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Purpose The major causes of mortality after allogeneic hematopoietic-cell transplantation (allo-HCT) are relapse, graft-versus-host disease (GVHD), and infection. We have reported previously that alterations in the intestinal flora are associated with GVHD, bacteremia, and reduced overall survival after allo-HCT. Because intestinal bacteria are potent modulators of systemic immune responses, including antitumor effects, we hypothesized that components of the intestinal flora could be associated with relapse after allo-HCT. Methods The intestinal microbiota of 541 patients admitted for allo-HCT was profiled by means of 16S ribosomal sequencing of prospectively collected stool samples. We examined the relationship between abundance of microbiota species or groups of related species and relapse/progression of disease during 2 years of follow-up time after allo-HCT by using cause-specific proportional hazards in a retrospective discovery-validation cohort study. Results Higher abundance of a bacterial group composed mostly of Eubacterium limosum in the validation set was associated with a decreased risk of relapse/progression of disease (hazard ratio [HR], 0.82 per 10-fold increase in abundance; 95% CI, 0.71 to 0.95; P = .009). When the patients were categorized according to presence or absence of this bacterial group, presence also was associated with less relapse/progression of disease (HR, 0.52; 95% CI, 0.31 to 0.87; P = .01). The 2-year cumulative incidences of relapse/progression among patients with and without this group of bacteria were 19.8% and 33.8%, respectively. These associations remained significant in multivariable models and were strongest among recipients of T-cell–replete allografts. Conclusion We found associations between the abundance of a group of bacteria in the intestinal flora and relapse/progression of disease after allo-HCT. These might serve as potential biomarkers or therapeutic targets to prevent relapse and improve survival after allo-HCT.

e19520 Background: Scoring systems, such as DIPSS-plus, prognosticate outcomes of myelofibrosis (MF) at diagnosis and at transplant. In this study, we evaluated the impact of individual components of these scoring systems, along with other factors previously reported to significantly prognosticate transplant outcomes in patients with MF. Methods: We identified 65 consecutive patients conditioned uniformly with Fludarabine(40 mg/m2X4days)/Busulfan(AUC-4000X4days) and ATG(MUD), tacroliumus and methotrexate for GVHD prophylaxis for allo-SCT during 2007-2019 at MD Anderson Cancer Center, USA. Associations between factors of interest and overall survival(OS), cumulative-incidence-of-relapse(relapse) and non-relapse mortality(NRM) were evaluated. Results: At transpant, median age was 61(range = 27-73) years; 42% were transfusion-dependent, 31% had secondary MF and 53% patients were intermediate2 and 42% were high-risk by DIPSS-plus. Forty percent of the 35 patients who had 28-gene panel tested had atleast one high-molecular-risk mutation, per MIPSS. Median follow-up for survivors was 35.6 months(range = 0.5-123). One-year and 5-year rates for OS were 78% and 51%, for relapse were 21% and 30%, and for NRM were 16% and 28%, respectively. Our multivariate analysis shows the following significant prognostic factors: HCT-CI > 3[hazard ratio(95% CI):5.63(1.48-21.27)p = 0.011], peripheral-blood blasts≥5%[5.98(1.33-26.89)p = 0.020] and prior splenectomy[6.41(1.83-22.47)p = 0.004] were associated with worse OS. Matched-unrelated donor[4.07 (1.38-12.08)p = 0.011) and mismatched-unrelated donor[7.36 (1.36-39.83)p = 0.021] versus matched-related donor as well as peripheral blasts≥5%[4.10(1.00-16.83)p = 0.05] were associated with worse NRM. Diagnosis to transplant duration > 12months[5.81(1.33-25.420)p = 0.020] was associated with higher relapse. Presence of 2 or more poor-risk mutations [6.39(1.35-30.21)p = 0.019] predicted higher relapse on univariate analysis and was not included in multivariate analysis(as data was available in 35 patients only). Conclusions: Of the IPSS-components used at diagnosis, only peripheral-blood blasts(at threshold ≥5%) was associated with worse outcome(OS and NRM). Unrelated-donor source was associated with higher NRM. Diagnosis to transplant duration > 12months predicted higher relapse. The effect of mutations needs to be validated in a bigger study.

7007 Background: Myeloablative stem cell transplants have a lower rate of relapse than reduced intensity regimens. Timed sequential busulfan (TSB) with fludarabine (Flu) is a promising myeloablative regimen for patients undergoing matched sibling (MSD) or unrelated (MUD) donor transplantation (HCT) with low non-relapse mortality (NRM) (Popat et al Lancet Haematology 2018), but was not tested in haploidentical (haplo). Also, whether this approach can be used with post-transplant cyclophosphamide (PTCy) in MSD, MUD and haplo HCT is unknown. To address these issues, we conducted a prospective phase II study. Methods: Patients with hematological malignancies with MSD, MUD or haplo donor were eligible. They received fixed doses of Busulfan(BU) 80mg/m2 either on day -13 and -12 (n=45) or on -20 and -13 (n=10). Then, Flu 40mg/m2 was given on day -6 to -2 followed by Bu dosed to achieve target area under the curve (AUC) of 20,000 umol/min for the whole course based on pharmacokinetic studies. Thiotepa 5mg/kg was given on day -7 to haplo group. GVHD prophylaxis was PTCy 50mg/kg on day 3 and 4 and tacrolimus. Haplo and later MUD recipients also received mycophenolate mofetil. Results: 55 patients with a median age of 47 (15-65) years were enrolled. 30 patients had AML or MDS, 9 CML or MPD, 5 lymphoma, 5 myeloma and 6 ALL. About half had haplo 26 (47%); others had MUD 18 (33%) or MSD 11(20%). Disease risk index was high in 18 (32%), intermediate in 32 (58%), and low in 5 (9%) patients. Comorbidity score was ≥3 in 22 (40%) patients. With a median follow up of 17 months (5-28), 1-year OS, PFS, NRM and relapse rates were 71% (60-84%), 63% (51-77%), 20% (9-31%), and 17% (7-27%), respectively [Table]. There were no graft failures. Day 100 grade II-IV and III-IV acute GVHD rates were 38% (25-51%) and 9% (95% CI 1-17%), respectively; 1-year chronic GVHD and extensive chronic GVHD rates were 10% (2-28%) and 8% (0-15%), respectively. 1-year OS in MSD, MUD and haplo groups were 91% (75-100%), 72% (54-96%), and 62% (45-83%) respectively (P=0.11). Conclusions: Myeloablative TSB with PTCy is feasible in MSD, MUD and haplo HCT. It lowers the incidence of severe acute and chronic GVHD without apparent increase in relapse. Clinical trial information: NCT02861417. [Table: see text]

7016 Background: Molecular data and minimal residual disease (MRD) have been shown to influence outcomes in AML patients undergoing allogeneic hematopoietic cell transplantation (AHCT). Here we developed and validated a novel AML-specific Disease Risk Group (AML-DRG) and revise our previously developed Hematopoietic Cell Transplant - Composite Risk (HCT-CR) model by incorporating molecular data and MRD status before transplant to predict post-transplant outcomes of patients with AML. Methods: The study included 1414 consecutively treated adult AML patients, who received first AHCT between 1/2005-8/2018 at our institution. Patients were randomly assigned into a training (N = 944) and validation set (N = 470). To develop the AML-DRG model, the coefficient of all significant AML-related variables in multivariable Cox’s regression analysis (MVA) in a training dataset was converted into scores.The AML-DRG was the sum of scores from all significant covariates, while the AML-HCT-CR was the sum of disease-related factors assessed by the AML-DRG model with the addition of weighted scores from patient-related factors. Results: Based on results of MVA, the following scores were assigned to each AML-related variable; 1 point to secondary AML; 1 point to the 2017 ELN adverse risk; 2 points to CR with MRD positive/unknown; and 4 points to active disease at transplant. These were used to generate the AML-DRG (low-risk score 0-2; intermediate-risk score 3-4; and high-risk score > 4) with significantly different OS with HR of 2.02 (P < 0.001), and 3.85 (P < 0.001) for intermediate and high risk group compared with low risk group. By adding 1 point for patients > / = 60 years or HCT-CI > 3 to the AML-DRG, we created 4 risk groups of AML-HCT-CR (low-risk: score 0-2; intermediate-risk: score 3; high-risk: score 4 and very high-risk: score ≥5) with distinct survival outcomes. The AML-DRG and AML-HCT-CR model had C-index of 0.672 and 0.715, respectively which were better compared with DRI, ELN2017 and cytogenetic risk model. Conclusions: Prognostic models incorporating molecular data and MRD status before transplant allow better stratification and improved survival estimates of AML patients post-transplant.

Purpose Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after matched unrelated, related, or mismatched related donor hematopoietic stem-cell transplantation (HSCT). Improved GVHD prevention methods are needed. Pentostatin, an adenosine deaminase inhibitor, leads to lymphocyte depletion with low risk of myelosuppression. We hypothesized that addition of pentostatin to GVHD prophylaxis with tacrolimus and mini-methotrexate may improve outcomes, and we conducted a Bayesian adaptively randomized, controlled, dose-finding study, taking into account toxicity and efficacy. Patients and Methods Success was defined as the patient being alive, engrafted, in remission, without GVHD 100 days post-HSCT and no grade ≥ 3 GVHD at any time. Patients were randomly assigned to pentostatin doses of 0, 0.5, 1.0, 1.5, and 2.0 mg/m2 with drug administered on HSCT days 8, 15, 22, and 30. Eligible patients were recipients of mismatched related (n = 10) or unrelated (n = 137) donor HSCT. Results Median age was 47 years. Thirty-seven, 10, 29, 61, and 10 patients were assigned to the control and four treatment groups, respectively, with comparable baseline characteristics. Pentostatin doses of 1.0 and 1.5 mg/m2 had the highest success rates (69.0% and 70.5%) versus control (54.1%). The posterior probabilities that the success rates were greater with 1.5 mg/m2 or 1.0 mg/m2 versus control are 0.944 and 0.821, respectively. Hepatic aGVHD rates were 0%, 17.2%, and 11.1%, respectively, for 1.5 mg/m2, 1.0 mg/m2, and control groups. No grades 3 to 4 aGVHD occurred in 11 HLA-mismatched recipients in the 1.5 mg/m2 group. Conclusion Pentostatin increased the likelihood of success as defined here, and should be further investigated in larger randomized, confirmatory studies.

7046 Background: We previously reported 6% 100 day NRM with a MA fludarabine (Flu) and busulfan (Bu) in older patients with a median age of 60 years. MA dose of Bu in this timed sequential (TS) regimen was administered over a longer period of time. To assess its impact on survival, we compared the outcomes of older patients treated with the TS Bu (TS cohort) or the RIC Flu/Bu regimen, which is used as standard (ST) for older patients at our center (ST cohort). Methods: Patients in the TS cohort received IV Bu 80 mg/m2/d on day -13 and -12 and Flu 40 mg/m2/d followed by IV Bu on day -6 to -3, dose adjusted to achieve a total Bu course AUC of 20,000 μmol-min based on PK studies. Patients in the ST cohort received Flu 40 mg/m2day followed by IV Bu daily for 4 days (day -6 to -3) dosed to achieve AUC of 16,000 μmol-min. Patients with AML or MDS were eligible for the study if they had adequate organ function, had matched related or unrelated donor and were treated between Jan 2012 and Sept 2016. Results: 162 patients, 50 with MDS and 112 with AML, were included in this study. Patient characteristics including age, sex, disease status, cytogenetic risk group, donor type, graft source CMV status and comorbidity were well balanced and without any significant difference in the two cohorts. Median age was 66 and 65 years in ST and TS cohorts, respectively. Overall survival (OS) and progression free survival (PFS) were significantly better in the TS cohort (see Table). This was due to a reduction in the disease progression without any increase in the non-relapse mortality (NRM). After adjusting for other covariates, the multivariate analysis for PFS confirmed longer PFS with TS Bu regimen (HR: 0.36; P=0.003). The benefit was mainly seen in patients with a comorbidity score ≤ 3. Conclusions: The myeloablative timed sequential Bu regimen improves survival and appears promising in older patients with AML/MDS. Clinical trial information: NCT01572662. [Table: see text]

7551Background: Patients with relapsed MCL remain incurable, especially if their tumors have a Ki-67 > 30%. We analyzed the long-term survival outcomes of 75 recipients of alloSCT. Methods: Patient...

7008 Background: We report final results of a prospective phase II clinical trial of busulfan(bu) and fludarabine(flu) conditioning in patients with myelofibrosis(MF). After observing a higher rela...

7011 Background: We did a prospective study of busulfan (bu) and fludarabine (flu) conditioning in patients with myelofibrosis. After observing a high relapse rate in the initial cohort, we increased the intensity of conditioning regimen for subsequent patients, hypothesizing that increased dose intensity delivered with PK guidance will reduce relapse rate without increasing non relapse mortality (NRM), thereby improving overall outcome. Methods: Patients with intermediate or high risk MF were eligible if they had adequate organ function and at least 9/10 matched related or unrelated donor. Of the 46 consecutive patients, 15 (bu low group) received IV busulfan 130 mg/m2 x 2 (day -3,-2). Of the remaining 31 (bu high group), 27 received IV busulfan dose to a target daily AUC of 4000 μmol.min x 4 (day -5 to -2) and 4 patients received a fixed dose of 100 mg/m2 x 4 (days -5 to -2). All patients received fludarabine 40mg/m2x 4 (day -5 to -2). Results: 23 males and 23 females with a median age of 58 years (27-74) had intermediate (25) or high-risk (21) disease. Donors were matched sibs (19), matched unrelated (23), or mismatched unrelated (4). With a median follow-up of 2.1 years (range 0.1-6 years), 3-year overall survival(OS), event-free survival (EFS), cumulative incidence (CI) of non-relapse mortality (NRM), and CI of relapse were 69%, 50% , 13%, and 37%, respectively. Multivariate Cox regression analysis showed that Bu-high dose (HR 0.41; p=0.04) and peripheral blood CD 34 count (HR 1.7; p=0.03) were significantly associated with EFS, and high CD-34 count was significantly associated with OS (HR 1.87; p=0.04). Table shows details of 3-year outcomes of low-dose and high-dose group. All patients engrafted with a median time to neutrophil engraftment of 13 (0-27) days and a median time to platelet engraftment of 24 (0-268) days. Cumulative incidence (CI) of grade II-IV, grade III, IV acute GVHD, and Chronic GVHD were 22%, 5%, and 39%, respectively. Conclusions: Higher dose busulfan, delivered with pharmacokinetic dose adjustment, reduces relapse without increasing non-relapse mortality, resulting in better EFS in patients with MF. Clinical trial information: NCT00475020. [Table: see text]

e18511 Background: We previously reported the use of fludarabine, rituximab and cyclophosphamide as a nonmyeloablative conditioning for lymphomas (Khouri et al, Blood 2008;111:5530). Bendamustine i...

6565 Background: Despite the advent of novel agents, outcomes of TCL with conventional chemotherapy are poor. We have previously reported encouraging results with ASCT (Rodriguez J, J Clin Oncol, 2001). Herein, we report our long-term experience in 126 patients (pts). Methods: This is a retrospective analysis of TCL pts treated at our institution between 1986 and 2009. Median age was 49 years and 65% were males. Histologies included 1)peripheral t-cell lymphoma not otherwise specified (PTCL -NOS=42, 2) anaplastic large cell lymphoma (ALCL=47) of which 9 pts were ALK(+), 3) angioimmunoblastic (AILT=15), 4) NK cell lymphomas (N=6), Hepatosplenic TCL (HS-TCL=6), others (n=10). Results: At transplant, 33% were in first remission (CR1), 51% had chemosensitive relapse, 16 % had refractory disease. Most pts received BEAM or BEAM like (82%) conditioning. With a median follow-up of 39 months, overall survival (OS) and progression-free-survival (PFS) estimates were 39% (95% CI, 28-50), and 30%(95% CI 20-41). Treatm...

e19507 Background: Age at diagnosis is a poor prognostic factor for overall survival after standard therapy for HD. Whether older age is a prognostic factor for outcome after autologous transplantation is not known. We sought to evaluate the effect of older age at diagnosis on transplant outcome. Patients and Methods: All patients with HD undergoing autologous transplantation with BEAM conditioning (BCNU, Etoposide, Cytarabine, and Melphalan) between January 1996 and December 2007 were included in this study. During these 12 years, 248 patients (103 males) underwent autologous transplantation. Seventy two patients (29%) were older than 40 years of age at the time of initial diagnosis. Median age at transplantation was 31 years (range 11–74). At transplantation, 63 (25%) were in complete remission (CR); 148 (60%) were in partial remission (PR); and 37 (15%) had stable (SD) or progressive disease (PD). Forty-six patients (19%) had received more than 3 courses of chemotherapy prior to transplantation. LDH was elevated in 131 (53%). Peripheral blood stem cells were used as stem cell source in 241 (97%) patients. Results: With a median follow up of 48 months (range, 1–143 months), the 48-month overall (OS) and event-free survival (EFS) were 72% (95% CI; 65%-77%) and 57% (95% CI; 50%-63%), respectively. The cumulative incidence of non-relapse mortality at 1 year was 1.6%. The cumulative incidence of secondary MDS or AML was 8%. In univariate analysis, disease status (p [Table: see text] No significant financial relationships to disclose.

7002 Background: RISCT was developed to harness graft versus leukemia effect to treat older patients (pts) and pts with comorbidities. Limited data are available on long term outcome of pts with high risk AML treated in complete remission (CR), a group most likely to benefit from this approach. Methods: Thirty six consecutive pts with AML in CR, treated between 1999 and 2006 with Fludarabine 120–125 mg/m2 and Melphalan 100–140 mg/m2 are included. Pts were not eligible for myeloablative transplantation because of age or comorbidity. Tacrolimus and Methotrexate were used as GVHD prophylaxis. Additionally pts receiving stem cells from an unrelated donor received rabbit antithymocyte globulin. Results: There were 24 males and 12 females with a median age of 57 (range 21–71). Eighteen(50%) pts had secondary AML. Thirty(83%) pts were in first CR and 6(17%) in second CR. Cytogenetic risk groups were as follows: 2 good risk (in CR2), 22 intermediate risk(61%), and 10(28%) poor risk. Source of stem cells was peripheral blood in 18 pts (50%) and bone marrow in 18 pts (50%). Donors were siblings in 21(58%) pts and unrelated in 15 (42%)pts. Hematopoietic cell transplant specific comorbidity score of 3 or higher was present in 26 pts (72%). All pts engrafted achieving full donor chimerism by day 30 with median time to neutrophil engraftment of 12.5 days (8–19 days). Cumulative incidence of grade 2–4 acute graft versus host disease (GVHD), grade 3–4 GVHD and chronic GVHD was 25% (95% CI; 14%–44%), 11% (95% CI; 4%–28%), and 63% (95% CI; 47%–84%) respectively. Cumulative incidence of nonrelapse mortality was 19% (95% CI; 8%–41%). With a median follow up of 852 days, 3 year overall and disease free survival is 75% (SE 9%) and 63% (SE 10%) respectively. Comorbidity scores didnot impact outcome. Conclusions: Reduced intensity allogeneic transplantation with Fludarabine and Melphalan conditioning produces durable long term remission in pts with high risk AML in complete remission. These results in older pts and/or pts with comorbidities are comparable to published results in younger pts receiving myeloablative transplantation. Comorbidity scores by themselves should not be used to exclude patients from receiving transplant. No significant financial relationships to disclose.

6518 Background: P/G status has been suggested to be an important predictor of outcome in pts with LBCL who receive an ASCT. Newer conditioning regimens which include HDR have been shown to improve results (Khouri, JCO, 2005). The influence of HDR on the outcome of pts based on P/G status has not been determined. Methods: A retrospective review of pts with chemo-sensitive, LBCL who received an ASCT on a research protocol at MD Anderson between 1995 and 2005 was performed. Results: A total of 188 pts were identified. Median age was 49 yrs with 108 (57%) male pts. 147 (78%) had de novo LBCL and 41 (22%) had an LBCL of follicular origin (LBCL-F). 83 (39%) pts received HDR with ASCT. At transplantation 95 pts (50%) were in PR, 71 pts (38%) in CRU and 22 pts (12%) in CR. 142 (76%) pts were P/G negative, 37 (20%) pts P/G positive and 9 (4%) pts unknown. The median follow-up was 44 months. Factors that were considered for outcome included: Age, IPI, # of prior chemotherapies, B2-microglobulin, disease status at transplant, HDR and P/G status. On multivariate analysis, P/G status and HDR were the only predictors for progression and PFS. Pts who were P/G negative and those that received HDR had a hazard ratio (HR) of 0.3 (p [Table: see text] No significant financial relationships to disclose.