Abstract: INTRODUCTION: High dose busulfan (Bu) is an integral component of many commonly-used preparative regimens for both allogeneic and autologous transplantation. Data on the efficacy and toxicity of q6 vs. q24 hour dosing are of significant clinical interest. In order to facilitate a therapeutic dose-monitoring protocol, we transitioned from q6 to q24 Bu dosing as part of our standard Bu/Cy/VP ASCT preparative regimen for patients with Hodgkin (HL) and Non-Hodgkin Lymphoma (NHL) in July 2012. We present comparative outcomes of q24 Bu dosing vs historical controls receiving q6 Bu. METHODS We retrospectively reviewed 400 consecutive eligible lymphoma patients who underwent ASCT from 2007-2013 with Bu/Cy/VP. All patients received Cy 60 mg/kg IV over 4 hours on days -3 and -2 and VP 60 mg/kg as continuous infusion on days -5 and -4. Bu was given at a dose of either 0.8 mg/kg q6 (N = 307) x 14 doses for patients transplanted between 2007-July, 2012 or 2.8 mg/kg q 24 hours (N = 93) on days -9 through -6 for subsequent patients. Outcomes assessed from date of transplant were: relapse, non-relapse mortality (NRM), relapse-free survival (RFS) and overall survival (OS). Toxicity was assessed using pulmonary and liver function tests (PFTs and LFTs) at specified time-points before and after ASCT. In addition, for a subset of 22 patients receiving q24 Bu, we measured serial Bu serum levels after the first dose of Bu with an in-house liquid chromatography-tandem mass spectrometry assay using turbulent flow online extraction technology (Bunch, et al. J Chromatogr B Analyt Technol Biomed Life Sci, 2010. 878(31): p. 3255-8) and subsequently determined the cumulative Bu area-under the curve (AUC). RESULTS Baseline patient and disease characteristics of patients dosed with q6 and q24 Bu were similar. The median age was 55 (range 20-78) years; 63% were males. 18% had HL and 82% had NHL with a comparable distribution of subtypes in both groups. Patients in both groups had comparable rates of prior chemotherapy regimens and of complete/partial remission at the time of ASCT. Due to a change in institutional guidelines, plerixafor was more commonly incorporated in peripheral blood stem cell mobilization regimen in the q24 group compared to q6 cohort (70% vs. 39%, P 〈 0.001). However, CD34+ doses were same in the two dosing cohorts. In terms of toxicity of the two dosing approaches, there was no significant difference in FEV1 or DLCO before and after transplant in the q6 vs q24 cohorts. LFTs measured at four time points were generally lower with q24 Bu, particularly AST and alkaline phosphatase (P=0.007 each), but these difference were not clinically significant. The median follow-up was longer in the q6 than q24 group (48.2 months vs. 21.3 months, P 〈 0.001). 18 month outcomes of the two dosing cohorts were comparable (see Table and Figure). We observed significant variation in AUC with weight-based dosing of Bu (AUC range 12,104 - 23,084 µM-min) with a median of 17,568 µM -min, which has served as a baseline for subsequent therapeutic-dose monitoring. CONCLUSIONS Q24 Bu dosing in combination with Cy/VP is more convenient than q6 hours, has equivalent outcomes, and results in no increase in either hepatic or pulmonary toxicity. Consistent with previous reports, there is a significant range of Bu AUC levels, with a standard deviation of 12%. These data provide rationale for our prospective clinical trial of real-time therapeutic dose monitoring with q24 Bu dosing. Table 1. Q6 dosing Q24 dosing P-value OS 78% 80% 0.79 RFS 63% 61% 0.99 NRM 5% 3% 0.95 Relapse 30% 36% 0.46 18 month outcomes of q6 vs q24 Bu dosing Figure 1. RFS and OS for lymphoma patients undergoing ASCT with Bu/Cy/VP treated with q6 vs. q24 hour weight-based Bu dosing. Figure 1. RFS and OS for lymphoma patients undergoing ASCT with Bu/Cy/VP treated with q6 vs. q24 hour weight-based Bu dosing. Figure 2. Figure 2. Disclosures Hill: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Majhail:Gamida Cell Ltd.: Consultancy; Anthem Inc.: Consultancy.

Abstract: Background: Recent data have shown that pre-transplant FDG-PET is prognostic in DLBCL patients undergoing autologous stem cell transplantation (ASCT). We retrospectively analyzed data on patients with DLBCL treated with ASCT to assess the impact of pre-transplant FDG-PET on relapse-free survival (RFS) and overall survival (OS). Methods: We reviewed medical records of 32 patients with DLBCL who underwent ASCT using high dose busulfan, cyclophosphamide, and etoposide (Bu/Cy/VP) at Cleveland Clinic from June 2008 to December 2012 and had both a relapse FDG-PET as well as a pre-transplant FDG-PET available for review. All images were interpreted by a staff nuclear medicine radiologist blinded to the outcomes. Visual analysis was performed using the Deauville five-point scale and semiquantitative analysis was done by measuring the maximum standardized uptake value (SUVmax). ΔSUVmax was calculated by determining the difference between the SUVmax at the time of relapse and the SUVmax immediately prior to transplant. Patients were grouped into pre-transplant Deauville score 1-3 or 4-5. Baseline characteristics were compared between groups using the Chi-square test or Wilcoxon rank test. Cox proportional hazards analysis was used to identify prognostic factors. Outcomes were calculated from the date of ASCT. Overall survival (OS) and relapse-free survival (RFS) were estimated using the Kaplan-Meier method and compared using the log-rank test Results: The median age of the patients at transplant was 57 and 69% were male. There was no significant difference in baseline characteristics of patients who had a Deauville score 1-3 compared to patients who had a Deauville score 4-5 including mean age, gender, race, Karnofsky performance status, number of prior chemotherapy regimens, prior radiation therapy, and IPI at diagnosis and transplant. There was a trend towards significance in the median SUVmax at relapse in the Deauville 1-3 group compared to the Deauville 4-5 group (11.1 vs. 18.1, p=0.08) and a significant difference in the median pre-transplant SUVmax (2.3 vs. 8.1, p 〈 0.001). Deauville score 4-5 was the only baseline variable that was prognostic for both RFS (HR=4.2, CI 1.6-11.5, p=0.004) and OS (HR=5.5, CI 1.6-18.9, p=0.006). The 3-year RFS for patients in the Deauville 1-3 group was 64% compared to 12% in the Deauville 4-5 group (p=0.002) and the 3-year OS for patients in the Deauville 1-3 group was 84% compared to 30%, respectively (p=0.002 [Figure 1]). The median ΔSUVmax was 74%. There was no difference in RFS or OS in patients who had a ΔSUVmax above or below this median. However, a high pre-transplant SUVmax( 〉 6 vs. 〈 6) was associated with significantly inferior RFS (p=0.03 [Figure 2]). Conclusions: Pre-transplant FDG-PET Deauville score is prognostic of RFS and OS in patients with DLBCL undergoing ASCT. High SUVmax( 〉 6) prior to transplant is predictive of poor RFS. Pre-transplant PET is a powerful tool for identifying DLBCL patients at high risk for treatment failure with ASCT and could be used to risk-stratify patients in prospective clinical trials of novel transplant strategies. Figure 1. OS of DLBCL patients undergoing ASCT based on pre-transplant Deauville score. Figure 1. OS of DLBCL patients undergoing ASCT based on pre-transplant Deauville score. Figure 2. RFS of DLBCL patients undergoing ASCT based on pre-transplant SUVmax. Figure 2. RFS of DLBCL patients undergoing ASCT based on pre-transplant SUVmax. Disclosures Smith: celegene, spectrum, genentech: Honoraria. Majhail:Gamida Cell Ltd.: Consultancy; Anthem Inc.: Consultancy.

Abstract: Background Cytomegalovirus (CMV) is a common infectious complication after allogeneic hematopoietic cell transplantation (alloHCT). Efforts to enhance immune reconstitution post-transplant have been pursued to help facilitate clearance of such infections. Assessment of natural killer (NK) cell allo-reactivity with investigation of killer cell immunoglobulin-like receptors has been reported to be associated with protection from CMV infection after alloHCT (Davis ZB et al, BBMT 2015). In addition, the activating NKG2D receptor controls immune responses by regulating NK cells, NKT cells and γδ-T cells. MHC class I chain-related gene A (MICA) is a polymorphic ligand of the NKG2D receptor on these immune effector cells. Given the potential benefit of NK cell allo-reactivity for protection from CMV infection after alloHCT we hypothesized that MICA polymorphisms may influence CMV infection rates after such transplants. Methods We conducted a single center, retrospective analysis of allogeneic HCTs for adults with hematologic malignancies in which MICA data were available for donors and recipients. Analysis was restricted to patients with T-cell replete HLA-8/8 matched related or unrelated donor. Fine and Gray regression was used to identify risk factors for CMV infection. The first episode of graft-versus-host-disease (GVHD) was analyzed relative to CMV as a time-dependent covariate. An analysis was performed examining dimorphisms at the MICA-129 position, which previously has been categorized as weaker (valine/valine: V/V), heterozygous (methionine/valine: M/V), or stronger (methionine/methionine: M/M) receptor binding affinity. Results From 2000-2016, 423 alloHCT patients were identified who had MICA data. Diagnoses included 197 AML, 82 MDS, 34 ALL, 34 NHL, 22 CML, 12 CMML, 9 CLL, 9 myelofibrosis, 9 plasma cell myeloma, 9 other leukemias, and 6 Hodgkin lymphoma. High, intermediate, and low co-morbidity index was seen in 42%, 33%, and 25% of patients, respectively. Median age at transplant was 52 years (range, 18-76), with 95% Caucasian. A myeloablative transplant was performed in 80% of patients and 52% had a bone marrow graft source. CMV infection occurred in 141 (33%) of patients at a median time of 46 days post-transplant (range, 0-609 days) with 29 (21%) occurring within 30 days, 108 (77%) within 100 days and 33 (23%) after day 100. Thirty-three (8%) patients were MICA mismatched with their donor. Donor MICA-129 dimorphisms included 203 (48%) V/V, 190 (45%) M/V and 30 (7%) M/M. Baseline donor(d)/recipient(r) CMV serostatus for V/V vs. M/V + M/M cohorts were 25% vs. 28% for d+/r+, 11% vs 9% for d+/r-, 39% vs. 37% for d-/r+, and 25% vs. 26% for d-/r- (P=0.75). In univariate analysis, MICA mismatch was associated with a higher risk of CMV (HR 1.64, CI 1.00-2.69, P=0.049), and V/V donor MICA-129 dimorphism with a marginally higher risk of CMV (HR 1.32, CI 0.85-1.83, P=0.10). In multivariable analysis, MICA mismatch was not associated with CMV infection (HR 1.38, CI 0.83-2.29, P=0.22) while V/V donor MICA-129 dimorphism was associated (HR 1.40, CI 1.00-1.96, P=0.05) (Figure 1). Other significant variables in multivariable analysis were year of transplant (HR 0.95, CI 0.92-0.99 P=0.01), non-Caucasian race (HR 2.15, CI 1.18-3.91, P=0.01), high-risk disease (HR 1.62, CI 1.13-2.32 P=0.008), baseline CMV serostatus (HR 7.51, CI 3.76-15.0, P & lt;0.001 for d+/r+, HR 7.73, CI 3.90-15.3, P & lt;0.001 for d-/r+, both relative to d-/r-), and development of GVHD prior to CMV (HR 2.02, CI 1.37-2.96, P & lt;0.001). There was no association of MICA mismatch with acute (HR 1.05, CI 0.66-1.68, P=0.83) or chronic (HR 0.94, CI 0.51-1.76, P=0.85) GVHD. As compared to the V/M+M/M cohort, patients with V/V donors had a longer interval from diagnosis to transplant (median 8.2 vs 6.2 months, P=0.036) and more often received myeloablative conditioning (P=0.030). Conclusion We conclude that the donor MICA-129 V/V dimorphism with weak NKG2D receptor binding affinity is associated with increased risk of CMV infection after alloHCT. The presence of at least one M residue encoding allele may confer enhanced NK cell anti-viral reactivity. These observations potentially may have implications in optimizing donor selection. Further investigation of MICA may also help better predict which patients are at higher risk of CMV infection in order to consider intervening sooner with CMV specific therapy or more rapid tapering of immunosuppression. Figure 1 Figure 1. Disclosures Gerds: CTI BioPharma: Consultancy; Incyte: Consultancy. Majhail: Sanofi: Honoraria; Anthem, Inc.: Consultancy.

Abstract: Abstract 3068 Advanced age is becoming less of a barrier to allogeneic hematopoietic cell transplantation (HCT) and transplantation has become an established standard of care for many older patients (pts) with hematologic malignancies. We previously reported superior quality of life (QOL) scores in pts age 60 and over undergoing high dose chemotherapy and autologous stem cell transplant compared with pts less than 60 (Dabney J et al, Blood 2008 112: Abstract 2381). These data prompted us to evaluate QOL assessments in pts≥60 undergoing allogeneic HCT compared to pts 〈 60 years. 435 adult pts underwent allogeneic HCT from June 2003 to December 2010. Prospective psychometric instruments were administered to 304 pts 〈 60 years of age (median 47, range 18–59) and 47 pts≥60 years of age (median 62, range 60–70) with acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia, non-Hodgkins lymphoma, Hodgkins disease, myeloproliferative neoplasms, aplastic anemia, and plasma cell neoplasms. Psychometric data was assessed longitudinally (at baseline, first post-discharge visit, day 100, 180, and 365) by validated questionnaires: Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), coping inventory (Brief COPE), and the Profile of Mood State- Short Form (POMS). The FACT-BMT measures five components of QOL: physical well being (PWB), social well being (SWB), emotional well being (EWB), functional well being (FWB), and additional concerns (AC). The POMS measures depression, vigor, anger, tension, confusion and fatigue. Brief COPE has 14 coping skills, such as use of emotional and instrumental support, venting, and positive reframing. Secondary endpoints included overall survival (OS), relapse-free survival (RFS), incidence of acute and chronic graft versus host disease (GVHD), and relapse. Imbalances between the two groups (p 〈 0.01 for all) included comorbidity index (HCT-CI), (62% of pts 〈 60 with a comorbid score of 〉 1 compared to 74% in pts≥60), preparative regimen, (84% myeloablative in pts 〈 60, 21% in pts ≥60%), and source of hematopoietic cells, (29% peripheral stem cells in pts 〈 60 versus 72% in pts≥60), with a higher median CD34+ cell dose (4.51×106/kg in pts≥60) compared with pts 〈 60 (2.51×106/kg). Psychosocial functioning and QOL differences were compared between age groups over time by repeated measures analysis of variance, using intensity of transplant as a variable given the imbalance. On FACT, pts≥60 reported better social (p=0.006) and functional well being (p=0.05), and had better total FACT scores, (p=0.043) across all time points. On POMS, pts≥60 reported less fatigue than patients 〈 60 (p=0.01), while COPE assessment indicated that older pts reported worse use of planning (p=0.012) and humor (p=0.041) compared with younger pts. Pts≥60 years also reported worse scores for active coping, but only at day 365 (p=0.019), and scored worse on behavioral disengagement at the first post-transplant time point (p=0.016), but this difference became non-significant by day 100 (p=0.81). With a median follow up of 49 months, there were no significant differences in OS, RFS, relapse, or chronic GVHD. There was a lower incidence of grade 3–4 acute GVHD in pts≥60 compared to pts 〈 60, (6.4% versus 15.8% at 6 months, p=0.016). This study provides further evidence that advanced age should not be a barrier in the decision to pursue allogeneic HCT. Older pts achieved better total scores in QOL assessments when compared to younger pts. One can hypothesize that older pts are more likely to have experienced adversity or family and personal health related problems, making them better able to endure symptoms than younger pts. In addition, younger pts may be more affected due to non-health related concerns including the adverse effect of transplantation on their careers, family, and finances. While our older population has proven to have similar medical outcomes and improved QOL, younger pts may benefit from social work interventions that focus on adapting to changes in functioning and social well-being. Disclosures: No relevant conflicts of interest to declare.

Abstract: Healthcare disparities, such as race/ethnicity and SES, can impact access to care and outcomes in cancer patients. ASCT is standard therapy for high-risk relapsed and refractory lymphoma, but is a highly specialized and resource-intensive procedure. The association of race and SES with outcomes in lymphoma patients undergoing ASCT has not been described previously. We conducted a retrospective cohort study of 687 consecutive ASCT recipients with Hodgkins (N=154, 22%) and non-Hodgkins (N=533, 78%) lymphoma transplanted between 2003 and 2013 at our institution. Zip code of residence was used to obtain median annual household income based on 2010 US Census data. Patients were categorized into low SES ( 〈 $50,000/yr) and high SES (≥$50,000/yr) based on the household income cutpoint identified by recursive partitioning analysis for predicting survival. Low SES patients were significantly more likely to live further away from our center (median 54 vs 28 miles), belong to non-White racial group (12% vs 3%), have lower performance status score (4% vs 1% with ECOG 〉 1/KPS 〈 80), and have high disease risk at ASCT (9% vs 5%). Patient, disease and transplant characteristics were otherwise comparable. 93% patients received a conditioning regimen consisting of high-dose busalfan, cyclophosphamide and etoposide. Median followup was 53 months. In univariate analysis, low SES patients had significantly higher relapse mortality and lower overall survival (OS) and progression-free survival (PFS) (see table and figures). This was confirmed on multivariable analysis for relapse mortality (for high SES vs. low SES: HR 0.74 [95% CI, 0.54-0.99], P=0.05), OS (HR 0.74 [0.58-0.95] , P=0.02) and PFS (HR 0.77 [0.63-0.95], P=0.02). We also conducted an analysis in the subgroup of patients who had survived in remission for ≥1-year post-HCT to investigate whether SES was associated with outcomes following transition from transplant center to community providers (see table and figures). Interestingly, in multivariable analysis, high SES patients had better OS (HR 0.73, P=0.05 vs low SES) that was primarily driven by a lower risk of NRM (HR 0.62, P=0.06). We did not observe any association between race/ethnicity and distance from transplant center with ASCT outcomes in multivariable analysis that included all recipients or in the analysis limited to 1-year survivors. In conclusion, lower SES is associated with poor survival in patients receiving ASCT for lymphoma. Low SES patients have higher risks of relapse related mortality compared to high SES patients. In patients surviving in remission for 〉 1 year, however, mortality in the low SES group in primarily mediated through non-relapse causes. Our study highlights the need for active interventions to mitigate health care disparities in this high risk population. Table. 5-year outcomes after ASCT for lymphoma by SES Outcomes All patients, N=687 1-yr survivors, N=551 Low SES High SES P-value Low SES High SES P-value Relapse mortality 29% 25% 0.03 16% 18% 0.53 NRM 16% 12% 0.18 14% 9% 0.07 OS 55% 64% 0.004 70% 74% 0.07 PFS 41% 47% 0.01 57% 58% 0.25 Figure 1. OS for all patients and 1-year survivors Figure 1. OS for all patients and 1-year survivors Figure 2. Figure 2. Disclosures Hill: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees. Majhail:Gamida Cell Ltd.: Consultancy; Anthem Inc.: Consultancy.

Abstract: Patients under consideration for allogeneic hematopoietic cell transplantation (HCT) undergo comprehensive evaluation, including psychosocial assessment, to evaluate their candidacy for transplant. Psychosocial factors such as presence of availability of a consistent care-partner, mental health needs, psychological issues such as depression and severe anxiety, and compliance can impact risks of toxicity and adverse outcomes including survival. However, instruments to objectively characterize psychosocial status in this population are generally lacking. Our group has previously assessed the Psychosocial Assessment of Candidates for Transplant (PACT) scale, originally developed for solid organ transplant recipients, to screen for psychosocial risk factors in allogeneic HCT patients (Foster et al, BMT, 2009). The PACT captures information in four domains (social support, psychological health, lifestyle factors, and patients understanding of the transplant process). The overall impression of the patient's suitability for transplantation is assigned a final PACT score ranging from 0 (poor candidate) to 4 (excellent candidate). We conducted a retrospective cohort study of 404 adult allogeneic HCT recipients (median age 50 [range, 18-73] years) between 2003 and 2014 at our institution to evaluate the association of PACT scale with other baseline clinical and sociodemographic factors and quality of life (QOL) prior to HCT, and its association with HCT outcomes. Patients were pre dominantly male (54%), White (89%), had acute leukemia/MDS (77%), had unrelated donor (55%), and received myeloablative regimens (78%). Based on ZIP code of residence, median annual household income for our cohort was $49,159 and 80% resided in Rural Urban Commuting Area designated urban area. Final PACT rating was poor/borderline (0-1) in 21 (5%), acceptable (2) in 87 (22%), good (3) in 177 (44%), and excellent (4) in 119 (29%) recipients. Significantly higher PACT ratings were observed in patients who were White (P=0.004), had higher household income (p=0.019), higher Karnofsky performance score (P=0.011), and low risk HCT-Comorbidity Index score (P=0.007). Final PACT rating was weakly correlated with the pre-HCT FACT BMT total QOL score (R=0.22), including its subdomains. A trend towards more days alive and outside the hospital in the first 100 days post-HCT was seen in patients with higher final PACT score (median 58, 65, 66, and 70 days for scores 0-1, 2, 3, and 4) in both univariable (P=0.07) and multivariable (P=0.09) analysis. At 1-year after HCT, cumulative incidence of non-relapse mortality for patients with PACT score 0-1 was 33%, for score 2 was 24%, for score 3 was 27% and score 4 was 16%. The 1-year overall survival probability for the four groups was 57%, 60%, 59% and 67%, respectively. In multivariable analysis that adjusted for patient and disease characteristics (including race/ethnicity, household income, place of residence and pre-HCT QOL), final PACT rating was associated with non-relapse mortality (HR 0.82 per point increase [95% CI, 0.69-0.98], P=0.03), but not with overall survival (HR 0.91 [95% CI, 0.79-1.05] , P=0.18). There was no association between final PACT rating and neutrophil or platelet engraftment, acute or chronic graft-versus-host disease, or relapse. In conclusion the PACT scale provides prognostic information for NRM independent of clinical and other sociodemographic factors as an indicator of psychosocial adjustment post-HCT. The PACT scale can serve as a useful tool for screening adult patients for psychosocial risk factors prior to allogeneic HCT and may identify patients who need additional social support and resources to minimize risks of mortality after transplantation. Disclosures No relevant conflicts of interest to declare.

Abstract: Background While allogeneic hematopoietic cell transplantation (alloHCT) can be curative for patients with acute myeloid leukemia (AML), relapse remains a significant challenge. Previous work has suggested that disease status at time of transplant and cytogenetics are important predictors of relapse. However, it is unclear if common somatic mutations or dimorphisms of MHC class I chain-related gene A (MICA), a ligand of the natural killer (NKG2D) receptor on immune effector cells that helps mediate NK cell alloreactivity, also contribute. Moreover, the mechanisms of early relapse are an area of ongoing investigation. We assessed risk factors for relapse within 6 and 12 months after alloHCT. Methods We conducted a single center, retrospective analysis of adults with AML who underwent a first alloHCT. Analysis was restricted to patients with T-cell replete HLA-8/8 matched related or unrelated donor. In addition to cytogenetic risk group stratification by European LeukemiaNet criteria (Döhner H, et al, Blood 2016), a subset of patients had a 36-gene somatic mutation panel assessed prior to alloHCT by next-generation sequencing. Dimorphisms at the MICA-129 position have previously been categorized as weaker (valine/valine: V/V), heterozygous (methionine/valine: M/V), or stronger (methionine/methionine: M/M) receptor binding affinity. Risk factors for early relapse were assessed with Fine and Gray competing risk regression with results as hazard ratios (HR) and 95% confidence intervals (CI). Results From 2000 - 2017, 319 adult AML patients were identified meeting inclusion criteria. Median age at transplant was 51 years (range, 18-74), with 95% Caucasian. The distribution of low, intermediate, and high HCT-CI scores was 28%, 28%, and 44%, respectively. 75% of patients were transplanted ≤12 months from diagnosis. Disease status at transplant included 48% in first complete remission (CR1), 19% in second CR (CR2), 33% in third CR or relapsed/refractory or untreated (collectively, 〈 CR2). By cytogenetic risk stratification, 13% of patients had favorable, 58% had intermediate, and 29% had adverse-risk cytogenetics. The four most common somatic mutations were FLT3 (12%), NPM1 (10%), DNMT3A (7%), and TET2 (6%). MICA mismatch was present in 10% of patients. The distribution of donor MICA-129 dimorphisms were 44% V/V, 51% M/V, and 5% M/M. 56% of patients had a related donor. A myeloablative transplant was performed in 88% of patients and 63% had a BM graft source. Conditioning with busulfan/cyclophosphamide was used in 56% of patients. In univariable analysis, non-Caucasian race, disease status 〈 CR2, and adverse cytogenetics were risk factors for relapse within 6 months; all but race were also risk factors for relapse within 12 months. None of the somatic mutations assessed, MICA mismatch, nor dimorphisms at the MICA-129 position were identified as risk factors for early relapse. In multivariable analysis, relative to CR1, patients in 〈 CR2 was a risk factor for relapse within 6 months (HR 2.21, CI 1.28-3.82, P=0.005) and 12 months (HR 2.23, CI 1.39-3.58, P 〈 0.001), while patients in CR2 also had higher risk of relapse within 12 months relative to CR1 (HR 2.02, CI 1.10-3.70, P=0.024) (Figures 1A, 1B). In addition, adverse-risk cytogenetics were a risk factor for relapse within 6 months (HR 3.96, CI 1.33-11.8, P=0.013) and 12 months (HR 3.58, CI 1.67-7.68 P=0.001) (Figures 2A, 2B). Relapse incidence estimates (CI) at 6 months were 16% (11-22) CR1, 15% (7-25) CR2, and 33% (24-42) 〈 CR2; estimates were 10% (3-22) for favorable, 17% (12-23) intermediate, and 31 % (22-41) adverse-risk cytogenetics. Relapse incidence estimates at 12 months were 21% (15-28) CR1, 30% (19-41) CR2, and 42% (33-52) 〈 CR2; estimates were 21% (10-36) for favorable, 21% (15-27) intermediate, and 47% (36-57) adverse-risk cytogenetics. Conclusion Relapse after alloHCT for AML remains a challenge. In our study, the strongest risk factors for early relapse after alloHCT remains absence of CR1 disease status at transplant and adverse-risk cytogenetics. We observed no prognostic effect of somatic mutations nor MICA dimorphisms prior to transplant on 6 or 12-month relapse post-transplant. Further interrogation of pre-transplant or post-transplant persistence of somatic mutations in a larger series may better risk stratify subjects who may benefit from more intensive or innovative approaches to prevent post-transplant relapse. Disclosures Nazha: MEI: Consultancy. Advani:Amgen: Research Funding; Pfizer: Honoraria, Research Funding; Novartis: Consultancy; Glycomimetics: Consultancy. Carraway:Novartis: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Balaxa: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; FibroGen: Consultancy; Jazz: Speakers Bureau; Agios: Consultancy, Speakers Bureau. Gerds:Celgene: Consultancy; Apexx Oncology: Consultancy; Incyte: Consultancy; CTI Biopharma: Consultancy. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees. Maciejewski:Apellis Pharmaceuticals: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Apellis Pharmaceuticals: Consultancy; Ra Pharmaceuticals, Inc: Consultancy; Ra Pharmaceuticals, Inc: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Majhail:Atara: Honoraria; Incyte: Honoraria; Anthem, Inc.: Consultancy.

Abstract: Allogeneic hematopoietic cell transplantation (alloHCT) is a curative therapy for high-risk acute lymphoblastic leukemia (ALL). However, long-term outcomes after alloHCT for adult ALL have not been well described. We conducted a retrospective cohort study of 72 consecutive adult ALL patients who underwent a first myeloablative alloHCT at our institution from January 2000-December 2013. Median age at HCT was 38 yrs (range, 18-62), 40 (56%) were male, 18 (38%) had high HCT CI score, 14 (19%) had prior CNS leukemia and 35 (49%) had BCR-ABL+ disease. Donor source was HLA-matched related donor for 50% patients and 90% received PBSC as graft source. All patients were transplanted in CR (72% were in 1st or 2nd CR) and 92% received T-cell replete grafts. Median time from diagnosis to alloHCT was 5 months (range, 2-90). The incidences of grade II-IV and III-IV acute GvHD, chronic GvHD and extensive chronic GvHD were 43%, 13%, 51% and 36%, respectively. The median follow-up for our cohort is 76 months. At 6 years after HCT, probability of overall survival (OS) was 33% (95% CI, 21-44%) and relapse-free survival (RFS) was 30% (95% CI, 19-42%), and the cumulative incidence of relapse was 36% (95% CI, 25-48%) and non-relapse mortality (NRM) was 37% (95% CI, 26-49%). The most common causes of death were relapse (43%) and infection (21%); majority of relapses occurred within the first 2-years post-transplantation. There were no second cancer related deaths. In multivariable analyses, factors significantly associated with OS were HCT CI score (HR 2.69 for high vs. low/int., P=0.002) and CMV status (HR 2.62 for donor+ vs. others, P=0.05). HCT CI score was the only predictive factor for RFS (HR 2.26 for high, P=0.007). We also compared outcomes by BCR-ABL status. BCR-ABL+ patients were older (median age 42 vs. 36 yrs, p=0.02), had low HCT CI score (34% vs 22%, p=0.01), were more likely to be in CR1 (74% vs. 32%, p=0.002), and as a result, proceeded to HCT sooner after diagnosis (median 4 vs 7 months, p= 〈 0.001). For BCR-ABL+ and BCR-ABL- patients, 6 year OS was 41% and 25%, RFS was 40% and 21%, relapse was 27% and 45% and NRM was 38% and 36% (P=NS for all comparisons). Myeloablative alloHCT can provide long-term survival for selected high-risk adult ALL patients. Relapses are relatively uncommon after 2 years post-transplant. Long-term NRM is high in this population and we did not observe a plateau in its incidence until 7.5 years post-transplant, suggesting the need for long-term follow up to prevent and manage late complications of alloHCT. Figure 1. Figure 1. Disclosures Majhail: Gamida Cell Ltd.: Consultancy; Anthem Inc.: Consultancy.

Abstract: Background MHC class I chain-related gene A (MICA) is a polymorphic ligand of the natural killer (NKG2D) receptor on immune effector cells. The activating NKG2D receptor controls immune responses by regulating NK cells, NKT cells and γδ-T cells. Dimorphisms at sequence position 129 of the MICA gene confers varying levels of binding affinity to NKG2D receptor. MICA previously has been associated with post-allogeneic hematopoietic cell transplantation (alloHCT) outcomes including graft-versus-host-disease (GvHD), infection, and relapse. However, it is unclear how MICA interacts with cytogenetic and somatic mutations in regards to these outcomes in acute myeloid leukemia (AML). Methods We conducted a single center, retrospective analysis of adult AML patients in first or second complete remission (CR1, CR2), who underwent T-cell replete matched related or unrelated donor alloHCT. Analysis was limited to those who had MICA data available for donors and recipients. In addition to cytogenetic risk group stratification by European LeukemiaNet criteria (Döhner H, et al, Blood 2016), a subset of patients had a 36-gene somatic mutation panel assessed prior to alloHCT by next-generation sequencing. Dimorphisms at the MICA-129 position have previously been categorized as weaker (valine/valine: V/V), heterozygous (methionine/valine: M/V), or stronger (methionine/methionine: M/M) receptor binding affinity. Fine and Gray or Cox regression was used to identify the association of MICA and outcomes with results as hazard ratios (HR) and 95% confidence intervals (CI). Results From 2000 - 2017, 131 AML patients were identified meeting inclusion criteria. Median age at transplant was 54 years (18-74), with 98% Caucasian. Disease status at transplant included 78% CR1 and 22% CR2. Cytogenetic risk stratification showed 13% of patients as favorable, 56% as intermediate, and 31% as adverse-risk. The five most common somatic mutations were FLT3 (15%), NPM1 (14%), DNMT3A (11%), TET2 (7%), and NRAS (6%). 60% of patients had a related donor. A myeloablative transplant was performed in 84% of patients and 53% had a bone marrow graft source. The most common conditioning regimen used was busulfan/cyclophosphamide (52%). 12% of patients were MICA mismatched with their donor. The distribution of donor MICA-129 polymorphisms were 41% V/V, 53% M/V, and 6% M/M. In univariable analysis, donor-recipient MICA mismatch tended to be associated with a lower risk of infection (HR 0.49, CI 0.23-1.02, P=0.06) and grade 2-4 acute GvHD (HR 0.25, CI 0.06-1.04, P=0.06) but was not associated with other post-transplant outcomes. In multivariable analysis, donor MICA-129 V/V was associated with a higher risk of non-relapse mortality (NRM) (HR 2.02, CI 1.01-4.05, P=0.047) (Figure 1) along with increasing patient age at transplant (HR 1.46, CI 1.10-1.93, p=0.008) and the presence of a TET2 mutation (HR 6.00, CI 1.77-20.3, P=0.004). There were no differences between the V/V and the M/V+M/M cohorts regarding somatic mutational status, cytogenetics and other pre-transplant characteristics and post-transplant outcomes. With a median follow-up of 65 months for both cohorts, 45% vs. 49% of patients remain alive, respectively. The most common causes of death between the V/V and the M/V+M/M cohorts was relapse (38% vs. 62%) and infection (31% vs. 8%), respectively. Conclusion While previous studies have demonstrated associations of somatic mutations and cytogenetics with survival outcomes after alloHCT for AML, we observed mutations in TET2 and the V/V donor MICA-129 polymorphism to be independently prognostic for NRM. Mechanistic studies may be considered to assess for possible interactions of TET2 mutations with NK cell alloreactivity. The weaker binding affinity to the NKG2D receptor by the V/V phenotype may diminish immune responses against pathogens that subsequently contribute to higher NRM. These observations may have implications for enhancing patient risk stratification prior to transplant and optimizing donor selection. Future investigation with larger cohorts interrogating pre-transplant AML somatic mutations with MICA polymorphisms on post-transplant outcomes may further elucidate which subsets of patients may benefit most from transplant. Disclosures Nazha: MEI: Consultancy. Mukherjee:Pfizer: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Projects in Knowledge: Honoraria; BioPharm Communications: Consultancy; Bristol Myers Squib: Honoraria, Speakers Bureau; Takeda Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; LEK Consulting: Consultancy, Honoraria; Aplastic Anemia & MDS International Foundation in Joint Partnership with Cleveland Clinic Taussig Cancer Institute: Honoraria. Advani:Amgen: Research Funding; Pfizer: Honoraria, Research Funding; Glycomimetics: Consultancy; Novartis: Consultancy. Carraway:Novartis: Speakers Bureau; Balaxa: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Speakers Bureau; FibroGen: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Speakers Bureau. Gerds:Apexx Oncology: Consultancy; Celgene: Consultancy; Incyte: Consultancy; CTI Biopharma: Consultancy. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees. Maciejewski:Apellis Pharmaceuticals: Consultancy; Ra Pharmaceuticals, Inc: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Ra Pharmaceuticals, Inc: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Apellis Pharmaceuticals: Consultancy. Majhail:Incyte: Honoraria; Anthem, Inc.: Consultancy; Atara: Honoraria.