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Background : Male-specific late effects after hematopoietic cell transplantation (HCT) include genital chronic graft-versus-host disease (GvHD), hypogonadism, sexual dysfunction, infertility, and subsequent malignancies, such as prostate, penile, and testicular cancer. They may be closely intertwined and cause prolonged morbidity and decreased quality of life after HCT. Objective : Here, we provide a systematic review of male-specific late effects in a collaboration between transplant physicians, endocrinologists, urologists, dermatologists, and sexual health professionals through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research, and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Study Design : We utilized systematic review methodology to summarize incidence, risk factors, screening, prevention and treatment of these complications and provide consensus evidence-based recommendations for clinical practice and future research. Results : Most of the evidence regarding male GvHD is still based on limited data, precluding strong therapeutic recommendations. We therefore recommend to systematically screen for male genital GvHD regularly and report it to large registries to allow for a better understanding. Future research should also address treatment since little published evidence is available to date. Male-specific endocrine consequences of HCT include hypogonadism which may also affect bone health. Since the evidence is scarce, current recommendations for hormone substitution and/or bone health treatment are based on similar principles as for the general population. Following HCT, sexual health decreases and this topic should be addressed at regular intervals. Future studies should focus on interventional strategies to address sexual dysfunction. Infertility remains prevalent in patients having undergone myeloablative conditioning, which warrants offering sperm preservation in all HCT candidates. Most studies on fertility rely on descriptive registry analysis and surveys, hence the importance of reporting post-HCT conception data to large registries. Although the quality of evidence is low, the development of cancer in male genital organs does not seem more prevalent than in the general population; however, subsequent malignancies in general seem to be more prevalent in males than females, and special attention should be given to skin and oral mucosa. Conclusion : Male-specific late effects, probably more under-reported than female-specific complications, should be systematically considered during the regular follow-up visits of male survivors who have undergone HCT. Care of patients with male-specific late effects warrants close collaboration between transplant physicians and specialists from other involved disciplines. Future research should be directed towards better data collection on male-specific late effects and on studies about the interrelationship between these late effects, to allow the development of evidence based effective management practices.

Renal dysfunction is a recognized risk factor for mortality after allogeneic hematopoietic cell transplantation (alloHCT), yet our understanding of the effect of different levels of renal dysfunction at time of transplantation on outcomes remains limited. This study explores the impact of different degrees of renal dysfunction on HCT outcomes and examines whether the utilization of incremental degrees of renal dysfunction based on estimated glomerular filtration rate (eGFR) improve the predictability of the hematopoietic cell transplantation comorbidity index (HCT-CI). The study population included 2 cohorts: cohort 1, comprising patients age ≥40 years who underwent alloHCT for treatment of hematologic malignancies between 2008 and 2016 (n = 13,505; cohort selected given a very low incidence of renal dysfunction in individuals age40 years), and cohort 2, comprising patients on dialysis at the time of HCT (n = 46). eGFR was measured using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method. The patients in cohort 1 were assigned into 4 categories-eGFR ≥90 mL/min (n = 7062), eGFR 60 to 89 mL/min (n = 5264), eGFR 45 to 59 mL/min (n = 897), and eGFR45 mL/min (n=282)-to assess the impact of degree of renal dysfunction on transplantation outcomes. Transplantation outcomes in patients on dialysis at the time of alloHCT were analyzed separately. eGFR60 mL/min was associated with an increased risk for nonrelapse mortality (NRM) and requirement for dialysis post-HCT. Compared with the eGFR ≥90 group, the hazard ratio (HR) for NRM was 1.46 (P = .0001) for the eGFR 45 to 59 mL/min group and 1.74 (P = .004) for the eGFR45 mL/min group. Compared with the eGFR ≥90 mL/min group, the eGFR 45 to 59 mL/min group (HR, 2.45; P.0001) and the eGFR45 mL/min group (HR, 3.09; P.0001) had a higher risk of renal failure necessitating dialysis after alloHCT. In addition, eGFR45 mL/min was associated with an increased overall mortality (HR, 1.63; P.0001). An eGFR-based revised HCT-CI was also developed and shown to be predictive of overall survival (OS) and NRM, with predictive performance similar to the original HCT-CI. Among 46 patients on dialysis at alloHCT, the 1-year probability of OS was 20%, and that of NRM was 67%. The degree of pretransplantation renal dysfunction is an independent predictor of OS, NRM, and probability of needing dialysis after alloHCT. An eGFR-based HCT-CI is a validated index for predicting outcomes in adults with hematologic malignancies undergoing alloHCT. The outcomes of alloHCT recipients on dialysis are dismal; therefore, one should strongly weigh the significant risks of being on hemodialysis as a factor in determining alloHCT candidacy.

Compared with reduced-intensity conditioning (RIC), myeloablative conditioning (MAC) is generally associated with lower relapse risk after allogeneic hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). However, disease-specific risk factors in AML/MDS can further inform when MAC and RIC may yield differential outcomes. We analyzed HCT outcomes stratified by the Disease Risk Index (DRI) in 4387 adults (age 40 to 65 years) to identify the impact of conditioning intensity. In the low/ intermediate-risk DRI cohort, RIC was associated with lower nonrelapse mortality (NRM) (hazard ratio [HR],.74; 95% confidence interval [CI],.62 to.88; P

Allogeneic transplantation is uniquely curative for a subset of patients with acute myeloid leukemia (AML) however, post-transplant relapse and graft versus host disease remain significant concerns. We have developed a vaccine in which patient-derived AML cells are fused with donor-derived dendritic cells (DCs), thereby presenting a broad array of antigens. Previous work (Rosenblatt Sci Transl Med) has suggested that such vaccines given in the first complete remission setting after chemotherapy consolidation elicit specific immune responses and can possibly lessen the risk of relapse. We hypothesize that donor-derived DC/AML vaccination post-transplant would elicit the durable expansion of leukemia- specific T cells within the donor T cell repertoire to effectively protect against disease relapse. We report the results of a phase 1 clinical trial (NCT03679650) evaluating the use of DC/AML fusion vaccine in patients with acute myeloid leukemia (AML) following allogeneic transplant. DC/AML fusion vaccine is generated with autologous leukemia blasts, cryopreserved at the time of diagnosis with AML, and donor-derived dendritic cells. DCs are collected via leukapheresis in pts in CR 25-70 days after an allogenic matched related or unrelated donor transplant (cohort A) or a haplo-identical donor (Cohort B). In order to proceed with leukapheresis, patients must demonstrate donor hematopoietic recovery and the absence of ongoing grade 2 or higher GVHD. For DC generation, donor-derived adherent mononuclear cells are cultured with GM-CSF, IL-4 and TNFa. Vaccine is administered subcutaneously starting day 70-100 post-transplant. 2 vaccines are given at 3 week intervals, in conjunction with 100 mcg GMCSF daily at the vaccine site for 4 days. A booster vaccine is given 30-60 days following the taper of immune suppression, in the absence of GVHD. Profiling of the immune microenvironment using single cell RNA sequencing from samples obtained before and after vaccination is being carried out. 17 participants have been enrolled. The median age was 59 years (range 23-74). 15 patients were enrolled to cohort A: 8 were transplanted with a matched unrelated donor and 7 were transplanted with a matched sibling donor. 2 participants were enrolled to cohort B. The median yield of leukemia cells was 207x10 6 (range 80-818x10 6)and mean viability was 96.5%. The median yield of DCs was 133x10 6 (range 29-182x10 6) and mean viability 72%. Fusion vaccine was successfully generated in 14/16 patients. One patient had insufficient DC, one patient relapsed prior to leukapheresis and one vaccine is currently in process. Mean fusion efficiency was 52% with viability of 78.6%. Mean fusion vaccine dose was 4.36 x10 6 cells. 3 patients from whom vaccine was generated did not meet eligibility to initiate vaccination due to ongoing toxicity following transplant or GVHD. 11 participants have initiated vaccine administration and are evaluable for toxicity and response. The most common side effects have been vaccine site reactions (n=10 grade 1, n=2 grade 2). 7 patients developed GVHD that was determined to be possibly related to vaccination, at a median time of 19 days after vaccination (range 5-70 days). 2 of these patients developed grade 2 acute GVHD of the skin, and 5 developed chronic GVHD affecting one to up to four organ systems ranging from mild to severe. There were 5 additional GVHD events with a median time of 115 days post vaccination (range 91-126 days), assessed as unlikely related or unrelated to vaccine based on timing of onset. 10 of 11 evaluable patients remain in a CR at a median time of 21 months post-transplant (range 6-33 months). One patient died of relapsed disease 15 months post transplant and another died of GVHD and infection unrelated to vaccine 21 months post transplant. Vaccination using patient-derived autologous leukemia cells and donor derived DC isolated following engraftment of hematopoietic cells appears safe and feasible. Toxicity of vaccination has included injection site reactions as well as graft versus host disease, primarily mild to moderate severity. Outcomes to date demonstrate that vaccination post-transplant may be a promising strategy to reduce relapse as 10 of 11 vaccinated patients remain relapse free. However this approach is limited to patients who have not had early relapse or early GVHD post-transplant. Immune correlates, including single cell RNA sequencing of the immune milieu, are ongoing. Disclosures Stone: Abbvie: Consultancy; Actinium: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Aprea: Consultancy; Arog: Consultancy, Research Funding; Astellas: Membership on an entity's Board of Directors or advisory committees; BerGen Bio: Membership on an entity's Board of Directors or advisory committees; Boston Pharmaceuticals: Consultancy; Bristol Meyers Squibb: Consultancy; Celgene: Consultancy; Elevate Bio: Membership on an entity's Board of Directors or advisory committees; Foghorn Therapeutics: Consultancy; Gemoab: Membership on an entity's Board of Directors or advisory committees; Glaxo Smith Kline: Consultancy; Innate: Consultancy; Janssen: Consultancy; Jazz: Consultancy; Macrogenics: Consultancy; Novartis: Consultancy, Research Funding; OncoNova: Consultancy; Syndax: Membership on an entity's Board of Directors or advisory committees; Syntrix/ACI: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy. Soiffer: Takeda: Consultancy; Jasper: Consultancy; Jazz Pharmaceuticals, USA: Consultancy; Precision Biosciences, USA: Consultancy; Juno Therapeutics, USA: Other: Data Safety Monitoring Board; Kiadis, Netherlands: Membership on an entity's Board of Directors or advisory committees; Rheos Therapeutics, USA: Consultancy; Gilead, USA: Other: Career Development Award Committee; NMPD - Be the Match, USA: Membership on an entity's Board of Directors or advisory committees. Stroopinsky: The Blackstone Group: Consultancy. Romee: Glycostem: Membership on an entity's Board of Directors or advisory committees; Crispr Therapeutics: Research Funding. Neuberg: Madrigal Pharmaceuticals: Other: Stock ownership; Pharmacyclics: Research Funding. Kufe: Canbas: Consultancy; Hillstream BioPharma: Current equity holder in publicly-traded company; Genus Oncology: Current equity holder in publicly-traded company; REATA: Consultancy, Current equity holder in publicly-traded company. Avigan: Chugai: Membership on an entity's Board of Directors or advisory committees; Partner Tx: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Parexcel: Consultancy; Janssen: Consultancy; Legend Biotech: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Consultancy, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Juno: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; Sanofi: Consultancy; Aviv MedTech Ltd: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Rosenblatt: Wolters Kluwer Health: Consultancy, Patents & Royalties; Parexel: Consultancy; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Imaging Endpoints: Consultancy; Bristol-Myers Squibb: Research Funding; Attivare Therapeutics: Consultancy.

Acute myeloid leukemia (AML) patients often undergo allogeneic hematopoietic cell transplantation (alloHCT) in first complete remission (CR). We examined the effect of depth of clinical response, including incomplete count recovery (CRi) and/or measurable residual disease (MRD), in patients from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry. We identified 2492 adult patients (1799 CR and 693 CRi) who underwent alloHCT between January 1, 2007 and December 31, 2015. The primary outcome was overall survival (OS). Multivariable analysis was performed to adjust for patient-, disease-, and transplant-related factors. Baseline characteristics were similar. Patients in CRi compared to those in CR had an increased likelihood of death (HR: 1.27; 95% confidence interval: 1.13-1.43). Compared to CR, CRi was significantly associated with increased non-relapse mortality (NRM), shorter disease-free survival (DFS), and a trend toward increased relapse. Detectable MRD was associated with shorter OS, shorter DFS, higher NRM, and increased relapse compared to absence of MRD. The deleterious effects of CRi and MRD were independent. In this large CIBMTR cohort, survival outcomes differ among AML patients based on depth of CR and presence of MRD at the time of alloHCT. Further studies should focus on optimizing post-alloHCT outcomes for patients with responses less than CR.

Young adult (YA) survivors of allogeneic hematopoietic cell transplantation (HCT) are at risk for late psychosocial challenges, including the inability to return to work post-HCT. Work-related outcomes in this population remain understudied, however. We conducted this study to assess the post-HCT work status of survivors of allogeneic HCT who underwent HCT as YAs and to analyze the patient-, disease-, and HCT-related factors associated with their work status at 1 year post-HCT. Using Center for International Blood and Marrow Transplant Research data, we evaluated the post-HCT work status (full-time, part-time work, unemployed, or medical disability) of 1365 YA HCT survivors who underwent HCT between 2008 and 2015. Percentages of work status categories were reported at 4 time points: 6 months, 1 year, 2 years, and 3 years post-HCT. Percentages of post-HCT work status categories at the 1-year time point were also described in relation to survivors' pre-HCT work status categories. Factors associated with 1-year post-HCT work status (full-time or part-time work) were examined using logistic regression. From 6 months to 3 years post-HCT, the percentage of survivors working full-time increased from 18.3% to 50.7% and the percentage working part-time increased from 6.9% to 10.5%. Of patients in full-time work pre-HCT, 50% were unemployed or on medical disability at 1 year post-HCT. Female sex (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.40 to 0.77), HCT Comorbidity Index score ≥3 (OR, 0.57; 95% CI, 0.39 to 0.82), pre-HCT unemployment (OR, 0.37; 95% CI, 0.24 to 0.56), medical disability (OR, 0.44; 95% CI, 0.28 to 0.70), development of grade III-IV acute graft-versus-host disease (OR, 0.52; 95% CI, 0.34 to 0.80), and relapse within 1 year post-HCT (OR, 0.34; 95% CI, 0.21 to 0.56) were associated with a lower likelihood of employment at 1 year post-HCT. Compared with myeloablative conditioning (MAC) with total body irradiation (TBI), MAC without TBI (OR, 1.71; 95% CI, 1.16 to 2.53) was associated with a greater likelihood of employment at 1 year post-HCT. Graduate school-level education (OR, 2.47; 95% CI, 1.49 to 4.10) was also associated with a greater likelihood of employment at 1 year post-HCT. Although the work status among YA HCT survivors continued to improve over time, a substantial subset became or remained unemployed or on medical disability. These findings underscore the need for effective interventions to support return to work in this population.

Allogeneic hematopoietic cell transplantation (HCT) is an important treatment for many severe hematologic disorders; however, HCT can be associated with significant complications, including organ toxicity, graft-versus-host disease, and relapse. Another serious, but rare, complication is the transmission of hematologic and nonhematologic diseases from the donor to the recipient. With older donors, the risk of an abnormality may be increased. Here we describe the transmission of an inversion 3 constitutional cytogenetic abnormality from an unrelated donor to a recipient, and review the clinical implications of the discovery of donor-derived constitutional cytogenetic abnormalities.

Background There is a paucity of outcome studies on HIV-associated lymphoma treated with chemotherapy with or without autologous hematopoietic stem cell transplantation (autoHSCT) in comparison to HIV-uninfected individuals with similar histology. Methods In our retrospective matched cohort study, we enrolled adult HIV-positive patients with lymphoma treated with chemotherapy with (group 2) or without autoHSCT (group 1) between January 1, 2007 to December 31, 2018 at the University of Kansas Medical Center and followed until May 1, 2020. Group 1 were matched 1:1 to HIV-negative patients based on age, gender, lymphoma histology, stage at diagnosis, year of lymphoma diagnosis, and Group 2 were matched 1:2 to HIV-negative patients based on age at autoHSCT, gender, lymphoma histology, stage at diagnosis and year of transplantation. Overall survival (OS) and progression-free survival (PFS) at 2 years were calculated using Kaplan-Meier (KM) analysis, and adjustment for ECOG and IPI/IPS scores was done using multivariate Cox model. Results We had 37 HIV+ patients with lymphoma in our cohort: 9 Hodgkin’s disease (HD), 28 Non Hodgkin’s Lymphoma (NHL). Eleven underwent autoHSCT (3 HD, 8 NHL). The majority were white (76.2%), non-hispanic (92.9%), males (90.5%) and mean age was 46 years. Median CD4 was 172.5, HIV viral load was < 50 copies/mL in 43..2%, and 76.2% were on antiretroviral therapy (ART) at diagnosis. ART was interrupted in 14.6% and adjusted in 40.5% of patients. After excluding rare histological types, 22 in group 1 and 9 in group 2 were included in the matched analysis. On KM survival at 2-years, group 1 had worse OS (75% vs 95%, p=0.02), and a trend for worse PFS (75% vs 90%, p=0.07) than the matched referent group, while group 2 had similar OS (100% vs 94%, p= 0.47) and better PFS (100% vs 70%, p=0.02) than the matched referent group. On Cox models adjusting for ECOG and IPI/IPS, HIV status was no longer independently associated with OS in group 1 or PFS in group 2. Group 1 HIV lymphoma cases and controls characteristics Group 2 HIV lymphoma with HSCT cases and controls characteristics Conclusion In patients with HIV and lymphoma treated with chemotherapy with or without autoHSCT, the outcomes are comparable to those without HIV in our single center contempory cohort. Disclosures Wissam El Atrouni, MD, ViiV (Advisor or Review Panel member)

Background Chronic kidney disease (CKD) is a known risk factor for post-HCT mortality. Currently, HCT-CI assigns a score of 2 for moderate-severe renal dysfunction based on serum creatinine (Cr), though Cr is not ideal marker of renal function and can be influenced by several factors. The aim of this study is to examine whether utilization of incremental degrees of renal dysfunction based on eGFR improves the utility of HCT-CI to predict allogeneic HCT outcomes. Method Patients age ≥40 years receiving HCT for malignancies from 2008 to 2016 were included. Estimated glomerular filtration rate (eGFR), calculated using CKD-epidemiology collaboration method, was used to categorize patients into 4 groups: eGFR ≥ 90ml/min (n=7062), eGFR 60-90 (n=5264), eGFR 45-59 (n=897) and eGFR Results eGFR groups were similar on disease risk index, graft and donor source, but patients with eGFR≥90 were younger and received a myeloablative regimen more frequently. Patients with eGFR Conclusion These findings provide support that degree of renal dysfunction is independent predictor of OS and TRM after allogeneic HCT. In addition, the newly developed RA-HCT-CI is valid in predicting both TRM and OS and performs similarly to original HCT-CI.

e19020 Background: Allogeneic stem cell transplantation (alloSCT) is increasingly being offered to older patients with acute myeloid leukemia (AML) due to availability of reduced-intensity conditioning regimens and better supportive care. Though studies have shown improving alloSCT survival outcomes in older age groups, it is still not known if older age confers higher mortality and morbidity during transplant hospitalization. We queried a national inpatient database to evaluate in-hospital mortality and resource utilization during alloSCT for AML in patients >70 years compared to a younger age group. Methods: We conducted a retrospective study of alloSCT for AML patients ≥ 18 years using the 2018 National Inpatient Sample database. Hospitalizations were selected using International Classification of Disease, tenth revision (ICD-10) codes. Demographics, comorbidities, transplant, and outcome variables were compared between a reference age group (18-70 years) and a comparator group (> 70 years). Study outcomes were in-hospital mortality, length of stay (LOS) and transplant complications. Regression models were fit to assess the association between predictors and outcomes. Results: During the study period, 2610 alloSCT met the inclusion criteria. This cohort consisted of 50% males and 77% Caucasians. Only 7% of these alloSCT were performed for patients > 70 years. Patients >70 yrs had a lower proportion of females compared to the reference age group (32% versus 52%, p70 years were 3% and 5% respectively (p=0.35). In a multivariable model, we found no association between age >70 years and in-hospital transplant mortality. Acute graft versus host disease was more frequent among the reference age group (14% versus 2%, p=0.04), but there were no differences in LOS or rates of graft failure, respiratory failure, sepsis, and acute renal failure between the 2 groups. Conclusions: Despite similar in-hospital transplant outcomes as their younger counterparts, patients >70 years comprised only a small proportion of alloSCT performed for AML in our study. Females were more disproportionately affected by this age disparity. More studies are necessary to identify barriers to alloSCT for older AML patients, more so for older females.

The 'HLA conundrum in bone marrow transplantation': correct interpretation of anti-HLA antibodies in haploidentical donor selection

Allogeneic stem cell transplantation (SCT) is a potentially curative treatment for MDS. Besides the innate heterogeneity of MDS, intensity of the conditioning regimen (myeloablative (MAC) versus reduced intensity/non-myeloablative (RIC)), specific agents used in conditioning, donor and source of stem cells and GVHD prevention regimens further influence outcomes. We sought to determine how conditioning regimens influenced MDS subgroup cohort outcomes. We retrospectively analyzed outcomes of 107 MDS patients (63 male and 44 females) with median age 61.8 (17-73 years) who underwent allogeneic SCT at our institution between 2008 and 2017. For the purposes of this report, patients were grouped according to WHO classification into non-RAEB (RCMD, RA, RARS RCUD or 5q deletion, n=49) and RAEB (RAEB1 and RAEB2, n=58) categories. Median time from MDS diagnosis to transplantation was 139 days (20-3175). No patients were in complete remission (CR) at time of SCT. Allogeneic donor types were matched related, matched unrelated, haplo-identical and cord blood in 30, 65, 10 and 2 patients, respectively. Stem cell source was peripheral blood (91 patients) and bone marrow in 14. Forty patients (median age 52.2 (17-61) years) underwent MAC and 67 (median age 63.7 (23-73) years) RIC. Twelve patients died within 100 days of transplantation, 3 due to disease progression, 5 to acute GVHD, and 4 to other transplant-related causes. Median overall survival (OS) for all 107 patients was 1.3 years with 54%, 47% and 40% alive at 1, 2 and at 5 years. OS was slightly higher in patients undergoing RIC with OS of 57%, 48% and 40% (median 1.532 years) versus 50%, 40% and 38% with MAC (median 0.92 years) at the same time points (p>0.1). Median OS of the 49 patients with non-RAEB and 58 patients with RAEB MDS was 3.01 years versus 0.92 years (p>0.1). GVHD was the most frequent cause of death (46%), followed by relapse/progression (28%), infection (14%) and other (12%). Of 29 patients undergoing RIC with non-RAEB MDS, median OS was 3.78 years while for 38 RAEB patients it was 1.17 years (p>0.1). See table for OS according to conditioning regimen and WHO classification. For MAC, in 20 non-RAEB patients median OS was 2.2 years while the median OS was 0.69 years for 20 RAEB patients (p>0.1). CR after SCT was achieved in 57 patients (53%), 33 receiving RIC (CR 49.2%) and 24 receiving MAC (CR 60%). Seven patients subsequently relapsed, 4 RIC and 3 MAC. Of the non-RAEB patients achieving CR, median OS in the 16 patients treated with 111 RIC was not reached and in 14 patients receiving MAC, median OS was 3.75 years (p>0.1). For the 27 RAEB patients achieving CR, median OS was 4.4 years in 17 patients treated with RIC versus not reached in 10 patients treated with MAC. Overall, death in non-RAEB patients occurred in 26/49 (53%) compared to 38/58 (66%) RAEB patients and in 40/67 (59%) patients undergoing RIC versus 25/40 (63%) MAC patients (p>0.5). The hematopoietic transplant comorbidity index did not predict OS outcomes in these MDS patients (p>0.1) and the cytogenetic score according to the IPSS-R "very good -very poor" groups indicated no differences in OS in the non-RAEB patients but in RAEB patients significant differences according to the cytogenetic score was evident (P Conclusions: In this retrospective analysis of MDS patients undergoing allogeneic SCT, achieving CR led to improved survival. In non-RAEB MDS patients achieving CR, OS was similar irrespective of conditioning intensity (RIC or MAC). Furthermore, outcomes did not differ in RAEB patients who achieved CR according to intensity of conditioning regimen. However, those receiving MAC had not reached median OS at 5 years. The outcomes in this analysis indicate that improvement in the incidence of deaths due to GVHD would likely have the greatest impact in improving survival in MDS patients undergoing allogeneic transplantation. Table Disclosures Abhyankar: Therakos: Other: Consulting, Speakers Bureau; Incyte: Speakers Bureau. Lin:Jazz Pharmaceuticals: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees. Yacoub:Incyte: Consultancy, Speakers Bureau. Ganguly:Kite Pharma: Honoraria, Other: Advisory Board; Seattle Genetics: Speakers Bureau; Janssen: Honoraria, Other: Advisory Board; Daiichi Sankyo: Research Funding. McGuirk:Pluristem Ltd: Research Funding; Gamida Cell: Research Funding; Kite Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bellicum Pharmaceuticals: Research Funding; Astellas: Research Funding; Fresenius Biotech: Research Funding; Novartis: Research Funding; Juno Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; ArticulateScience LLC: Other: Assistance with manuscript preparation.

Introduction Renal dysfunction is a recognized risk factor for mortality after HCT, as it is included in the comorbidity index (HCT CI). Yet, further understanding on outcomes in patients with different level of renal dysfunction or undergoing hemodialysis (HD) at time of transplant remains scant. This study explores the impact of different levels renal dysfunction on major HCT outcomes in a large population using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Methods The study population included 8,102 patients age 40 years and older who received HCT for treatment of malignancies from 2008 to 2016, with available pre-transplant creatinine measurement. eGFR, calculated using CKD-EPI (CKD-epidemiology collaboration) method, was used to assigned patients in four categories: eGFR ≥ 90ml/min (eGFR≥ 90, N=4,237, reference), eGFR 60-90ml/min (eGFR 60-90, N=3,158), eGFR 45-59ml/min (eGFR 45-59, N=538) and eGFR Results Patient characteristics are shown in table 1. The groups were comparable on disease risk index, graft and donor source, but patients with eGFR>90 were younger and received myeloablative conditioning more frequently. The cohort of eGFR Conclusion These findings indicate that degree of renal dysfunction is an independent predictor of OS, TRM, probability of receiving HD and SOS when adjusted for other risk factors. The impact of eGFR on the need of HD, a complication that increases morbidity post HCT is an important finding. Additionally, the outcomes of a subset of patients on HD at time of transplants are dismal. These results can further assist the prognostic assessment of candidates for an allogeneic HCT. Disclosures Stadtmauer: Celgene: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Amgen: Consultancy; Novartis: Consultancy, Research Funding; Tmunity: Research Funding; Abbvie: Research Funding. Wingard:Ansun: Consultancy; Pluristem: Consultancy; Celgene: Consultancy; Merck: Consultancy; Shire: Consultancy. Ganguly:Seattle Genetics: Speakers Bureau; Daiichi Sankyo: Research Funding; Kite Pharma: Honoraria, Other: Advisory Board; Janssen: Honoraria, Other: Advisory Board. Pasquini:Pfizer: Other: Advisory Board; Amgen: Consultancy; Medigene: Consultancy; BMS: Research Funding; Novartis: Research Funding; Kit Pharma: Research Funding.

Introduction: Disease relapse remains one of the major causes of treatment failure in hematopoietic stem cell transplant (HSCT) following reduced-intensity conditioning (RIC) regimens. Donor chimerism assessment early after HSCT may help identify patients at risk for relapse who may benefit from additional therapeutic interventions but its precise role in this setting is unclear. In addition, the differential impact of conditioning regimen is not well studied. Aim: 1. Study the impact of early full T-lymphocyte chimerism (T-lymphocyte chimerism ≥ 90% on day 30 to 60) on relapse incidence (RI) and acute graft versus host disease (aGVHD) in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) following RIC-HSCT. 2. Looking at the tempo of achievement of complete donor T-lymphocyte chimerism based on the two most common RIC regimens, Fludarabine/Melphalan (FM) and Fludarabine/Busulfan (FB). Method: After IRB approval, patients with AML or MDS who underwent RIC-HSCT with FB or FM between 2008 and 2014 at our institution were identified. Post-transplantation CD3 (lymphocyte) and CD33 (myeloid) donor chimerism were measured per protocol using PCR-based analysis of short tandem repeats. Categorical and continuous variables were analyzed using Pearson's chi-squared and Wilcoxon / Kruskal-Wallis, respectively. Survival estimates were calculated using the Kaplan-Meier and log-rank test. RI was estimated accounting NRM on a competing event analysis using Grey's model. Cox proportional regression was used to compute hazard ratios (HR). Results: Baseline characteristics: Out of 134 patients who received FM or FB, 75 patients had evaluable early sorted chimerism data. 42 and 33 patients received FB and FM, respectively. Patient, disease and transplant variables were balanced in both FM and FB (Table 1). The median follow up of the cohort was 37 months (2.4-43) and at last follow up 29.1% of patients relapsed and 59% died. All patients achieved early complete myeloid chimerism whereas T-lymphocyte chimerism was complete in 50 patients and mixed in 25 patients. Characteristics of early lymphocyte chimerism by status are shown in table 1. Notably, likelihood of achieving complete T-lymphocyte chimerism ≥ 90% at 60 days was 100% versus 47% in FM and FB respectively (p Acute graft versus host disease: There was no significant difference in incidence of grade II-IV aGVHD between patients with full early donor T-lymphocyte chimerism in comparison to those with early mixed donor chimerism (46% vs. 48%, p =0.87). Impact of full chimerism and conditioning regimen on RI and overall survival (OS): Among the entire cohort, patients achieving early full T-lymphocyte chimerism had a significantly lower RI compared to those with mixed chimerism with a HR of 0.38 (CI 0.14-0.97; p=0.044) but OS was not significantly different with HR 0.69 (CI 0.33-1.51; p=0.34). In patients conditioned with FB, there was no difference in 2-year RI between complete or mixed early T-lymphocyte chimerism at 38.2% and 40.7% respectively (p = 0.9). After FM conditioning, all patients achieved early T-lymphocyte chimerism and the 2-year RI was 6.9%. Achievement of early complete lymphocyte chimerism post FB in comparison to FM was associated with significantly higher risk of relapse (HR 8.6 CI 2.07-57, p=0.0025). Furthermore, there was a trend towards worse OS with FB vs. FM with a median of 23 vs. 44 months, respectively (p = 0.058). Conclusion: Similar to prior reports, we observed that full T-lymphocyte chimerism is associated with decreased relapse risk without an increase in aGVHD. Our findings also suggest that RIC with FM yields a higher incidence of early complete T-lymphocyte chimerism and is significantly associated with decreased risk of relapse compared to FB. There was a greater risk of relapse in the FB group, even among those achieving early complete donor lymphoid chimerism. This needs further validation given the small sample size. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.