration. Sezary syndrome is an advanced form of mycosis fungoides with generalized erythroderma (T4) and peripheral blood involvement (B1) at presentation. Cytologic transformation from a low-grade lymphoma to a high-grade lymphoma sometimes occurs during the course of these diseases and is associated with a poor prognosis. A common cause of death during the tumor phase is sepsis from Pseudomonas aeruginosa or Staphylococcus aureus caused by chronic skin infection with staphylococcus species and subsequent systemic infections.
The natural history of mycosis fungoides is typically indolent. Symptoms may present for long periods, an average of 2-10 years, as waxing and waning cutaneous eruptions prior to biopsy confirmation. The prognosis of patients with mycosis fungoides/Sezary syndrome is based on the extent of disease at presentation and its stage. Lymphadenopathy and involvement of peripheral blood and viscera increase in likelihood with worsening cutaneous involvement and define poor prognostic groups. The median survival following diagnosis varies according to stage. Patients with stage IA disease have a median survival of 20 or more years, with the majority of deaths for this group typically unrelated to mycosis fungoides. In contrast, more than 50% of patients with stage III through stage IV disease die of their disease, with a median survival of less than five years.
Appropriate therapy of CTCL depends on a variety of factors, including stage, the patient's overall health, and the presence of symptoms. In general, therapies can be categorized into topical and systemic treatments that include ECP. In contrast to more conventional lymphomas, CTCL, possibly excepting ones in the earliest stages, is not curable. Thus, systemic cytotoxic chemotherapy is avoided except for advanced-stage cases. Partial or complete remission is achievable, although the majority of patients require lifelong treatment and monitoring.
CTCL Staging (based on the TNM classification system)
According to the World Health Organisation-European Organisation for Research and Treatment of Cancer (WHO-EORTC), Sezary syndrome is defined by the triad of erythroderma, generalized lymphadenopathy, and the presence of neoplastic T cells (Sezary cells) in skin, lymph nodes, and peripheral blood. The International Society of Cutaneous Lymphomas recommends an absolute Sezary cell count of at least 1,000 cells per cubic mm, in the presence of immunophenotypical abnormalities (CD4/CD8 ratio greater than 10, loss of any or all of the T-cell antigens CD2, CD3, CD4, and CD5, or both), or the demonstration of a T-cell clone in the peripheral blood by molecular or cytogenetic methods.
Treatment of Autoimmune Disease
The use of ECP as a treatment of autoimmune disease is based on the premise that pathogenic lymphocytes form an expanded clone of cells, which are damaged when exposed to UV light in the presence of 8-MOP. It is hypothesized that the resulting damage induces a population of circulating suppressor T cells targeted against the light-damaged cells. It is further hypothesized that these suppressor T cells are targeted at a component of the cell that is common to the entire clone of abnormal cells (i.e., not just the light-sensitized cells), thus inducing a systemic effect. However, although scleroderma and other autoimmune diseases are associated with the presence of circulating antibodies, it is not certain how these antibodies are related to the pathogenesis of the disease, and, as discussed in this policy, photopheresis is not associated with consistent changes in autoantibody levels.
Regulatory Status
In the U.S., the UVAR® XTS Photopheresis System was approved via premarket application (PMA) by the U.S. Food and Drug Administration (FDA) for use in the ultraviolet-A (UVA) irradiation (in the presence of the photoactive drug, methoxsalen) of extracorporeally circulating leukocyte-enriched blood in the palliative treatment of the skin manifestations of cutaneous T-cell lymphoma (CTCL) in persons who have not been responsive to other therapy.
8-MOP (UVADEX®) is approved by the FDA for use in conjunction with UVAR XTS Photopheresis System for use in the UVA irradiation in the presence of the photoactive drug methoxsalen of extracorporeally circulating leukocyte-enriched blood in the palliative treatment of the skin manifestations of CTCL in persons who have not been responsive to other therapy.
The use of the UVAR XTS Photopheresis System or UVADEX for other conditions is an off-label use of a FDA-approved device/drug.
Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.
Medically Necessary
Organ Rejection after Solid-Organ Transplant
Blue Cross and Blue Shield of Montana (BCBSMT) may consider extracorporeal photopheresis (ECP) medically necessary to treat cardiac allograft rejection, including acute rejection, that is either recurrent or that is refractory to standard immunosuppressive drug treatment.
Graft-Versus-Host Disease
BCBSMT may consider extracorporeal photopheresis (ECP) medically necessary as a technique to treat chronic graft-versus-host disease that is refractory to medical therapy.
Cutaneous T-cell lymphoma
BCBSMT may consider extracorporeal photopheresis (ECP) medically necessary as a technique to treat:
BCBSMT considers extracorporeal photopheresis (ECP) experimental, investigational and unproven in all other situations related to treatment or prevention of rejection in solid-organ transplantation.
BCBSMT considers extracorporeal photopheresis (ECP) experimental, investigational and unproven as a technique to treat acute graft-versus-host disease or chronic graft-versus-host disease that is either previously untreated or is responding to established therapies.
BCBSMT considers extracorporeal photopheresis (ECP) experimental, investigational and unproven as a technique to treat early stage (I/II) cutaneous T-cell lymphoma that is either previously untreated or is responding to established nonsystemic therapies.
Autoimmune Diseases
BCBSMT considers extracorporeal photopheresis (ECP) experimental, investigational and unproven as a technique to treat either the cutaneous or visceral manifestations of autoimmune diseases, including but not limited to scleroderma, systemic lupus erythematosus, rheumatoid arthritis, pemphigus, psoriasis, multiple sclerosis, diabetes, or autoimmune bullous disorders.
Literature Review
A literature search using MEDLINE identified one randomized controlled trial (RCT) for the use of extracorporeal photopheresis (ECP) in cardiac transplant recipients and one nonrandomized comparative trial in liver transplant recipients. Other published data comes from small case series and/or case reports.
Acute Rejection
One RCT was published in 1992 on the efficacy of ECP versus corticosteroids in treating heart transplant rejection. Costanzo-Nordin and colleagues enrolled 16 heart transplant patients and randomly assigned them to either ECP (n=9) or corticosteroids (n=7). Recipients of orthotopic transplanted hearts were eligible if endomyocardial biopsy (EMB) showed moderate rejection (grades 2, 3A, and 3B). Participants were excluded for leukopenia, hemodynamic compromise manifested clinically or by decrease in cardiac output equal to or greater than 25% and an increase in mean pulmonary artery wedge pressure equal to or greater than 25%, and/or an allergy or intolerance to psoralen. Corticosteroids were dosed at 100 mg/day oral prednisone for three days or 1g/day IV (intravenous) methylprednisolone for three days at the discretion of the managing physician. The treatment was repeated if EMB at day seven showed no improvement in rejection grade. If the rejection grade persisted after retreatment, patients were given 10 mg oral methotrexate at weekly intervals for eight weeks. Participants were followed for a mean of 6.2 months, and all participants completed the study. ECP participants were given one ECP treatment unless an inadequate number of cells were treated. In that case, an additional treatment was given 48 hours later. Of the nine rejection episodes treated with ECP, all but one improved; all seven of rejection episodes treated with corticosteroids resolved. Improvement was seen in a mean of seven days (range: 5–20) for ECP and eight days (range: 6–67 days) after corticosteroid treatment. Seven infections occurred during follow-up, five in the corticosteroid groups and two among those receiving ECP. No other adverse events were observed with ECP. The authors noted the major limitations of the study included the small sample size and the wide range of time from transplant to study entry. They concluded that ECP and corticosteroids in this small group with short-term follow-up appear to have similar efficacies for the treatment of moderate heart transplant rejection. They also noted the lower number of infections with no other observed harms associated with ECP.
Recurrent, Multiple and/or Refractory Rejection
Kirklin and colleagues published a comparative study of 343 patients in 2006 who received heart transplants. Thirty-six of those patients were treated with ECP for rejection and formed the treatment group. Patients were at least 18 years or older, treated from 1990-93, and followed to May 2004. Indications for ECP were episodes of rejection with hemodynamic compromise (HC) (n=12), recurrent (n=9) or persistent (n=11) rejection, or as prophylaxis in the presence of anti-donor antibodies. ECP consisted of psoralen in a two-day treatment protocol every 3-6 weeks for 18 months; maintenance immunosuppression utilized cyclosporine or tacrolimus-based therapy with prednisone for the first 4-6 months and azathioprine, which was replaced by mycophenolate mofetil during the later years of the study. The primary outcome was hazard rate of subsequent HC rejection after at least one HC had already occurred. Hazard functions were used for analysis. Patients with at least three months of ECP were considered to have effective photopheresis treatment; if less than three months, they were considered to not have had treatment but were analyzed as part of the photopheresis group. Risk factor analysis showed those who received photopheresis were at high risk for HC rejection. The period after three months of ECP was associated with a reduction in risk of HC rejection or rejection death (risk reduction [RR]: 0.29). A sustained decrease in the risk of HC rejection or HC death was observed for the photopheresis group through two years of follow-up. This study was not randomized; there was imbalance in the pretreatment risk of rejection or rejection death between the two groups. Changes in maintenance immunotherapy over time may confound the results, as patients in the comparison group did not receive a consistent regimen. However, these changes in maintenance immunotherapy would tend to make the identification of an effect of ECP created by the ever-evolving immunotherapy regimen more difficult. This only strengthens the authors' conclusion that ECP reduces the risk of subsequent HC rejection and/or death from rejection when initiated for patients with high risk of rejection.
Dall'Amico et al. reported in 2000 on a case series of 11 patients with recurrent rejection after heart transplant. Participants were eligible if they had acute rejection and at least two rejection episodes in the three months prior to ECP, which recurred after standard immunosuppressive therapies. ECP was performed with the UVAR photopheresis instruments, with two consecutive treatments at weekly intervals for one month, two treatments twice weekly during the second and third months, then monthly for three additional months. One patient, showing 3B rejection, received pulse IV corticosteroids during the first ECP cycle. Patients were followed for 60 months. During follow-up, one patient died from hepatitis C virus and one dropped out due to rejection unresponsive to ECP and high-dose corticosteroids; all others completed the study. All acute rejection episodes were successfully reversed after a mean of 14.2 days (range: 7–32 days). In terms of rejection relapse, the fraction of EMB with a grade of 0/1A increased during ECP from 46% to 72%, and those showing 3A/3B rejection decreased from 42% to 18%. One of 78 EMB during ECP showed 3B rejection compared to 13 of 110 during the pre-ECP period. Six rejection relapses were observed during follow-up, two during the tapering of oral corticosteroids. Four were reversed by ECP, one by IV corticosteroids, and the last by methotrexate after failure of both ECP and IV corticosteroids. Mean dose of immunosuppressive drugs (corticosteroids, cyclosporine, and azathioprine) was reduced after six months of ECP therapy. One patient with anemia and low body weight experienced symptomatic hypotension episodes during treatment, and one patient had interstitial pneumonia. The authors concluded ECP to be a well-tolerated treatment, which allows for better recurrent rejection control and significant reductions in immunosuppressive therapy. The follow-up time and patient population are adequate; the study is limited by its small size and lack of a comparison group.
Maccherini and colleagues presented a case series of 12 patients treated with ECP for recurrent rejection. Inclusion criteria were recurrent rejection (n=5), recurrent infections associated with acute rejection (n=2), and 3A acute rejection two years after transplantation (n=5). Mean post-ECP follow-up was 23.3 months. ECP was performed as two treatments per week for one month, once a week for two months, then once a month for two months, totaling 20 ECP treatments during six months. Total number of rejection episodes decreased from a mean of three per patient per-ECP to 0.4 per patient post-ECP. Reduction in immunosuppressive therapy was achieved by all patients. There were no adverse effects or infections reported during follow-up. The authors concluded that ECP was safe and effective for heart transplant patients with recurrent rejection, allowing for both a reduction in rejection episodes and immunosuppressive therapy.
Similar results were presented by Lehrer and colleagues describing the experience of four patients treated with ECP for severe refractory (grade IIIA to IV) cardiac allograft rejection. All four patients experienced reversal of their rejection. Three patients improved following two consecutive days of treatment, and the fourth patient responded following three 2-day treatments. Two of these patients subsequently died of acute rejection at nine weeks and 10 weeks after completion of ECP. The other two were without signs of rejection, one for six years and the other's last report was four months after ECP ended. This small case series adds to the evidence provided by the prior two slightly larger studies.
Prevention of Rejection
An RCT by Barr and colleagues investigated ECP for the prevention of rejection after cardiac transplant. Sixty consecutive adult cardiac transplant recipients at 12 clinical sites (nine U.S., three in Europe) were randomly assigned to both immunosuppressive therapy and ECP (n=33) or immunosuppressive therapy alone (n=27). Standard immunosuppressive therapy consisted of cyclosporine, azathioprine, and prednisone. To be eligible, participants needed adequate peripheral venous access and had to reside less than two hours away from the transplant center. ECP treatment was delivered on days 1, 2, 5, 6, 10, 11, 17, 18, 27, and 28 in month 1; then two consecutive days every two weeks in months 2 and 3; and two successive days every four weeks for months 4-6 for a total of 24 ECP procedures per patient. Primary endpoint of the study was the number and frequency of histologic acute rejection episodes. Pathologists were blinded to treatment assignment. Follow-up for the primary endpoint was six months; an additional six months of follow-up was completed to assess safety and survival.
Average number of acute rejection episodes per patient was statistically different, with 1.44 in the standard therapy group and 0.91 in the ECP group. In the standard therapy group, five patients had no rejection episodes, 9 had one, 9 had two, and 4 had three or more. In the ECP group, 13 had none, 14 had one, 3 had two, and 3 had three or more. These differences were statistically significant. There were no differences in survival at six months between the two groups or number of infections. Time to a first rejection also did not differ between the groups. During the second six months of follow-up, there were no differences between the numbers of acute rejection episodes between the two groups; however, due to time management issues, institutions reverted to nonstandardized protocols during this time. The authors concluded that using ECP in addition to standard immunosuppressive therapy significantly reduced the risk of cardiac rejection without increasing the rate of infections. More long-term follow-up will be necessary to see the effects of a reduction of acute rejection on long-term graft function, the survival over time of the transplant recipient, and the development of graft vasculopathy.
Villanueva and colleagues reported in 2000 on a retrospective review of data on 14 transplants (seven bilateral lung, six single lung, one heart-lung) recipients who received ECP for bronchiolitis obliterans syndrome (BOS). All patients were refractory to standard immunosuppressive therapy. ECP was administered every two weeks for two months followed by once a month for the next two months for a total of six treatments. Four of eight patients with initial BOS grade of 0 or 1 had improvement in BOS or stabilization of BOS after treatment. Mean survival after ECP was 14 +/- 12 months. Three of these patients received ECP during a concurrent episode of acute rejection. All three of these patients had complete resolution of the acute rejection following therapy. Another study published in 1999 completed by Salerno et al. reported on two patients with histologic reversal of concurrent acute rejection after treatment with ECP. These two studies reported on only five cases of ECP used to treat acute rejection. Additional prospective trials are needed to determine the efficacy of ECP to treat acute rejection after lung transplantation.
In 2008, Benden and colleagues published a single-center experience with ECP, which included 24 patients treated with ECP, 12 for recurrent acute rejection and 12 for BOS (see review in the next section). Patients had biopsy-confirmed chronic acute rejection, defined as two or more biopsy-proven episodes of acute rejection prior to the start of ECP. The primary outcome measure was clinical stabilization of rejection after ECP. All but one patient had follow-up biopsies during treatment; two patients had an episode of biopsy-proven acute rejection. All patients with recurrent acute rejection experienced clinical stabilization after 12 cycles of ECP; none experienced BOS. Treatment was well-tolerated with no adverse events related to ECP reported. Median patient survival was 7.0 years (range: 3.0–13.6 years), the median patient survival post-ECP was 4.9 years (range: 0.5–8.4 years). However, these rates are for the 24 patients as a whole, not broken down by indication for ECP.
Chronic Rejection Refractory to Corticosteroid/Refractory Bronchiolitis Obliterans Syndrome (BOS)
Lucid and colleagues published a review of nine patients treated with ECP between July 2008 and August 2009. Median follow-up was 23 months post-transplant (range: 9-93 months) and the median age was 38 years (range: 21-54 years). The primary indication for ECP was symptomatic progressive BOS, which failed prior therapy. Patients were treated weekly with two sessions of pheresis for 3-4 weeks. Treatment then decreased in frequency to every 2-3 weeks, with the goal of getting treatment to every four weeks. Clinical response was defined as symptomatic improvement, decreased dependency on supplemental oxygen, and improvement in pulmonary function tests (PFTs). Sixty-seven percent (6 of 9) patients responded to ECP after a median of 25 days. No ECP-related complications occurred in this series. As with prior studies, this report has no control group for comparison.
Morrell et al. published a retrospective case series of all lung transplant recipients treated with ECP for progressive BOS at Barnes-Jewish Hospital-Washington University. Ninety-five percent of the patients had received a bilateral lung transplant and were BOS grade 3. The indication for ECP was progressive decline in lung function that was refractory to standard immunosuppressive therapy. Primary endpoint of the study was the rate of change in lung function before and after the initiation of ECP. ECP was delivered as two cycles on days 1, 2, 5, 6, 10, 11, 17, 18, 27, and 28 during the first month (10 treatments); biweekly for the next two months (eight treatments); and then monthly for the following three months (six treatments), for a total of 24 treatments. Patients were followed from the time of lung transplantation to death or the end of the study (July 1, 2008). Median follow-up time was 5.4 years (range: 1.0–16.6 years). Sixty patients were followed; at the end of the study, 33 patients were still alive, with four deaths occurring early in the study. The majority of deaths were due to progression of respiratory failure, except for one death due to sepsis and one to graft failure. The mean rate of decline in forced expiratory volume in the first second of expiration (FEV1) in the six months prior to ECP was -116.0 mL per month; after ECP, the mean rate of decline decreased to -28.9 mL per month. The mean difference in the rate of decline was 87.1 mL (95% confidence interval [CI]: 57.3–116.9 mL per month). The rate of decline in lung function was reduced in 44 patients (78.6%), and lung function improved for 14 (25%) of these patients, with an increase in the FEV1 above pretreatment values. Through 12 months of follow-up, the mean improvement in FEV1 was 145.2 mL. Ten of 60 patients experienced adverse events. Eight were hospitalized for catheter-related bacteremia; one case resulted in death. All cases resulted from indwelling pheresis catheters. The authors concluded that ECP was associated with a significant reduction in the rate of decline in lung function. This reduction was sustained through 12 months of follow-up. The major limitation of this study is its retrospective nature and the lack of a control group for comparison. A majority of these patients had BOS grade 3, and therefore, may be different than patients with other grades. The statistical analysis was well done, with robust methods to analyze the available data.
As noted above, Villanueva and colleagues retrospectively reviewed data on 14 transplant patients (seven bilateral lung, six single lung, one heart-lung) recipients who received ECP for BOS. All patients were refractory to standard immunosuppressive therapy. ECP was administered every two weeks for two months followed by once monthly therapy for the next two months, for a total of six treatments. Four of eight patients with initial BOS grade of 0 or 1 had improvement in BOS or stabilization of BOS after treatment. Mean survival after ECP was 14 +/- 12 months. The six patients with initial BOS grade 2 or higher suffered progression of their BOS after ECP. Mean survival after ECP was 14 +/- 10 months. Four of these patients died of chronic rejection, one of lung cancer. The remaining patient survived to retransplantation. Two of the 14 patients developed line-related sepsis, which was cleared with antibiotics and the removal of the vascular catheter.
Also as mentioned earlier, Benden and colleagues published a single-center experience with ECP, which accounted for 24 patients treated with ECP (12 for BOS and 12 for recurrent acute rejection, see previous section). ECP was delivered once the BOS grade worsened, despite standard therapy. At the start of therapy, the distribution of BOS was as follows: BOS grade 1 (n=5), BOS grade 2 (n=2), BOS grade 3 (n=5). Before ECP, the decline in FEV1 was 112 mL per month, compared to 12 mL per month post-ECP, mean change in rate of decline of FEV1 of 100 (range: 28–171); however, ECP did not seem to have an effect on absolute FEV1 among this subgroup. Treatment was well-tolerated with no adverse events related to ECP reported. Median patient survival was 7.0 years (range: 3.0–13.6 years), the median patient survival post-ECP was 4.9 years (range: 0.5–8.4 years). However, these are for the 24 patients as a whole, not broken down by indication for ECP.
O'Hagan and colleagues published in 1999, case reports of six patients at the Cleveland Clinic who received ECP for BOS refractory to standard immunosuppressive therapy and various other strategies including antithymocyte globulin, methotrexate, monomurine anti-C3 antibody, and tacrolimus. ECP was performed on two consecutive days twice a month until stabilization of the FEV1. Treatment was then repeated every 4-6 weeks. Four of the six patients had temporary stabilization of their airflow obstruction with minimal adverse effects. Grade of BOS was not reported. Case report data suffer from the lack of a control group, which allows for a measurement of the difference in outcomes between two treatments. In this case, that would be the difference in FEV1 between those receiving immunosuppressive therapies alone versus those being treated with immunosuppressive therapy combined with ECP.
Larger prospective RCTs are necessary to examine the comparative effects of ECP for patients with BOS stratified by BOS grade.
Prevention of Bronchiolitis Obliterans Syndrome (BOS) and/or Rejection
There are no studies addressing the prophylactic effects of ECP for lung transplant recipients.
The published evidence on the use of ECP in liver recipients is from one group in Italy. Urbani and colleagues have published a series of papers on various potential applications of ECP for liver transplant patients. The first paper is a retrospective review of five patients who received liver transplants and ECP for biopsy-proven allograft rejection, in which the indications for ECP were recalcitrant ductopenic rejection with Hepatitis C virus recurrence, corticosteroid-resistant acute rejection in two patients, severe acute rejection in a major ABO-incompatible liver graft, and severe acute rejection in a patient with a proven corticosteroid allergy. ECP was performed twice a week for four weeks, then every two weeks for two months and once a month, thereafter. ECP was stopped when indicated by biopsy-proven rejection reversal or the absence of clinically evident rejection relapse. Liver function tests improved to baseline in all but one patient, and no procedure-related complications were reported. At a median follow-up of 7.9 months, three patients were off ECP with normal liver tests and low-level immunosuppressive therapy. Two were receiving continued ECP treatments with full dose immunosuppressive therapy.
The second paper from 2007 was a nonrandomized comparative study of 36 patients (18 treatment and 18 historic matched controls) who were treated with ECP to delay the introduction of calcineurin inhibitors (CNI) with the goal of preventing toxicity. Patients were included if they were at risk of post-liver transplant renal impairment and neurologic complications, defined as having at least one of the following risk factors: a calculated glomerular filtration rate equal to or less than 50 mL/min at transplantation; severe ascites; history of more than one hospitalization for encephalopathy within one year of transplant and/or one hospitalization within one month of transplantation; or age 65 years or older. Outcome measures were treatment success rate, defined as the ratio of patients with full CNI-sparing or delayed immunosuppression, interval from liver transplant to CNI introduction, safety of ECP, and need for biopsy. ECP was initiated in the first week post-transplant; two different systems (Therakos and PIT) for photopheresis were used, and treatment was given according to a common schedule for the system used. All 18 patients completed the scheduled course and tolerated the ECP. CNI was introduced at a mean number of eight days for 17 patients, while one patient remained CNI free for 22 months. Acute rejection was higher but not significantly higher in the ECP group (5/18) versus in controls (3/18). One-, 6-, and 12-month survival rates were 94.4, 88.1, and 88.1%, respectively, for ECP recipients versus 94.4, 77.7, and 72.2%, respectively, among controls. The authors concluded that the addition of ECP offers better management of liver transplant patients in the early transplant phase, delayed CNI introduction, and lower CNI-related mortality. This study was not randomized and had a small number of patients.
The third paper (2008) was a report on three fields of interest for ECP as prophylaxis of allograft rejection in liver transplant patients. The three fields include use of ECP:
Except for the first area, these studies were small and had no comparison group. Randomized, clinical trials are needed for the proper assessment of outcomes.
The largest reported group of renal patients to receive ECP was at the Royal Prince Alfred Hospital, Sydney, Australia. In 2009, Jardine et al. published a prospective case series of 10 patients treated with ECP for recurrent and/or refractory rejection after renal transplant at this center. ECP was delivered weekly for four weeks, then every two weeks. Total treatment range was 2-12 treatments for more than 5-20 weeks. Median follow-up time was 66.7 months following transplant and 65.0 months from commencement of ECP. Indication for ECP was acute resistant/recurrent rejection in nine patients and the need to avoid high-dose corticosteroids in another. Refractory rejection was resolved in all patients through the stabilization of renal function. The authors concluded that ECP may have a role as an adjunct to current therapies in patients with refractory rejection. While this is the largest series of renal patients, it is small and there is no comparison group. It also suffers from the fact that renal biopsies were not used to document therapeutic response.
The remainder of the evidence in renal transplant recipients comes from case reports on 32 patients. Twenty-six of these patients had refractory rejection. After ECP, renal function improved in 19 of 26 patients, three patients were stable, and four patients returned to dialysis due to deteriorating function. Reports of long-term outcomes varied. Among the 22 patients who showed initial improvement and or stabilization of renal function, five had improved function at one year, one was stable at 25 months, five were stable at one year, seven were rejection-free at 2-5 years, and one graft was lost. Three patients did not have long-term outcome reports.
Summary—Solid-Organ Rejection
The evidence for the use of ECP in cardiac transplant patients relates to three indications: acute rejection; recurrent, multiple and/or refractory rejection; and prevention of rejection. For acute rejection, a randomized trial was published in 1992 which enrolled 16 heart transplant patients. ECP in combination with immunosuppressive therapy had similar efficacy compared to immunosuppressive therapy alone, with fewer infections in the ECP group. This study was of a small size, and there was heterogeneity in the time from transplant to study entry. For prevention of rejection, there is a randomized trial from 12 clinical sites in which 33 patients were randomly assigned to immunosuppressive therapy and ECP and compared to 27 on immunosuppressive therapy alone. Differences between numbers of acute rejection episodes were statistically significant; however, there were no differences in survival at six months. Thus, the evidence to date is insufficient to permit conclusions concerning the effect of ECP on net health outcome for the treatment and prevention of acute cardiac rejection. Therefore, ECP is considered experimental, investigational and unproven for the treatment and prevention of acute rejection in cardiac transplant recipients. Studies with more patients and longer follow-up are needed.
ECP for recurrent, multiple and/or refractory cardiac allograft rejection has been the focus of most of the research on ECP. While the data are from nonrandomized studies, a comparative study of 343 cardiac transplant patients in which 36 received ECP has been completed. The authors present data showing that at three months, ECP was related to a risk reduction of hemodynamic compromise (HC) rejection or rejection death (risk ratio [RR]: 0.29). A reduction in HC rejection or rejection death was observed through two years of follow-up. While the results of this trial may be confounded by altercations in the immunosuppressive therapy regimen over time, they are consistent with the remainder of the literature for this indication showing a benefit of ECP in patients with recurrent or refractory cardiac rejection. Thus, the evidence to date, which consists of one nonrandomized comparative study, two case series and a case report of four patients, provides consistent evidence for a beneficial effect of ECP for cardiac transplant patients with rejection refractory to standard therapy. Therefore, ECP is considered medically necessary for the treatment of recurrent, multiple and/or refractory cardiac rejection.
The evidence on the use of ECP in lung transplant recipients falls under two indications: acute rejection and chronic rejection refractory to corticosteroids/refractory BOS. The data for acute rejection are very limited and do not permit any conclusions. These are subsets of patients who have been pulled from a larger group because they were treated with ECP during a period of acute rejection. This area needs a prospective, randomized, clinical trial focused specifically on the treatment of patients in acute rejection.
The bulk of the ECP in lung transplant literature focuses on treatment of refractory BOS. The primary limitations in these data are that they are nonrandomized with no control group. Further, the evidence is not entirely consistent, with some studies reporting ECP to be beneficial in those with early refractory BOS but not those with grade 2 or higher, which is in contrast to the largest series of 60 patients who responded well to ECP (nearly 60% of these patients were BOS grade 3). Prospective, RCTs are necessary, and analyses should be stratified by BOS grade, as there is some preliminary evidence that ECP may work differently based on BOS grade at the start of therapy.
The evidence to date, which consists of small case series, is insufficient to permit conclusions concerning the effect of this procedure on health outcomes in lung transplant. Studies with larger numbers of subjects and longer follow-up are needed. Therefore, ECP is considered experimental, investigational and unproven when used in lung transplantation.
In liver transplantation, the evidence for the use of ECP is limited, and the research to date has been generated by one group in Italy. While there is one comparative (nonrandomized) study, this trial involves only 18 cases and 18 controls. There is a need for RCTs. The effort in liver transplant patients has been on prevention of rejection with ECP. This question lends itself well to an RCT comparing immunosuppressive therapy alone to immunosuppressive therapy with ECP. The evidence to date, which consists of small case series and one comparative study, is insufficient to permit conclusions concerning the effect of ECP on net health outcome for liver transplant patients. Therefore, ECP is considered experimental, investigational and unproven in liver transplant patients for any indication.
For renal transplant recipients, the evidence for the use of ECP is sparse. There are a total of 42 patients whose treatment has been reported in the literature. The available evidence appears to consistently report evidence of benefit from ECP for those with refractory rejection. However, there are no comparative studies and current numbers are too small to permit conclusions. A prospective, randomized trial, with histologic confirmation of treatment response is needed. This trial would randomize patients to immunosuppressive therapy or immunosuppressive therapy with ECP with the primary aim of addressing the question of whether there is an additional benefit from ECP for patients with refractory rejection after renal transplant. The evidence to date, which consists of small case series, is insufficient to permit conclusions concerning the effect of ECP on net health outcome for renal transplant patients. Therefore, ECP is considered experimental, investigational and unproven in renal transplant patients for any indication
A search of www.ClinicalTrials.gov found no registered clinical trials seeking to assess ECP as a treatment of solid-organ transplant rejection in any organ.
Technology Assessments, Guidelines, and Position Statements
United Network of Organ Sharing (UNOS) does not have any policies related to ECP in the treatment or prevention of any form of rejection following solid-organ transplant.
Graft-versus-Host Disease (GVHD)
Extracorporeal photopheresis (ECP) for the treatment of acute and chronic GVHD was initially addressed by a 2001 Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) Assessment that offered the following observations and conclusions: For acute GVHD or chronic GVHD in previously untreated patients or in those responding to conventional therapy, no studies met selection criteria and reported results of ECP, alone or in combination with other therapies. Therefore, photopheresis for these indications failed to meet TEC criteria. Studies focusing on patients with chronic GVHD unresponsive to other therapies reported resolution or marked improvement of lesions in approximately 50% of patients. Finally, studies of patients with acute GVHD also reported a successful outcome in 67–84% of patients with grade III disease, but patients with grade IV disease rarely responded.
Following the TEC Assessment in 2001, two small studies that focused on photopheresis for treatment of GVHD in children were published. In one study, eight children (aged 5–15 years) with refractory extensive chronic GVHD were treated with ECP and either oral 8-methoxypsoralen (8-MOP) or infusion of an 8-MOP solution into the pheresed lymphocytes. Cutaneous status reportedly improved in seven patients. Five patients stopped treatment and three others decreased doses of immunosuppressive therapy. In addition, gut involvement resolved in all patients, and liver involvement resolved in 4 of 6 patients. Two years following discontinuation of photopheresis, five patients remained in remission without immunosuppressive therapy. Salvaneschi and colleagues reported on photopheresis results in refractory GVHD in nine acute pediatric cases and in 14 chronic pediatric cases (aged 5.4–11.2 years). In the acute GVHD cases, 7 of 9 experienced either partial response (PR) or complete response (CR), while in the chronic GVHD patients, 9 of 14 experienced either partial or complete remission. These findings are consistent with the current policy statements.
Several additional publications subsequently reported on the use of ECP for the treatment of GVHD. Foss and colleagues reported results of a prospective (non-randomized) study of ECP in 25 patients who had extensive corticosteroid-refractory or corticosteroid-resistant chronic GVHD secondary to allogeneic stem-cell transplantation. ECP was administered for two consecutive days every two weeks in 17 patients and once weekly in eight until best response or stable disease was achieved. With a nine-month median duration (range 3–24 months) of ECP, 20 patients had improvement in cutaneous GVHD, and six had healing of oral ulcerations. ECP allowed cessation or reduction of immunosuppressive medication treatment in 80% of patients. Overall, improvement was reported in 71% of cases with skin and/or visceral GVHD and 61% of those deemed to be high-risk patients. These results are consistent with the current coverage statements.
Greinix and coworkers reported findings from a Phase II (nonrandomized) study to evaluate the efficacy of intensified ECP as second-line therapy in 59 patients with post-stem cell transplant acute (grades II-IV), steroid-refractory GVHD. ECP was initially administered on two consecutive days (one cycle) at 1- to 2-week intervals until improvement was noted and thereafter every 2-4 weeks until maximal response. At the start of ECP, all patients had been receiving immunosuppressive therapy with prednisone and cyclosporine A. Complete resolution of GVHD was documented in 82% of cases with cutaneous manifestations, 61% with hepatic involvement, and 61% with gut involvement. A CR was noted in 87% and 62% of patients with exclusively skin or skin and liver involvement, respectively; only 25% with GVHD of skin, liver and gut involvement and 40% with skin and gut involvement obtained a CR of GVHD with ECP therapy. The probability of survival was 59% among patients with CR to ECP, compared to 11% of those who did not respond completely. While these results suggest ECP may be beneficial in the treatment of acute GVHD, the small size, few study details in the report, and lack of a standard treatment comparator group limit inferences as to the clinical efficacy of ECP for acute GVHD.
In 2006, the Ontario Health Technology Advisory Committee (OHTAC) published results of a systematic review of ECP for the treatment of refractory chronic GVHD. In summary, OHTAC reported that there is low quality evidence that ECP improves response rates and survival in patients with chronic GVHD who are unresponsive to other forms of therapy. Limitations in the literature related to ECP for the treatment of refractory GVHD mostly pertained to the quality, size, and heterogeneity in treatment regimens and diagnostic criteria of available clinical studies. The committee did, however, recommend a two-year duration field evaluation of ECP for chronic GVHD, using standardized inclusion criteria and definitions to measure disease outcomes including response rates, quality of life, and morbidity.
A retrospective case series published in 2007 reported results of ECP for steroid-resistant GVHD in pediatric (aged 6–18 years) patients who had undergone hematopoietic stem-cell transplantation to treat a variety of cancers. Patients had acute GVHD (aGVHD, n=15, stages II-IV) or chronic GVHD (cGVHD, n=10, 7 deemed extensive) that did not respond to at least seven days of methylprednisolone therapy. Patients received ECP on two consecutive days at weekly intervals for the first month, every two weeks during the second and third months, and then at monthly intervals for a further three months. ECP was progressively tapered and discontinued based on individual patient response. Response to ECP was assessed three months after ECP ended or after six months if the ECP protocol was prolonged. Among patients with aGVHD, a CR was observed in 7 of 7 (100%) with grade II and 2 of 4 (50%) with grade III illness, whereas none with grade IV responded to ECP. In the group with cGVHD, 3 of 3 (100%) with limited disease had CR, compared to 1 of 7 (14%) with extensive disease who had CR; 5 of 7 (71%) of patients with extensive cGVHD had no response to ECP. Adverse effects of ECP were generally mild in all cases. These results are similar to those summarized in the 2001 TEC Assessment cited previously and thus do not alter the current coverage statements.
In 2008, Perfetti and colleagues reported on a retrospective review of 23 patients with corticosteroid-refractory acute GVHD, 10 grade II, seven grade III, and six grade IV. Median duration of ECP was seven months (1–33 months) and median number of cycles per patient was 10. Complete responses were seen in 70%, 42%, and 0% of patients with GVHD grades II, III, and IV, respectively. Eleven patients (48%) survived and 12 died: 10 of GVHD and two of relapse of their leukemia. Patients treated within 35 days from onset of GVHD had a higher but not statistically significant different response (83 vs. 47%, respectively; p=0.1). While these findings suggest that ECP may provide benefit for patients with refractory acute GVHD, they are limited by the small sample size and non-comparative nature of the study.
One study was published in 2010 by Shaughnessy and colleagues using ECP to prevent acute GVHD in patients undergoing standard myeloablative conditioning and allogeneic transplant. ECP was administered prior to a standard conditioning regimen. Results were compared to historical controls from the Center for International Blood and Marrow Transplant Research (CIBMTR) database. Multivariate analysis indicated a lower rate of grade II-IV acute GVHD in patients receiving ECP. Adjusted overall survival at one year was 83% in the ECP group and 67% among historical controls (relative risk [RR]: 0.44; 95% confidence interval [CI]: 0.24-0.80). Additional prospective randomized trials are necessary to confirm these findings.
Cutaneous T-Cell Lymphoma
Stage III/IV MF and Sezary Syndrome
The initial report on the use of ECP as therapy for cutaneous T-cell lymphoma (CTCL) was published by Edelson and colleagues. Twenty-seven of 37 (73%) patients with otherwise resistant CTCL responded to the treatment, with an average 64% decrease in cutaneous involvement after 22 + 10 weeks (mean + SD). The responding group included 8 of 10 (80%) patients with lymph-node involvement, 24 of 29 (83%) with exfoliative erythroderma, and 20 of 28 (71%) whose disease was resistant to standard chemotherapy. Side effects that often occur with standard chemotherapy, such as bone marrow suppression, gastrointestinal erosions, and hair loss, did not occur. These results showed that ECP is safe and effective in advanced, resistant CTCL. Subsequent results from numerous small, nonrandomized studies have been generally consistent with the initial conclusion that ECP treatment can produce clinical improvement and may prolong survival in a substantial proportion of patients with advanced-stage CTCL.
Together, these data provide the basis for several evidence-based guideline or consensus statements on the use of ECP in CTCL, as well as the position of the National Cancer Institute (NCI) available online at <http://www.cancer.gov>. They consistently recommend ECP as first-line treatment for patients with stage III/IV CTCL. Therefore, in this policy, ECP may be considered medically necessary as a technique for the treatment of patients with stages III/IV CTCL.
In 2006, OHTAC published results of a systematic review of ECP for the treatment of erythrodermic CTCL. In summary, OHTAC reported that there is low-quality evidence that ECP improves response rates and survival in patients with CTCL who are unresponsive to other forms of therapy. Limitations in the literature related to ECP for the treatment of refractory erythrodermic CTCL mostly pertained to the quality, size, and heterogeneity in treatment regimens and diagnostic criteria of available clinical studies. The committee did, however, recommend a two-year duration field evaluation of ECP for refractory erythrodermic CTCL, using standardized inclusion criteria and definitions to measure disease outcomes including response rates, quality of life, and morbidity.
Early Stage (I/II) CTCL
Between 1987 and 2007, data were reported from at least 16 studies including 124 patients with CTCL in early stages IA, IB, or II who were treated with ECP alone (n=79) or in combination with other agents (n=45) including retinoids and interferon-alfa. Many of these patients were refractory to numerous other therapies, including topical corticosteroids, interferon alfa, or whole-skin irradiation. Response rates (partial plus complete) in these studies ranged from 33% to 88% with monotherapy and 50–60% with ECP and adjuvant therapies. While these findings suggest ECP may provide benefit in early-stage CTCL, none of the studies was randomized or comparative. Furthermore, many of the studies preceded universal acceptance of standardized elements of classification and diagnosis of CTCL, such as those proposed by the World Health Organization and European Organization for Research and Treatment of Cancer (WHO-EORTC). Thus, the actual disease spectrum and burden represented in the available database likely vary between studies, and this complicates conclusions about the efficacy of ECP in this setting. Nonetheless, given the unfavorable prognosis for patients with early-stage CTLC that progresses while receiving nonsystemic therapies, the relative lack of adverse events with ECP compared to other systemic treatments, and the good response rates often associated with ECP, ECP may be considered medically necessary as a technique for the treatment of patients with refractory or progressive early-stage CTCL. By contrast, because early-stage CTCL typically responds to less-invasive, topical therapies, patients whose disease remains quiescent under such treatments usually experience a near-normal life expectancy. As a consequence ECP is considered experimental, investigational and unproven as a technique for the treatment of patients with stage I/II CTCL that is either previously untreated or is responding to established therapies.
National Cancer Institute (NCI) Physician Data Query (PDQ®) Database
The NCI PDQ database indicates no RCTs on the use of ECP in CTCL are recruiting or are otherwise in development.
ClinicalTrials.gov indicates there are at least nine active Phase II/III clinical trials seeking to assess the efficacy of ECP as a treatment of acute or chronic GHVD or for the prevention of GVHD. No trials of ECP for any autoimmune disease were identified (available online at >http://www.clinicaltrials.gov>).
National Comprehensive Cancer Network (NCCN)
The NCCN 2010 guidelines for the treatment of CTCL recommend the use of ECP alone or in combination with other agents (retinoids, interferon alfa, denileukin diftitox) as first-line systemic therapy for advanced (stages III/IV) disease as well as for patients either with earlier stage mycosis fungoides with Sezary syndrome involvement or with disease that has failed multiple courses of topical skin-directed treatments
Autoimmune Disease
ECP for the treatment of autoimmune diseases was initially addressed by a 2001 TEC Assessment, which offered the following observations and conclusions. A variety of autoimmune diseases were considered, including systemic sclerosis, pemphigoid, systemic lupus erythematosus, multiple sclerosis, psoriatic arthritis, rheumatoid arthritis, and type I diabetes. For all of these indications, the available evidence was insufficient to permit conclusions on outcomes. At the time, photopheresis had been most thoroughly studied as a treatment of scleroderma. However, the data on this indication include one single-blind RCT and three small, uncontrolled series. While the randomized study reported positive outcomes in terms of skin manifestations, a number of methodologic flaws have been discussed in the literature, including inadequate treatment duration and follow-up, excessive dropouts, a mid-study change of primary outcome, and inadequate washout of prior penicillamine therapy. Results reported from other small case series regarding systemic sclerosis conflict with each other and do not resolve the difficulties in interpreting the randomized trial.
One clinical trial on diabetes was found for a subsequent update of the original policy through 2003. No clinical trials were found on photopheresis for other autoimmune diseases. For diabetes, Ludvigsson and colleagues reported a double-blind, RCT on photopheresis in 49 children with newly diagnosed type 1 diabetes. A total of 40 children aged 10–18 years completed the study and were followed up for three years. All patients received standard treatment with insulin therapy and diet, exercise, and self-management education. Of these patients, 19 received active photopheresis treatment with oral 8-MOP, and 21 received placebo tablets and sham pheresis in the control group. Hemoglobin A1C results, a key clinical outcome in diabetes control, were not statistically different in the two groups.
In 2007, one small series was identified in which ECP was administered to treat immunorefractory relapsing-remitting multiple sclerosis in five patients. ECP appeared safe and tolerable in these patients, with some evidence for a reduction in the relapse rate and symptom stabilization. However, the data are insufficient to alter the coverage statement for this use of ECP.
In 2010, Sanli and colleagues published a retrospective report on 11 patients with drug-resistant autoimmune bullous diseases. ECP was performed between January 2005 and January 2010. Eight of these patients had pemphigus vulgaris (PV), while the others had epidermolysis bullosa acquisita (EBA). Patients were treated on two consecutive days at four-week intervals. Among the patients with PV, all experienced complete remission after 2-6 cycles, except one. Two patients with EBA had complete remission, while one patient had partial remission. Corticosteroids were reduced in all patients with PV. Decrease in the frequency of ECP resulted in progression of lesions for three patients with PV and in two of the patients with EBA. No adverse effects were observed. RCTs are necessary to adequately assess the efficacy of ECP for patients with drug-resistant autoimmune bullous diseases.
Disclaimer for coding information on Medical Policies
Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.
The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.
Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member's benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.


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May 20, 2013
These stuffed Portobello mushrooms from Citron Limette are inspired by summer vegetables. Baked portobello mushrooms are filled with roasted tomatoes, roasted red peppers, basil and feta cheese. You can also grill the mushrooms instead of baking them. This recipe is so simple and delicious that you'll want to make it throughout the season. For full recipe instructions, click here.
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Naked Pizza opens tomorrow on East Colfax
New Orleans-based Naked Pizza made it a mission to give pizza a healthier image, starting with a probiotic crust chock-full of grains such as spelt and quinoa, and finishing with toppings cut from fresh ingredients.
The idea caught on quickly: The pizza chain has franchised across the country -- and crossed the border into Dubai -- since it was founded in 2006. And starting tomorrow, you'll be able to get a slice of Naked Pizza right here in Denver.
Franchisee Gay Burke is about to officially open a spot on East Colfax, the first of nine she has rights to in the city. The shop, which was originally slated to debut in May, was "delayed by construction," says Anne Zilvitis, vice president of marketing for Naked Pizza in Denver. "I wish I could tell you a more exciting story."
But it's ready to go now: The joint has been in soft-opening mode since last week, she notes, and it'll start showing Denver diners the naked truth tomorrow at 11 a.m.
"We're not just a regular tak-out and delivery joint," she explains. "The best word I can use to describe it is 'artisan.' We use fresh ingredients, and they don't come in chopped already -- we do that on-site daily. Our crust is hand-stretched, and it contains our ancestral blend of grains like quinoa and spelt, which makes the pizza healthier and taste better." For a side of more health, salads are also available, and the dough is also made into breadsticks.
There is another Naked Pizza already open on Boulder's 28th Street, but that one isn't owned by Burke. And although she has the rights to expand in Denver, for now she's concentrating on the Colfax location -- with one caveat. "Gay bought the rights to this pizza and the frozen line," Zilvitis says. So she's also responsible for those Naked frozen pizzas now available at Sunflower Markets across the country, including here in Denver.
Related Location
2207 E. Colfax Ave.
Denver, CO 80206
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Tasktop Summer 2008 Released: Offload Your Brain, July 24th, 2008
The Tasktop Team is very pleased to announce the release of Tasktop Summer 2008. Summer is a great time to offload your brain, so we've packed this release with features that will help you do just that. This release's splash screen commemorates a summer hike in the mountains overlooking Vancouver.
The coolest thing in this release is the new time tracking and reporting feature, which gives you full transparency into your work activities with automatic to-the-minute tracking of time spent working both within and outside of Eclipse. As usual, we put all of the control at your finger tips, enabling you to do things like adjusting timings. You also get flexible reports so that you don't have to stress the creative side of your brain when needing to report activity or fill out time sheets, and can save your creativity for more interesting activities like coding. As an example, take a look at my time report for the week after the Mylyn 3.0 release, from which I can immediately see that I spent most of my time on the Tasktop working set (blue part of pie chart on far right), a bunch of time went to managing (the gray bars in the graph) and thankfully a higher proportion to working on the tasks I had scheduled (colored bars in the graph). From this I can immediately see why I was itching to write code by the end of the week, since most of my week went into non-programming activities.
Eclipse Mylyn users will be pleased to learn that we are now providing a free version of Tasktop called Tasktop Starter. This allows us to deliver to you some valuable features that are out of the scope of Eclipse and Mylyn. Below you can see a snapshot of the welcome screen that will get you started exploring the features in Tasktop Starter, such as one-click install of partner connectors, automatic Mylyn updates to either release or weekly builds, and a time tracking dashboard for the current week. We've also included the Gmail connector for free, which lets you easily tag conversations in Gmail have them appear in Mylyn's Task List and be accessible when working offline. You need Tasktop Pro for the main productivity features such as focused web browsing, desktop integration, customized time reporting and additional connectors such as Microsoft Outlook. But with Tasktop Starter you get both a useful day-to-day tool and a glimpse at what it's like to have Mylyn's task-focused interface keep you focused and productive for the non-coding parts of your workday.
I drive at least 90% of my workday from Tasktop/Mylyn/Eclipse, and one of my favorite new features is the one-click switching of working sets. It seems so rudimentary, but this makes switching your project/work/role contexts as easy as switching task contexts. In addition, you get to see how far behind you're getting on any particular working set, thanks to an indication of the number of incomings. This is just one part of the additional streamlining that we're providing with Tasktop as part of our mission to save you clicks. Less is more.
We hope that you enjoy this release of Tasktop and continue sending us your feedback and votes for future enhancements and integrations. For more info see:
|InfoQ interview about the release
|Upated Tasktop site and product tours


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Embedded Chain plate maint/replacement
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Re: Embedded Chain plate maint/replacement
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The only neg effect moving the chains farther outside is on the ability to close haul, in this case it is only couple inches otherwise the plates are in the same location. The effect on the rig is to actually make it stronger... the base is wider. As to the cosmetics to each his own. The one absolute fact about glassed in plates is that they are 02 starved and water will get in there eventually, 30 years down the road, or 2 and along with that comes crevise corrosion. The only way to inspect these plates is to have gamma radiography done. $1500 just to inspect the plates, hmmm pass.
I've seen gamma shots of chains on a big Irwin and they weren't enough to really tell the state of them. You HAVE to remove them to know if they are O/K and I pretty well guarantee that, after 25 or 30 years buried under glass, at least some of them won't be.
I, myself, personally intend to continue being outspoken and opinionated, intolerant of all fanatics, fools and ignoramuses, deeply suspicious of all those who have "found the answer" and on my bad days, downright rude.
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Intel i5 Core Demonstration at CES 2011
January 10, 2011
The Intel core i5 micro processor is also able to double as a graphics card. This video demonstrates both its processing capabilities and its graphics capabilities through touch technology at the CES event in Las Vegas. credit: redOrbit.com
Topics: Technology Internet, Intel Core i5, Intel Corporation, semiconductor companies, Intel Core, Centrino, ATI Technologies, Business Finance


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- chewy3326
- Reviews: 932
Lake O'Hara Campground: Lake O'Hara Campground
Lake O'Hara Campground lies about a kilometer away from Lake O'Hara itself. This campground has sites that are roughly 9x9 feet as well as two cook shelters and decently clean outhouses. As it's not possible to drive to the campground, you'll have to pack everything with you when you head in on the Lake O'Hara bus. Bear boxes are provided. The entire campground is in a wooded, peaceful spot. The location of the campground makes it convenient for getting to the lake: a 12-15 minute walk on the road takes you to the lakeside and Le Relais Day Shelter. However, the more scenic alternative is to follow Cascade Creek instead of the road to the lake.
From the road right outside the campground, there are good views of Cathedral Mountain.
- RockiesTraveler
- Reviews: 27
Rocky Mountain Ski Lodge, Canmore, Alberta: Affordable and Scenic
This was a very nice find that I found on the web. They are one of the few places in Canada that honor the AAA discount. And, during the off season plus the discount this place was very affordable. There is a playground for kids, and outside barbeques for sharing. You have a choice of 2 different mountain ranges for viewing from your suite. They had a hot tub, but it was in maintenance when we arrived so we could not use it. Staff is very friendly and is locally owned and operated.
Right in the heart of downtown Canmore, Alberta. Close to shops and Boston Pizza pub and lounge. Good view of the Three Sisters mountain peaks and one other but I forgot the name.
- cfuentesm
- Reviews: 833
Hillside Lodge and Chalets in Golden: Hillside Lodge and Chalets in Golden
Secluded 1 kilometer from the highway, amongst beautiful woods, you will find these cute lodge and chalets. The cabin we got was very ample and extremely cozy, with its fireplace, kitchenette and a dining table and bed that reminded us of the 3 little bears. Central heating worked just fine. The only weird thing was the shower water... it smelled like sulfur. It was a charming night at a GREAT price.
- madamx
- Reviews: 640
Post Hotel
When you want to feel like you are a million bucks, stay at the Post Hotel. Affiliated with the Relais and Chateau Swiss chain, service is impeccable and they make you feel like you're a famous movie star, not some schmuck from Calgary. The rooms are a unique blend of luxury and simple rustic. Cleanly whitewashed walls and elegantly simple pine furniture combine with luxurious granite and heated slate floor bathrooms. Relax under a fluffly down comforter after your jazucci bath with Aveda products. Most rooms have wood-burning fireplaces.
Also, their restaurant is rated one of the top dining rooms in the world, with their wine cellar winning a Wine Spectator Award. The waiters even have those roller crumb removers that they pull out after you finish your meal. Now, that's classy.
Travel and Leisure Magazine voted The Post Hotel one of the top 10 places to stay in North America for 2004 (best value resort) and #44 of the top 100 North American Hotels (2005)
Andre and George Schwarz , two brothers that own the hotel, are always on hand supervising the facilities, which ensures good quality control. The employees seem happy and genuinely want you to have a good experience. There's a decent pool and jacuzzi, with a recently added spa and exercise room with state-of-the-art equipment, and skating on the front lawn in the winter. You can indulge in afternoon tea from 2:00 pm until 5:00 pm in their comfy and elegant front lobby (the raspberry yogurt cake is my favorite) while gazing onto Mt. Temple.
Also most rooms have a balcony. Just make sure to book on the "preferred side" not the "standard side" and your stay will be very quiet. The standard side includes the parking lot and the railroad tracks. To be totally honest, I'm a light sleeper, and the train isn't a problem (the engineers mercifully don't blow the whistle) but the people using the parking lot is. Go all out and book one of the cabins on the Pipestone River.
This is the best deal for a luxury hotel in the Rockies, taking into account location, price, and amenities, plus none of those pesky hidden "resort fees".
- madamx
- Reviews: 640
Lake O'Hara Lodge
The Lake O'Hara Lodge is located on the shores of Lake O'Hara, and I feel that it unfortunately caters to the more wealthier of mountain park visitors. We have not personally stayed here, but got the chance to tour the building extensively with a returning ex-staff member, so saw all areas of the building.
Prices are extremely expensive for what you get -- approx $685 per night per couple, for one of the prime lakeside cabins, and $465 per night per couple for a lodge room, both rates including full board. Plus, there is a minimum stay for 2 nights. Judging from the very rustic environment of the lodge v. the luxury prices of the rates, I would not shell out that much just to say that I stayed overnight on the shores of the famous Lake O'Hara.
You MUST book very early, as there is a waiting list for reservations. All reservations are given to returning clientelle first, then new reservations are considered, which I don't think is a very fair practice.
Touring the lodge rooms, I found them dark and depressing; there is a shared washroom each for men and women, and it reminded me of staying at a boarding school. The furniture almost appears to be made from orange crates, and the rooms cramped. The cabins are just as rustic and cramped.
However, I must say that I've heard rave reviews about the copious amounts of gourmet food, the staff are extremely friendly and efficient, and though simple, the lodge is very, very, clean. There is a comfortable seating area downstairs with large sofas and tables for eating, and a separate "mud room" to store hiking or skiing equipment, so the lodge stays clean and orderly. You get to ride in a better, roomier bus than the regular visitors to Lake O'Hara and you can't beat the gorgeous surroundings. However, for the prices charged, one can stay at the Post Hotel 15 minutes east on the main highway for comparably the same price and be a lot more comfortable with many more amenities. Or, you would be better off staying at the Lake Louise Hostel or a simple motel in Golden, pay each day for entry to the park, and be so much further ahead. I was that unimpressed and disappointed with the rooms.
- madamx
- Reviews: 640
Hillside Lodge and Chalets
This quaint lodge is located just off the Trans Canada near Golden, BC and is an affordable alternative to pricey National Park accomodation. It is about 45 minutes west of Yoho National Park.
We arrived late one evening, and left the next morning, but from what little we saw, we would love to return again. Our room was huge, and decorated simply but pleasantly with Scandanavian-style furniture. There was a sitting area, as well as a beverage centre with coffee maker, complete with coffee, tea and hot chocolate and bar fridge.
You would never know you were just off the highway -- the setting is a wooded area near the Blaeberry River, and everything about this place just charms the dickens out of you, especially the llama farm located next door.
Our back balcony looked out onto the Blaeberry River, and we sat and watched the sun set, and felt very much at peace indeed. Wander down the back dirt road and there are plenty of raspberries and suprisingly sweet thimbleberries for snacking. The lodge is set up very thoughtfully, and the management seem to want to keep their guests as comfortable as possible. The breakfast is not bad, as I'm not a fan of European breakfasts, but is satisfying enough.
The cabins usually do not include breakfast.
- madamx
- Reviews: 640
Emerald Lake Lodge
Approximately 20 minutes past Lake Louise, the Emerald Lake Lodge is located on a peninsula on the gorgeous shores of the appropriately named Emerald Lake, in Yoho National Park, BC. The original lodge was built in 1902, and was one of the Canadian Pacific Railway hotels, along with The Chateau Lake Louise, but is now owned by The Rocky Mountain Resort Group. The lodge and cabins as you now see them are a result of an extensive renovation done in 1986.
This place is not cheap; it is rustic elegance at it's best, and the off-season rate for a suite on the lake is approximately $260 CDN a night. However, if you can afford one night, go for it. We were fortunate enough to spend a long weekend at the lodge, and all I can say is it is a five-star experience from the moment the shuttle bus driver picks you up from the hotel lot. The rooms are decorated in eclectic rustic elegance -- antiqued pine furniture and fieldstone wood-burning fireplaces, slate bathroom tiles, with a Nygard designer microfibre duvet cover on the down duvet. 100% cotton sheets and soft, fluffy white robes -- need I say anything more?
Generous-sized suites are located in cabin-style buildings, and I recommend asking for an upstairs suite, as the common door can bang very loudly with people coming and going. Bring binoculars, as there are many chances for viewing wildlife -- we saw foraging bear early one morning across the lake on an avalanche slope. Even though the lodge and cabins are in a prime tourism spot, the way the hotel is situated, the area remains quiet and secluded.
The hot tub/exercise area are immaculate ( anyone who would want to use a treadmill when they are in such beautiful hiking country is beyond me). There are many easy walking paths located around the lodge, as well as hikes. Make sure to do the lake circuit, a gorgeous, easy walk, that is 5.2 km, and takes perhaps an hour to complete.
The only tv is in the guest lounge, located in the upstairs of the main lodge. Satellite fed, it has extensive channel choices. There is also free internet access -- complete with a new flat-screen computer. There is phone service in each guest room.
If you are staying at the hotel, you must park in the designated overnight guest lot approx 5 minutes from the lodge and lake. The shuttle bus is operational 24 hours a day, 7 days a week. They will deposit your luggage in your suite, as you could have a fair walk from the main lodge.
- GuthrieColin
- Reviews: 590
Emerald Lake Lodge: Emerald Lake Lodge
I did not stay at this lodge but the views I found from it's grounds were the best I could find. The buildings looked very fairly plain on the outside but very luxurious inside. From their website I could also see that they serve breakfast and dinner as well. I would love to return some day and stay there.
Spectacular Views.
- mht_in_la
- Reviews: 881
Emerald Lake Lodge: Lake side paradise
This resort by Emerald Lake is both luxurious and rustic. Originally built by CPR (Canadian Pacific Railway) in the early 20th Century, Emerald Lake Lodge is currently operated by CRMR (Canadian Rocky Mountain Resorts), a company that also owns several similar resorts throughout Yoho and Banff National Parks. The main building has meeting rooms, a couple of restaurants, and a games room. The living unit is made of 24 cabin-style buildings accommodating up to 200 guests.
If you plan to stay here and arrive by car, don't drive all the way to the Lodge. Instead, park your car at the over-night parking and take the shuttle to the Lodge. This is so that Lodge guests and regular visitors to the lake don't compete for the same parking. Also, National Park permit is not required in the Lodge's over-night parking. Behind the parking is the dorm for Lodge employees.
This is an all-season resort. In the winter you can ski or snowshoe. In the summer you can hike, bike, or canoe.
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Hutton in the Forest, Penrith, Cumbria, CA11 9TH
Historic house and gardens based on a medieval pele towers with substantial 17th, 18th and 19thC additions. Extensive gardens in woodland setting walled garden, topiary, woodland walk and lake with cascade.
The Pier House, Glenridding, Penrith, Cumbria, CA11 0US
The 'Steamers' create the perfect opportunity to combine a cruise with some of the most famous and spectacular walks in the lake District.
Carlisle, Cumbria, CA3 8UR
A massive medieval fortress founded to protect historic city of Carlisle in 1092. Hear about its role in sieges and stories about the ghastly prison.
Coniston, Cumbria, LA21 8AD
Brantwood, the former home of eminent Victorian John Ruskin and a treasure house of art and memorabilia. The 250-acre estate comprises 8 unique gardens, ancient woodland, high moors and meadows.
Lowther Castle, Penrith, Cumbria, CA10 2HG
Striking castle ruins with 130 acres of historic garden dating back 350 years, undergoing gradual recovery and restoration. A beautiful fully restored stable courtyard offers cafe and shop facilities.
Honister Pass, Borrowdale, Keswick, Cumbria, CA12 5XN
The last working slate mine in England. Fully guided mine tours and Via Ferrata. Browse the visitor centre. Our Sky Hi cafe serves freshly prepared, locally sourced, paninis, and soups.
Newby Bridge, Ulverston, Cumbria, LA12 8NN
Family-friendly park with green lawns sloping down to the lakeshore. Just the place to enjoy access to Lake Windermere with picnic areas, boat hire and tea room.
Southey Works, Keswick, Cumbria, CA12 5NG
Enter the museum through a replica of the Seathwaite mine, journey through the history of pencil making at the worlds longest pencil and finally relax in our coffee shop, while the kids follow the quiz trails.
Lodore Boat Landings, Derwentwater, Borrowdale, Keswick, Cumbria, CA12 5UX
Tuition/hire in canoes, kayaks, sailing boats, dragon boat, Viking longship voyager canoe on Derwentwater, individuals/groups/families/special needs catered for.
Watermillock, Penrith, Cumbria, CA11 0JS
The tumbling waterfall of Aira Force, drops an impressive 65 feet and can be reached by strolling through ancient woodland and landscaped glades. The perfect place for a family and picnic.
Grizedale, Hawkshead, Cumbria, LA22 0QJ
Grizedale Forest has activities for all ages from mountain biking to relaxing walks, Go-Ape to sculpture in the forest. The visitor centre includes the forest shop, Cafe in the Forest and Grizedale Mountain Bikes bike hire and shop.
Waterhead Pier, Waterhead, Ambleside, Cumbria, LA22 0EY
Windermere Lake Cruises offer more than just a ferry service. We hold private charters, lunch cruises, buffet cruises, corporate hospitality, public sailings, group travel.Steamers and launches sail daily throughout the year from Waterhead.
Whinlatter Pass, Braithwaite, Keswick, Cumbria, CA12 5TW
Whinlatter Forest Park is England's only true mountain forest. Rising to 790 metres above sea level Whinlatter offers spectacular views of the Lake District and into Scotland.
Mill Lane, Beetham, Milnthorpe, Cumbria, LA7 7PQ
A living heritage site, with Grade II* listed working watermill and hydropower station.
Old Blue Mill, Backbarrow, Newby Bridge, Cumbria, LA12 8TA
A unique combination of interrelated stories and a fascinating visitor experience. Over 100 years of motoring history, the Campbell Bluebird exhibition, IOM TT tribute display and the Leven Valley heritage centre. Gift shop and Cafe Ambio.
Lake Road, Keswick, CA12 5DJ
Keswick Canoe and Bushcraft is based in the heart of the Lake District National Park in the bustling town of Keswick. We are specialist providers of canoe tours, bush craft and wilderness skills, river trips and canoe expeditions.
Ravenglass, Cumbria, CA18 1SW
Heritage steam journey with a choice of open-top and cosy covered carriages. The journey traverses seven miles from the Lake District coastal village of Ravenglass to the foot of England's highest mountains, Scafell


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Golden Yunnan Black Full-Leaf
Elevate The Senses Tea - From the cloud-veiled mountains of Yunnan, the birthplace of tea, this rare, high-grown, golden tippy Yunnan is one of the most prized China black teas in the world. Exquisitely smooth and malty with pleasing floral overtones and a tinge of citrus, enjoy this brew with a touch of sugar and a splash of milk. Delicious hot or over ice.
Black Tea has less than half the amount of caffeine per cup than in a similar-sized cup of coffee. More about caffeine.
Steeping Instructions
Steeping black tea is easy. Simply heat fresh, filtered water to a rolling boil. Then pour water over tea and steep for 3-5 minutes if using a tea bag or full-leaf.
GTFOP Yunnan black tea leaves
Country of Origin
Yunnan, China
- 5
What our Citizens are saying about this great gift of the leaf...
|One of My Two Favorites
|August 14, 2014
|This Golden Yunnan variety is one of my favorites from ROT. It is a great tasting tea that suits me early in the morning and it really can brighten my mood.....try it, and see if you agree.
|My STANDARD
|February 13, 2014
|Fabulous find. Rich, perky, unbitter, forgiving, malty, mysterious, dark, warming, beckoning. This was an accidental find for me and I'm so glad. This now is the number 1 tea in my stash - the one I will not run out of. I drink others, but only so I'll have contrast when I return to this friend. Fabulous, but I recommend 200 degree water - not boily. 1min 45sec. 2nd steep is almost as good as first if kept short
|An Amazing Experience
|December 26, 2013
|Golden Yunnan is by far my most favorite tea in the world. It's flavor is deep and smooth. I alternate between tea and coffee, and Golden Yunnan is at once a calming and invigorating experience.
|This has become our standard for excellence
|November 29, 2012
|I bought the small tasting tin for this one--given the price, I didn't want to take a risk of not liking it--at the same time as 3 other teas. Without my having said anything about it, my husband and son commented on how much they liked the Golden Yunnan. It's a great tea, with a deep, smooth, rounded flavor; truly worth brewing in whole leaf and savoring.
|Subtle Excellence
|October 02, 2012
|A smooth taste without an overwhelming astringency. Subtle notes of earth and wind in this tea bring one to a level of relaxation that is much in demand at the end of a long day. The full leaf allows for a mellow piquancy that has no equivalent. I will continue to acquire this purity on a perpetual basis.
|my feel good tea
|April 14, 2012
|Pleasurably earthy with sweet undertones. When i feel drained this tea brings warmth and healing. I keep coming back the golden yunnan my brother and I drink almost half a pound of this tea a month.
|My Favorite!
|March 24, 2012
|Golden Yunnan is my favorite tea! I haven't met too many teas that I don't like, but this is my all around, "go to" tea when I really want a great tasting tea. I highly recommend Golden Yunnan; it has a smooth, golden flavor and it tastes great by itself or with food and pastries.
|aanother new favorite
|February 16, 2012
|Now I have another favorite. I am a dedicated Oolong tea drinker, but I tried Golden Yunnan for the 1st time, intrigued by the description of "Elevate the Senses", from the cloud-veiled mountains of China. It is everything it is reputed to be. From the 1st sip to the end of the cup and a 2nd infusion, I just love it. I had to write this commentary, so more citizens are inspired to try it ASAP.
|Golden Yunnan
|February 13, 2012
|Overall the tea is lovely. Wish it were a little bolder.
|old favorite
|November 13, 2011
|This was a reorder. Brews up smooth, flavorful without bitterness even when made stronger. A favorite of guests
|November 07, 2011
|A nice mid morning or brunch tea Smooth and mellow yet and rich
|Lovely cup of tea
|October 17, 2011
|This is a very nice tea. It is worth the extra money. The taste is relaxing and smooth. I usually buy this and the earl greyer and that gives me a nice choice.
|Probably the best Black Tea I've found
|August 26, 2011
|I can't think of a better black tea. This is the one I pull out when I have company, or want something special. It has a lovely black tea flavor, but it's delicate, not overpowering, and not inclined to bitterness. Just delightful. We turned around an avowed black tea hater with this one.
|My daily brew
|July 27, 2011
|This is a wonderful tea. My first taste a few years ago was a WOW experience. I've tried a few others since then, but nothing compares to this tea. I drink a small pot (or two) each day. I make it very strong and make it at night so it steeps until morning. Add a good amount of milk, and a 1/2 tsp of brown sugar. Heaven in a cup.


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Epcot 2012
A Planet Explorers Travel Guide for Kids
Planet Explorers
Copyright 2012 by Planet Explorers
Cover image courtesy Priwo via Wikimedia Commons.
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Smashwords Edition, License Notes
This ebook is licensed for your personal enjoyment only. This ebook may not be re-sold or given away to other people. If you would like to share this book with another person, please purchase an additional copy for each recipient. If you're reading this book and did not purchase it, or it was not purchased for your use only, then please return to Smashwords.com and purchase your own copy. Thank you for respecting the hard work of this author.
Planet Explorers is not affiliated with Walt Disney World or the Disney Company. All references to Walt Disney World, Epcot, Disney Characters, Disney attractions or lands, Imagineers, Disney films, Disney television shows, Pixar films, or Pixar characters are for editorial purposes only. The author makes no claims on trademarks owned by Disney and references them to report facts. All facts are current as of the publication date to the best of the author's ability.


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Ways to Give
In making your gift to CSUSB, you decide how and where to make that important difference. Cal State San Bernardino accepts gifts ranging from cash to stock donations, with immediate to long-term commitments.
The Office of Development and the CSUSB Philanthropic Foundation want to ensure that as many opportunities are available as possible. Below you will find a listing of the many ways you can make a gift to CSUSB. The CSUSB Philanthropic Foundation's TAX ID number is: 45-2255077
Kinds of Gifts
Cash gifts, made by check or credit card, are the simplest and most common types of gifts and allow CSUSB to put your contribution to use right away, benefiting students and programs immediately.
Checks*: To make a gift by check, make your check payable to the CSUSB Philanthropic Foundation. In the memo section of your check, please note if the gift is to be used to support the university or a specific program. Please mail it to: Office of Development, California State University, San Bernardino, 5500 University Parkway, San Bernardino, California 92407-2397.
Credit Cards**: Using your Visa, MasterCard, or American Express to make a gift is a growing convenience for donors. To make a gift by credit card please select the Make a Gift Now! button at the bottom of this page and follow the instructions for making a gift online.
Wire Transfers: If you would like to make a gift to the University via wire transfer, please follow the information listed below and wire to:
Citizen's Business Bank
301 Vanderbilt Way
San Bernardino, CA 92408
Routing No: 122234149
For Deposit to Account of:
CSUSB Philanthropic Foundation
Account No: 245122619
Matching Gifts: Visit your employer's human resources office to see if your employer matches employee gifts. You may be able to significantly increase the value of your total gift to CSUSB with a matching gift from your employer.
Stocks: Giving stock is an excellent way to support the CSUSB Philanthropic Foundation. You avoid capital gains taxes and get full value as a charitable deduction. To make a gift of stock, please contact the Office of the CSUSB Philanthropic Foundation at 909-537-7769.
Bequests: Making a bequest in your will or living trust is a common and efficient avenue of support. You make a contribution without reducing your assets during your lifetime. The bequest can take the form of a specific dollar amount, a percentage of your estate, or a particular asset.
Charitable Trusts: Establish a charitable trust (charitable remainder trust, charitable lead trust, charitable remainder annuity trust) and you may receive income for life from the trust assets. You will also gain significant tax benefits that could include reduction of capital gains taxes as well as an immediate tax reduction. Funding a charitable trust with highly appreciated assets such as real estate or stocks is ideal.
Charitable Gift Annuities: CSUSB is part of the California State University Foundation Gift Annuity Consortium, offering competitive rates for gift annuities. In return for your gift, you receive annual payments, a part of which is tax-free. The rate of return may be significantly higher than many other fixed-income investments. Gift annuities may be funded with cash or marketable securities and they provide significant tax benefits.
Retirement Plans: You may designate CSUSB as a beneficiary for an IRA, TSA, Keogh Plan 403(b), 401K and other qualified pension and profit-sharing plans.
Life Insurance: Gifts of life insurance provide a way to make a sizeable gift at a relatively low cost. Such a gift can be made by either delivering and assigning ownership of the policy to the institution or naming the institution as the beneficiary. An outright gift of a paid life insurance policy naming CSUSB as the irrevocable owner and beneficiary, allows an immediate tax deduction equal to the replacement value of the policy. Partially paid-up policies allow for a tax deduction equal to the cash surrender value of the policy.
Real Estate: An outright gift of a residence, vacation home, ranch, commercial building or vacant land (entirely or fractional interest) can be an excellent way to support CSUSB. You can also "gift" your personal residence and retain life interest-gift of life estate - the ability to live in it for the remainder of you and your spouse's lives. This also applies to second or vacation homes that are used as personal residences.
Tangible Personal Property: Gifts of tangible personal property may consist of furniture, equipment, books, gems, precious metals, art, stamps, coins, fixtures or nearly any kind of property. Such gifts are often designated for a specific use within the university.
For more information on any of the other ways to give to CSUSB, please contact the Office of Development at 909/537-5005. We strongly recommend that you also confer with your attorney and financial advisors to assist you in selecting the best gift opportunities for you and your family.
A gift fee of 5% is assessed on all gifts administered by the Foundation. This fee may change through CSUSB's policies and procedures as they exist from time to time. For further information please refer to the California State University, San Bernardino Gift Acceptance Policy.


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Toronto Raptors v Brooklyn Nets
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C.J. Watson of the Brooklyn Nets shoots against Jose Calderon of the... News PhotoBarclays Center - Brooklyn,Basketball - NBA Pro,Basketball - Sport,Borough - District Type,Brooklyn - New York,Brooklyn Nets,C.J. Watson,Horizontal,Jose Calderon,Making a Basket,Match - Sport,New York City,Pattern,Season,Sport,Taking a Shot - Sport,Toronto Raptors,USAPhotographer Jesse D. GarrabrantCollection: National Basketball Association 2012 NBAENEW YORK, NY - NOVEMBER 3: C.J. Watson #1 of the Brooklyn Nets shoots against Jose Calderon #8 of the Toronto Raptors during the first ever regular home season game at the Barclays Center on November 3, 2012 in the Brooklyn borough of New York City. NOTE TO USER: User expressly acknowledges and agrees that, by downloading and/or using this photograph, user is consenting to the terms and conditions of the Getty Images License Agreement. Mandatory Copyright Notice: Copyright 2012 NBAE (Photo by Jesse D. Garrabrant/NBAE via Getty Images)