Citations

Patients who develop therapy-related myelodysplastic syndromes (t-MDSs) or acute myeloid leukemia (t-AML) following prior chemotherapy or an autologous hematopoietic cell transplant (HCT), have a poor prognosis. An earlier analysis of allogeneic HCT (n=868, 1990-2004) showed 5-year overall survival (OS) and disease free survival (DFS) were 22% and 21% (reference). Furthermore, older age, graft source other than a HLA-matched sibling or HLA well matched unrelated donor (URD), t-AML not in remission or advanced t-MDS, and poor risk cytogenetics were associated with worse outcomes. Modern supportive care and conditioning regimens including reduced intensity (RIC) regimens may have improved outcomes. Therefore we analyzed 1531 HCT for t-AML (n = 772) or t-MDS (n = 759) performed from 2000 to 2014. The median age at transplant was 52 (18-77) for t-AML and 59 (18-74) for t-MDS. Eleven percent of patient with t-AML and 24% of patient with t-MDS had a prior autologous transplant. A myeloablative regimen was used for conditioning in 61% of patients with t-AML and 49% of patients with t-MDS (Table 1). For t-AML, the 5-year non-relapse mortality (NRM) and relapse rates (RR) were 33% (95% confidence interval [CI], 30-36) and 43% (40-47), respectively. For t-MDS, the 5 year TRM and RR were 32% (29-36) and 46% (43-50), respectively. Five year DFS and OS were 24% (21-27) and 25% (22-28), respectively, for patients with t-AML. Five year DFS and OS were 21% (18-24) and 27% (23-31), respectively, for patients with t-MDS. In multivariate analysis, t-AML OS and DFS was worse for: previous autologous transplant, relapsed disease at HCT, intermediate or adverse cytogenetics, partially matched and cord blood grafts, and RIC. For t-MDS: age greater than 60, previous autologous transplant, very high IPSS score, and use of HLA-partially matched unrelated grafts. A significant minority of patients with t-AML and t-MDS can achieve long-term remission with allogeneic HCT, yet risks of both NRM and relapse are still excessive. Relapse is the major cause of treatment failure. Disclosures Metheny: Takeda: Speakers Bureau; Incyte: Speakers Bureau. Weisdorf:Incyte: Research Funding; Fate Therapeutics: Consultancy; Pharmacyclics: Consultancy. Kebriaei:Jazz: Consultancy; Amgen: Research Funding; Pfizer: Honoraria; Kite: Honoraria.

Although some data (Scott, JCO 2017) suggest that myeloablative conditioning (MAC) is preferred for allogeneic hematopoietic cell transplantation (HCT) in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), these data were not informed by analysis of disease specific risk factors. We analyzed AML and MDS HCT outcomes stratified by the disease risk index (DRI) in order to identify the preferred transplant conditioning intensity (reduced-intensity conditioning [RIC] vs. MAC). In this large CIBMTR registry study we identified 4387 adult patients (age 40-65 years) who received HCT for AML (68%) or MDS (32%) between 2009 and 2015. DRI was stratified as low/ intermediate risk (1539 MAC and 999 RIC) and high/ very high risk (1121 MAC and 728 RIC). Examining the low/ intermediate risk DRI cohort (Table), RIC was associated with lower risk of TRM (HR=0.74, 95% CI 0.62-0.88; p<0.001) but significantly higher risk of relapse (HR=1.54, 95% CI 1.35-1.76; p<0.001). As a result, RFS in this cohort was significantly worse with RIC (HR=1.19, 95% CI 1.07-1.33; p=0.001). In the high/ very high risk DRI cohort, RIC resulted in similar TRM (HR=0.83, 95% CI 0.68-1.00; p=0.051) but again significantly higher risk of relapse (HR=1.23, 95% CI 1.08-1.41; p=0.002). RFS in high/ very high risk DRI cohort was similar between RIC and MAC. Adjusted outcome curves for the 3 endpoints are shown in the Figure. In this large study of HCT for AML or MDS stratified by DRI, RIC was independent predictor of lower TRM, but significantly higher risk of relapse. The MAC was an independent predictor of lower relapse in both low/ intermediate and high/very high DRI groups. However, MAC only resulted in RFS benefit in the low/ intermediate group where the magnitude of impact on relapse was not offset by the higher TRM. In adults with AML or MDS aged 40-65 years, these data support MAC as the preferred conditioning intensity for low/ intermediate risk DRI, whereas MAC does not provide significant benefit in those with high/ very high risk DRI. Safer, yet still potent MAC regimens could benefit this higher risk group. Disclosures Bejanyan: Kiadis Pharma: Other: advisory board. Brunstein:Gamida: Research Funding; Astex: Research Funding; Magenta: Research Funding. Kebriaei:Amgen: Research Funding; Jazz: Consultancy; Pfizer: Honoraria; Kite: Honoraria; Pfizer: Honoraria; Kite: Honoraria. Weisdorf:Fate Therapeutics: Consultancy; Pharmacyclics: Consultancy; Incyte: Research Funding.

Introduction: AML patients with intermediate or high-risk features often undergo allogeneic hematopoietic cell transplantation (alloHCT) during first complete remission (CR). The 2017 European LeukemiaNet guidelines for AML specify categories of CR: both with and without count recovery (CR vs. CRi) and with and without measurable residual disease (MRD). Previous smaller retrospective studies have suggested poorer survival outcomes after alloHCT for patients with responses less than CR. Methods: Eligible cases were determined using the CIBMTR registry. Each had AML in CR1, was ≥ 18 years, and underwent alloHCT between January 1, 2007 and December 31, 2015. MRD was defined based on the answers to qualitative questions on standard clinical reporting forms that ask if the patient is in either molecular or cytogenetic remission and if disease is detected in marrow by flow cytometry at time of HCT. The primary outcome was overall survival (OS), and secondary outcomes were non-relapse mortality (NRM), relapse and disease-free survival (DFS). The Kaplan-Meier method was used to estimate survival and cumulative incidence function was used to estimate relapse and NRM. Multivariable analysis (MVA) was performed using the Cox proportional hazards model to adjust for patient-, disease-, and transplant-related factors. Adjusted probabilities of DFS and OS, adjusted cumulative incidence curves of NRM and relapse were generated from final Cox regression models stratified on CR vs. CRi and weighted averages of covariate values using pooled sample proportion as weight function. Results: We identified 2492 cases (CR, n=1799; CRi, n=693). The main effect variable (CR vs. CRi) was missing in 262 additional patients; these patients were excluded when univariate analysis confirmed no significant associations, suggesting a random distribution of missing data. Patient characteristics are summarized in Table 1. Compared with patients with CR, patients with CRi were more likely to have a Karnofsky score <90 (38% vs. 31%) and an HCT-CI score 3+ (47% vs. 40%). Other variables were well matched between the groups. MVA demonstrated significantly increased likelihood of mortality in patients with CRi compared to those with CR with hazard ratio (HR) 1.27; 95% confidence interval (CI) (1.13-1.43) (Figure 1A). Other covariates significantly associated with shorter OS included older age, poor-risk cytogenetics, lower Karnofsky score, higher HCT-CI score, and higher white blood cell count at diagnosis. The adjusted OS probabilities at 5 year post-HCT accounted for factors from MVA model are 50% (95%CI 47-52) for patients with CR and 43% (95%CI 39-47) for patients with CRi. CRi was also associated with significantly increased NRM [HR 1.33, 95%CI(1.11-1.59)] with only a trend in increased relapse [HR 1.15, 95% CI(0.99-1.34), p=0.07] resulting in inferior DFS [HR 1.20, 95%CI(1.07-1.35)]. MRD status was available in a subset of 2297 patients, and pairwise comparison demonstrated that presence of MRD was associated with shorter OS, shorter DFS, higher NRM, and increased relapse compared to absence of MRD (Figure 1B). Pairwise interaction between the main effects (CR vs. CRi) and MRD status were tested with no significant findings at a level of 0.01, demonstrating that the effects of incomplete count recovery and MRD are independent of each other. Conclusions: Analysis of this large CIBMTR cohort demonstrates that survival outcomes differ among AML patients nominally in CR at the time of alloHCT. Patients with CRi and/or MRD have significantly shorter OS after alloHCT compared to those in CR, as well as shorter DFS and higher NRM. Further studies should focus on limiting NRM and reducing relapse to optimize post-alloHCT outcomes for patients with responses less than CR. Disclosures Percival: Pfizer Inc.: Research Funding; Nohla Therapeutics: Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees. Kebriaei:Jazz: Consultancy; Pfizer: Honoraria; Amgen: Research Funding; Kite: Honoraria. Weisdorf:Fate Therapeutics: Consultancy; Incyte: Research Funding; Pharmacyclics: Consultancy.

Abstract Introduction: The preferred post-remission therapy for older patients (pts) with AML remains uncertain. We compared outcomes for older AML pts in CR1 receiving HCT reported to the CIBMTR to older AML pts achieving CR1 on National Clinical Trials Network induction and non-HCT consolidation therapy (CT) trials. Methods: This study focused on pts 60-75 years of age treated between 2004 to 2013. CT pts (n=211) underwent induction and consolidation on Alliance for Clinical Trials in Oncology, ECOG-ACRIN or SWOG clinical trials for initial therapy for newly diagnosed AML; the CIBMTR provided data for HCT pts (n=431). CT patients received at least one cycle of CT on study and were excluded if HCT occurred at any time. Time to event started at CR1 and pts entered at CT or HCT, respectively, using left-truncation to account for differential entry times. Results: For the CT cohort, first consolidation included standard therapy (e.g., cytarabine or a hypomethylating agent) and additional study drug (e.g., bortezomib, dasatinib, sorafenib, and Zosuquidar, gemtuzumab) or tipifarnib alone. Among HCT pts, the donor was a HLA-matched sibling or unrelated donor (URD) in 66% and the others were partially HLA-matched/mismatched URD (10%) or cord blood (24%). HCT pts were younger and more frequently had high-risk AML (high WBC, secondary AML and unfavorable cytogenetics) (Table). The median time from CR1 to HCT and CT was 3.2 and 0.5 months, respectively. Allogeneic HCT showed worse overall survival (OS) (HR=1.52, p=0.02) prior to 9 months and better OS thereafter (HR= 0.53, p <0.0001) relative to CT (figure 1A). Treatment-related mortality (TRM) was worse after HCT in the first 9 months (HR=2.8, CI: 1.5 -5.2, p=.0009), while relapse was less frequent beyond 9 months after treatment (HR = 0.42, CI: 0.29 to 0.61, p<.0001). Despite higher early TRM, HCT recipients went on to manifest superior OS [5 year OS: HCT 29% (24-34%), CT 13.8% (9 -22%)] (Figure 1A). The benefit of HCT for survival after 9 months was more prominent in those with unfavorable cytogenetics (Figure 1B). Multivariate analysis for OS showed no statistically significant effect of age or performance status, while unfavorable cytogenetics were detrimental (HR=1.74, p<.0001). Conclusions. Allogeneic HCT led to heightened early risks from TRM, but resulted in superior long-term survival in older AML pts receiving HCT relative to CT by reducing relapse. Efforts to attenuate early TRM after allogeneic HCT may further improve HCT outcomes for older pts. Disclosures Ustun: novartis: Speakers Bureau. Attar:Agios: Employment, Equity Ownership. Larson:Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; BristolMyers Squibb: Consultancy, Research Funding; Ariad/Takeda: Consultancy, Research Funding. Roboz:Roche/Genentech: Consultancy; Eisai: Consultancy; Cellectis: Research Funding; Aphivena Therapeutics: Consultancy; Sandoz: Consultancy; Janssen Pharmaceuticals: Consultancy; Otsuka: Consultancy; Jazz Pharmaceuticals: Consultancy; Sandoz: Consultancy; AbbVie: Consultancy; Celltrion: Consultancy; Cellectis: Research Funding; Eisai: Consultancy; Astex Pharmaceuticals: Consultancy; Argenx: Consultancy; Pfizer: Consultancy; Celgene Corporation: Consultancy; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy; Bayer: Consultancy; Bayer: Consultancy; Roche/Genentech: Consultancy; Orsenix: Consultancy; Astex Pharmaceuticals: Consultancy; Celgene Corporation: Consultancy; Daiichi Sankyo: Consultancy; Pfizer: Consultancy; Janssen Pharmaceuticals: Consultancy; Otsuka: Consultancy; Orsenix: Consultancy; Daiichi Sankyo: Consultancy; Celltrion: Consultancy; Novartis: Consultancy; Aphivena Therapeutics: Consultancy; Argenx: Consultancy; AbbVie: Consultancy. Uy:GlycoMimetics: Consultancy; Curis: Consultancy. Stone:Fujifilm: Consultancy; Ono: Consultancy; Orsenix: Consultancy; Otsuka: Consultancy; Agios: Consultancy, Research Funding; AbbVie: Consultancy; Argenx: Other: Data and Safety Monitoring Board; Celgene: Consultancy, Other: Data and Safety Monitoring Board, Steering Committee; Arog: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Jazz: Consultancy; Astellas: Consultancy; Merck: Consultancy; Pfizer: Consultancy; Sumitomo: Consultancy; Amgen: Consultancy; Cornerstone: Consultancy. Foran:Agios: Research Funding; Xencor, Inc.: Research Funding. Weisdorf:Seattle Genetics: Consultancy; Equillium: Consultancy; FATE: Consultancy; SL Behring: Consultancy; Pharmacyclics: Consultancy.

Abstract Multiple Myeloma (MM) is the most common indication for autologous hematopoietic stem cell transplantation (auto HCT). However, little information is available regarding the outcome of patients (pts) with the rarer immunoglobulin subtypes IgD and IgM, which represent 2% and 0.5%, respectively, of all MM cases. In addition, IgD MM has been reported previously to have a poorer prognosis, at least after conventional therapy. The CIBMTR conducted a retrospective analysis of MM pts transplanted between 1995–2005 to describe the characteristics and results of auto HCT in IgD (n=36) and IgM (n=11) among 3578 MM patients with auto HCT during this period. Median follow-up of survivors was 41 (range 2–130) months for pts with IgD and 58 (range 5–101) months for those with IgM MM. Among pts with IgD subtype, median age was 52 years (yrs), 67% were male, 36% had a creatinine >2 mg/L, 61% had Durie-Salmon stage III disease at diagnosis and 33% had Kappa Serum Light chain; the corresponding values for IgM pts were 58 yrs, 36%, 73% and 55% respectively. Prior to auto HCT, 75% of IgD pts were chemosensitive and 25% had received >2 lines of chemotherapy, while all IgM pts were chemosensitive and none had received more than 2 lines of prior therapy. Median time from diagnosis to auto HCT was 9 months in both subtypes. The most common conditioning regimen was singleagent melphalan, and all but 1 pt with IgD disease were grafted with blood stem cells. The small sample size precluded multivariate analysis for potential prognostic factors for outcome. Below table summarizes the post-auto HCT results in these pts contrasted with a reference pool of IgG and IgA MM receiving auto HCT in the same time period. Outcomes, probability (95% CI) IgD IgM IgG/IgA (n=36) (n=11) (n=1475) 100-day mortality, % 0 9 ( 0 – 32) 7 (5 – 8) Non MM deaths, % @ 1 yr 0 9 (0 – 32) 5 (4 – 7) @ 3 yrs 3 (0 – 13) 21 (2 – 51) 16 (14 – 18) Relapse/ Progression, % @ 1 yr 21 (9 – 37) 20 (2 – 49) 18 (16 – 20) @ 3 yrs 59 (41 – 76) 32 (8 – 64) 36 (34 – 39) Progression-free survival, % @ 1 yr 79 (63 – 91) 71 (41 – 93) 77 (74 – 79) @ 3 yrs 38 (21 – 56) 47 (17 – 78) 47 (44 – 50) Overall survival, % @ 1 yr 87 (74 – 97) 91 (68 – 100) 79 (77 – 85) @ 3 yrs 69 (51 – 84) 68 (36 – 93) 53 (50 – 57) No striking differences are apparent in the post auto HCT outcomes of patients with IgD and IgM MM. These results are also consistent with published outcomes of pts with IgD/ IgM MM (Wechaleker et al Ann Hematol. 2005 Feb; 84(2):115–7; Maisner et al Bone Marrow Transplant. 2008 Jan; 41(1):51–4).

Abstract Abstract 532 Primary Plasma cell leukemia (PCL) is a rare plasma cell disorder characterized by an aggressive clinical course. The efficacy of autologous and allogeneic HCT in PCL is uncertain due to the small number of patients that have been reported in the literature. To determine the potential for long-term disease control using HCT in PCL, we performed a retrospective review of 160 patients with primary PCL who received autologous (n=107), allogeneic (n=52) or syngeneic (n=1) HCT and were reported to the CIBMTR between 1995 and 2006. Kaplan–Meier analysis was used for overall survival (OS) and progression free survival (PFS). Cumulative incidence estimates of non-relapse mortality (NRM), relapse, acute and chronic GVHD were calculated. Median age at the time of autologous HCT was 57 years (range, 32-74 years) and allogeneic HCT was 48 years (range, 24-62 years). Median time from initial treatment to autologous HCT was 7 months and allogeneic HCT was 6 months. At the time of transplant, in the autologous HCT group, 19% patients were in complete remission, 56% in partial remission and 1% had relapsed/progressive disease; in the allogeneic HCT group, 17% were in complete remission, 46% in partial remission and 10% had relapsed/progressive disease. In the allogeneic HCT group, 83% of the patients received myeloablative conditioning regimens and 17% received nonmyeloablative/reduced-intensity conditioning. The rate of acute GVHD was 35% (95% confidence interval [CI], 22%-49%) and the rate of chronic GVHD at 3 years was 27% (95% CI, 13%-40%). After a median follow-up of 38 months, 20 of the 52 patients (38%) are alive in the allogeneic HCT group and 68 of the 107 pts (64%) are alive in the autologous HCT group (Figure 1). Progressive disease accounted for 38% of the deaths in the allogeneic HCT group and 86% of the deaths in the autologous HCT group. The outcomes are summarized in table 1. The remarkable overall survival of patients after autologous HCT in this analysis is noteworthy and indicates that autologous HCT is a safe and acceptable treatment option for patients with primary PCL. Although relapse rates are lower, allogeneic HCT carries a much higher risk of NRM and should be considered primarily in the context of a clinical trial. Disclosures: Lonial: Celgene: Consultancy; Millennium: Consultancy, Research Funding; BMS: Consultancy; Novartis: Consultancy; Gloucester: Research Funding.

Abstract Abstract 54 Despite its curative potential, the role of allogeneic stem cell transplant (allo-SCT) in MM has been limited by high treatment related mortality (TRM). Autologous stem cell transplant (auto-SCT) thus remains the standard of care for eligible patients (pts) with MM. Recently interest in allo-SCT has been increasing due to the incurable nature of MM, better risk stratification models, improved supportive care and finally the increasing experience with less toxic reduced intensity conditioning. We analyzed the trends in practice of allo-SCT for MM over the past two decades. A total of 1211 pts undergoing allo-SCT for MM between 1989 and 2005, reported to the CIBMTR were analyzed in three cohorts based on year of allo-SCT: 1989–1994 (n=346), 1995–2000 (n=285), and 2001–2005 (n=580). Probabilities of progression-free survival (PFS) and overall survival (OS) and cumulative incidence estimates of TRM and relapse were calculated. Patient characteristics are summarized in table 1. Patients transplanted in the later cohort (2001–2005) were of higher age with 53% above age 50 years (vs. 12% in 1989–1994). There was decreasing use of myeloablative regimens and bone marrow grafts over time (82% vs. 62% vs. 9% for myeloablative regimens and 99%, 62% and 13% for marrow grafts respectively). Increasing number of pts in the later cohort received an auto-SCT prior to allo-SCT (Table 1). The proportion of unrelated allo-SCTs increased over time (5% vs. 21% vs. 33%). Graft versus host (GVH) prophylaxis changed over time with increasing use of cyclosporine with agents other than methotrexate and increasing use of ATG in the recent years. Median survival increased over the three time periods from 1989 – 2005: 11.1 months (mos.) vs. 12.2 mos vs. 20.3 mos. The 100 day mortality decreased steadily over successive time periods; 35% (95% CI; 29–31), 29% (24–35) and 19% (16–23) respectively. Similarly, the TRM at 5 years remained steady between the first two periods, but decreased in the last period (40 & 48% vs. 29%). The incidence of chronic GVHD increased in the later cohort but the incidence of acute GVHD was similar over the years. While PFS was the lowest for the most recent group (15% at 5 years), the overall survival at 5 years was similar among the groups (30, 32, and 29 mos). Long term PFS at 10 years was 18% in the 1989–1994 cohort and 17% in 1995–2000. Long term OS at 10 years was 23% in 1989 – 1994 and 1995–2000 cohorts. Results are summarized in table 1. A clear trend towards reduced intensity conditioning, unrelated donor SCT, use of PBSC grafts and selection of older patients was noted. There was increasing use of tandem auto-allo SCT with an increasing proportion of patients with a prior auto-SCT. While the TRM has decreased significantly in the last cohort, this did not translate into an improvement in survival primarily because of increased risk of relapse in the latter cohort. Long term (>10yr) progression free survival which may approach a cure has remained unchanged over the past two decades at <20%. Disclosures: Lonial: Celgene: Consultancy; Millennium: Consultancy, Research Funding; BMS: Consultancy; Novartis: Consultancy; Gloucester: Research Funding.

Abstract Abstract 53 Prior studies have demonstrated a graft-versus-malignancy effect following allogeneic HSCT that is variably linked to acute or chronic GVHD. Although a graft vs. Myeloma (MM) effect has been shown after myeloablative allogeneic HSCT, a higher treatment related mortality (TRM) risk leads to inferior survival compared with autologous HSCT. Non-myeloablative (NMA) and reduced intensity conditioning (RIC) approaches are used to reduce the risk of TRM while preserving the graft vs. MM effect. The clinical benefit of lower intensity conditioning regimens is thus especially dependent on the impact of acute or chronic GVHD on graft vs. MM effect and TRM. We analyzed the outcomes of 177 matched sibling allogeneic HSCT recipients reported to the CIBMTR between 1997 and 2005 following NMA (n=120) or RIC (n=57) performed within 18 months of diagnosis. Median age was 50 (range 24-69) years and 62% were Durie-Salmon Stage III. Tandem autologous followed by allogeneic HSCT (autologous+ allogeneic) recipients (n=105) were more likely to receive NMA conditioning vs. recipients of an upfront allogeneic HSCT (n=72). Majority (98%) received peripheral blood stem cell grafts. Outcomes at a median follow-up of 36 (3 - 98) months are summarized in table 1. In order to assess the impact of GVHD on outcomes, Cox proportional hazards regression models were built with GVHD as the main effect treating it as a time dependent covariate (Table 2). Other covariates in the multivariate models included age, sex, performance status, IgG vs. non IgG myeloma, disease status and chemosensitivity, prior lines of chemotherapy, donor-recipient sex match, NMA vs. RIC and year of transplant. AGVHD was associated with an increased risk of TRM. Tandem autologous + allogeneic HSCT was associated with reduced relapse risk (RR= 0.49, p=0.008). AGVHD had no impact on relapse/progression of MM while cGVHD was associated with a reduced risk of relapse (Figure. 1). The protective effect of cGVHD on relapse was significant in the non IgG MM subgroup. AGVHD had no impact on PFS whereas cGVHD was associated with superior PFS and lower risk of treatment failure. Later year of HSCT was also associated with superior PFS. Overall survival was not affected by cGVHD while recipients of tandem autologous + allogeneic HSCT had a higher mortality in the presence of aGVHD (RR=3.60, p= 0.01). After matched sibling allogeneic HSCT for MM, aGVHD is associated with a higher risk of TRM whereas cGVHD decreases the risk of relapse and improves PFS. The effect of cGVHD may vary with the type of MM with greater impact in non IgG MM. Further study to identify subtypes of MM susceptible to an immune mediated graft vs. MM effect is suggested. Disclosures: Lonial: Celgene: Consultancy; Millennium: Consultancy, Research Funding; BMS: Consultancy; Novartis: Consultancy; Gloucester: Research Funding.

Abstract Abstract 680 Cytogenetics play an essential role in determining the prognosis of patients with AML. However, there is still no validated cytogenetics grouping scheme that specifically applies to patients undergoing allogeneic stem cell transplantation, which hampers accurate prognostication and risk stratification. We studied 821 adult patients (median age 41, range 18–74) who underwent SCT between 1999 and 2004 for AML (excluding APL) in CR1 or CR2 and who were reported to the CIBMTR from centers with >20 patients meeting study criteria. 75% of patients received a myeloablative conditioning. 496 patients had a normal karyotype. The primary cytogenetics reports were manually reviewed for 92% of the patients with an abnormal karyotype. We compared the ability of the 6 existing grouping schemes (MRC, CALGB, EORTC/GIMEMA, SWOG/ECOG, DFCI, and Monosomal Karyotype (MK) classifications) to stratify patients, using both the Akaike Information Criterion in multivariable models and the C-statistic. Among all existing schemes, the DFCI system provided a marginally superior stratification for overall and leukemia-free survival. We also built a new classification using individual cytogenetic abnormalities in a Cox model that included other significant covariates (performance status, therapy-related disease, conditioning intensity, graft source, donor match, duration of CR1, and gender match). This CIBMTR scheme (see Table), which is similar to the DFCI scheme except for the inclusion of patients with t(8;21) in the intermediate group, could stratify patients into 3 groups with similar treatment-related mortality but significantly different overall survival, leukemia-free survival, and incidence of relapse. This scheme appeared to apply to both patients in CR1 and in CR2 (see FiguresF2). This transplant-specific scheme could be adopted for prognostication purposes and to stratify patients with karyotypic abnormalities entering transplantation clinical trials. Future studies may clarify the relative outcome of patients with t(8;21) and refine this scheme with the inclusion of molecular abnormalities. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 897 Recent changes in allogeneic hematopoietic cell transplantation (HCT) including increased use of reduced-intensity conditioning, peripheral blood cells as the graft source (PB) and unrelated donors (URD) warrant re-evaluation of risk factors for acute graft-versus-host disease (aGVHD) and its impact on overall survival (OS). Risk factors for these outcomes were analyzed using more recent data from CIBMTR observational database. Methods: The cohort included adult patients ≥ 20 y transplanted from an HLA-identical sibling (SD) (n=3191) or URD (N=2370) for acute myelogenous leukemia (AML), acute lymphoid leukemia (ALL), chronic myeloid leukemia (CML), or myelodsyplastic syndrome (MDS) using a T-cell replete graft from 1999–2005. Six groups were created to evaluate the impact of conditioning [(myeloablative (MA) and reduced-intensity or non-myeloablative (RIC)], total-body irradiation (TBI) and graft source [(bone marrow (BM) or PB] as follows: MA+TBI+PB (group 1), MA+TBI+BM (group 2) MA+ no TBI+PB (group 3), MA+ no-TBI+BM (group 4), RIC+PB (group 5) and RIC+BM (group 6). Separate analyses were performed for SD and URD. IBMTR grade was used to classify aGVHD. A p-value of ≤ 0.01 was considered significant. Results: Among the SD cohort, the probability of aGVHD grade B-D and grade C-D at 100 days was 39% (95% CI, 37–41%) and 16% (95% CI, 14–17%). In multivariate analyses, non-TBI based MA regimens with a BM graft (group 4), RIC conditioning with PB (group 5) and tacrolimus plus methotrexate aGVHD prophylaxis were associated with lower odds ratio of grade B-D aGVHD (Table 1). The probability of OS was 51% (95% CI: 49–53%) at 3 y and 46% (95% CI: 44–49%) at 5 y. In multivariate analyses, grade B-D aGVHD was associated with a higher risk of death. Other independent risk factors for OS are shown in Table 2. Among the URD cohort, the probability of aGVHD grade B-D and C-D at 100 days was 59% (95%, CI 57–61%) and 32% (30-34%). In multivariate analysis, BM with MA (TBI and no TBI) or RIC conditioning (groups 2, 4 and 6) were significantly associated with lower odds ratio of grade B-D aGVHD (Table 1). Other independent risk factors included a diagnosis of CML. HCT from a 7/8 HLA-mismatched URD showed a trend for higher incidence of aGVHD (p=0.02). The probability of OS was 38% (95% CI: 35–40%) at 3 y and 33% (95% CI: 31–35%) at 5 y. In multivariate analysis, grade B-D aGVHD was associated with a higher mortality. Table 2 shows other independent risk factors for OS. Conclusion: Intensity of the conditioning regimen, TBI and the graft source has a combined effect on the risk of aGVHD. In both SD and URD cohorts, BM with MA, non-TBI regimens were associated with lower risk of aGVHD. In URD cohort, BM after a RIC also was associated with a reduced risk of aGVHD. Modulation of these risk factors is needed to reduce acute GVHD incidence and death after allogeneic transplantation. Disclosures: No relevant conflicts of interest to declare.