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Abstract 1355 Background: Overall survival for patients with MM has improved significantly over the past 10 years primarily as a result of novel therapeutics. High dose therapy with ASCT continues to be an effective modality but the progression-free survival following ASCT has improved minimally over the same period of time due to a continued reliance on single agent melphalan. Many chemotherapy/chemoradiotherapy regimens have been used in preparation for stem cell transplantation. However, no regimen has proven superior to high dose melphalan 200 mg/ m2 (MEL 200) which is considered the standard conditioning for patients with MM with relatively predictable results. In order to improve progression free survival (PFS) and overall survival (OS), continued efforts in developing effective preparative regimens are needed. Busulfan is an alkylating agent that affects cells in an AUC-dependent manner. Recent data suggests that the combination of BU and MEL delivers better PFS compared to MEL 200 alone (Grande and Lahuerta; PETHEMA, 36th EBMT meeting. Vienna 2010). Moreover, the addition of bortezomib following MEL 200 appears to increase the VGPR rate when compared to historical cohort receiving MEL 200 alone (Lonial, et al; Blood. ASH Annual Meeting Abstracts, Nov 2008; 112: 3332). Furthermore, the recently published IFM trial of MEL 200 plus BTZ also demonstrated superior response rates and PFS compared to historical controls (Roussel et al Blood. 2010;115:32-7). Rationale: The combination of intravenous BU and MEL followed by BTZ (BuMelVel) will be an effective preparative regimen with acceptable toxicity for patients with MM. Methods: Patients received intravenous BU 130 mg/kg over 3 hours daily × 4 days from D-6 to D-3. Based on the pharmacokinetics of the first two doses, the subsequent 2 doses were adjusted to achieve an AUC of 20,000 mMol-min (5,000 mMol-min/day). MEL was administered at 140 mg/ m2 IV over 15–30 minutes on day -2. Bortezomib was administered IV push over 3–5 seconds on day -1. Bortezomib administration followed a phase I dose escalation design starting at 1.0 mg/m2 for the first cohort; then, 1.3 mg/m2 for the second cohort; then, 1.6 mg/m2/kg for the 3rd cohort and subsequent subjects at the 3rd dose level if no limiting toxicity was observed. Autologous stem cell infusion occurred on day 0. Results: 20 patients have been enrolled to date, with 19 evaluable for toxicity and 13 for response assessment at D +100. The median age is 61 (47 - 69). The median time for engraftment for ANC ≥ 500 and plts ≥ 20, was 10 days. The median length of stay (LOS) was 18 days (16 – 21 days). 12 patients required a median of 2 units of PRBC and 16 patients required a median of 1 platelet transfusion. PRBC and PLT transfusions as well as LOS are not significantly different to what has been observed at our institution with MEL 200 (2 PRBC, 2 RD PLT transfusions, and 15 days LOS, respectively). All patients responded including: 77% ≥ VGPR and 54% nCR, CR, or sCR. The most common grade ≥ 3 toxicities were neutropenic fever (n = 11), mucositis (n = 9), and hypophosphatemia (n = 7). Three patients developed reversible transaminitis. One patient developed Clostridium difficile colitis and Klebsiella pneumonia UTI. Another patient developed E. coli UTI. No cases of VOD or interstitial pneumonitis were observed. There were no treatment related deaths and no re-admissions post discharge. Conclusion: BuMelVel proved to be an effective preparative regimen with ≥ VGPR and nCR/CR/sCR of 77% and 54%, respectively, as compared to responses reported with MEL/BTZ (70% and 32%, respectively); and to MEL 200 alone (43% and 11%, respectively) by Roussel et al. Furthermore, BuMelVel had an acceptable toxicity profile without any cases of VOD or interstitial pneumonitis, and mucositis/infections incidence and severity are comparable to our institutional experience with MEL 200. Therefore, the regimen of BuMelVel may lead to improvements in PFS and OS, critical criteria to improve the outcomes of patients with MM. These promising results will be further evaluated in a planned Phase III clinical trial with MEL 200. Disclosures: Rodriguez: Otsuka: Consultancy, Research Funding, Speakers Bureau; Millennium: Consultancy, Speakers Bureau; Celgene: Speakers Bureau. Kaufman:Celgene, Millenium: Consultancy; Celgene, Merck: Research Funding. Lonial:Millennium: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; BMS: Consultancy, Speakers Bureau. Vesole:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millenium: Speakers Bureau.

9132 Background: Depression and decreased quality of life (QL) develop frequently in BMT patients. We conducted a prospective randomized trial to assess whether pretreatment of BMT patients with th...

Abstract 3331 Poster Board III-219 Introduction Current data suggests that recipient age above 50 is associated with an inferior outcome after myeloablative allogeneic stem cell transplantation (SCT). Overall survival (OS) of 31%, and transplant related mortality (TRM) of 17% at 100 days have been reported in this population (Ditchkowski, et al 2005; Yanada, et al. 2004). Encouraging results are observed with non-myeloablative conditioning regimens. However, for patients with a high relapse risk, this approach may not be sufficient to achieve long term disease control. In these cases, a reduced toxicity, yet ablative stem cell transplantation (RT-SCT) may give adequate time to the transplanted cells to mature and mount an immune-mediated antitumor response. This study evaluated the outcome after RT-SCT using a conditioning regimen consisting of intravenous busulfan (Bu) and pentostatin (Pent). Methods Consented adult patients up to 70 years with a fully-matched related (MRD) or unrelated donor (MUD) were screened for enrollment. Conditioning consisted of Bu 1.6 mg/kg every 12 hours days -7 to -4, and Pent 4 mg/m2 on day -3 and -2 prior to stem cell infusion on day 0. GVHD prophylaxis was methotrexate 10 mg/m2 on day 1, and 5 mg/m2 on days 3, and 6. Tacrolimus was started on day -2, and then tapered over 1 month after day +100. Characteristics Twenty six patients were analyzed. Male to female ratio was 1:1. Stem cell source was from MRD in 15 patients and MUD in 11. Median age was 62, with 92% of patients being older than 50 years. Indications for treatment were AML (35%), MDS (42%), Refractory CLL (23%), Relapsed NHL (12%), and Philadelphia (+) ALL (4%). All AML patients were high risk either due to poor cytogenetic, transformation, or relapse and only two of them were transplanted in first complete remission. MDS patients were RAEB (36%), secondary MDS (36%), or multilineage dysplasia (18%). Two patients had prior autologous transplants. Results No graft failure was observed. All patients achieved neutrophil (NEU) engraftment. Two patients expired prior to platelet (PLT) engraftment. Median engraftment days for NEU and PLT were 13 days. At a median follow up of 25 months, the OS and progression free survival for the entire group was 40% and 38% respectively. The OS in the MRD group was 58%. TRM at 100 days was seen in one patient (4%) due to veno-occlusive disease (VOD). Limited chronic GVHD was the most common observed toxicity (54%), followed by diarrhea (30%) and mucositis (23%). Mucositis was mainly grade 1 (8%) and grade 2 (8%). No grade 3 mucositis was observed. There was only one case of VOD and one case of acute GVHD. Conclusion To our knowledge, this is the first report of a RT-SCT using BuPent. This study demonstrates the efficacy of the regimen in patients older than 50 years. No graft failure was observed and the regimen related toxicity was acceptable in this high-risk population. The overall survival of 40% at a median follow up of 25 months compares favorably with prior reports of myeloablative allogeneic stem cell transplatation in patients older than 50 years. This regimen provides an exciting opportunity to extend the benefits of allogenic transplant to an older population, and warrants replication with larger controlled trials. Disclosures Rodriguez: Otsuka: Membership on an entity's Board of Directors or advisory committees, Research Funding. Vesole:Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Speakers Bureau; Millenium: Speakers Bureau; Centocor Ortho Biotech: Speakers Bureau.

Abstract 2267 Poster Board II-244 Introduction: Both acute and delayed nausea and vomiting are a major problem for patients undergoing highly emetic high dose preparative regimens prior to hematopoietic stem cell transplant (HSCT). Aprepitant (APR) is an NK-1 antagonist FDA approved for the prevention of N/V due to standard dose highly and moderately emetogenic chemotherapy. While several small Phase II studies have suggested its benefit in HSCT, no completed prospective comparisons have been reported. In addition as APR is known to interact with cytochrome P450 isoenzymes involved in the bioactivation of high dose cyclophosphamide, and may interfere with etoposide pharmacokinetics, its impact on regimen related toxicity and long term survival post transplant is unknown. Patients and Methods: We performed a randomized (1:1 randomization) blinded Phase III trial to determine the safety and efficacy of APR for N/V due to ablative preparative regimens. Patients received either placebo (PBO) or oral APR 125mg PO day 1 then 80mg daily during and for 3 days after the preparative regimen was completed, in addition to oral ondansetron 8 mg PO q 8hrs + IV dexamethasone daily during and for 1 day after the preparative regimen. Only PRN lorazepam was permitted for nausea. Due to a known drug interaction between APR and dexamethasone, patients also received blinded dexamethasone doses of 10mg on the placebo arm and 7.5mg on the APR arm. Patients were stratified based on gender, and patients with heavy ETOH use were excluded. Clinical evaluations were performed daily during therapy with the primary endpoint being a CR, defined as: no emesis and no or mild nausea [less than grade (gr) 3 using CTC 2.0 criteria]. Other endpoints included; major response (MR): 1 episode of emesis or moderate nausea; minor response (mR): 2–4 episodes of emesis; and failure (F) : >4 episodes of emesis. Major efficacy (ME) = CR + MR. Other analyses performed included subjective nausea based on a 100 mm visual analog scale (VAS) with 0 = no nausea; amount of PRN antiemetics used to control breakthrough N/V and no emesis all days.. Safety analyses performed included time to engraftment, 30 day survival and progression free survival (PFS) and overall survival (OS). The study began 9/20/04 and completed enrollment 7/18/08. The study was powered (90 pts per arm) to detect a difference of 20 % between the two groups with a significance level of 0.05 using a two-sided t-test. The 181 randomized patients were balanced with respect to age, weight, donor source and h/o N/V with prior chemotherapy. Patients received one of 5 ablative prep regimens: CY/TBI/VP16 (36), CY/TBI (79), IV BU/CY (14), PO BU/CY (34), and BCV(16) Two pts never proceeded to transplant so only 179 pts are eligible for analysis. Ten pts (6 APR/4 PBO) failed to complete the study; data were analyzed as intent to treat. Results: Efficacy: There was a difference in CR rate (primary endpoint) in favor of APR: 81.9% vs 65.8 % for those receiving PBO with 48.9% vs 14.6% respectively meeting this endpoint for the entire study period (p Conclusions: When used daily up to 10 days with ablative preparative regimens, aprepitant significantly improved control of acute and delayed regimen-related N/V with a major impact on emesis rates. It appears safe for this indication with no impact on WBC and PLT engraftment as well as PFS and OS. Disclosures: Stiff: Merck: Research Funding. Off Label Use: Aprepitant in BMT setting.

Abstract 1034 Poster Board I-56 Background: Poor-risk groups with AML – defined as those above age 50, those with secondary or treatment-related disease, and individuals relapsing after or refractory to initial therapy – have a very disappointing response to therapy and a dismal overall survival, on the order of 6 months. Therapeutic options are limited by age, comorbidities and toxicities from prior treatment. Hypomethylating agents, such as Azacitidine (AZA) may induce remission in up to 20% of patients. We have previously published a pilot study of a regimen combining AZA and low-dose gemtuzumab ozogamicin (GO) for the treatment of newly diagnosed, elderly patients with AML or high-risk MDS. (Leuk Lymphoma. 2008:49:2141-7) The combination produced a 70% CR/CRi rate, a median OS of 10 months and formed the basis of a national cooperative group trial in this select population. Based on these results, our institution broadened the use of this regimen to patients not otherwise eligible for standard therapy or a clinical trial, including patients with relapsed or refractory disease. We have retrospectively analyzed the clinical characteristics and outcomes of 56 patients treated with this regimen at our institution between September 2006 and July 2009. Methods: With IRB consent, all off-study patients with AML and MDS as well as those with relapsed/refractory AML were included in this analysis. Patients were included if they received at least one full cycle of AZA at a dose of 75mg/m2 SQ or IV daily for seven days followed by GO 3mg/m2 IV on day 8. A second cycle could be given after a day 15 bone marrow (BM) if there was no evidence of a CR or aplasia. Patients could receive consolidation therapy with the same regimen for one or more additional cycles and/or could continue on monthly maintenance therapy with single-agent AZA. Results: Patient characteristics: Between September 2006 and May 2009, a total of 56 patients received the regimen, 26 (46%) for the treatment of relapsed or refractory disease and 30 (54%) as first-line therapy. Most were treated for AML, but 11 (20%) had high-risk MDS, including three with CMMoL. The average age of patients at the time of treatment was 63 yrs, range of 23-85 yrs. Following induction, 17 patients received AZA alone as monthly maintenance therapy and nine were treated with allogeneic transplantation. The treatment-related mortality was 10% (n=6). Grade 3 or 4 non-hematologic toxicities, primarily infection or infusion reactions related to GO, were recorded in 17 patients (30%). Response rate/Overall survival Of the 56 patients, 15 (27%) achieved a CR or CRi. An additional seven patients cleared their peripheral blood blasts or had hematologic improvement but did not have BM documentation of remission. CR or CRi was achieved in five of 22 patients (22%) with poor-risk cytogenetics and seven of the 24 (29%) patients who had therapy-related disease or disease that had evolved from pre-existing hematologic malignancy. The median OS was 21 weeks (range: 1-118). In patients who achieved a CR or CRi, the median OS was 40 weeks (range: 9-118). Most notably, seven of 26 patients (26%) with relapsed or refractory disease achieved a documented CR or CRi – including two patients with primary refractory disease and two who had relapsed after allogeneic transplantation. The median OS of these seven patients was 40 weeks (range: 9-118). Maintenance therapy with monthly AZA monotherapy was administered to 17 patients, 11 of whom had achieved a documented CR or CRi. The mean number of months of maintenance therapy was four; 8 received 5-10 cycles. Patients receiving maintenance therapy after achieving CR or CRi had a median OS of 45 weeks (range 20-118). Conclusions: The combination of AZA and low-dose GO produced a CR/CRi of 27% and a low TRM in an extremely poor-risk group of patients with AML and high-risk MDS. Responses were seen in patients with primary refractory disease and those who relapsed following allogeneic stem-cell transplant. Patients who were able to achieve a CR or CRi appeared to benefit from several months of maintenance AZA and had a median survival of nearly one year. Based on these results we are opening a prospective trial of this regimen for patients with relapsed or refractory disease with responders continuing on azacitidine indefinitely or proceeding to allogeneic transplantation. Disclosures: Off Label Use: I will describe the use of Azacitadine for acute myeloid leukemia. Smith:Celgene: Speakers Bureau. Nand:Pharmion/Celgene: Consultancy, Research Funding, Speakers Bureau.

Abstract 43 We have previously shown that TNF Receptor 1 (TNFR1) levels early after myeloablative hematopoietic cell transplant (HCT), especially following unrelated donor (URD) HCT, predict later graft-versus-host disease (GVHD), non-relapse mortality (NRM), and overall survival (OS). Given this data we hypothesized that augmenting standard GVHD prophylaxis with the TNF-inhibitor etanercept would protect against GVHD and NRM while improving survival. We therefore conducted an IRB-approved Phase II trial at two centers to determine whether prophylactic TNF blockade with etanercept decreases the rates of acute GVHD and day 100 NRM seen after high-risk allogeneic matched (n=68, 71%) or single antigen mismatched URD (n=25, 26%) or single antigen mismatched related donor (RD) (n=3, 3%) HCT. Follow-up data are available for 96/100 patients (pts) enrolled between 2005 and 2009. HLA matching used high-resolution DNA-based techniques for HLA-A, B, C, and DR. Patients received tacrolimus, methotrexate (5 mg/m2 on days 1, 3, 6, 11) and etanercept (0.4 mg/kg, max 25 mg) twice weekly from the start of conditioning to day 56. All pts received myeloablative regimens; either TBI/cyclophosphamide (TBI, n=29), fludarabine and 12.8 mg/kg IV busulfan (FluBu4, n=31) or other myeloablative chemotherapy regimens, either BCNU/etoposide/cyclophosphamide or busulfan/cyclophosphamide (BCNU/Busulfan, n=36). The median age of the pts was 45y (range 2-61y). To determine whether the administration of etanercept effectively reduced post-transplant TNFR1 levels we compared day 7 post-transplant TNFR1 levels in the 96 study pts to 132 control pts who received standard GVHD prophylaxis of tacrolimus/methotrexate and were matched for age, conditioning regimen, degree of HLA-match, and disease status. The median day 7 TNFR1 levels in study pts was 2518 pg/ml, significantly lower than the median day 7 level of 3529 pg/ml in control pts (p We have evidence that etanercept effectively lowers TNFR1 levels at day 7 post-transplant, a time point associated with GVHD and HCT outcomes. However, the degree of TNFR1 level reduction appears to depend in part on the conditioning regimen. The median day 7 TNFR1 levels were statistically different across conditioning regimens, and those with low TNFR1 levels have improved outcomes (FluBu4>BCNU/Busulfan>TBI). In fact, for the FluBu4 pts in particular, preliminary data suggest superior outcomes, including low rates of GVHD and remarkably high 2 year OS for high-risk transplant pts, without use of thymoglobulin. After highly intense conditioning regimens, such as TBI-based, TNFR1 levels remained high despite TNF reduction with etanercept and outcomes are similar to those expected with standard GVHD prophylaxis. With the less toxic, but still myeloablative FluBu4 conditioning regimen, however, the addition of etanercept appeared to lower TNFR1 levels to levels that were protective against NRM. Thus, the effectiveness of etanercept may depend on the conditioning regimen, warranting a randomized trial to explore this interaction further. Disclosures: Off Label Use: Etanercept - for GVHD prophylaxis.

Platelet transfusion refractoriness following allogeneic bone marrow transplantation usually stems from HLA alloimmunization. However other platelet antigens may serve as targets of alloimmune reactivity. A 24-year-old Palestinian male with atypical CML in chronic phase underwent matched unrelated donor bone marrow transplant from a 39-year-old female, HLA-A, B, C and DR allele level matched donor. Conditioning was with busulfan 0.8mg/Kg IV q6 hours day -8 through -4, cyclophosphamide 60mg/Kg IV daily day -3 & -2 and rabbit anti-thymocyte globulin 1.5mg/Kg IV daily day -5 & -4. Graft versus host disease prophylaxis was with mini-dose methotrexate and tacrolimus, with filgrastim given for hematopoietic reconstitution. The cell dose was 1.86x106 CD34+ cells/Kg recipient body weight (3.66x108 mononuclear cells/Kg). Neutrophil engraftment occurred on day +14, and was complicated by a diffuse purpuric skin rash, with hypoxia and pulmonary infiltrates which resolved with corticosteroid therapy. His post-transplant course was also complicated by severe, transfusion refractory thrombocytopenia (to random donor pools, apheresis and crossmatched platelet units) starting on day +5 with platelet counts of 98% donor chimerism. As his immunosuppression has been tapered over time, the antibody titer has declined (Fig) as has his platelet transfusion requirement (41 doses transfused between day 31 and 120). However he remains dependent upon directed donor platelet transfusions from his CD36 negative family members at 120 days from transplant. The CD36 negative phenotype is rare in Caucasians, however, platelets from about 5% of individuals of Asian or African descent lack CD36. DNA sequencing to determine CD36 mutations in this patient is underway. We hypothesize that this patient developed a host vs. graft humoral response against donor derived and transfused platelets resulting in sustained severe thrombocytopenia. Patient serum CD36 antibody titers following transplant Patient serum CD36 antibody titers following transplant

Introduction: Myeloid colony stimulating factors accelerate engraftment and shorten hospital stay following PBSCT. Pegfilgrastim (Peg-G), a pegylated granulocyte colony-stimulating factor is equivalent to filgrastim (G) when used to hasten neutrophil recovery after conventional chemotherapy. While small non-randomized trials suggest that Peg-G could be used in lieu of G to speed hematopoietic reconstitution after PBSCT, no large Phase III trial data exist. This phase III, randomized, double-blind, placebo controlled comparative trial of Peg-G vs G After autologous PBSCT compared the efficacy, costs and safety of the two treatments. Methods: Consented adult patients undergoing an autologous PBSCT at our institution were eligible if they had collected > 2 × 106 CD34/kg for transplant. Patients were randomized to either fixed-dose Peg-G at 6 mg SQ x1 dose plus daily G-placebo or daily G at 5 mg/kg/day plus Peg-G placebo × 1, all starting on day +1 posttransplant. G or G-placebo continued until sustained engraftment, defined as neutrophils > 5000/ml × 3 days, or 10,000/ml × 1 day, or through day +25 posttransplant. They were stratified based on prep regimen (TBI vs other) and CD34 cell dose/kg (< 5 vs ≥ 5 × 106/kg). The primary endpoint was time to neutrophil engraftment of >500/ml × 3 days. Patients not engrafting to this level by day +19 were permitted to receive open label G. Analysis of infectious complications and cytokine costs as defined by the number of days of G vs the cost of Peg-G plus any rescue doses of G was determined. Results: We enrolled 78 patients who underwent myeloablative autologous PBSCT for myeloma, lymphoma, testicular, or ovarian carcinoma between 11/03 and 5/07 of whom 39 were randomized to each group. The mean CD34 doses were 4.1 and 4.7 × 106/kg (p = .68) for the Peg-G and G groups respectively. The groups were matched for age, sex, weight, and underlying disease. The median time to neutrophil engraftment was 9 and 10 days respectively for the Peg-G and G groups (p = 0.15). No patient required rescue G to achieve engraftment. The median time to an ANC of 1500/ml × 3 or 5000/ml × 1 was the same in both groups (12 days), but only 45% vs 97% of patients reached a WBC of 5000/ml × 3 or 10,000/ml × 1 (p < .0001) in the Peg-G vs G groups. For the Peg-G vs G groups there were no differences in: platelet engraftment (11 vs. 13 days, p = 0.29), the number of platelet transfusions (5 vs. 4, p = 0.3), incidence of positive cultures for bacterial pathogens (23 vs. 15%, p = 0.39), days of fever (1 vs 2, p = 0.2) or duration of hospital stay (19 vs 19 days). There was 1 death in each group prior to engraftment each due to sepsis. The number of days of G given to that arm to reach an ANC of 1500/ml × 3 or 5000/ml × 1 was 12. Considering the Average Wholesale Price for the actual doses used in this trial for the two groups there was a per-patient savings of $961 for the Peg-G group compared to the G-group using this engraftment endpoint (p < .001). Conclusions: This Phase III study demonstrated equivalency between Peg-G and G in the ability to achieve prompt neutrophil recovery post PBSCT. There was no difference in infectious complications and the use of Peg-G did achieve a significant cost savings over G.

8079 Background: Almost 50% of patients with intermediate grade non-Hodgkin's lymphomas (NHL) treated with standard CHOP- like therapy will have less than a complete response (CR) after treatment or will relapse after obtaining a CR. Salvage chemotherapy followed in responders by an autologous stem cell transplant (ASCT) can be curative. For many patients, this is not an option due to age, comorbidities, or lack of response. A non-cross resistant agent with activity in NHL which could salvage more patients is gallium nitrate Methods: We conducted a phase II clinical trial investigating the combination 3 non-myelosuppressive agents, gallium nitrate, rituximab and dexamethasone (GaRD) for relapsed or refractory DLBCL, MCL or transformed follicular lymphomas. Gallium is given at 200mg/m2 CIV days 1–7, rituximab 375mg/m2 IVPB day 1 and dexamethasone 40 mg po days 1–4. Eligible patients had relapsed or refractory disease and had a SWOG PS ≤3. Patients may have failed prior ASCT or allogeneic SCT. This was a 2 stage, phase II study with initial evaluation after 22 patients of whom at least 10 responders were needed for completion of the study, as determined prior to start of trial Results: We enrolled 22 patients on study. 15 had large cell, 6 had transformed follicular and 1 had mantle cell NHL. Most of these patients were refractory to one or several prior salvage regimens [13/22 (59%)]; all had prior rituximab 22/22 (100%) and 18/22 (82%) had it with there most recent treatment. No patients developed grade 3 or 4 toxicities, except grade 4 lymphopenia in 7/22 (32%). The overall response rate was 10/22 (45%); CR/CRu 8/22 (36%); PR 2/22 (9%); SD 4/22 (18%); and PD 8/22 (36%). Five patients went on to receive stem cell transplant (including 3 allogeneic and 2 ASCT). Two of the responders were patients who had failed a prior stem cell transplant: 1 ASCT failure who remains in CR >18 months and an allograft failure in CR >14 months after relapse. Of the 22, 10 (46%) are alive at a median f/u of 17.2 months, of whom 7 are currently NED Conclusions: This regimen appears to be effective and relatively non-toxic for patients with relapsed and refractory NHL, including stem cell transplant failure. As CR at ASCT may be associated with an improved outcome, a trial of GaRD combined with RICE is planned to improve cytoreduction prior to ASCT in patients with relapsed NHL. No significant financial relationships to disclose.

Polyclonal anti-thymocyte globulin (ATG) reduces the risk for primary graft rejection as well as acute graft-versus-host disease (GVHD) by depleting T cells in both the host and the infused allograft. However, the impact of ATG on late outcomes is less certain. We report the results of a retrospective landmark analysis of consecutive patients who underwent an unrelated donor bone marrow transplant at our center between January 2001 and October 2005 (n=45) and survived at least 90 days following transplant. We compared late outcomes in patients who either recieved ATG (n=25) or did not (n=20) as a part of their conditioning regimen. Conditioning was with either busulfan and cyclophosphamide (n= 28; 17 without ATG) or BCNU, etoposide, cytarabine, and melphalan (n=18; 3 without ATG). Most patients (20) received rabbit ATG at a median dose of 3 mg/kg (range: 1.5–9 mg/kg) on day -4 and -3. Others were given equine ATG. GVHD prophylaxis consisted of tacrolimus + methotrexate in both groups. Median age was 42 years (range 18–65; 14 female). Bone marrow from unrelated donors matched at HLA-A, B, C, and DRB1 (7/8 and 8/8 matches) was used as the stem cell source. Diseases treated were CML (11), HD (9), AML (8), MDS (6), NHL (3), MM (3), and other (5). A median of 3 prior therapies had been given before transplant (range 1–5). There was no significant difference (Pearson χ2) in the number of patients beyond CR1/CP1 (n=25) and those having failed a prior autograft (n=17) between the two groups. The median overall survival in the recipients of ATG was 1382 days (95% CI: 373– 2391 days) as opposed to 364 days (95% CI: 0–851) in those not receiving ATG (P=0.125 by Log-Rank test); with a 1-year overall survival of 76% (59%–93%) vs. 50% (28–72) in the ATG vs. no ATG cohorts respectively, and 69% (49–89) vs. 44% (22–66) at 2-years. The 1-year progression free survival was 84% (69–98) vs.90% (77–100) in the ATG vs. no ATG cohorts, and 84% (69–98) vs. 67% (37–97) at 2 years. Chronic GVHD developed in 15/20 (75%) patients not receiving ATG (45% extensive), and in 12/25 (48%) in those recieving ATG (16% extensive) (P=0.06 Pearson χ2). Graft rejection was seen in 2/20 patients in the non-ATG arm and 1/25 patients in the ATG arm. Despite a lower incidence of chronic GVHD, the relapse rate was similar in the two groups (16% in the ATG group vs. 20% in the non-ATG group; P=0.73). Lymphoid recovery was similar in the two groups. The absolute lymphocyte counts at day-90 and day-180 post transplant were 680 vs 800/microL and 1100 vs. 1500/microL in the no ATG vs. ATG cohorts (P=0.275 repeated measures ANOVA). Serious late infections requiring parenteral antimicrobial treatment occured in 8 patients (32%) receiving ATG, and in 9 patients (45%) in the non-ATG arm ((P=0.248). CMV reactivation was seen in 8 patients (32%) receiving ATG, and 7 (35%) in the non-ATG arm. Eleven patients (55%) have died in the no ATG cohort from either relapse (2), GVHD (4) or infection (5); whereas in the ATG cohort 9 (36%) have died of either relapse (4), GVHD (3) or infection (2). In conclusion, ATG appears to reduce delayed transplant related complications, such as chronic GVHD and infections, in patients receiving bone marrow from unrelated donors. This may lead to a favorable trend towards improved survival in patients recieving ATG as a part of non-total body irradiation based conditioning.

Limbic encephalitis is a rare complication reported in patients receiving an allogeneic hematopoietic stem cell transplant (HCT). It is characterized by a syndrome of short-term memory deficit, altered mental status, seizures and coma accompanied by characteristic MR imaging findings of abnormal high signal intensity on flair and T2 weighted images in the mesial temporal lobes. The incidence and risk factors for the development of of limbic encephalitis are not well studied in patients undergoing HCT. In this study we retrospectively reviewed the medical records of 399 allogeneic HCT recipients transplanted at our institution from June 1995 to June 2006 to determine the incidence of limbic encephalitis among these patients. Forty-nine of these patients received umbilical cord blood transplants (UCBT). We identified 66/399 patients who underwent MRI of the brain to evaluate neurologic symptoms; 28 patients had abnormal MRIs. The MRIs were then examined to determine if the findings were consistent with limbic encephalitis. Seven of the twenty-eight MRIs showed changes compatible with limbic encephalitis. Five of the seven patients with limbic encephalitis had undergone UCBT and 2 had received matched unrelated donor HCT. The median age of the patients was 44 years (range 32–54), 5 were female. Diseases treated were AML (3), Hodgkins disease (2), Burkitt’s lymphoma(1) and Multiple Myeloma (1). Four patients had failed prior autologous transplant. Six patients had persistent disease at the time of transplant. Total body irradiation based conditioning was given in 4 of 7 patients. All patients had received anti-thymocyte globulin (ATG) as a part of their conditioning. GVHD prophylaxis was with methylprednisolone + tacrolimus (5), mycophenolate mofetil + tacrolimus(1) and methotrexate + tacrolimus(1). The 2 patients that did not have methylprednisolone as part of GVHD prophylaxis received it as treatment for acute GVHD. All of the patients received prophylactic high dose acyclovir or valacyclovir. The median time from transplant to diagnosis was 39 days, (range 28–148). Symptoms included: short term memory deficit/confusion (6), seizures (5) and coma(4). SIADH was seen in 4 patients with a mean serum sodium of 125 mmol/L. Four patients had elevated CSF protein (median for the entire cohort 48 mg/dL; range 20–105) and glucose (82 mg/dL; 68–97). Three patients had an elevated CSF WBC count (4 cells/μL; 0–34) with lymphocyte pleocytosis (81%; 0–100). CSF bacterial and viral cultures were negative on all of the patients. Five patients had HHV-6 PCR performed; 4 of these had HHV-6 DNA detected in the CSF. Six of the seven patients recieved second line antiviral therapy with either ganciclovir or foscarnet. Three of the patients who had therapy started at the onset of symptoms had clinical improvement. Short term memory deficit persisted in all the patients. Six of the seven patients have died with the median survival of 39 days (range 4–110) from diagnosis of limbic encephalitis. One patient is alive 11 months after diagnosis with severe neurologic dysfunction. We describe a rare, but devastating complication of allogeneic transplantation affecting approximately 2% of our allografts and 10% of UCBT recipients. Heavily pretreated patients, and those receiving ATG and corticosteroids appear to have a higher risk of limbic encephalitis.

17510 Background: More than 56,000 new cases of non-Hodgkin’s lymphoma (NHL) will be diagnosed this year in the United States. As our aging patient population develops worsening performance status and co-morbidities, it seems appropriate to develop effective lymphoma treatments, which have fewer toxicities and lower costs for administration. One approach is to combine non-myelosuppressive therapies. One non-myelosuppressive agent, which has efficacy in lymphoma, is gallium nitrate. Investigation of gallium nitrate for cancer treatment dates back to the 1970’s and it has been shown to inhibit ribonucleotide reductase and bind transferrin and potentially complex with transferrin and/or transferrin receptor, which is highly expressed in intermediate and aggressive histology lymphomas. It appears that the binding of the transferrin receptor on the lymphocyte as well as its inhibition of ribonucleotide reductase, eventually impairs iron metabolism, which is a necessary component of the intracellular cytochrome systems/mitochondrial function and ultimately oxidative phosphorylation. Methods: The current study is a phase II clinical trial investigating the combination of gallium nitrate, rituximab and dexamethasone (GaRD) for relapsed or refractory DLBCL, MCL or transformed follicular lymphomas. The gallium nitrate is given at 200mg/m2 CIV days 1–7, rituximab 375mg/m2 IVPB day 1 and dexamethasone 40 mg po days 1–4. Eligible patients must have proven relapsed or refractory disease and have a SWOG PS ≤3. Patients may have failed prior ASCT or allogeneic SCT. The accrual goal was 37 patients however the study was stopped after 22 patients were accrued as the primary endpoint was reached after the initial interim analysis. Results: ORR 12/22 (55%); CR/CRu 6/22(27%); PR 6/22(27%); SD 3/22 (14%); and PD 7/22 (32%). Most of these patients were refractory to prior salvage regimens 15/22 (68%), including ESHAP, DHAP or high-dose cyclophosphamide. No patients developed grade 3 or 4 toxicities, with the exception of grade 4 lymphopenia. Conclusions: Gallium nitrate, rituximab and dexamethasone (GaRD) appears to be an effective and non-toxic salvage regimen for patients with relapsed DLBCL [Table: see text]

More than 56,000 new cases of non-Hodgkin’s lymphoma (NHL) will be diagnosed this year in the United States. Despite advances in treatment modalities such as radiation, biologic agents, and cytotoxic chemotherapeutic regimens, only 25–30% of these patients will be cured of their disease. Standard salvage regimens such as DHAP, ESHAP, ICE and EPOCH have proven efficacy at the cost of increasing toxicity and hospitalization costs. The reported response rates for these are on the order of 50–75% as first-line salvage regimens. However, as our aging patient population develops worsening performance status and co-morbidities, it seems appropriate to develop effective lymphoma treatments, which have fewer toxicities and lower costs for administration. One approach is to combine non-myelosuppressive therapies. One non-myelosuppressive agent, which has efficacy in lymphoma, is gallium nitrate. Investigation of gallium nitrate for cancer treatment dates back to the 1970’s. While it is currently approved for the treatment of bisphosphonate resistant hypercalcemia of malignancy, it has also been shown to inhibit ribonucleotide reductase and bind transferrin and potentially complex with the transferrin receptor, which is highly expressed in intermediate and aggressive histology lymphomas. It appears that the binding of the transferrin receptor on the lymphocyte as well as its inhibition of ribonucleotide reductase, eventually impairs iron metabolism, which is a necessary component of the intracellular cytochrome systems/mitochondrial function and ultimately oxidative phosphorylation. The current study is a phase II clinical trial investigating the combination of gallium nitrate, rituximab and dexamethasone (GaRD) for relapsed or refractory DLBCL, MCL or transformed follicular lymphomas. The gallium nitrate is given at 200mg/m2 CIV days 1–7, rituximab 375mg/m2 IVPB day 1 and dexamethasone 40 mg po days 1–4. Eligible patients must have proven relapsed or refractory disease and have a SWOG PS Conclusions: gallium nitrate, rituximab and dexamethasone (GaRD) appears to be an effective and relatively non-toxic salvage regimen for patients with relapsed DLBCL, MCL or transformed FL.

Non-myeloablative allogeneic SCT is associated with acute GVHD rates similar to conventional allografting which adversely impacts the survival of elderly patients typically receiving this therapy. In an attempt to modify the incidence of GVHD, we have developed conditioning regimens combining Thymoglobulin (THY) with low dose TBI in patients with hematologic malignancies. We report outcomes of two patient cohorts transplanted using either THY 2.5 mg/kg/day (day −4 to −1) with 2-Gy TBI on day 0 in cohort 1 (n=16) or THY 2.5 mg/kg/day (day−10 to −7) with 4.5-Gy TBI (day -1 to 0; 1.5 Gy fractions) in cohort 2 (n=7). This later modification was instituted because of early relapse and/or graft rejection seen in some patients in cohort 1. The patients received SCT from either matched sibling (MSD; n=14, all GCSF mobilized) or URD (n=9, marrow in 6). GVHD prophylaxis consisted of tacrolimus + methotrexate (day 1,3 & 6) in cohort 1 and tacrolimus + mycophenolate mofetil (day 0–30) in cohort 2. There were 8 female patients; median age was 57 years (range 70–43). Diseases treated were MM (9), NHL (6), CLL/SLL (3), AML (2) and other (3). A median of 3 (range 1–5) prior therapies had been given; 12 (52%) patients had failed a prior autograft. Disease status at transplant was, CR (4), Persistent disease (13) untreated relapse (6). No treatment-related grade IV or V toxicities were seen. Combined overall day-100 survival in the two cohorts is 87% (95% confidence interval 72–100%); and 1-year survival is 81% (95% CI 62–100%) in cohort 1. With a median follow-up of 32 months (range 44–13 mo) in cohort 1 and 6 mo (9–2 mo) in cohort 2, 16/23 (70%) patients are alive (6 died of progression and one of infection; 5 deaths were seen in cohort 1). 15/16 (93%) surviving patients are without disease progression (10 in CR). 11/23 (48%) are event-free (DLI, relapse or death), 8 of these were transplanted with URD. Only 3/23 patients (all receiving URD-PBSCT) developed steroid responsive GII–III AGVHD. Chronic GVHD developed in 7 patients undergoing URD-SCT. Graft rejection was seen in cohort 1 (3; all with disease relapse) but not in cohort 2. Hematopoietic chimerism as measured by PCR for STR loci in blood at day 30 was 95% (range 53–100) donor derived in all patients; 95% (68–100) at day 60, 95% (25–100) at day 90 and 95% around day 180 (1–100). The surviving patients are >90% donor chimeric in blood (8 URD, 7 MSD). WBC subset chimerism analysis at 30, 60 and 90 days showed similar neutrophil (96, 94, 96 vs. 96, 95, 98 %; P= 0.40) but superior T cell (96, 100, 99 vs. 85, 86, 71; P= 0.018) engraftment in cohort 2 when compared with cohort 1. There was rapid normalization of NK cell (CD3−, 56+) counts in patients with URD BMT compared with T cells (CD3+, 56−); median 46/μ L & 140 vs. 20 & 240 at 4 and 8 weeks. Ten patients (all MSD; 9 in cohort 1) received DLI, for mixed chimerism (4) or persistent disease (6). Six patients had increased donor chimerism following DLI, however only 4 developed GVHD requiring therapy. In conclusion, selected patients conditioned with reduced intensity TBI in combination with THY achieve rapid and sustained engraftment with minimal acute GVHD, especially when an URD is used.

Most umbilical cord blood (UCB) transplant studies indicate that the minimum nucleated cell dose needed for adequate engraftment is > 2 x 107 cells/kg, which eliminates most adults. Using a novel, post-thaw cell manipulation without washing, we explored the notion that the minimum ‘safe’ transplant cell dose/kg could be lowered to 1 x 107/kg, which would permit most adults to be transplanted. Washing UCB cells post-thaw before transplantation is a common practice, but is associated with a modest, non-specific cell loss. Our method utilizes rapid thawing at 37°C followed by a slow, progressive dilution to a final DMSO concentration of 1% over 10 minutes with a 10% Dextran, 8% human albumin solution, without washing and with subsequent infusion over 15 minutes. To date 27 adults who did not have a matched sibling (5/6, 6/6) or unrelated (8/8) matched donor have been transplanted using cells processed by this method. Their median age was 42 (22–58) and their median weight was 84 (49–109) kg. Of the group, 18 (67%) had an active refractory hematologic disorder, and only 1 was in CR1 (AML with monosomy 7), and 11 (41%) had failed a prior ablative transplant. HLA matching (serologic for class I, and allele for class II) was 4/6 in 14, 5/6 in 11, and 6/6 in 2. Preparative regimens were ATG plus Cy/TBI in 14, Busulfan/cyclophosphamide in 3 or high dose BCNU-based in 10. GVHD prophylaxis consisted of tacrolimus (Day −2 to Day + 100) and steroids (D + 7 to day +80). Median cell doses infused were: nucleated cells: 1.47 x 107/kg and CD34: 0.48 x 105/kg; 22 (82%) received a nucleated cell dose < 2 x 107/kg. Median post-thaw cell recovery and viability were 97% and 97.5% respectively. Survivals at 100 days and 1 year were 76% (95% CI = 59 – 93)and 44 % (95% CI = 22 – 67) respectively. Median nucleated cell dose infused for the 1+ year survivors was 1.32 x 107/kg with all but one transplanted with < 2 x 107 cells/kg. There were 4 early deaths, early on in the trial at day +5, +13, +17 and +22, all in patients with refractory disease, due to sepsis. The median time to neutrophil engraftment (> 500/μl) was 19 days (range = 11–38 days) and time to platelet engraftment (> 20,000/μl) was 45 days (18–114+); however 2 patients died at day + 33 (VOD) and +114 (fungal pneumonia complicating refractory acute GVHD) without platelet recovery. Acute GVHD was seen in 56% (30% grade III/IV); chronic GVHD was seen in 57%. Within the limited cell dose range used, increasing nucleated cell and CD34 doses, as well as HLA match and disease stage were not predictive of survival or ANC engraftment in univariate analyses. In summary, our survivals are similar to those seen when blood, marrow or UCB stem cells with higher minimum cell dose thresholds are used as the transplant source in similar patients. Using a non-wash post-thaw procedure for our 27 transplants, few viable cells are lost allowing successful UCB transplantation at nucleated cell doses < 2 x 107/kg in adults who do not have a living HLA-matched related or unrelated donor and who otherwise have no option for potentially curative therapy.

6671 Background: To evaluate all patients with relapsed or refractory HD who underwent autologous transplants with either chemotherapy or total body irradiation (TBI) based preparative regimens to ...

Non-myeloablative allogeneic SCT is associated with AGVHD rates similar to conventional allografting. Animal models have consistently shown engraftment across MHC barriers when anti-T cell antibodies are combined with low doses of thymic irradiation or TBI. In December 2001, we initiated a prospective study evaluating a novel conditioning regimen for allogeneic SCT, combining Thymoglobulin 2.5 mg/kg/day given from day -4 to d -1 with 2-Gy TBI on d 0, followed by G-CSF mobilized hematopoeitic stem cells from matched sibling (MSD) or unrelated donors (URD). GVHD prophylaxis consisted of tacrolimus (d-4 to 30, tapered thereafter) and methotrexate (5mg/m2; d 1, 3 & 6). Sixteen patients (7 female) have been transplanted; 5 each with MM & NHL, 3 with CLL/SLL, 1 each with WM/MDS, CMPD & MDS-AML. A median of 2 prior therapies had been given (range 1–5; 7 patients had prior autografts); 3 patients were in CR, 8 had persistent disease and 5 were in untreated relapse at transplant. Median age was 57 years (range 70-43); 11 received grafts from MSD and 5 from URD (3 BMT). Median CD34+ cell dose infused was 5x106 /KG and CD3+ cell dose 3.4x108 /KG. The regimen was well tolerated with only 5 patients developing reversible grade II-III non-hematopoeitic toxicities in the peritransplant period. Despite 14 patients having major or minor (8) ABO incompatibility, only one patient developed allo-immune hemolysis requiring blood transfusions. Fifteen patients (93%) had hematopoeitic reconstitution by d30 with a median 94% (range 53–100) donor derived hematopoiesis by PCR for STR loci in blood; 95% at d60 (68–100; n=13), 95% at d90 (25–100; n=13) and 95% around d180 (1–100; n=11). WBC subset chimerism analysis in the first 3 months showed neutrophils (96, 95, 98 % donor derived) correlating with monocytes (95, 96, 100); total T cells (85, 86, 71) matched helper T cells (93, 86, 85) and cytotoxic T cells (82, 83, 80). The lower proportion of donor derived lymphocytes was reflective of poor lymphoid recovery related to the ATG based conditioning, with median absolute lymphocyte count at 3 months being 500/μL (100-900). As of August 2004, with a median follow-up of 18 mo (1–31 mo), 12/16 (75%) patients are alive; 38% are event-free (DLI, relapse or death). Day-100 and 1-year survival are 86 & 76% respectively. 10/12 (83%) surviving patients are without disease progression (7 in CR). These patients are 92–100% donor chimeric in blood (5 URD: 4 with prior autografts, 5 MSD: 2 with autografts). Despite withdrawal of immunosuppression by d100 in 11/13 evaluable patients only two patients (12%) receiving URD-PBSCT developed GII-III AGVHD (steroid responsive). Limited chronic GVHD developed in 4 patients undergoing URD-SCT. Three patients (19%; all gender matched MSD) developed graft rejection in the context of relapsing disease; 4 have died with disease progression. Nine patients (all MSD) received donor cell reinfusion (4 with reconditioning) at median d 121 (66–217); 4 for mixed chimerism alone and 5 with persistent disease. Five patients had increased donor chimerism following DLI. In conclusion, in selected patients this approach leads to rapid donor engraftment with minimal acute toxicities and GVHD despite early withdrawal of immunosuppression, especially in patients with a prior autograft or in those being transplanted using an URD.

Background: Patients with AML-M2 with t (8;21) generally have a good prognosis. However, the subset who have CD56 expression on their leukemic cells have poor prognosis, with frequent extramedullary involvement, short initial remissions, and high mortality. To date, little is known about the outcomes after allogeneic transplantation for patients with these unique characteristics. Methods: The Loyola transplant registry was searched for patients who underwent allogeneic transplantation at Loyola University Chicago Medical Center, Illinois during the period between June, 1998 and May, 2004 with these features. Patients were included in the analysis if their bone marrow examination at presentation met the FAB criteria for AML-M2; t (8;21) (q22;q22) was present by conventional karyotyping or by fluorescence in-situ hybridization (FISH); and CD56 expression was demonstrated by flow cytometric analysis of the leukemic blasts. Results: Five patients were identified; median age was 40 years (range 26–57 years); three were male. Median time from diagnosis until transplant was 12 months (range 3–93 months). Two patients had extramedullary diseases manifested by paraspinal and orbital granulocytic sarcoma at presentation or at relapse. One patient had 9q- in addition to the t (8;21). Patients had received a median of three prior therapy regimens (range 1–10) before transplant, including one patient who underwent high-dose chemotherapy and autologous stem cell transplant. Despite this, 4/5 patients had relapsed or refractory disease at transplant. Preparative regimens were total body irradiation 12Gy plus cyclophosphamide 120mg/kg in four patients and IV busulfan 14mg/kg plus cyclophosphamide 120 mg/kg in one; graft versus host disease (GVHD) prophylaxis was with tacrolimus and methotrexate. Three patients received grafts from matched unrelated donors; the rest from siblings. Three patients received bone marrow ranging from 2.0–4.4 x108/kg WBC and two received peripheral stem cells 4.0–6.07 x106/kg CD34+. The median time to neutrophil engraftment (the first of three consecutive days with absolute neutrophil count above 500/ml) was 14 days (range 12–17). The median time to platelet engraftment (the first of seven days with platelet count above 20,000/ml without transfusion) was 15 days (range 11–29). At day 100, all assessable patients (N=4) were in remission by bone marrow morphology with undetectable t (8;21) by FISH. As of August 2004, three patients survive at a median follow-up of 21 months (range 2–74 months); all remain in complete remission. Grade IV GVHD of skin occurred in one patient and grade II GI GVHD occurred in two. One patient, who received ten chemotherapy regimens over a 93-month period before transplant, died from pneumonia and venoocclusive disease of the liver; the other died from aspergillosis. Conclusions: Long-term disease free survival is possible with allogeneic transplant among patients with AML-M2 with t (8;21) and CD56 expression despite relapsed or refractory diseases. Clinicians should consider allografts, even from unrelated donors, early in the course of the disease to avoid the likely relapses after conventional therapy and to reduce the morbidity and mortality often seen in heavily pre-treated patients.

Introduction Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), is a rare and potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT). Severe cases, historically defined by multi-organ dysfunction (MOD), may be associated with mortality rates of >80%. There is no FDA-approved treatment for VOD/SOS. Defibrotide (DF) has a proposed mechanism of action that includes stabilization of endothelial cells and restoration of thrombo-fibrinolytic balance. Earlier analyses of a pivotal phase 3 trial of DF in VOD/SOS plus MOD (Richardson et al. Blood. 2009;114:Abstract 654) underpinned approval of DF in the EU to treat severe hepatic VOD/SOS after HSCT. Additional data were obtained at the request of US health authorities. Here we present the final analysis: day +100 survival (primary endpoint) and complete response (CR; secondary). Methods This was a multicenter, open-label, phase 3 historical control (HC) study assessing DF. Eligible patients met Baltimore VOD/SOS criteria (total bilirubin ≥2.0 mg/dL with ≥2 of: hepatomegaly, ascites, or 5% weight gain) by day +21 post-HSCT, plus MOD (renal [trebling of creatinine levels, reduced creatinine clearance, or dialysis] and/or pulmonary [oxygen saturation ≤90%, need for oxygen supplementation/ventilator dependence]) by day +28 post-HSCT. Exclusion criteria included severe graft-versus-host disease (GvHD) of liver or gut, clinically significant bleeding, or need for ≥2 pressors. HC patients were reviewed for inclusion/exclusion criteria in a sequential review of medical charts starting 6 months prior to use of DF at each site; a blinded medical review committee made the final determination of HCs unequivocally meeting criteria for VOD/SOS with MOD. DF dose was 25 mg/kg/d in 4 divided 2-hour IV infusions q6h; recommended treatment duration was ≥21 days. Primary endpoint was day +100 survival. CR by day +100 was a secondary endpoint. Treatment difference in survival and CR rates and their 95% confidence intervals were estimated using propensity-stratified and weighted (Koch-adjusted) estimates of differences in proportions that account for baseline prognostic factors of survival (ie, ventilator and/or dialysis dependency at entry, age ≤/>16 years, transplant type, and prior HSCT). Analyses included patients treated with DF and HCs. Results There were 102 patients in the DF group and 32 cases selected as HCs. Baseline characteristics were similar in the DF and HC groups: mean age (26 and 25 years; 43% and 44% ≤16 years), allogeneic graft (88% and 84%), prior HSCT (13% and 9%), ventilator- and/or dialysis-dependent at study entry (33% and 22%), myeloablative conditioning (87% and 94%), and the most common underlying diseases (acute leukemias: 45% and 47%), respectively. In the DF-treated group, common GvHD medications included tacrolimus (49%), methotrexate (41%), and cyclosporine (38%); in the HC group, common medications were cyclosporine (72%) and methotrexate (63%). Survival at day +100 in the DF and HC groups was 38% and 25%, respectively. The propensity-stratified difference in survival was 23.0% (95.1% CI, 5.2-40.8, P = .0109). Respective observed CR rates by day +100 were 25.5% and 12.5%, and the propensity-stratified difference in CR was 19.0% (95.1% CI, 3.5-34.6, P = .0160). Comparing the earlier EU and final analyses, the survival rates at day +100 in each group did not vary; however, the propensity adjusted final analysis provided a different level of statistical significance. Day +100 CR rates in the original analysis were slightly lower in both arms at 24% and 9% due to increased data capture to investigate CR; the P value was essentially unchanged. For the DF group, 45% had an adverse event (AE) at least possibly related to study drug, and 21% had a serious AE at least possibly related to study drug. In this very sick population, percentages of patients with ≥1 AE leading to death were similar between DF and HC patients (64% and 69%), as were hemorrhagic AEs (64%, 75%) and hypotension (39%, 50%). Conclusions Based on observed study data and using a propensity-adjusted rate difference estimator, patients treated with DF had a 23% reduction in risk of death by day +100 and 19% improvement in CR rate. Overall incidence of hemorrhage and fatal AEs were similar between groups with AEs consistent with those expected in this critically ill population. Support: Jazz Pharmaceuticals. Disclosures Richardson: Novartis: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Gentium S.p.A.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium Takeda: Membership on an entity's Board of Directors or advisory committees. Off Label Use: Marizomib, pmalidomide, and low dose dexamethasone in RR MM. Defibrotide is an investigational treatment for hepatic veno-occlusive disease/sinusoidal obstruction syndrome in the United States. . Kernan:Gentium S.p.A.: Research Funding. Grupp:Novartis: Consultancy, Research Funding. Guinan:Gentium SpA/Jazz Pharmaceuticals: Other: My institution received fees for research.. Martin:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Gentium SpA/Jazz Pharmaceuticals: Research Funding. Steinbach:Gentium SpA/Jazz Pharmaceuticals: Research Funding. Krishnan:Celgene: Consultancy, Speakers Bureau; BMS: Consultancy; Janssen: Consultancy; Onyx: Speakers Bureau; Jazz: Consultancy; Millenium: Speakers Bureau. Giralt:SANOFI: Consultancy, Honoraria, Research Funding; CELGENE: Consultancy, Honoraria, Research Funding; AMGEN: Consultancy, Research Funding; JAZZ: Consultancy, Honoraria, Research Funding, Speakers Bureau; TAKEDA: Consultancy, Honoraria, Research Funding. Rodriguez:Gentium SpA/Jazz Pharmaceuticals: Research Funding. Doyle:Gentium SpA/Jazz Pharmaceuticals: Research Funding. Antin:Gentium SpA/Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. D'Agostino:Gentium SpA/Jazz Pharmaceuticals: Consultancy. Massaro:Gentium SpA/Jazz Pharmaceuticals: Consultancy. Miloslavsky:Jazz Pharmaceuticals: Employment, Equity Ownership. Hume:Jazz Pharmaceuticals: Employment, Equity Ownership. Iacobelli:Gentium SpA: Employment. Nejadnik:Jazz Pharmaceuticals: Employment, Equity Ownership. Hannah:Gentium SpA: Other: Personal fees during conduct of the study.. Soiffer:Gentium SpA/Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.