ALBERT

Description: Abstract 1224 Poster Board I-246 Multiple myeloma (MM), is a monoclonal plasma cells disorder that constitutes 10% of all hematologic malignancies. Patients with a good performance status are usually offered high-dose therapy (HDT) followed by autologous stem-cell transplantation (ASCT). HDT/ASCT is associated with complete response (CR) rates of up to 40%. Although a significant proportion of patients have a durable response after HDT/ASCT, others relapse relatively quickly and do not appear to benefit from the procedure, which may impact the overall survival (OS) of these patients. We attempt here to define the role of infusing mobilized myeloma cells on the survival of patients undergoing ASCT. Methods After obtaining an Institutional Review Board approval, we conducted a retrospective analysis on MM patients undergoing ASCT at our center. Data of disease status, graft characteristics, and outcome were collected. As part of the flow panel used to assess the mobilized ASC, monoclonal myeloma cells were identified by gating on a population of cells that express high levels of CD38 but do not stain or weakly with CD45 (CD38+/CD45−). OS was calculated from the date of ASCT to the time of death or last contact. Survival analysis was performed using the method of Kaplan and Meier (KP). Univariate and multivariate analysis was performed using the Cox proportional hazards model. Results 349 patients underwent ASCT between January 1999 and April 2008. Complete data on autograft characteristics were available on 303 patients. The mobilization regimen was Cyclophosphamide and GCSF for the majority of the patients and GCSF for the more recent transplants. Melphalan at 200 mg/m2 was give 18 hours prior ASC infusion. In 199 patients there was no CD38+/CD45- cells detected. Among the 104 patients with evidence of CD38+/CD45- cells the range was 0.1-10.2 ×10 6 cells/kg and there was no difference in survival in this patient group compared to the group without evidence of contaminating myeloma cells (p= 0.54). Continuous variable analysis also did not reveal any relationship between the dose of CD38+/CD45- cells and survival (p=0.84). There may be a survival advantage after 40 moths for those receiving CD38+/CD45- cells, however the scientific rational is not well understood. Neither B2 microglobulin nor the numbers of plasma cells in the bone marrow were relevant in multivariate analysis (p= 0.42 and 0.13, respectively). Conclusion The presence of myeloma cells in the autograft does not appear to influence overall survival and the inclusion of CD45 and CD38 flow cytometric analysis of mobilized stem cells may not be necessary. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Cyclophosphamide/Fludarabine (Cy/Flu) nonmyeloablative conditioning for the treatment of acute myeloid leukemia (AML) in remission and myelodysplastic syndrome (MDS) permits engraftment with minimal tissue injury. Unrelated donor (URD) recipients experience rapid neutrophil engraftment, quicker rates to full donor T cell and peripheral blood mononuclear cell (PBMC) chimerism and significantly more effective disease control. Following allogeneic PBMC infusion on day 0, peripheral blood leukocyte counts on day (+) 1 are uniformly less 〈 200/mm3. Mixed chimeric, predominately donor T and NK lymphocytes are detectable on day (+) 6-8 prior to neutrophil engraftment. The lack of respiratory symptoms or splenic enlargement post-infusion suggested that cells may be detectable in the marrow at a much earlier time point post-transplant than is classically recognized after myeloablative allotransplant. We hypothesized that mature lymphocytes would be detectable in a cellular marrow environment by day (+) 8. To begin to test this hypothesis, we collected marrow between day (+) 7-9 (avoiding weekends) from 6 consenting participants with AML, MDS or chronic lymphocytic leukemia (CLL) who participated in a single institution, phase II clinical trial at Indiana University and the IU Melvin and Bren Simon Cancer Center. Methods: Marrow aspirate H and E stains, biopsies, and flow cytometric analyses (including CD2, CD3, CD56 and CD19) were obtained pre-transplant and on day (+) 7-9 following PBMC infusion in the setting of minimal intensity cyclophosphamide/fludarabine conditioning. PMBC chimerism was analyzed on day (+) 7-9. Clinical characteristics and peripheral blood cell counts were recorded. Results: Three patients had AML or MDS and 3 patients had CLL. All patients achieved full engraftment. In the AML/MDS subgroup day (+) 7-9 cellularity ranged from less than 5 to 70% with PBMC chimerism from 39.2 to 93.4% donor. In the CLL subgroup day (+) 7-9 cellularity ranged from 50 to 70% with PBMC chimerism from 0.9 to 5.6% donor. Baseline cellularity, corresponding peripheral cell counts, and marrow flow cytometric analyses from day (+) 7-9 are included in Table 1. Conclusion: Cy/Flu conditioning appears to be associated with early marrow cellularity at a time when peripheral blood chimerism is mixed. Day (+) 7-9 marrow examinations after Cy/Flu are generally quite cellular. Patients with AML/MDS and CLL appear to differ substantially in histological appearance, cell differentials and flow cytometric analyses. This suggests a unique engraftment kinetic that has yet to be appreciated and may be a useful platform for the study of cellular immune anti-cancer activity. Abstract 5851 Table 1 Disease Disease state Baseline cellularity Cellularity Day 7-9 WBC Day 7-9 BM CD2% BM CD3% BM CD19% BM CD56% PBMC chimerism (donor%) AML CR1 60 20 300 75 12 1 86 93.4 MDS active 70 70 900 6 17 3 17 39.2 Secondary AML active 80

Description: Introduction: Solid organ transplant recipients may receive calcineurin inhibitor therapy for years without lethal consequences. Severe aplastic anemia is a cellular immunological rejection of hematopoiesis that is amenable to calcineurin-based immunosuppressive therapy. A general guideline exists to discontinue immuno-suppressive therapy following a complete response or after 4-6 months, despite a relapse rate of 30-50% and often less than optimal choices for second-line treatment. Anecdotal conversions from late and/or lengthy partial remissions to complete responses prompted this single-institutional retrospective analysis of patients who received extended calcineurin inhibition (ECI). Objective: To assess outcomes of extended cyclosporine therapy (greater than six months) in patients with aplastic anemia with one of the following circumstances: (1) no matched sibling bone marrow donor; (2) relative contraindication to a second course of intensive immunosuppressive therapy; or, (3) not able to access a promising investigational protocol. Design, Setting, and Patients: Fifty patients with severe aplastic anemia treated at Indiana University Melvin and Bren Simon Cancer Center between 1994 and 2014 were screened. Treatment groups included extended calcineurin inhibitor (n=16) and matched sibling-donor (MRD) bone marrow transplantation (BMT, n=9). Patients who received matched unrelated (MUD) BMT or supportive care or those with missing data were excluded from analysis. Methods: After an initial treatment with anti-thymocyte globulin, glucocortico-steroids and calcineurin inhibition, patients who received MRD-BMT were compared to those who received ECI. Changes in hemoglobin (Hb), white blood cell (WBC) and platelet (Plt) counts were monitored and survival rates were analyzed for the two groups. Results: Median follow-up was 93 months. Table 1 describes improvements in cell counts with ECI and BMT over 6 months, 12 months, 24 months and 36 months. Survival for ECI group was 87.5% versus 88.9% for patients undergoing BMT, p-value 0.759. Conclusion: Patients with severe aplastic anemia who received MRD-BMT had a more rapid improvement in Hb, WBC and plt counts compared to those who received ECI. However, the difference of improvement in Hb, WBC and plt counts at 36 months and survival between these two groups was not statistically different. Table 1: ECI BMT p-value WBC Improvement at 6 months 1.1 k/cumm 1.5 k/cumm 0.629 WBC Improvement at 12 months 0.9 k/cumm 2.9 k/cumm 0.034 WBC Improvement at 24 months 1.0 k/cumm 3.0 k/cumm 0.023 WBC Improvement at 36 months 1.8 k/cumm 3.2 k/cumm 0.289 Hb Improvement at 6 months 2.0 GM/dl 5.8 GM/dl 0.002 Hb Improvement at 12 months 2.0 GM/dl 6.8 GM/dl 0.001 Hb Improvement at 24 months 2.5 GM/dl 7.1 GM/dl 0.012 Hb Improvement at 36 months 3.3 GM/dl 7.0 GM/dl 0.130 Plt improvement at 6 months 25 k/cumm 151 k/cumm 0.001 Plt improvement at 12 months 37 k/cumm 172 k/cumm 0.007 Plt improvement at 24 months 45 k/cumm 164 k/cumm 0.010 Plt improvement at 36 months 54 k/cumm 167 k/cumm 0.078 Disclosures No relevant conflicts of interest to declare.

Description: Abstract 2345 Background: Graft-vs-Host Disease (GvHD) remains a significant complication of allogeneic stem cell transplantation from matched unrelated donors (MUD). Compared to MTX-based regimen, Tacrolimus/Sirolimus was found to decrease the incidence of acute GvHD (Keil et al, Biol Blood Marrow Transplant. 2009;16(2):S319, and Cutler et al, Blood. 2007;109:3108–14), whereas, the incorporation of Antithymocyte globulin (ATG) into MTX-based regimen decreases the incidence of chronic GvHD (Bacigalupo et al, Biol Blood Marrow Transplant. 2002;8(12):656–61). There are no reports of the outcome of the combination of Tacrolimus/Sirolimus and ATG. We compared the results of MUD using tacrolimus and sirolimus (day-3 to day +180) combined with ATG (2.5 mg/kg day −3,−2, and −1) (TSA) prophylaxis in consecutive patients treated at our institution from September 2006 to March 2009, with those using MTX-based prophylaxis without ATG in consecutive patients treated from January 2000 to August 2006. The primary endpoints were incidence of acute and chronic GvHD, lethal infectious complications, relapse, and survival. Result: Between 1/2000 and 3/2009, 71 MUD stem cell transplants were performed. 27 patients received TSA regimen as GvHD prophylaxis and 44 patients received traditional MTX-based prophylaxis without ATG. More patients in the TSA group received PBSC compared to the MTX group (63% vs. 36%; P=0.029), otherwise both groups were matched for age, sex, underline malignancies, disease risk per ASBMT criteria, degree of HLA-match, CMV serology, and conditioning regimens. The cumulative incidence of Grade II-IV classic acute GvHD at day +100 was significantly lower in the TSA group compared to control group (11.7% vs. 41.6%; Gray's test P =0.008). However, the cumulative incidence of aGvHD at day +365 was not statistically significant between both groups (33.1% vs. 44.4%; Gray's test P=0.154); this was due to an increase rate of delayed-onset aGvHD in TSA group (18.5%) compared to MTX group (2.3%). The rate of limited cGvHD was 7.1% vs. 30% in the TSA group and MTX group, respectively (Fisher's P= 0.12). 23% of patients surviving beyond day +100 in MTX group developed extensive/overlap cGvHD, whereas, there were no cases in the TSA group. The rate of CMV infection in patients not receiving corticosteroid treatment for GVHD was higher in the TSA group, although not statistically significant (36.8% vs. 16%, P=0.27). The rate of invasive fungal infections was similar (10.7% vs. 11.8%). The cumulative incidence of relapse at 2 years was 38.5% vs. 22.8% in the TSA and MTX groups, respectively (Gray's test P=0.18). Non-relapse mortality at 2 years was similar in both groups (42% vs. 48%; Grays's test P=0.8). Day +100 mortality was 14.4% and 27.3% in TSA and MTX group respectively. The median survivals were 251 days (95% CI, 170–332) vs. 349 days (95% CI, 236–462) for TSA and MTX groups, respectively. The 1- and 2-year overall survival were 42.3% and 31.7% for TSA group vs. 47.7% and 34.1% for MTX group, respectively (P=0.704). While the mortality rate from bacterial sepsis were equivalent, more patients in the TSA group who were not receiving corticosteroid treatment for aGvHD died from viral and fungal infection (14.3% vs. 0% at 12 months, Fisher's P=0.014). Summary: This is the first report of the combination of TSA for GvHD prophylaxis in MUD transplants. This regimen resulted in a significant decrease in classic aGvHD as previously reported for combination of Tacrolimus/Sirolimus, and decrease in incidence of cGvHD as reported previously in the studies incorporated ATG in MTX-based regimens. Hence, this did not translate into benefit in overall survival due to an increased rate of relapse and lethal viral and fungal infections with TSA regimen. Our study does not demonstrate an appreciable benefit for the addition of ATG, at the dose used, to sirolimus and tacrolimus for GvHD prophylaxis. Further studies directed at optimizing the dose of ATG to lower the rate of lethal infections may result in an overall benefit. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 3402 Poster Board III-290 Clofarabine (Clo) is a second-generation purine nucleoside antimetabolite, which unlike other purine nucleoside analogues, has a higher resistance to the action of adenosine deaminase and improved affinity for the activating phosphorylating enzyme deoxycytidine kinase, contributing to more potent activity against neoplastic cells. Recently, Clo was shown to have significant single agent activity in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL), but resulted in prolonged myelosuppression (Blum et al. Leuk Lymphoma 2009, 50: 349-56), suggesting that it may be a useful agent in high-dose therapy with stem cell support. We conducted a phase I trial to determine the maximum tolerated dose (MTD) of Clo in combination with high-dose Etoposide and Cyclophosphamide followed by autologous stem cell rescue in patients with relapsed or refractory NHL. Patients received Clo at 30-70 mg/m2/day on days -6 to -2 in successive cohorts, in combination with Etoposide 60 mg/kg day -8, and Cyclophosphamide 100 mg/kg days -6. G-CSF-mobilized autologous PBSC were infused on day 0. Patients were eligible if aged 18-70 years, had primary refractory or relapsed and refractory diffuse large cell lymphoma (DLCL), mantle cell lymphoma (MCL), or follicular lymphoma (FL), had Karnofsky performance status ≥70%, and adequate organ function. Toxicity was scored using the Common Terminology Criteria for Adverse events, version 3.0. Dose limiting toxicity (DLT) was defined as any grade 3-4 non-hematologic toxicity that did not resolve to grade 2 or less by day 30. Fifteen patients were treated at 5 Clo dose levels, 30 (n=3), 40 (n=3), 50 (n=3), 60 (n=3), and 70 (n=3) mg/m2/day. Seven males and 8 females of median age 55 (32-67) years, with DLCL (n=8), MCL (n=3), and FL (n=4) were treated. At transplant, NHL was primary refractory (n=2), in first resistant relapse (n=7), and in second or third relapsed (n=6). Median number of lines of treatment failed before transplant was 3 (2-6). Median CD34+ count infused was 1.9 (0.9-3.7) x106/kg. The median time to neutrophils 〉0.5×109/l was 10 (9-13) days, and to platelets 〉20×109/l was 16 (10-33) days. Only 1 patient treated at the 30 mg/m2 dose level and infused with 0.9×106 CD34+cell/kg failed to achieve platelets 〉 20×109/l. No DLT was observed. Grades 3-4 non-hematological toxicity included neutropenic fever (n=9), vomiting (n=2), diarrhea (n=2), mucositis (n=1), and hemorrhagic cystitis (n=1); all toxicities resolved by day 30. Only grade 1-2 elevation of transaminases (AST/ALT) occurred; 2 of 3 patients at 30 mg/m2, 3 of 3 at 40 mg/m2, 2 of 3 at 50 mg/m2, 1 of 3 at 60 mg/m2, 2 of 3 patients at 70 mg/m2 dose levels. AST/ALT peaked at day -1 to +1 and returned to baseline in all patients by day 10, with no long-term sequelae. There was no correlation between clofarabine dose and peak AST/ALT. No treatment related deaths occurred. Fourteen of the 15 patients (93%) achieved a response; complete response (CR) or CR unconfirmed (CRu) in 12, and partial response in 2 patients. Only patient treated at the 30 mg/m2 dose level failed to respond. Four patients had progression of disease or relapse at 30 to 135 days after transplant. With a median follow-up of 199 days to date, the 1-year progression-free survival is 72% ± 12%, and the 1-year overall survival is 93% ± 6%. Clo at doses as high as 70 mg/m2/day x 5 days in combination with high-dose Etoposide (60 mg/kg) and Cyclophosphamide (100 mg/kg) are well tolerated, and showed promising efficacy in very-high risk NHL patients. The MTD has not been reached. We recommend the dose of Clo 70 mg/m2/day x 5 days in combination with high-dose Etoposide and Cyclophosphamide for Phase II testing as a preparative regimen in NHL patients undergoing autologous PBSC transplantation. Disclosures: Off Label Use: Clofarabine for high-dose chemotherapy and autologous stem cell transplantation.

Description: Abstract 198 Fludarabine in combination high-dose busulfan (Bu) is an effective myeloablative preparative regimen for allogeneic stem cell transplantation. At doses used, however, fludarabine has only modest anti-leukemic activity. Clofarabine (Clo) is a second-generation purine nucleoside antimetabolite with significant single agent activity in patients with AML and ALL. The novel combination of Clo with Bu may provide improved disease activity safely. Therefore, we conducted a phase I trial to determine the maximum tolerated dose (MTD) of Clo in combination with Bu in patients with high-risk acute leukemia. Patients received i.v. Bu (Busulfex) 0.8 mg/kg q 6 hrs on days −6 to −3 and Clo at 30–60 mg/m2/day on days −6 to −2 in successive cohorts. Stem cells were infused day 0. GvHD prophylaxis included sirolimus plus tacrolimus starting day −2 to day 100, tapering to day 180. Patients were eligible if they were 18–60 years, had primary refractory or relapsed and refractory AML or ALL, or were in CR2 or higher, had Karnofsky performance status ≥70%, and adequate organ function. Donors were HLA-matched related (5/6 or 6/6 antigen-matched) or unrelated (10/10 allele-matched). Toxicity was scored using the Common Terminology Criteria for Adverse events, version 3.0. Dose limiting toxicity (DLT) was defined as any grade 3–4 non-hematologic toxicity that did not resolve to grade 2 or less by day 30. A total of 15 patients were treated at 4 Clo dose levels, 30 (n=3), 40 (n=3), 50 (n=3), and 60 mg/m2 (n=6). Seven males and 8 females of median age 48 (30–58) years, with AML (n=13) or ALL (n=2) were treated. At transplant, leukemia was relapsed and refractory (n=8), primary refractory (n=6), or in CR2 (n=1). Median number of lines of treatment failed before transplant was 2 (1–3). Median marrow blasts at transplant was 12% (3%–83%). Hematopoietic cell transplants were from related (n=9) and unrelated (n=6) donors. All patients engrafted. Median time to neutrophils 〉0.5×109/l was 16 (12–20) days, and to platelets 〉20×109/l was 15 (10–42) days. One patient treated at the 30 mg/m2 dose level failed to achieve platelets 〉 20×109/l. No DLT was observed. Transient Grades 3–4 non-hematological toxicities were evenly distributed across all 4 dose levels, and included vomiting (n=3), mucositis (n=9), hand-foot syndrome (n=1), and elevation of AST/ALT (n=10). Grades 3–4 elevation of AST/ALT occurred in 2 of 3 patients treated at 30 mg/m2, 3 of 3 at 40 mg/m2, 2 of 3 at 50 mg/m2, and 3 of 6 patients at 60 mg/m2 dose levels. AST/ALT peaked at day −1 or 0 and returned to baseline in all patients by day 10, with no long-term sequelae. There was no correlation between Clo dose and peak AST/ALT. One patient developed acute renal failure at the 60 mg/m2 dose on day +12 in association with elevated tacrolimus levels, although the creatinine subsequently normalized. Two patients, both at the 30 mg/m2 dose, developed mild veno-occlusive disease of the liver which was self-limiting. One treatment-related death due to sepsis was observed at day +104 in a patient treated at the 30 mg/m2 dose. Thirteen of 15 patients were in CR by day 30; 2 patients, treated at 40 mg/m2 and 50 mg/m2, respectively, failed to achieve CR. Day 100 mortality was 0. With a median follow-up of 313 days, the 1-year relapse-free survival was 51% ± 15%, and the 1-year overall survival was 61% ± 14%. Clo at doses as high as 60 mg/m2/day × 5 days in combination with Bu 3.2 mg/kg/day × 4 days is well tolerated and demonstrates promising efficacy in a very-high risk acute leukemia population. The MTD has not been reached. We recommend Phase II testing of Clo 60 mg/m2/day × 5 days in combination with high-dose Bu as a myeloablative regimen for allogeneic stem cell transplantation in patients with acute leukemia. Disclosures: No relevant conflicts of interest to declare.

Description: Background: The optimal setting to treat AYA patients remains a complex decision involving access to different treatment regimens, clinical trial availability, and appropriate psychosocial support. There are data to support that AYA patients with acute lymphoblastic leukemia (ALL) have better outcomes and improved overall survival when treated on pediatric inspired treatment protocols. However, limited data exist for similar patients with AML. We, therefore, sought to assess the variation in outcomes between AML patients within the AYA population treated in our pediatric setting versus adult setting. Methods: A retrospective review of patients with newly diagnosed AML aged 17-25 years old (n=33) treated at either the Indiana University Simon Cancer Center (n=20) or Riley Hospital for Children at Indiana University Health (n=13) between 2006 and 2018 was completed. All patients in the adult setting received standard induction therapy with the 7+3 (standard-dose cytarabine, anthracycline) regimen, while patients in the pediatric setting received an ADE (daunorubicin, cytarabine, etoposide) backbone +/- investigational agents per clinical trial protocols. Data were analyzed with t-tests using IBM SPSS v25 software. This study was approved by the Indiana University Institutional Review Board. Results: Median age was 23 years in patients treated in the adult setting (range 19-25) compared with 17 years (range 17-20) in the pediatric setting. As per the most recent NCCN risk classification for AML, patients in the adult setting were classified as 55% poor risk, 35% intermediate risk, and 10% favorable risk; in the pediatric setting, risk classification was 15% poor risk, 62% intermediate risk, and 23% favorable risk. The incidence of FLT3 mutations was n=4 (20%) in the adult setting and none in the pediatric setting. Clinical trial enrollment was markedly lower in the adult setting with no patients enrolled compared with 54% (7/13) enrolled in the pediatric setting. Complete response (CR) was achieved in 85% of patients treated in the adult setting, but only 62% of patients treated in the pediatric setting. Relapse post induction was higher in the pediatric setting (n=6, 46%) compared to the adult setting (n=5, 40%), and median time to relapse was shorter in the pediatric setting (275 days vs. 344 days). During induction, no statistically significant differences in toxicities were found as measured by ICU interventions (dialysis, mechanical ventilation/NIPPV, and/or use of vasopressors) and identified infections (bacteremia, pneumonia, and/or clostridium difficile). Clostridium difficile infections were increased in the adult setting (15% vs. 0%), but identified bacteremia was higher in the pediatric setting (38% vs. 20%). The median time to allogeneic stem cell transplantation in the adult setting was 117.5 days compared to a median of 223 days seen in the pediatric setting. Incidence of relapse post stem cell transplantation was higher in the adult setting (36% vs. 17%). Proportion of overall survival was 50% (n=10) in the adult setting and 28% (n=8) in the pediatric setting. The highest mortality was seen in poor-risk patients (90%) in the adult setting and intermediate risk patients (62.5%) in the pediatric setting. A trend was seen towards improved overall survival in the adult setting with median overall survival of 739.5 days in the adult setting compared to 415 days in the pediatric setting (p=0.11). In both settings, patients that proceeded to stem cell transplantation had conferred survival benefit: median 1128 vs. 414.5 days in the adult setting and median 530.5 vs. 486.5 days in the pediatric setting. Conclusion: Despite having a higher risk population and lower clinical trial enrollment, we found a trend towards higher complete response rate after induction, reduced relapse rate after induction, shorter time to transplant, longer time to relapse post-transplant, improved survival in the transplant population, and improved median overall survival without a clear increase in toxicity in patients treated in our adult setting. This is in contrast to data in ALL, which suggests improved patient outcomes in AYA patients treated with pediatric based regimens. Our data is limited by a small sample size and a single institution experience. Larger, multicenter studies are needed to understand the optimal AML treatment strategy in the AYA population. Table. Table. Disclosures No relevant conflicts of interest to declare.

Description: The purpose of this study was to examine the efficacy of cyclosporine (CsA) alone versus CsA/mycophenolate mofetil (MMF) as GVHD prophylaxis in older patients who received a minimally-intensive allogeneic hematopoietic cell transplant (MIHCT) for the treatment of hematological malignancies (AML=26, MDS=15, NHL=8, CLL=5, MM=3, HD=4, CML=1, ALL=1). Patients (median age, 55 years; 41 males, 22 females) received HLA-matched related (n=33) or unrelated (n=30) peripheral blood hematopoietic cell infusions following immunosuppressive dosages of cyclophosphamide and fludarabine (Childs R, et al. Blood 94; 1999). The initial 28 consecutive patients received monitored CsA from day −1 through day +180 (if no GVHD). The next 35 subjects received CsA/MMF: CsA, day −1 through day +180 and MMF, 1000 mg twice daily, day +1 through day +60 (if no GVHD, then a taper). Patients were followed until death or at least 7 months. There were no differences between recipients of MRD and MUD transplants with respect to sex, age of the recipient, disease status, ABO matching, recipient CMV status or number of CMV-negative donor/recipient pairs. MUD donors were significantly younger and more likely to be CMV-negative. There was no difference in disease distribution between those who recieved CsA and those who recieved CsA/MMF prophylaxis. Follow-up ranged from 25–2241 days (median, 461 days for the CSA group; 449 days for the CSA/MMF group, 1290 days for survivors). All patients engrafted without growth factor support and no subjects experienced sinusoidal obstruction syndrome, mucositis or post-transplant lymphoproliferative disease. Thirty and 100-day transplant-related mortality for the cohort was 1.6% and 15.9% respectively. The incidence of Grade 2–4 aGVHD (n=63) was 49.2% (CsA, 57.1%, CsA/MMF, 42.9%, p=0.315). Grade 3 or 4 aGVHD occurred in 30% (CsA, 32.1%, CsA/MMF, 28.6%, p=0.788). Chronic extensive GVHD occurred in 53.8% (CsA, 61.5%, CsA/MMF, 46.2%, p=0.404) of at risk (survival greater than 100 days) recipients. The incidence of acute or chronic GVHD was not statistically different for MRD versus MUD recipients for either prophylaxis group (p=0.32 and 0.23, respectively). One-year, two-year and three-year overall Kaplan-Meier survival analyses were estimated to be 60.7%, 42.9% (CsA group) and 42.9%and 60%, 45.2% and 32.8% (CsA/MMF group, 0.708). Twenty-seven (42.9%) of the entire cohort are alive at a median of 1290 days post-transplant [CSA, 12/28, (42.9%); CsA/MMF, 15/35, (42.9%)]. Grade 3 or 4 aGVHD was associated with poor overall survival (p=0.0001) for the cohort. These findings provide evidence that MMF does not seem to provide substantial GVHD preventive or overall survival benefit when added to CsA after matched related/unrelated cyclophosphamide/fludarabine MIHCT in older patients with hematological malignancies.