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Combination tacrolimus and sirolimus graft-versus-host disease (GVHD) prophylaxis for allogeneic transplant in patients conditioned with a fractionated total body irradiation–based regimen has shown encouraging results. We studied this prophylaxis combination in 85 patients receiving a matched-sibling transplant conditioned with 3 different regimens:fludarabine-melphalan (n = 46); total body irradiation–etoposide (n = 28), and busulfan-cyclophosphamide (n = 11). The conditioning regimens were completed on day −4. Sirolimus and tacrolimus were started on day −3 to avoid overlap with conditioning therapy. All patients engrafted, with a median time to neutrophil engraftment of 15 days. The cumulative incidence of acute GVHD grades II to IV and III to IV was 43% and 19%, respectively, with no significant difference by conditioning regimen. The 2-year cumulative incidence of chronic GVHD was 46%. With a median follow-up of 26 months, disease-free survival was 58% and overall survival, 66%. The day-100 and 2-year nonrelapse mortality was 4.8% and 10.2%, respectively. The overall incidence of thrombotic microangiopathy was 19%, and it was significantly higher with busulfan/cyclophosphamide (55%, P = .005). Tacrolimus plus sirolimus is an effective combination for acute GVHD prophylaxis and is associated with very low nonrelapse mortality. Thrombotic microangiopathy is a significant complication with this regimen, particularly in patients receiving busulfan/cyclophosphamide.

We conducted a phase 1/2 trial of high-dose 90Y-ibritumomab tiuxetan in combination with high-dose etoposide (VP-16) 40 to 60 mg/kg (day -4) and cyclophosphamide 100 mg/kg (day -2) followed by autologous stem cell transplantation (ASCT) in 31 patients with CD20+ non-Hodgkin lymphoma (NHL). Patients underwent dosimetry (day -21) with 5 mCi (185 MBq) 111In-ibritumomab tiuxetan following 250 mg/m2 rituximab, followed a week later by 90Y-ibritumomab tiuxetan to deliver a target dose of 1000 cGy to highest normal organ. Bone marrow biopsy was done on day -7 to estimate radiation dose and stem cells were reinfused when the radiation dose was estimated to be less than 5 cGy. The median 90Y-ibritumomab tiuxetan dose was 71.6 mCi (2649.2 MBq; range, 36.6-105 mCi; range, 1354.2-3885 MBq). Histology included follicular lymphoma (n = 12), diffuse large B-cell (n = 14), and mantle cell (n = 5). The median number of prior chemo-therapy treatments was 2. The treatment was well tolerated. The median times to reach an absolute neutrophil count greater than 500/μL and platelet count more than 20 000/μL were 10 days and 12 days, respectively. There were 2 deaths and 5 relapses. At a median follow-up of 22 months, the 2-year estimated overall survival and relapse-free survival rates are 92% and 78%, respectively. We conclude that high-dose 90Y-ibritumomab tiuxetan can be combined safely with high-dose etoposide and cyclophosphamide without an increase in transplant-related toxicity or delayed engraftment. (Blood. 2005;106:2896-2902)

Introduction Febrile neutropenia (FN) is a serious adverse effect of myelosuppressive chemotherapy, which often results in hospitalization and chemotherapy dose modification. FN risk depends on patient characteristics and chemotherapy regimen risk. Understanding the FN risk associated with individual chemotherapy regimens can help guide the use of prophylactic granulocyte colony-stimulating factor (G-CSF) and patient monitoring. To this end, the NCCN has classified regimens into high (≥20%), intermediate (10%-20%), or low ( Methods Included were patients diagnosed with incident non-Hodgkin's lymphoma (NHL), breast cancer (BC), or multiple myeloma (MM) between 2008 and 2013 at KPSC who initiated the following chemotherapy regimens: bendamustine ± rituximab for NHL; docetaxel, carboplatin, and trastuzumab (TCH) or docetaxel and cyclophosphamide (TC) for BC; or Q4W lenalidomide 25 mg/dexamethasone for MM. Bendamustine ± rituximab, TCH, and lenalidomide are not classified by NCCN; TC is classified as intermediate FN risk but has shown considerable variability of FN incidence when used in clinical practice. Data on cancer diagnosis, chemotherapy use, G-CSF use, neutrophil count, and infections were obtained from KPSC's electronic medical records to estimate the incidence proportions of FN and grade 3 and 4 neutropenia. FN was defined as (1) hospitalization with absolute neutrophil count (ANC) Results Overall, 40 (12%) NHL patients; 149 (24%) and 340 (28%) BC patients who received TCH and TC, respectively; and 0 (0%) MM patients were excluded due to prophylactic G-CSF. Over the first 6 cycles of bendamustine (median 338.4 mg/m2) ± rituximab for NHL patients (n = 307), 7.2% experienced FN, 4.2% grade 3 neutropenia, and 17.6% grade 4 neutropenia. Over the first 6 cycles of TCH for BC patients (n = 462), 24.2% experienced FN, 10.6% grade 3 neutropenia, and 44.6% grade 4 neutropenia. Over the first 6 cycles of TC for BC patients (n = 859), 20.5% experienced FN, 9.5% grade 3 neutropenia, and 37.5% grade 4 neutropenia. Over the first 4 cycles of lenalidomide/dexamethasone for MM patients (n = 186), 3.8% experienced FN, 5.9% grade 3 neutropenia, and 18.3% grade 4 neutropenia (Table 1). Conclusions Using NCCN criteria, bendamustine ± rituximab for NHL and lenalidomide/dexamethasone for MM would be classified as low-FN-risk regimens (20%) based on our data. These results could help inform prophylactic G-CSF use for the selected regimens in clinical practice. Table 1. Number and Incidence Proportion of Neutropenic Outcomes Overall and by Cycle Cancer: Regimen Cycle Patients n FN Events n (%) Grade 3 Neutropenia Events n (%) Grade 4 Neutropenia Events n (%) NHL: Bendamustine ± rituximab Overall 307 22 (7.2) 13 (4.2) 54 (17.6) 1 307 12 (3.9) 5 (1.6) 28 (9.1) 2 225 3 (1.3) 4 (1.8) 21 (9.3) 3 173 2 (1.2) 4 (2.3) 15 (8.7) 4 130 2 (1.5) 4 (3.1) 10 (7.7) 5 92 4 (4.4) 4 (4.4) 8 (8.7) 6 69 2 (2.9) 2 (2.9) 0 (0) BC: TCH Overall 462 112 (24.2) 49 (10.6) 206 (44.6) 1 462 70 (15.2) 39 (8.4) 138 (29.9) 2 326 13 (4.0) 15 (4.6) 42 (12.9) 3 282 17 (6.0) 9 (3.2) 39 (13.8) 4 247 6 (2.4) 8 (3.2) 31 (12.6) 5 199 4 (2.0) 6 (3.0) 25 (12.6) 6 169 8 (4.7) 3 (1.8) 12 (7.1) BC: TC Overall 859 176 (20.5) 82 (9.5) 322 (37.5) 1 859 126 (14.7) 51 (5.9) 266 (30.9) 2 649 21 (3.2) 42 (6.5) 82 (12.6) 3 571 19 (3.3) 23 (4.0) 62 (10.9) 4 511 14 (2.7) 22 (4.3) 45 (8.8) 5 94 1 (1.1) 3 (3.2) 9 (9.6) 6 84 2 (2.4) 1 (1.2) 2 (2.4) MM: Lenalidomide / dexamethasone Overall 186 7 (3.8) 11 (5.9) 34 (18.3) 1 186 2 (1.1) 8 (4.3) 17 (9.1) 2 101 3 (3.0) 5 (5.0) 14 (13.9) 3 63 2 (3.2) 2 (3.2) 8 (12.7) 4 37 0 (0) 0 (0) 4 (10.8) Disclosures Family: Amgen Inc.: Research Funding. Klippel:Amgen Inc.: Employment, Equity Ownership. Li:Amgen Inc.: Employment, Equity Ownership. Page:Amgen Inc.: Employment, Equity Ownership.

Background: Anemia is a common complication of chemotherapy that can cause clinically important symptoms and reduced quality of life. It is unclear how management of chemotherapy induced anemia (CIA) has evolved over time given the changes in the US prescribing information, reimbursement, and implementation of a risk evaluation and mitigation strategy (REMS) for the use of erythropoiesis-stimulating agents (ESAs). Objective: To describe treatment trends and current treatment patterns for anemia during chemotherapy in 2000 to 2013. Methods: Patients diagnosed with incident breast, lung, colorectal, ovarian or gastric cancer who developed moderate to severe anemia (i.e., grade II-IV based on the CTCAE grading system, or hemoglobin Results: A total of 7,266 patients were included in this study (3,374 breast, 1,751 lung, 1,406 colorectal, 503 ovarian and 232 gastric cancer). Overall, 16% of the patients were diagnosed at stage I, 31% at stage II, 30% at stage III and 23% at stage IV. The mean age at diagnosis was 60 years. The observed grade II-IV anemia episodes were 1741 (7,159 pts) in P1, 880 (3,285 pts) in P2, and 1011 (3699 pts) in P3. Figures 1 and 2 show the proportion of various CIA treatment modalities by CIA severity. Proportion of anemia episodes with ESA use decreased from 2006 to 2013 (P1: 28%; P2: 21%; and P3: 3%). An increased trend of transfusion use was observed (P1: 8%; P2: 14%; and P3: 16%), with the greatest increase observed in grade III CIA (P1: 21%; P2: 41%; and P3: 54%). There was also an increase in the proportion of untreated CIA (P1: 66%; P2: 68%; and P3: 80%). When we examined the level of hemoglobin concentration prior to CIA intervention, there was a slight decrease in the hemoglobin concentrations prior to ESA use across calendar periods [mean (SD): 9.7 (1.1) g/dl in P1; 9.6 (1.1) in P2; 9.1 (1.2) in P3, p Similar trends for CIA treatment modalities across the three calendar periods were observed when we restricted the analyses to stage 4 cancer (Figure 3). Conclusion: The study indicates that along with the decreased utilization of ESA, utilization of RBC transfusion has increased significantly over the calendar periods in patients diagnosed with five solid tumors. Approximately 80% of patients with moderate to severe anemia (Hg < 10g/dL) in patients of these common solid tumors remained untreated in most recent calendar period (March 25, 2010–June 30, 2013). Disclosures Chao: Amgen Inc.: Research Funding. Xu:Amgen Inc.: Research Funding. Sattayapiwat:Amgen Inc.: Research Funding. Page:Amgen Inc.: Employment, stockholder Other. Cannavale:Amgen Inc.: Research Funding. Rodriguez:Amgen Inc.: Research Funding. Bohac:Amgen Inc.: Employment, stockholder Other. Xu:Amgen Inc.: Employment, stockholder Other.

Background: Anemia is a common complication of cancer and its treatment, causing fatigue, drowsiness, depression, dyspnoea, tachycardia, dizziness and reduced quality of life. Yet, little data exist on the burden of chemotherapy induced anemia (CIA) in current oncology practice. Methods: Patients diagnosed with incident cancers of breast, lung, colon/rectum, stomach and ovary who received chemotherapy were identified from Kaiser Permanente Southern California Health Plan (2010-2012). Patients who had a diagnosis of myelodysplastic syndrome or anemia before chemotherapy (i.e., diagnosis of inherited anemia or hemoglobin measurement Results: A total of 4426 patients who received chemotherapy were included. The mean age was 59.3 years. Across cancers, 3962 (89.5%) patients developed anemia during the course of chemotherapy (58% grade 1, 34% grade 2, 8% grade 3 and Conclusion: Our study suggested that the burden of anemia remained high in patients with solid tumors receiving chemotherapy. The risk of anemia is greater in patients with distant metastasis. The incidence of anemia varied significantly by chemotherapy regimens. Disclosures Xu: Amgen: Employment, Equity Ownership. Xu:Amgen Inc.: Research Funding. Page:Amgen Inc.: Employment, Equity Ownership. Sattayapiwat:Amgen Inc.: Research Funding. Rodriguez:Amgen Inc.: Research Funding. Chao:Amgen Inc.: Research Funding.

Abstract 3671 Background: Chemotherapy induced febrile neutropenia (FN) is a clinically important adverse event as it can impact patient survival by delaying or reducing chemotherapy dose administered. Clinical guidelines recommend granulocyte-colony stimulating factors (G-CSF) be used in cancer patients when febrile neutropenia (FN) risk is >20%. Although the myelotoxicity of the chemotherapy regimen is a key determinant of FN risk, it is now recognized that patient characteristics may increase this risk further. We conducted a retrospective cohort study to evaluate the association of chronic comorbidities to FN in patients with non-Hodgkin lymphoma (NHL). Methods: Incident NHL cases diagnosed between 2000–2009 who received chemotherapy within 12 months of cancer diagnosis were identified from Kaiser Permanente Southern California, a large managed care organization. Those who had prophylactic G-CSFs, dose-dense chemotherapy or bone marrow transplant were excluded. Comorbidities of interest included cardiovascular, liver, renal, metabolic and autoimmune disorders, anemia, previous cancer and HIV infection. History of comorbidity of interest were assessed in the 12 months prior to NHL diagnosis, and identified by ICD-9 codes or disease registries. FN was assessed only in the first chemotherapy cycle, and identified by absolute neutrophil count (ANC), ICD-9 codes for neutropenia and fever, or hospitalization with bacterial/fungal infection. Patients were followed from their first chemotherapy treatment to the start of the second cycle, death or day 28, whichever came first. Logistic regression was used to estimate the propensity score for each comorbidity; these propensity scores included patient characteristics and other comorbidities as covariates. Each comorbidity and propensity score were included in Cox models to determine associations between comorbidities and FN. We also evaluated models that additionally adjusted for cancer stage, baseline ANC, chemotherapy regimen, dose reduction, and radiation treatment prior to chemotherapy. Results: A total of 2,480 NHL patients who received chemotherapy were included. The mean age was 63.3 years. Fifty-five percent of the cases were male, and the majority of the cases were of white race (65.6%). Sixty percent of the cases received CHOP or R-CHOP. There were 236 (9.5%) patients that had FN in the first chemotherapy cycle. Anemia [adjusted hazard ratio adjusted (HR) =1.6, 95% CI, 1.2–2.2], HIV infection [HR=3.0, 95% CI 1.6–5.3], AIDS [HR=2.4, 95% CI 1.2–4.6], and rheumatoid diseases [HR=2.1, 95% CI 1.2–3.6] were all associated with a statistically significantly increased FN risk (Table 1). In addition, peptic ulcer disease, renal disease and connective tissue disease were also associated with risk of FN, although these associations were not statistically significant. HR estimates did not change materially after also adjusting for cancer stage, ANC, chemotherapy regimen, dose reduction and radiation therapy prior to chemotherapy in the Cox model. Conclusions: Our findings suggest that several chronic comorbidities may be associated with increased FN risk in the first chemotherapy cycle among NHL patients not already receiving prophylactic G-CSFs. This information, if confirmed by others, may aid clinical decision making with respect to use of prophylactic G-CSF use during chemotherapy treatment. Disclosures: Chao: Amgen,Inc: Research Funding. Page:Amgen, Inc: Employment, Shareholder Other. Rodriguez:Amgen, Inc: Research Funding. Yang:Amgen, Inc: Research Funding. Huynh:Amgen, Inc: Research Funding. Chia:Amgen, Inc: Employment, Shareholder Other.

Abstract 4551 Background: Acute graft versus host disease continues to affect approximately 60% of patients undergoing UHSCT, with significant mortality and morbidity. Methods: We prospectively evaluated the efficacy of combining Thymo (4.5 mg/kg divided doses on days -1,-2, and -3), tacrolimus and sirolimus in preventing aGVHD. The cumulative incidence (CI) rate of grade II-IV aGVHD was calculated using death without grade II-IV aGVHD and relapse as competing risks (Cr). The Cr: for non relapse mortality (NRM) CI was death due to relapse, for relapse CI was death without relapse, for chronic GVHD CI was relapse & non relapse mortality without cGVHD. Kaplan-Meier method was used to calculate overall (OS) and progression free survival (PFS). The incidence of infections and other complications were reported with the Wilson's 95% Confidence Interval (in table below). Results: Between August 2008 and November of 2010, we enrolled 47 patients (pts) with median age of 50(20–70) years. The Median follow-up time is 23.6 months (18.8–27.9). There were 21 AML, 10 MDS, 4 ALL, 2 CML, 2 CMML, 1 CLL, 3 Myelofibrosis, 2 multiple myeloma, 2 NHL. Preparative regimens included Bu/Flu 30, Bu/Flu-TBI 10, VP16/TBI 3, R-BEAM 1, and Flu/MEL-TBI 3. All pts received peripheral blood stem cells mobilized with G-CSF. Median CD34+ dose was 7.31×10 6/kg (1.9–18.6). Median donor age was 32.6 (19.0–61.0) years. All patients received daily G-CSF starting day +6 till engraftment. Twenty two pts received 8/8 and 25 received 7/8 HLA matched grafts respectively. All patients' engrafted, with median day of 11 (9–15). Twenty deaths occurred throughout the whole follow up period, due to: relapse 6, aGVHD 4, cGVHD 2, sinusoidal obstruction syndrome (SOS) 2, bleeding 1, multi organ failure 2, sepsis 2 and pneumonia 1. Twelve patients experienced disease relapse. Fourteen patients had non-relapse mortality. Twelve pts developed Grade II-IV aGVHD, 5 grade II, 4 grade III, and 3 grade IV. The CI rate for grade II-IV aGVHD at 200 days post transplant is 0.23.4% (12.4, 36.3); CI of NRM at day 1057 is 31.9% (18.4, 46.2). CI of relapse at day 1057 is 30.4% (15.2,47.1). CI of cGVHD at day 890 is 40.2(21.5, 58.2), with total of 16 cases: 8 mild, 7 moderate and one sever based on NIH consensus criteria. Median PFS is 17.7 months. PFS at 6 months is 63% and 54% at 1 year. Median OS has not been reached. OS at 6 months is 73%, and 65% at one year. The incidence of infections and other transplant related morbidities are shown in the table below. There were 2 cases of thrombotic thrombocytopenic purpura (TTP) before day 100. 16 CMV by PCR, 10 EBV by PCR, 9 HSV, 10 BK cystitis, 31 bacterial infections, 4 oral candidiasis, and 3 SOS. Conclusion: These early results suggest that the combination of Thymo, tacrolimus and sirolimus in pts undergoing UHSCT is well tolerated and is associated with a low rate and severity of acute GVHD. Disclosures: Al-Kadhimi: Genzyme Pharmaceuticals: Research Funding. Off Label Use: The use of thymoglobulin, Sirolimus and Tacrolimus in blood and marrow transplant. Lum:Transtarget Inc: Equity Ownership, Founder of Transtarget.

Thrombotic microangiopathy (TMA) is a multifactorial complication of related and unrelated allogeneic hematopoietic stem cell transplant (allo-HSCT). The true incidence of TMA is difficult to estimate due to lack of agreement on a single definition. Diagnosis is often complicated by multiple potential etiologies for the clinical findings. Sirolimus (SIR), an inhibitor of mammalian target of Rapamycin (mTOR), is a novel immunosuppressive agent that works synergistically with calcineurin inhibitors (CNI) to prevent graft-versus-host disease (GVHD) in allo-HSCT. Recently, the addition of SIR to CNIs was reported to result in a higher than expected incidence (10.8%) of TMA (Cutler et al. BBMT2005; 11:551–7). We evaluated the incidence and risk factors for TMA in a cohort of patients undergoing matched unrelated (MUD) HSCT using SIR combined with tacrolimus (TAC) and mini-methotrexate for GVHD prophylaxis at City of Hope. TMA was defined as SCr increase of ≥ 50% above baseline, LDH twice the institutional upper normal limit, presence of schistocytes or persistent presence of nucleated red blood cells, and prolonged or progressive thrombocytopenia (platelets

The current paradigm of cytarabine-based induction chemotherapy followed by repetitive cycles of similar consolidation has yielded 2-year disease-free survival (DFS) of no more than 20% in older pts (≥60 yrs) who achieve remission. Induction failure (IF) is also high in this population (20–35%), depending on cytogenetic risk. Regimen-related toxicities have been a barrier to allogeneic HCT in older pts. RI conditioning provides a means to harness graft vs. leukemia in this group. Between 2/2000 and 3/1/2007, 46 pts ≥ 60 yrs (median 63 yr, range 60–71) received RI HCT from either related (26) or unrelated (20) HLA matched donors. In 23 pts, RI HCT was used as consolidation of remission (CR1 [19 pts] + CR2 [4 pts]) while 23 had active disease, including 10 IF. Karyotype was favorable in 9%, intermediate in 48% and poor in 41%. The median % marrow blasts for non-remission pts was 31% (6–80%) and peripheral blood blast was 5% (0–78%). The majority (41 pts) received fludarabine (FLU)/melphalan (MEL) for conditioning. Four pts received FLU with either 200G total body irradiation (TBI) (3 pts) or busulfan (1 pt) and one received TBI alone. Graft vs. host disease (GVHD) prophylaxis was based on either cyclosporine/mycophenolate mofetil alone or with methotrexate (MTX) (20/10) or tacrolimus/sirolimus +/− MTX (2/14 pts). The graft source was peripheral blood in 43 pts and marrow in 3 pts. Engraftment occurred at a median of 15 days (0–27 days) in 98% of recipients; graft failure occurred in one sibling HCT. Donor engraftment based on DNA analysis ranged from 30–100% at 4–6 wks post-HCT (median 100%) in the 33 analyzed pts. Mortality at day 100 was 10.8%. Acute GVHD (Grade 2–4) occurred in 61% of recipients and chronic GVHD has occurred in 23/33 evaluable pts. With a median follow-up of 24.5 months (m) for surviving pts (4–83 m), 25/46 (64.5%) pts are alive. For remission pts, the 2 yr DFS is 65% (CI 51–76%). For pts who received RI HCT as “salvage”, 34% are DF at 2 yrs. (CI 27–41%). Relapse rates were 11% for remission pts and 60% for non-remission pts. Deaths post HCT were attributed to relapse in 12 pts and treatment related mortality due to GVHD (6 pts) or infection (3 pts). Conclusion: DFS can be improved for older patients with the use of RI HCT as remission consolidation. RIC also provides a meaningful salvage option for pts with IF or early relapse. Evaluation of donor options including both siblings and unrelated donors should be considered during induction for patients with good performance status.

Based on encouraging phase 2 data, we are prospectively testing the combination of tacrolimus and sirolimus (tacro/siro) as GVHD prophylaxis in patients undergoing HLA-MRD HCT. Seventy patients evaluable for this report (>100 days post-HCT) were stratified according to preparative regimen as follows: Fludarabine/melphalan (38), FTBI/VP-16 (23), and Bu/Cy (9). Regimens were given through day -4; tacro/siro was started on day -3 and dosed as published (Cutler et al, BBMT 10 (5), 328–336, 2004). Median age was 50 years (range, 10–67). Diagnoses by regimen were flu/mel: AML (16), NHL (7), MPD (4), HD (4), MM (3), MDS (2), ALL (1), CLL (1); FTBI/VP-16: ALL (12), AML (10), NHL (1); and Bu/Cy: CML (5), MDS (3), AML (1). Stem cell source was PB (n=66) and bone marrow (n=4). Donor gender F:M was 34:36. Median CD34+ cell dose was 5.1 x 106/kg. Median time to neutrophil >500/ml was 15 days (range, 10–26); median day 30 bone marrow MNC chimerism was 100% (65–100%). CTC toxicities >3 were low (2 DAH, 1 ARDS, 1 IP, 1 mucositis); as expected, mucositis was more common with FTBI/VP-16; however, therapeutic sirolimus level was similarly achieved with all conditioning regimens (median level 6.5 ng/ml, range 2.1–61 in the FTBI/VP-16 arm). Opportunistic infections included CMV reactivation (6), Aspergillus pneumonia (2), candidemia (3) and parainfluenza pneumonia (1). Reversible TTP/HUS (IWG definition) was diagnosed in 14 patients (20%) and was more common with Bu/Cy (55%) than with FTBI/VP-16 (22%) or flu/mel (11%); median tacro and siro level in patients with TTP was 9.8 and 15 ng/ml, respectively. Six patients died before day 100 from relapse (2), DAH (2) and multi-organ failure MOF (2), for a day 100 non-relapse mortality of 6%. With a median follow-up of 6 months, 60 patients are alive and 10 patients have died from progressive disease (6), MOF (2) and DAH (2). Disease-free and overall survival at day 100 are 88% and 91%, and at 1 year are 72% and 75%, respectively, with no significant differences by regimen. Acute GVHD grade 2–4 and 3–4 was observed in 25 (36%) and 13 patients (19%), respectively; by conditioning regimen, grade 2–4 acute GVHD incidence was: flu/mel, 11/38 (29%); FTBI/VP-16, 9/23 (39%); and Bu/Cy, 5/9 (56%). A temporal relationship between GVHD and TTP could not be established, with some patients developing GVHD before and others after TTP. Chronic GVHD has been diagnosed in 17/45 evaluable patients. This study shows a low TRM when tacro/siro is given with 3 different conditioning regimens; adequate sirolimus levels can be achieved even in patients with significant mucositis; a high incidence of TTP in patients conditioned with Bu/Cy suggests synergistic endothelial toxicity with this combination. Acceptable rates of acute GVHD in this study support plans for a national phase 3 study comparing tacro/siro with tacro/methotrexate.

Background: T cell NHL represent approximately 10–15% of all lymphomas. Pts with T cell NHL are often treated similarly to patient with B cell NHL, although the clinical outcomes of most patients with T- NHL tend to be worse with the exception of ALK positive anaplastic large cell lymphomas (ALCL). Updated classifications in recent years have recognized specific clinical and pathologic T cell entities with distinct clinical courses and this poses a challenge to the systemic study of these diseases. The exact role of allogenic transplant in T- cell NHL is unknown. Methods: We looked at 45 pts who underwent an allogeneic HSCT for T cell lymphomas between Jan 2000 to Dec 2005. There were 18 males, 27 females. Median age at transplant was 32 (7–74). Histology was Mycosis fungoides /Sezary syndrome (SS/MF) n=10, T cell lymphobalstic leukemia (PTLL) n=16, PTCL including AILD and ALCL n=14, NKT cell n=5. Syngeneic donor 1, Sibs 31, MUD 13. Median time from diagnosis to transplant was 12.5 (3.6–88.3) mo. Source of stem cells BM 9, PBSCT 35, cord blood 1. Conditioning, fully ablative 29, reduced intensity 16. Median number of prior regimens MF/SS 5, PTLL 2, PTCL 3, NKTL 2 with only 2 pts with prior auto transplants. 18 pts were in remission at the time of transplant and 12 pts had induction failure. Results: Median follow up from transplant was 45.3 mo(0.7–64.7) with a 55.6%OS. Incidence of GVHD was Acute n= 27 extensive chronic n=20. Cause of death was transplant related in 16 pts with only 3 pts dying of disease progression. The overall survival is 61.2 % at 1 year,55.4% at 2 years and 48.5% at 5 years with a 5 year progression free survival at 48.5%. Based on different histologies, the results are 50.0% overall survival at 1 year and 40.0% at 2 and 5 years for SS/MF, 55.6% at 1 and 2 years for PTLL, 70.1% at 1 and 2 years and 52.6% at 5 years for PTCL and 80% at 1 year for NKT shown in fig 1 and 2. Conclusion: Allogenic transplant can result in long term survival for some patients with T cell NHL suggesting a graft vs lymphoma effect. Timing of transplant needs to be better defined. Most patients are heavily pretreated which may have resulted in more transplant related mortality with 11/20 pts dying of infection. Most patients did not have a prior auto transplant indicating early progression of disease after standard therapies defined for B cell malignancies. Overall Survival by Histology T-Cell Lymphoma with Allogenic Transplant Sample Size: 45 patients Overall Survival by Histology T-Cell Lymphoma with Allogenic Transplant Sample Size: 45 patients Progression-Free Survival by Histology T-Cell Lymphoma with Allogenic Transplant Sample Size: 45 patients Progression-Free Survival by Histology T-Cell Lymphoma with Allogenic Transplant Sample Size: 45 patients

The majority of patients (pts) with PTCL present with advanced stage with high-intermediate or high-risk IPI and their prognosis are poor with current standard induction chemotherapy. HDT followed by ASCT has been shown to be effective therapy for relapsed and refractory PTCL, although the outcomes of transplant varied depending upon the histologic subtype, disease status and IPI at transplant. Given the poor outcome with current treatment approach, HDT and ASCT as consolidative therapy during first remission are being investigated in pts with PTCL. We performed retrospective analysis of all pts with T-cell, NK cell and null cell lymphomas who underwent HDT and ASCT between 2/1991 to 6/2005. We analyze the outcome based on disease status at transplant and the subset of PTCL. There were 57 pts (35 male, 22 female) with a median age of 45 years (range 5–68). Histology included 6 (10.5%) angioimmunoblastic T-cell lymphoma (AILD), 26(46%) Anaplastic large cell lymphoma (ALCL), 22 (39%) PTCL, unspecified (NOS), 1 panniculitis like T-cell, 1 NK-T, and 1 adult T-cell lymphoma. Twelve (21%) were transplanted during first remission; 11 were high intermediate-high risk IPI, and 1 for histology NK-T. Twenty-eight (49%) were transplanted during relapse or ≥second remission and 17 (30% ) induction failure or primary refractory disease. Twenty-one (37%) had advanced stage III-IV at transplant. The median number of chemotherapy regimens was 2 (range 1–5). For ALCL subtype, 9 were anaplastic lymphoma kinase (ALK) positive, 9 ALK negative, 8 unknown. Results: At a median follow-up of 22 months (range 0.5–179), 29 are alive in remission, 25 relapsed and 3 died from transplant related mortality. One patient developed therapy induced myelodysplasia at two years post ASCT and is alive in remission after allogeneic stem cell transplant. The 2 years overall survival (OS) and disease-free survival (DFS) for the whole group were 53% (95% CI 46–60), and 45% (95% CI 39–50), respectively. The OS and DFS were significantly better for pts. who were transplanted in first complete remission (Figure1). The 2-year OS and DFS were both 83% (95% CI 55–94) for pts. transplanted in first remission compared to 45% (95% CI 38–52%, p=0.03) and 35% (95% CI 30–40, p= 0.006), respectively for those transplanted beyond first remission. Univariate models showed that the risk of death and/or relapse was significantly less among the pts. transplanted in first complete remission (OS, DFS and time to relapse: p < 0.05). When compared the outcome among the 3 subtypes, AILD, ALCL and PTCL NOS, there were no significant differences in survival or relapse among the 3 groups. Conclusion: our results suggest that HDT and ASCT can improve prognosis and survival of pts. with PTCL. The outcome of ASCT is best when performed during first complete remission. The role of HDT and ASCT during first remission should be further investigated in larger multi-center studies. In contrast to other reports, the prognosis of pts. with ALCL is similar to other PTCLs. Disease-Free Survival: ASCT for PTCL Startified by Disease Status: 1CR (n=12) vs. > 1CR (n=45) Disease-Free Survival: ASCT for PTCL Startified by Disease Status: 1CR (n=12) vs. > 1CR (n=45)

The use of sirolimus combined with tacrolimus and low-dose methotrexate recently showed a promising result in preventing GVHD after unrelated donor hematopoietic stem cell transplantation (Antin et al. Blood2003; 102: 1601). We studied this approach in 33 patients who received an unrelated donor transplant after full-intensity conditioning or reduced intensity conditioning from April 2005 to March 2006. All patients gave written informed consent for City of Hope protocols approved by the local institutional review board. Patient age ranged from 21 to 65 (median 46). Ten were female and 23 were male. The cohort consisted of 12 patients with AML, 9 with NHL, 6 with ALL, and the remaining 6 with other diagnosis (MDS=2, MPD=2, CML=1, HD=1). Patients were conditioned with either full-intensity regimen (FTBI-VP16=8, FTBI-Cy=6, BuCy=2) or reduced-intensity regimen using fludarabine (125mg/m2) plus melphalan (140mg/m2) (n=17) and received either a bone marrow graft (n=8) or peripheral blood stem cell graft (PBSC: n=25). GVHD prophylaxis consisted of tacrolimus (target serum level 5–10 ng/ml) and sirolimus (target serum level 3–12 ng/ml) started on day -4, and methotrexate 5mg/m2 for 3–4 days (days 1, 3, 6, +/− 11). High-resolution (HR) molecular HLA typing was performed for class I and II. Twenty pairs were in HR molecular match in all 10 antigens (HLA-A, B, C, DR, and DQ), five were in HR molecular 6/6 match (mismatch in C and/or DQ), and the remaining 8 pairs had a molecular mismatch in HLA-A (n=4), B (n=3), and DR (n=1). Eight transplants were from female donors to male recipients. After a median follow up of 7 months (range: 3–15), 26 patients are alive. Causes of death include relapse (3), VOD (2), and sepsis with multiorgan failure associated with grade 4 GVHD (1). The probabilities of 1-year overall survival, disease-free survival, and relapse were 74% (95%CI: 59–85%), 59% (95%CI: 41–75%) and 28% (95%CI: 16–45%), respectively. The probability of transplant-related mortality was 9% (95%CI: 5–18%) at 100 days and 19% (95%CI: 10–32%) at 1 year. Thrombotic microangiopathy was observed in two patients and were reversible. The probability of grade 2–4 acute GVHD was 44+9% (grade 3–4: 24+8%). Of 26 patients evaluable, 12 developed chronic GVHD (7=extensive, 5=limited). There was no difference in GVHD between full-intensity transplants and reduced-intensity transplants. There was a trend for reduced grade 2–4 acute GVHD in HR 10/10 match transplants (n=20: 31%) compared with the others (n=13: 62%, p=0.08). The current data compare favorably to our historic control (n=181: reduced intensity=98, full-intensity=83) using tacrolimus plus methotrexate or cyclosporine plus MMF with the incidence of grade 2–4 acute GVHD at 64% (p=0.02). In summary, our result show the combination of sirolimus, tacrolimus and low-dose methotrexate is associated with improved GVHD prophylaxis and acceptable toxicity. However, transplants others than 10/10 HR molecular match require further improvement.

Tandem cycle high-dose melphalan (Mel) followed by Mel +/− total body radiation therapy improves progression-free (PFS) and overall survival (OS) in comparison to single cycle Mel, but is associated with 3% treatment-related mortality (TRM). We tested a new tandem regimen (THDCT) followed by maintenance therapy in order to lower TRM, while enhancing efficacy. Between 5/94 and 8/04, 114 patients (pts) were enrolled on 2 sequential studies. First, pts received Mel 150 mg/m2 [cycle 1 (C1)], oral busulfan (bu 16 mg/kg; 46 pts), and cyclophosphamide 120 mg/kg (Cy; C2); the next cohort received the same THDCT but bu was given intravenously (i.v. 12.8 mg/kg; 68 pts). All pts were to receive maintenance IF 3 million units/m2 given subcutaneously, 3 times/week. Pts participating on the 2nd study were to receive thal together with IF provided that they were not in CR at 6 months post-THDCT. Peripheral blood progenitor cell mobilization consisted of G-CSF 10 microgram/kg to procure 4 x 106 CD34+ cells/kg without (first 46 pts) or with Cy 1.5 g/m2 (last 68 pts). Pts ≤65 years, with responsive or stable MM, with

Patients undergoing allogeneic HCT are known to be at an increased risk of AVN. Chronic steroid use, to treat chronic graft vs. host disease (cGVHD) has been identified as a risk factor. Previous studies reporting AVN after allogeneic HCT are limited either due to small cohort size or reliance on registry data for passive reporting on outcomes such as AVN. Furthermore, little is known about the risk of AVN after autologous HCT. We report a retrospective chart review of 1595 consecutive patients undergoing HCT at City of Hope Cancer Center between 1976 and 1998, and surviving one or more years after HCT. The median age at HCT was 35 years (range, 0.6–71.5) and the median length of follow-up was 7.0 years (1–25.3). The cohort included 940 males (59%). In this cohort, 78 patients developed AVN of 163 joints, resulting in a mean of 2.1 affected joints per patient (range, 1 to 8). Diagnosis of AVN was confirmed by review of radiologic evidence of necrosis in the presence of clinical symptoms. The hip joint was the most common joint affected (70.5% of patients), followed by the knee (35%) and shoulder (26%). Symptoms developed a median of 38.7 months from HCT (12 to 199 months). The overall cumulative incidence was 6.2% at 15 years from HCT for the first reported AVN developing one or more years after HCT. Nineteen of 741 autologous HCT survivors developed AVN (cumulative incidence: 3.5% at 10 years), while 46 of the 746 allogeneic sibling donor HCT survivors (cumulative incidence, 6.2% at 10 years), and 12 of the 108 unrelated donor HCT recipients developed AVN (cumulative incidence 13.9% at 10 years, p

The treatment of high-risk MCL remains a challenge. High dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) has been used for some of these patients (pts). However, relapse rates remain high. RIT with single agent 90Yttrium(90Y) ibritumomab tiuxetan (Zevalin®) has demonstrated activity in pts with relapsed MCL. Therefore, we postulated that the combination of 90Y with HDC and ASCT may reduce relapse rates of pts with high- risk MCL. Between 5/00 and 9/04 eighteen pts with MCL were enrolled on one of two RIT ASCT trials. The first was a phase I/II dose escalation trial of high-dose 90Y + cyclophosphamide 100mg/kg (day -4) and etoposide 60mg/kg(day-2). Pts underwent dosimetry day-21 with 5mCi Indium111 followed a week later by 90Y to deliver a maximum target dose of 1000cGy to normal organs. The second study was a phase I/II trial of standard dose 90Y (0.4mCi/kg) administered day-14 and BEAM (day-8 to day-2, BCNU300mg/m2, cytarabine 800mg/m2, etoposide 800mg/m2, melphalan 140mg/m2). Ten pts who were>60yrs or had received prior dose-limiting radiation were placed on the 90Y BEAM trial while the other 8 received high-dose 90Y. The median age at ASCT was 58 years (range 44–72). Disease status at ASCT included 1st CR -9(high or high intermediate IPI score), 1st PR-4, 1st relapse -4, 2nd CR-1. Fifty percent had received HyperCEVAD chemotherapy and 56% had Rituximab prior to ASCT. Thirteen pts had stage IV disease, 5 had stage III disease. The median 90Y dose administered was 40mCi (range 27–100). Treatment was well tolerated. Engraftment to anc>500 occurred at a median of 10 days (range 9–26). Reversible grade 3 pulmonary toxicity occurred in 5 pts. This included steroid responsive pneumonitis in four and acute respiratory distress related to sepsis in one. One pt with a prior history of heavy alcohol use died of liver failure at four months post ASCT. Four pts have relapsed and two have died of disease progression. With a median follow up of 19 months (range 6–60), the estimated overall survival and disease free survival at two years are 79% (CI 55–91) and 59% (CI 43–73) respectively. By univariate analysis 90Y dose did not correlate with risk of relapse. To date, no relapses were seen beyond the first twelve months (see figure). In conclusion 90Y based transplant conditioning regimens are well tolerated, even in older pts. The apparent plateau in the relapse rate is encouraging and suggests that this approach may lead to durable remissions in pts with high-risk MCL. Figure Figure

Peripheral blood stem cells (PBSC) have been increasingly used in the matched unrelated donor (MUD) transplant setting, but the impact of CD34 cell dose on outcomes following MUD-PBSC transplant have not been well characterized. Between 8/00-12/04, a total of 181 patients underwent MUD-PBSC transplantation at our institution under IRB-approved protocols. Patient’s age at transplant ranged from 1 to 67 years (median 44). Eighty-two were female and 99 were male. The cohort consisted of 68 patients with AML, 38 with ALL, 18 with CML, 18 with NHL, 17 with MDS, and the remaining 22 with other diagnosis (CLL, MM, MPD, etc.). Of 181 patients, 35 were considered to have low-risk disease (acute leukemias in CR1 or CML-CP). Patients were conditioned with either full-intensity regimen (TBI+Cy or VP16, or BuCy: n=83) or reduced-intensity regimen (fludarabine+melphalan or busulfan: n=98). GVHD prophylaxis consisted of tacrolimus+methotrexate for full-intensity transplants and cyclosporine+mycophenolate+/− methotrexate for reduced-intensity transplants. Median (range) CD34+ cell, lymphocyte (Ly), and mononuclear cell (MNC) doses were 6.7 (0.6–28) x106/kg, 440 (40–2640) x106/kg, and 710 (50–5060) x106/kg respectively. A strong correlation exists between Ly and MNC doses (r2=. 52, p 9.5 x106 (the highest quartile) in transplant outcomes including acute GVHD and TRM.

Natural killer (NK) cells are becoming increasingly recognized as an important part of the immune system. Killer Ig-like receptors (KIRs) are the major form of receptors used by human NK cells. KIRs transmit either inhibitory or activating signals regulating NK cell activity. Some inhibitory KIRs specifically recognize HLA-A, B or -Cw allotypes on target cells. Thus differences in inhibitory ligand (iKIRL) phenotypes between donors and patients could result in NK cell alloreactivity that further results in different HCT outcomes. To test this hypothesis, the present study evaluated 362 patients with either ALL (99), AML/MDS (141), or CML (122). The patients were transplanted (1996~2003) with T-replete bone marrow, or peripheral blood stem cells from unrelated donors. High resolution HLA typing with DNA-based methods had been prospectively performed for donor selection. The KIR genes of patients and donors were retrospectively typed by a multiplex PCR-SSP method. The cohort was divided into three groups by the HLA and KIR profiles: 247 cases with matched HLA at the antigen level of HLA-A, B, Cw, DRB1, and DQB1 (MH), 64 with mismatched HLA (mMH) and 51 with mMH plus mismatched iKIRL (mMH+miKIRL). A significantly different rate (P=0.009) of estimated one year overall survival was found between the MH (61%, 95%CI 55–67%), the mMH (46%, 34–59%), and the mMH+miKIRL (29%, 18–43%) groups. When analyzing the event free survival, a similar difference (P=0.003) was observed between the MH (57%, 51–63%), the mMH (43%, 32–56%) and the mMH+miKIRL (25%, 15–39%) groups. Further analysis demonstrated a different rate (P=0.02) of relapse between the MH (two-year estimation: 21%, 16–28%), the mMH (16%, 7–31%), and the mMH+miKIRL (36% 18–58%) groups. That the MH group experienced more relapses than the mMH is consistent with the GvL effect. The mMH+miKIRL group experienced the most relapses implied miKIRL undermine the GvL effect. We also tested the influence of lacking iKIRL in patients within the MH group, and found a significant survival difference (P=0.05) among the patients lacking two iKIRLs (n=67, 54% 42%–65%), one iKIRL (n=104, 59% 49%–68%), or none (n=76, 70% 58%–79%). This finding contrasts with the previously reported beneficial role of potential NK cell alloreactivity in T-depleted HCT. Additional studies are required to resolve these issues.

We conducted a retrospective analysis of 58 patients who underwent allogeneic stem cell transplantation at our center from 1994 to 2004. Among these 58 patients, 56 received allogeneic transplant from HLA matched sibling and 2 patients received transplant from a matched unrelated donor. Fourteen patients received standard transplant (ST) using different myeloablative chemotherapy regimens with or without fractionated total body irradiation (FTBI, 9 patients). Thirty four patients underwent tandem transplants (autologous transplant followed by non-myeloablative allogeneic transplant; auto-allo group). Conditioning consisted of melphalan (200mg/m2) prior to the autograft, and TBI (200cGy) as part of non-myeloablative allograft. Ten patients received reduced intensity conditioning (RIC) allograft with fludarabine (25 mg/m2 x 5 days) and melphalan (140 mg/m2). The source of stem cells was bone marrow in 14 patients (ST) and peripheral blood in 44 patients. Median age was 44 yrs for ST group (range 25–53), 51 yrs for auto-allo group (range 38–66) and 48 yrs for RIC group (range 43–64). Median follow up was 2.8 yrs for ST group (range 0.2–13.0), 2.8 yrs for auto-allo group (range 0.2–5.0) and 1.1 yrs for RIC group (range 0.2–3.6). There was a statistically significant difference in overall survival (OS) between the different groups with an observed 2 year OS of 50% in the ST group, 76% in the auto-allo group and 42% in RIC group (P=0.04). Disease free survival (DFS) was also statistically different between the different groups at 2 years: 21% in the ST group, 59% in auto-allo group, and 40% in RIC group (p=0.04). The incidence of severe grade III–IV acute graft versus host disease (GVHD) was less in auto-allo group (6% & 6%), as compared to the RIC group (20% & 10%) and ST group (14% & 14%). 2 year non-relapse mortality rates were 43% in ST, 20% in auto-allo group and 29% in the RIC group, and relapse-related mortality rates were 7% in ST group, 4% in auto-allo group and 29% in the RIC group. There was no statistically significant correlation between GVHD and DFS. Our data suggest an improvement in DFS and OS following tandem auto-non-myeloablative allotransplantation or RIC allotransplantation as compared to standard allogeneic transplant. The better outcome following an auto-allograft approach suggests that cytoreduction prior to an allograft may be important for optimal disease control in MM.

Autologous stem cell transplantation(ASCT) can cure up to 50% of patients with relapsed or refractory HD. However, for patients who relapse post ASCT or develop post transplant myelodsyplasia (t-MDS), standard chemotherapy options offer little chance of long-term disease free survival (DFS). The use of allogeneic stem cell (alloSCT) may provide a means of control of the HD through the immune mediated effects of an allogeneic approach and also be curative for concomitant t-MDS. While traditional alloSCT in HD patients was fraught with high treatment related mortality, a reduced intensity conditioning regimen may reduce upfront mortality while still providing long term DFS. Between 11/00 and 1/04, fourteen patients underwent reduced intensity alloSCT at the City of Hope Cancer Center. Median age at alloSCT was 31years (range18–47). Median time from HD diagnosis to alloSCT was 36mos (range 3–123). Eleven patients had relapsed post ASCT and one post syngeneic transplant. One of the pts also had t- MDS. The median time from ASCT to alloSCT was 20 mos(range1–45). Ten pts received sibling alloSCT and four unrelated donor. The conditioning regimen consisted of Fludarabine 125mg/m2+ Melphalan 140mg/m2. All patients received a Cyclosporin(CSA) based graft versus host disease (GVHD) prophylaxis regimen; nine in conjunction with Mycophenolate Mofetil and three in conjunction with Methotrexate. Seven developed acute GVHD (3-GrIII-IV). Two patients died of GVHD. There was no other significant regimen related toxicity. Median length of followup for surviving patients is 55 mos. For eleven evaluable pts, one year OS and DFS are 77% (95%CI 49–100) and 58% (95%CI 25–91) respectively (figure 1). The pt with concomitant t-MDS also achieved a hematologic remission. In conclusion, reduced intensity alloSCT may provide a salvage for heavily pretreated patients with HD that have failed ASCT and who otherwise have a poor prognosis, and it can also provide a treatment for late secondary complications of transplantation such as t-MDS.

Granulocyte Colony-Stimulating Factor (GCSF) at 10 microg/kg (with or without chemotherapy) is the standard dose commonly administered to patients undergoing Peripheral Blood Stem Cell (PBSC) mobilization and collection. Due to various host and disease factors, 10–20% of our patients failed to mobilize sufficient PBSC at this standard dose. At our institution it is common practice to increase GCSF from 10 microg/kg to 16–20 microg/kg during the initial or second mobilization attempt if the patient is able to tolerate the increased dose. To assess the clinical efficacy of increased GCSF administration among patients who fail to mobilize at the standard dose, we performed a retrospective chart review of 112 patients who underwent stem cell mobilization and collection between 01/31/2000 and 11/6/2003. The median age at the start of collection was 51.2 (range: 1.3–72.2); the case-series was made up of 52 men and 60 women. The majority of the cases were Lymphoma patients (Non-Hodgkin’s Lymphoma=52; Hodgkins Disease=15) with the remaining patients classified as Acute Myeloid Leukemia (AML=12), Multiple Myeloma (MM=13), or ‘Other’ (N=20). Initially all 112 patients received 4–10 days of GCSF at 10 microg/kg per day before the first day of PBSC collection. Because these patients failed to collect sufficient daily CD34 cells, the GCSF dose was increased to 16–20 microg/kg. Before increasing the GCSF dose, the median CD34 daily yield was 0.19 (range: 0.03–0.90), and the median peripheral WBC was 27.6 (range: 1.3–61.8). The median number of collection at 10 microg/kg was 4 (range 2–15), and the median number of days from the end of collection at 10 microg/kg to the start of 16–20 microg/kg was 1 (range: 0–53). After increasing the GCSF dose the median peripheral WBC was 37.1 (range: 3.1–70.2), and the median CD34 daily yield was 0.28 (range: 0.03–3.43). The median CD34 total yield was 3.1 (range 0.6–12.3). Ultimately 90 patients (80%) reached a CD34 cell target of 2*10–6/kg (range: 2.0–12.3), and 22 patients (20%) did not reach this target. The overall difference in CD34 counts pre-post increased GCSF administration was statistically significant (Wilcoxon p

Reduced intensity regimens (RIR) have largely replaced conventional myeloablative regimens (CMR) for patients with NHL undergoing allogeneic transplant. However, the impact of dose reduction on relapse has not been extensively studied. We performed a retrospective analysis of 88 patients conditioned with CMR (n=48) and a RIR (n=40) of fludarabine 125mg/m2 and melphalan 140mg/m2. GVHD prophylaxis was with cyclosporine + MTX +/− prednisone for CMR and cyclosporine + MMF +/− MTX for the RIR. CMR RIR P Value N 48 40 Low grade B-cell 18 16 NS Intermediate grade B-cell 16 12 NS Mantle cell 10 5 NS T cell 4 7 NS Age (years, median, range) 44 (18–54) 51 (20–67) 0.0002 No of prior regimens (median) 3 2 0.02 Previous autologous transplant 5 16 0.002 Chemosensitivity at transplant 24 31 0.007 FTBI regimen 41 0 CMR were significantly associated with a lower rate of relapse (RR) of 15% versus 38% after RIR (p=0.017). The 1-year TRM was 38% for CMR and 24% for RIR (p=NS). Kaplan-Meier 2-year OS/PFS for CMR is 52%/48% versus 57%/48% for RIR (p=NS). When analyzed by diagnosis, CMR were significantly associated with decreased RR (10% vs 60%, p=0.004) for intermediate grade B-cell (figure 1). Univariate analysis of patient and treatment-related prognostic factors showed improved survival with chemosensitive disease; treatment intensity was the single predictor of relapse for the entire group, but, when stratified by diagnosis, for intermediate grade B-cell only. In conclusion, CMR provide better disease control for intermediate grade B-cell NHL. Figure Figure

Mantle cell lymphoma (MCL) carries a poor prognosis with standard therapy. Both allogeneic (ALLO) and autologous stem cell transplant (ASCT) approaches have been used to intensify therapy in an attempt to achieve lasting remissions. 77 patients were transplanted at City of Hope over a 10-year period (1994–2003), including 13 ALLO and 64 ASCT. Demographics: The majority of patients were male (92% ALLO, and 73% ASCT). Median age was significantly younger for the ALLO, 47 years vs. 55 years for ASCT (p=0.003). ALLO patients had received more prior regimens than ASCTs-- avg 3 in ALLO and 1 in ASCT (p-value 0.0031). Median time from diagnosis to transplantation was 1.3 years for ALLO, 0.81 for ASCT. For ALLO patients, 8% were in first complete remission (CR1), 62% in second or subsequent remission, 23% in relapse, and 8% in unknown status. For ASCT patients, 47% were in CR1, 31% in second or subsequent remission, 14% in relapse, 2% in unknown status. Methods: Conditioning regimens for ASCT include FTBI/VP16/CTX (36), BCNU/VP16/CY (14), BEAM (2), Zevalin/BEAM (4), and other (8). One patient received an ASCT transplant, then received a reduced intensity ALLO transplant at the time of second relapse. Conditioning for ALLO included FTBI/CTX (9), Flu/Mel (3), or BU/CY (1), Results: Median follow-up was 57 months for ALLO, and 26 months for ASCT. 3-year Overall Survival (OS), progression free survival (PFS), and relapse rate was 51%, 53%, and 14% , respectively, for ALLO, and 66%, 57%, and 27% for ASCT. Patients transplanted in 1st CR had a significantly higher 3-year OS (85% vs. 52%, p = 0.0153) and PFS (78% vs. 44%, p = 0.027) a trend to a lower RR than patients transplanted in more advanced disease status. Conclusions: MCL patients transplanted in CR1 fared better than those transplanted with more advanced disease status, regardless of transplant approach. While relapse rates were lower in ALLO patients, this did not translate into improvement in OS or PFS, possibly due to a higher transplant related mortality (TRM). Analysis of PFS curves suggests no plateau on the ASCT curve, while late relapses were uncommon in ALLO patients.