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Abstract 4534 Myelofibrosis is a clonal myeloproliferative disorder, characterized by ineffective hematopoesis and bone marrow fibrosis. The disease can present de novo or secondary to an antecedent chronic myeloproliferative neoplasm such as essential thrombocythemia (ET) or polycythemia vera (PV). Allogeneic hematopoetic stem cell transplantation (AHSCT) is a curative approach for myelofibrosis, and produces durable donor engraftment and regression of myelofibrosis in approximately 50% of eligible patients. We retrospectively evaluated 31 consecutive patients that were treated for MF with AHSCT at our institution between 1998 and 2011. Thirty-one patients, 33 to 70 years of age, with a median age of 47, males 17 and females 14 with primary myelofibrosis or myelofibrosis evolving from antecedent polycythemia vera 4 (12%) or essential thrombocythemia 10 (32%) received AHSCT. Seven (22%) patients had transformed to acute myeloid leukemia prior to transplant. JAK 2 V617F was present in 15 patients, 9 patients were JAK 2 wild type, 5 patients were not tested and 2 were unknown. Patients received AHSCT from related (n= 11) or unrelated (n= 20) donors. Fourteen patients (45%) had a normal karyotype, 16 patients (51%) had an abnormal karyotype and one was unknown. Twenty eight patients received reduced intensity conditioning regimen and three received a fully ablative transplant. The source of stem cells was marrow in 4 patients and peripheral blood in 27 patients. Median time to neutrophil engraftment was 13 days in 28 patients (90%) and three patients had primary graft failure and were re-transplanted. One of the patients receiving a second AHSCT is alive and in complete hematological remission 19 months post-transplant.Twenty-eight patients showed 95–100% donor chimerism at day 30. Two patients had mixed chimerism at day 90. Twenty-six patients (83%) survive more than 100 days, 3 patients died (10%) from relapsed/progressive disease, and 5 (16%) from TRM. However at a median follow up of 31 months post-transplant 15 patients (48%)survived, 11 (45%)with chronic myelofibrosis, and 4 out of 7(57%)who had transformed to AML prior to transplant. Of note all five patients who were greater than 65 years of age at the time of transplant engrafted and enjoyed full hematological and clinical remission, one of these individuals subsequently died of a solid tumor. In addition, one of the patients with AML had an extramedullary relapsed 36 months post-transplant. One of the unanticipated complications observed in these patients who underwent AHSCT was massive peripheral edema in some cases anasarca of unclear etiology that required diuresis and albumin infusions and that occasionally preceded the date of engraftment and persisted for several weeks after engraftment. We conclude that AHSCT is an important therapeutic modality for not only PMF patients 65 years of age and individuals with blastic transformation of MF. Disclosures: No relevant conflicts of interest to declare.

The addition of rituximab to mobilization regimens does not adversely affect collection of adequate numbers of CD34+ PBSC and may decrease tumor cell contamination. Prior administration of rituximab may sensitize lymphoma cells to chemotherapy, but its use with high dose chemotherapy has not been studied. In this study, eligible patients had intermediate grade NHL either primary refractory, relapsed or in CR1 with an intermediate/high risk IPI score. Eight patients with a median age of 49 years (28–61) were enrolled in this study. Four patients had relapsed disease, chemosensitive to salvage in 3 patients, and untested in 1 patient. Two patients had primary refractory disease, chemosensitive to salvage. Two patients had intermediate-high risk IPI scores and were in CR-1. One patient in CR-1 declined to undergo transplant following stem cell collection. All patients had received rituximab previously. Stem cell mobilization was rituximab 375mg/M2 followed by CY 2gm/M2/day for 2 doses and filgrastim 10ug/kg/d. High dose chemotherapy consisted of rituximab 375mg/M2 on day -8, carmustine 300mg/M2 on day -7, etoposide 200mg/M2/d on days -6 to -3, cytosine arabinoside 200mg/M2 on days -6 to -3 (8 doses) and melphalan 140mg/M2 on day -2. Patients received filgrastim post transplant. RESULTS: The median CD34+ cell dose collected was 12.5 x 106/kg (1.1 to 33.2). There was one inadequate CD34+ cell collection requiring bone marrow harvesting which yielded 0.72 x 106/kg CD34+ cells. Engraftment of neutrophils and platelets occurred at a median of 8 and 11 days post transplant respectively. Infectious complications included febrile neutropenia in one patient following mobilization and in 6 patients following R-BEAM. Transient grade I–II (common toxicity criteria) hepatic enzyme elevation occurred in 2 patients following R-CY. Following R-BEAM, 3 patients developed grade II-IV LFT elevation without evidence of VOD, which resolved. One patient developed moderate hemorrhagic cystitis which resolved. One patient developed bilateral pulmonary infiltrates of unkown etiology (BAL negative for organisms) which resolved. Immunoglobulin levels remained normal in two patients, but decreased in all other patients for up to a year post transplant. Peripheral blood flow cytometry and T cell subset analysis showed absent B cell populations, decreased CD4 cells and increased CD 8 cells in all patients up to a year post transplant. Five patients are alive with no evidence of disease 381 to 676 days post transplant. Three of these patients developed PET positive lymph nodes that showed florid follicular hyperplasia on biopsy, with no evidence of lymphoma. Two patients had persistent disease following transplant. One patient underwent a non-myeloablative allogeneic transplant and died of progressive disease. CONCLUSIONS: R-CY was well tolerated as a mobilization regimen and led to adequate stem cell collection. The addition of rituximab to the high dose chemotherapy regimen did not appear to increase the incidence of infections or peritransplant complications in this Phase I study. The effect, on disease free survival, of the addition of rituximab to the collection and preparative regimens requires further investigation.

Acute GvHD is a frequent complication of non-myeloablative transplantation although it is seen at a lower rate and severity than after myeloablative transplantation. The use of ATG in transplant conditioning produces substantial host immunosuppression. Furthermore, the persistence of ATG in the circulation after transplantation is thought to accomplish an in-vivo T-cell depletion of the stem cell inoculum. Non-myeloablative stem cell transplantation using low dose TBI (200cGy) and fludarabine results in a high rate of full donor chimerism. We previously showed that the addition of ATG to TBI 200 cGy and fludarabine can improve donor engraftment. Whether it also impacts on acute and chronic GvHD and on graft versus tumor effect is less known. Forty-seven patients, not eligible for conventional fully ablative allogeneic SCT by virtue of age or co-morbidities, underwent non-myeloablative allogeneic transplantation using ATG 15 mg/kg/day (equine) or 1.5mg/kg/day (rabbit) days −4 to −1, TBI 200 cGy on a single fraction on day −5, fludarabine 30 mg/kg/day on days −4 to −2. Oral immunosuppression with MMF and CSA were started on day −5. Allografts were unmanipulated peripheral blood progenitor cells collected on day 5 of mobilization with filgrastim 10 mcg/kg/day. Thirty-two patients (68%) had match related donors, 9 (19%) match unrelated (10/10), 1(2%) mismatch related (9/10) and 5 (10.6%) mismatch unrelated donors (9/10). Twenty-five patients had sex matched donors (53.2%). Full donor chimerism was documented in 85% and partial (>50%) in 11% of patients. At a median follow up of 309 days, graft versus host disease grade II–IV developed in 13 patients (27.6%). Fatal GvHD of liver and/or gut occurred in 8 patients (17%). The mean age of patients who developed GvHD was 54 years and 57 for those who did not (p=ns). The corresponding mean ages for their donors were 47 vs. 50 years (p=ns). Seven out of fourteen (50%) unrelated transplants recipients and 6/33 (18%) with related donors develop GVHD (p=0.023). Infectious complications were seen in 8 patients (17%) and were the cause of death in 6 (12%). Thirteen of the 47 patients (27.6%) underwent transplant for AML. Six patients had relapsed/refractory disease at the time of transplant, 3 were in CR2 and 4 in CR1. Eleven patients (84.6%) relapsed with AML after transplant. Previously reported data on non-myeloablative stem cell transplant using 200 cGy of TBI and fludarabine with no ATG showed an incidence of acute GvHD grade II–IV of 64% and 24% GvHD related mortality. Similar rates have been reported with fludarabine and melphalan reduced-intensity conditioning. In our cohort of 47 patients the addition of ATG resulted in decreased incidence of acute GvHD grade II–IV and GvHD related mortality without a high rate of infectious complications. A high incidence of disease relapse in patients with AML may reflect the high proportion of patients with advanced leukemia enrolled in the study. However, it also warrants further investigation to rule out that ATG may hinder graft versus leukemia effect.