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BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for patients with acute myeloid leukemia (AML). However, post-HCT relapse and regimen-related toxicity remain significant barriers to long-term survival. In recent years, new conditioning regimens have been explored to improve transplantation outcomes in patients with AML. Treosulfan combines a potent immunosuppressive and antileukemic effect with a low toxicity profile. METHODS: To investigate the role of treosulfan-based conditioning, the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party performed a registry analysis of 520 adult patients with AML who received treosulfan-based conditioning and underwent HCT between 2000 and 2012, including 225 patients in first complete remission, 107 in second or later complete remission, and 188 with active/advanced disease 188 (88 with primary refractory disease). The median patient age was 57 years (range, 20-73 years). Donors were human leukocyte antigen-identical siblings (n = 187), unrelated donors (n = 235), or mismatched related donors (n = 98). Conditioning regimens included treosulfan (42 g/m2 [n = 396], 36 g/m2 [n = 109], or 30 g/ m2 [n = 15]) with fludarabine or alkylating agents followed by infusion of hematopoietic stem cells (bone marrow, n = 52; peripheral blood, n = 468). RESULTS: At a median follow-up of 61 months, the 5-year overall survival, leukemia-free survival, relapse incidence, and nonrelapse mortality rates were 38%, 33%, 42%, and 25%, respectively. The incidence of grade II-IV acute and chronic graft-versus-host disease was 24% (grade III-V, 11%) and 38%, respectively. Only 11 patients (2%) developed veno-occlusive disease, with two deaths (0.4%) from veno-occlusive disease. CONCLUSIONS: Treosulfan-based conditioning regimens provide an acceptable long-term survival with favorable nonrelapse mortality and a very low risk of veno-occlusive disease. Further studies are needed to optimize the treosulfan-based conditioning regimen for patients with AML. Cancer 2017;123:2671-79. © 2017 American Cancer Society.

Patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) have a poor prognosis with conventional chemotherapy. In the present study, we retrospectively analyzed the outcome of patients with BPDCN who underwent allogeneic stem cell transplantation (allo-SCT) or autologous stem cell transplantation (auto-SCT). A total of 39 patients (allo-SCT, n = 34; auto-SCT, n = 5) were identified in the European Group for Blood and Marrow Transplantation registry. The 34 allo-SCT patients had a median age of 41 years (range, 10-70) and received transplantations from sibling (n = 11) or unrelated donors (n = 23) between 2003 and 2009. MAC was used in 74% of patients. Nineteen allo-SCT patients (56%) received transplantations in first complete remission. The 3-year cumulative incidence of relapse, disease-free survival, and overall survival was 32%, 33%, and 41%, respectively. By univariate comparison, being in first remission at allo-SCT favorably influenced survival, whereas age, donor source, and chronic GVHD had no significant impact. We conclude that high-dose therapy followed by allo-SCT from related or unrelated donors can provide durable remission even in elderly patients with BPDCN. However, it remains to be shown if graft-versus-malignancy effects can contribute significantly to BPDCN control after allo-SCT.

The feasibility and efficacy of high-dose melphalan followed by autologous hematopoietic stem cell transplantation in newly diagnosed elderly patients with multiple myeloma was analyzed prospectively. Fifty-six multiple myeloma patients, aged 65 years or over, from 6 French centers were studied. The induction therapy was bortezomib-based in combination with dexamethasone and either thalidomide, cyclophosphamide or lenalidomide, for 4-6 cycles. Peripheral blood stem cells were collected after high-dose cyclophosphamide plus G-CSF or G-CSF alone, with plerixafor if needed. The conditioning regimen consisted of melphalan at 140 mg/m2 in 18 patients (36%) and 200 mg/m2 in 32 (64%). Three months post autologous hematopoietic stem cell transplantation, a 2-month consolidation phase with either lenalidomide plus dexamethasone or bortezomib-based combination therapy was allowed, but maintenance treatment was not given. All but 6 patients underwent autologous hematopoietic stem cell transplantation and 3 had tandem transplantations. The treatment-related mortality was 0% at 100 days post transplantation. Sixty-eight percent received consolidation therapy following transplantation. The best response achieved was 40% complete response, 36% very good partial response, and 18% partial response. After a median follow up of 21 months (range 6-31), the estimated progression-free and overall survival rates at two years were 76% [95%CI: (61.6-94.1)] and 88% [95%CI: (76.7-100)], respectively. The higher dose of melphalan (200 mg/m2) afforded superior progression-free and overall survival rates. This prospective study provides evidence for the safety and efficacy of autologous hematopoietic stem cell transplantation as a first-line treatment approach in elderly multiple myeloma patients. (clinicaltrials.gov identifier: 01671826).

In the attempt to harmonize clinical practices between different centers belonging to the Francophone society of bone marrow transplantation and cellular therapy (SFGM-TC), our society set up the sixth annual series of workshops which brought together practitioners from all member centers and took place in September 2015 in Lille. Here, we report our recommendations regarding diagnosis and disease status coding in the ProMISe database used by the SFGM-TC.

BACKGROUND: Autologous stem cell transplantation (ASCT) for adult acute myelogenous leukemia (AML) is a valid therapeutic option for patients with good-risk and intermediate-risk disease. The authors used the registry of the European Society for Blood and Marrow Transplantation to compare combined busulfan and melphalan (BUMEL) with combined busulfan and cyclophosphamide (BUCY) before transplantation. METHODS: From 2005 to 2013, 853 patients with available cytogenetics underwent ASCT in first remission, including 257 after receiving BUMEL and 596 after receiving BUCY. The proportion of patients with good-risk AML was lower in those who received BUMEL (14% vs 20% ; P = .02). More patients who received BUMEL underwent autograft in molecular remission (89% vs 78% ; P = .02). Three years after transplantation, the relapse incidence (RI) was 48.7%, the leukemia-free survival (LFS) rate was 47.7%, the overall survival (OS) rate was 66.2%, and the nonrelapse mortality (NRM) rate was 3.6%. RESULTS: Patients who underwent an autograft after receiving BUMEL fared better than those who underwent an autograft after receiving BUCY with a lower RI (39.5% vs 52.2% ; hazard ratio [HR], 0.65 ; 95% confidence interval [CI], 0.49-0.87 ; P = .003) a better LFS (55.4% vs 44.6% ; HR, 0.69 ; 95% CI, 0.53-0.89 ; P = .005), and a better OS (73.8% vs 63% ; HR, 0.62 ; 95% CI, 0.47-0.82 ; P = .0007). There was no difference in the NRM rate (BUMEL vs BUCY, 4.5% vs 3.2%, respectively). Among 74 patients in the BUMEL group and 187 in the BUCY group who underwent autograft in molecular remission, the RI was 30% versus 51%, respectively (univariate analysis ; P = .01), and the LFS rate was 66% versus 47%, respectively (univariate analysis ; P = .03). CONCLUSIONS: In patients with AML in first complete remission who undergo ASCT, the BUMEL combination is a better preparative regimen. Cancer 2017 ; 123:824-31. © 2016 American Cancer Society.

Background Increasing numbers of patients are receiving haplo-identical stem cell transplantation (haplo-SCT) for treatment of acute leukemia with reduced intensity (RIC) or myeloablative (MAC) conditioning regimens. The impact of conditioning intensity in haplo-SCT is unknown. Methods We performed a retrospective registry-based study comparing outcomes after T-replete haplo-SCT for patients with acute myeloid (AML) or lymphoid leukemia (ALL) after RIC (n = 271) and MAC (n = 425). Regimens were classified as MAC or RIC based on published criteria. Results A combination of post-transplant cyclophosphamide (PT-Cy) with one calcineurin inhibitor and mycophenolate mofetil (PT-Cy-based regimen) for graft-versus-host disease (GVHD) prophylaxis was used in 66 (25 %) patients in RIC and 125 (32 %) in MAC groups. Patients of RIC group were older and had been transplanted more recently and more frequently for AML with active disease at transplant. Percentage of engraftment (90 vs. 92 %; p = 0.58) and day 100 grade II to IV acute GVHD (24 vs. 29 %, p = 0.23) were not different between RIC and MAC groups. Multivariable analyses, run separately in AML and ALL, showed a trend toward higher relapse incidence with RIC in comparison to MAC in AML (hazard ratio (HR) 1.34, p = 0.09), and no difference in both AML and ALL in terms of non-relapse mortality (NRM) chronic GVHD and leukemia-free survival. There was no impact of conditioning regimen intensity in overall survival (OS) in AML (HR = 0.97, p = 0.79) but a trend for worse OS with RIC in ALL (HR = 1.44, p = 0.10). The main factor impacting outcomes was disease status at transplantation (HR ≥ 1.4, p ≤ 0.01). GVHD prophylaxis with PT-Cy-based regimen was independently associated with reduced NRM (HR 0.63, p = 0.02) without impact on relapse incidence (HR 0.99, p = 0.94). Conclusions These data suggest that T-replete haplo-SCT with both RIC and MAC, in particular associated with PT-Cy, are valid options in first line treatment of high risk AML or ALL. Electronic supplementary material The online version of this article (doi:10.1186/s13045-016-0248-3) contains supplementary material, which is available to authorized users.

Clofarabine (CLO), a second-generation purine analogue, has demonstrated an efficient anti-leukemia activity while showing a favorable toxicity profile. This retrospective multicenter report assessed the outcome of 90 patients who received a CLO-containing conditioning regimen before allo-SCT for AML (n = 69) or ALL (n = 21). Median age was 42 yr at transplant. The majority of cases (n = 66) presented with an active disease at transplant while 38 patients had received previous transplantation(s). A total of 88 and two patients received a reduced-intensity conditioning or a myeloablative regimen, respectively. Engraftment was achieved in 97% of evaluable patients. With a median follow-up of 14 months (range, 145), the 2-year OS, LFS, relapse, and NRM rates were 28 +/- 5%, 23 +/- 5%, 41 +/- 6%, and 35 +/- 5%, respectively. When comparing AML and ALL patients, OS and LFS were significantly higher for AML (OS, 35 +/- 6% vs. 0%, P < 0.0001); LFS: 30 +/- 6% vs. 0%, P < 0.0001). In a Cox multivariate analysis, an AML diagnosis was the only factor associated with a better LFS (HR = 0.37; 95%CI, 0.210.66; P = 0.001). We conclude that a CLO-containing conditioning regimen prior to allo-SCT might be an effective treatment. Prospective studies are needed to evaluate the potential role of CLO as part of conditioning regimens in acute leukemias.

This study analysed the outcome of 267 patients with relapse/refractory acute myeloid leukaemia (AML) who received sequential chemotherapy including fludarabine, cytarabine and amsacrine followed by reduced-intensity conditioning (RIC) and allogeneic haematopoietic stem cell transplantation (HSCT). The transplants in 77 patients were from matched sibling donors (MSDs) and those in 190 patients were from matched unrelated donors. Most patients (94·3%) were given anti-T-cell antibodies. The incidence of acute graft-versus-host disease (GVHD) of grades II-IV was 32·1% and that of chronic GVHD was 30·2%. The 3-year probability of non-relapse mortality (NRM) was 25·9%, that of relapse was 48·5%, that of GVHD-free and relapse-free survival (GRFS) was 17·8% and that of leukaemia-free survival (LFS) was 25·6%. In multivariate analysis, unrelated donor recipients more frequently had acute GVHD of grades II-IV [hazard ratio (HR) = 1·98, P = 0·017] and suffered less relapses (HR = 0·62, P = 0·01) than MSD recipients. Treatment with anti-T-cell antibodies reduced NRM (HR = 0·35, P = 0·01) and improved survival (HR = 0·49, P = 0·01), GRFS (HR = 0·37, P = 0·0004) and LFS (HR = 0·46, P = 0·005). Thus, sequential chemotherapy followed by RIC HSCT and use of anti-T-cell antibodies seems promising in patients with refractory AML.

Purpose Nucleated cell dose is an important and modifiable factor in hematopoietic stem cell transplantation (HSCT), however its association with outcomes in the context of reduced intensity conditioning regimen (RIC) HSCT for adults with acute myelocytic leukemia (AML) is not known. Patients and Methods From 1998 to 2003, 253 patients with de novo AML, received transplants with RIC and peripheral blood from a genoidentical donor. Median age was 55 years (range, 18 to 72) and the median follow-up was 17 months (range, 2 to 67). One hundred forty one patients received transplants in first remission (CR1), 47 received transplants in second remission (CR2), and 65 patients received transplants in a more advanced phase. Fludarabin-based RIC was used in 91% of patients and low-dose (< 4 Gy) total-body radiation in 23% of patients. The median nucleated and CD34 cell dose infused were 9.1× 108/kg and 5.8× 106/kg, respectively. Results Overall, 2-year leukemia-free survival (LFS) was 41% ± 4% and it was 46% ± 5% for patients receiving a higher cell dose (> 9.1× 108/kg) and 37% ± 5% for the remainders (P = .03). Higher cell doses exclusively benefited patients who received transplantations in CR2 or beyond, with LFS of 47 ± 8 versus 20 ± 8, with no detectable effect for patients who received transplants in CR1. In a multivariate analysis of the overall patient population, higher nucleated cell dose cells were associated with higher LFS (P = .04), higher incidence of chronic graft-versus-host disease (P = .01), and there was a trend towards a lower relapse incidence (P = .06). Interestingly, CD34+ cell dose was not associated with any outcomes. Conclusion Nucleated cell dose is an important factor that can be modified to improve results of RIC for patients with AML transplanted later than in CR1.

In 1402 patients allografted in Europe during the period 1990-2000 with an HLA-identical sibling in first remission (CR1), the median interval from CR1 to allotransplant (96 days) was a major prognostic factor, patients transplanted earlier having a worse outcome. We studied in depth the 414 fully evaluable patients transplanted less than 96 days after achieving CR1; in these patients, only three factors predicted for the outcome by multivariate analysis: patient age, CR1 achievement with one or more induction courses and the recipient/donor sex combination. These three factors overcame the information from cytogenetics and source of stem cells. Three prognostic groups could be identified in relation to the outcome, using a prognostic score affecting 1 to each poor risk factor (total from 0 to 3): Group 1 (good prognosis) includes patients35 years old, achieving CR1 with one induction course and to be transplanted with any other sex combination than female to male (score 0); group 2 (intermediate) with one adverse factor (score 1); and group 3 (bad prognosis) with two or three adverse criteria (scores 2 and 3). In these three groups, the 3-year leukaemia-free survival was 56+/-5%, 48+/-4% and 29+/-4% and the overall survival was 65+/-5, 53+/-4 and 29+/-5%, respectively. Therefore, adult patients with ALL and a score of 0 or 1 are good candidates for an early transplant if they have an identical sibling donor. Patient age, response to induction and the sex of the HLA-identical family donor (if existing) are the strongest easy predictors of the outcome for an early transplant in an adult patient with ALL. No additional information is mandatory.

We analysed data for 213 patients with ALL and AML who received either peripheral blood stem cells (PBSC) (n=74) or bone marrow (BM) (n=139) from an HLA-matched unrelated donor (EBMT acute leukaemia registry; January 1994 to January 1999). The two groups of patients (by cell source) were comparable with respect to age, sex, disease status, year at transplant and graft T cell depletion. Engraftment was achieved in about 90% regardless of stem cell source or leukaemia type. Kinetics of neutrophil and platelet recovery, similar for both sources in ALL patients, were faster for PBSC in AML patients. The incidence of acute graft-versus-host disease was similar for both sources in AML patients, but higher for PBSC in ALL patients (74 vs 54%, P=0.05). The 1-year probability of chronic graft-versus-host disease was 40 and 45% (P=0.66) in ALL patients compared to 49 and 35% (P=0.13) in AML patients (PBSC vs BM). In AML patients, none of the following differed significantly with cell source: transplant-related mortality, relapse incidence, leukaemia-free survival and overall survival. In ALL patients, the transplant-related mortality for PBSC vs BM was 61 vs 47% (P=0.13), the relapse incidence was 47 vs 39% (P=0.17), the leukaemia-free survival was 21 vs 32% (P=0.04) and the overall survival was 24 vs 34% (P=0.04). These data suggest that the short-term outcome of allogeneic PBSC is not significantly different from that of BM in AML patients who underwent a transplant from a matched unrelated donor but, conversely, that survival with PBSC may be decreased in ALL patients. In conclusion, the source of transplant cells needs to be evaluated by disease, especially when dealing with unrelated donors.

Second allogeneic hematopoietic stem cell transplantation (HSCT2) is a frequently used treatment option for relapse of acute leukemia after first allogeneic transplantation. Remission can be induced in selected patients, but data on long-term outcome and finally cure are limited. To estimate the long-term results of HSCT2, we retrospectively analyzed the course of 286 patients receiving myeloablative HSCT2 between 1985 and 2000, with a median follow-up of 11.3 years. Overall survival (OS) and leukemia-free survival (LFS) at 10 years from HSCT2 were 10±2 and 7±2%, respectively. Cumulative 10-year incidence of relapse and non-relapse mortality were 58±3% and 35±3%, respectively. CR at HSCT2, an interval from first transplant to relapse >10 months and TBI as part of the conditioning for HSCT2 favorably influenced LFS and OS. Patients with all three favorable factors had a 10-year OS of 36±10% and LFS of 25±9%, whereas patients showing no favorable factor had all died before year 5. Although retrospective, the long follow-up of this analysis supports the curative potential of alloHSCT2 in selected patients, who might be identified in advance, based on prognostic factors.

For adults with acute leukemia, it is important to know whether the therapeutic schemes initially planned were actually implemented. The European Group for Blood and Marrow transplantation Acute Leukemia Working Party prospectively followed 695 consecutive patients who were registered at the time of HLA typing. Of 304 patients with an available matched sibling donor (MSD), SCT was planned in 264, chemotherapy in 33 and autografting in 7. For the rest, an unrelated donor (UD) search was initiated in 198. Among these, 117 were transplanted, 114 received chemotherapy and 77 underwent autografting. Probabilities of receiving a planned treatment were 60 and 65% at 1 and 2 years, respectively. Patients scheduled to receive MSD SCT had an 82% probability, whereas those scheduled to undergo UD SCT had a 57% probability, of receiving their transplant at 1 year. The only factor associated with a lower probability of MSD SCT in first remission was delayed HLA typing (HR=0.82; P=0.03). One year after enrollment, 40% of patients did not follow their initial treatment plan. Because OS was 50% only at 3 years and only 57% of the patients without a MSD underwent SCT, this suggests room for improvement in outcomes for adults with acute leukemia.

Background Allogeneic stem cell transplantation (alloSCT) is the only curative treatment for most patients with CN AML. It is now well established that some relevant molecular markers can allow for the definition of risk groups after conventional chemotherapy. However, the role of these markers among other factors influencing outcome after alloSCT remains to be defined. Hence, we conducted an EBMT registry-based analysis aiming to define the exact prognostic role of molecular subgroups in conjunction with other classical risk factors after alloSCT for CN-AML. Patients, Methods and Results 752 adults (375 males) fulfilled the inclusion criteria, i.e. first alloSCT for CN-AML between 2000 and 2011, matched sibling (MSD) or unrelated (MUD) donor, and known mutational status of FLT3-ITD and NPM1, the two most frequently observed molecular markers in CN-AML. Median age was 51y (range, 18-71), disease status at time of alloSCT was CR1 (n=554), CR2/3 (n=90), primary induction failure (PIF, n=39), relapsed disease (n=62) and unknown (n=7). Myeloablative and reduced-intensity conditioning regimens were used in 371 and 378 patients, respectively. 597 received allogeneic PBSCs. With a median follow-up of 27 months, The 2-year estimates of overall survival (OS) and leukemia-free survival (LFS) were respectively 68±2% and 61±6% after alloSCT in CR1, 63±2% and 53±6% in CR2/3, 36±7% and 33±8% in PIF, and 28±7% and 25±6% in relapsed disease. In 554 patients transplanted in CR1, OS, LFS, cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were calculated according to molecular subgroups. Whereas NPM1mut had no influence on outcome, FLT3-ITD was associated with increased CIR (p . A multivariate Cox model of predefined risk factors including age, WBC at diagnosis, time to reach CR1, donor type, conditioning type (reduced vs. standard), and presence of NPM1mut and FLT3-ITD, was performed. Age >=50 years was the only risk factor for NRM (HR= 2.40, 95%CI: 1.32-4.37), while the presence of FLT3-ITD was the only risk factor for CIR (HR=2.85; 95%CI; 1.76-4.60). Both age >=50 years and FLT3-ITD were associated with inferior LFS (HR=1.65, 95%CI: 1.14-2.39, p=0.01 for age, HR=2.08, 95%CI: 1.43-3.01, p=0.001 for FLT3-ITD) and, most importantly, OS (HR=1,76; 95%CI: 1.19-2.61, p=0.005 for age, and HR=2.19; 95%CI: 1.48-3.26, p=0.0001 for FLT3-ITD). The latter data allowed to identify 3 prognostic groups with 2-years OS of 83±4% (younger age and FLT3-ITDneg), 70±4% (older age OR FLT3-ITD) and 48±5% (older age and FLT3-ITD), p Conclusion In the largest study on CN-AML performed thus far, we identified age >=50 years and FLT3-ITD as the major risk factors for OS after alloSCT in CR1, independently from other risk factors such as type of donor or conditioning. In patients harboring FLT3-ITD, a limited protective role for NPM1 mutation could be observed. These results underscore the importance of post-transplant strategies to prevent relapse in AML with FLT3-ITD. Encouraging results were observed after SCT in PIF, relapse or advanced CR. Disclosures: Schmid: Novartis: Honoraria, Research Funding, travel grant Other; Roche: travel grant, travel grant Other; MSD: Honoraria. Rambaldi:Novartis: Honoraria; Sanofi: Honoraria; Italfarmaco: Honoraria.

Background: Allogeneic stem cell transplantation is a potentially curative procedure to a long list of hematological malignancies, but involves substantial risk of morbidity and mortality. Means for accurately predicting outcome and assessing risk are thus greatly needed. The Disease Risk Index (DRI) is a prognostic tool developed and validated by Armand et al. across a wide range of hematological malignancies (Blood 2012, Blood 2014) on cohorts of American patients. The Index stratifies patients into 4 distinct risk groups (low, intermediate, high, very high) and has yet to be validated in an international cohort. We sought to evaluate the validity of the DRI in a large cohort of European patients. Methods: This was a retrospective validation study on an independent cohort of patients undergoing allogeneic HSCT and reported the European Society for Blood and Marrow Transplantation (EBMT). Patients included had a hematological malignancy and underwent allogeneic transplantation between the years of 2000 and 2015. Risk groups were coded in accordance with the refined DRI (Blood, 2014). Outcomes were evaluated 4 years after the allogeneic HSCT. Overall survival (OS) was calculated with the Kaplan-Meier method. The log-rank test was used for comparisons of Kaplan-Meier curves. Cumulative incidence curves for nonrelapse mortality (NRM) and relapse with or without death were constructed reflecting time to relapse and time to NRM, respectively, as competing risks. The difference between cumulative incidence curves in the presence of a competing risk was tested with the Gray method. The prognostic effect of the DRI strata was estimated using a Cox proportional hazard model for OS and a Fine and Gray model for NRM and relapse. Results: A total of 89,061 patients from 423 transplantation centers were included in the analysis. Median age was 48.3 (IQR 36.2-57.5). The most frequent indication for transplantation was AML (39,530 patients) followed by ALL (16,206) and MDS (9,750); other indications spanned the spectrum of hematological malignancies. The majority of patients were in 1st or 2nd complete remission (54%). The median follow-up period was 3.6 years. Approximately 63% of patients were classified as intermediate risk by DRI, suggesting that this group could be further partitioned. The 4 year overall survival (95% CI) of the low, intermediate, high, and very high risk groups was 60.8% (59.9-61.8), 51.3% (50.8‐51.8), 27.0% (26.1‐27.8), 18.4% (17.1-19.8) (Figure 1). The same groups corresponded with increasing cumulative incidence of relapse; 8.9% (8.3-9.4), 19.3% (18.9-19.7), 39.0% (37.8-39.6), 45.1% (43.4-46.7), respectively. The DRI groups also showed increasing hazard between strata in the overall survival setting; intermediate risk was associated with a hazard ratio of 1.32, high risk 2.67 and very high risk 3.71 relative to low risk. Relapse showed a similar pattern. NRM was less strongly stratified by DRI (Table 1). The DRI groups maintained a similar risk, regardless of whether the transplantation was performed prior or after 2008. DRI was the strongest determinant of overall survival and relapse when introduced to a multivariable model with additional covariates. AUC for the index at 4 years was 62.5 for OS, 58.5 for NRM and 68.2 for relapse. Conclusions: We have validated the Disease Risk Index in a massive European data set. The groupings suggested by the DRI corresponded with distinct risk groups for overall mortality and relapse. Overall, our results indicate the international applicability of this robust prognostic tool. Figure 1. Kaplan-Meyer survival curves for overall survival, stratified by DRI Figure 1. Kaplan-Meyer survival curves for overall survival, stratified by DRI Table 1 Table 1. Disclosures Bader: Medac: Consultancy, Research Funding; Riemser: Research Funding; Neovii Biotech: Research Funding; Servier: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Bonini:Molmed SpA: Consultancy; TxCell: Membership on an entity's Board of Directors or advisory committees. Dreger:Gilead: Consultancy; Janssen: Consultancy; Novartis: Speakers Bureau; Gilead: Speakers Bureau; Novartis: Consultancy; Roche: Consultancy. Kuball:Gadeta B.V,: Membership on an entity's Board of Directors or advisory committees. Montoto:Roche: Honoraria; Gilead: Research Funding.

Introduction CK AML patients have high relapse rate and poor outcomes when treated with conventional chemotherapy. Allogeneic hematopoietic stem cell transplantation (AHSCT) may cure this disease; however, relapse rate remains a major limitation and survival is one of the worst amongst AML patients. Here we aimed to identify prognostic factors associated with survival in patients with AML and CK using combined data from the EBMT and MDACC. Methods A total 1,342 consecutively transplanted patients with CK (>3 cytogenetic abnormalities) AML reported to EBMT (N=1,118) and at MDACC (N=224) between 01/2000-12/2015 were included.The median age was 52 years (range 18-76 years), 335 patients (25%) were older than 60 years. Seven hundred and twenty-nine patients (54.3%) were male, 239 patients (17.8%) had secondary AML. Disease status before transplant was CR1, CR2 and activediseasein 877 (65.3%), 77 (5.7%) and 388 (29%), respectively. Donors were matched related (MRD), matched unrelated (MUD) and mismatched unrelated (MMUD) in 749 (55.8%), 513 (38.2%) and 80 (6%), respectively. Conditioning regimens were various, mostly eitherbusulfan-based (53.7%) or TBI-based (26.7%). Seven hundred and thirty-nine patients (55%) and 603 patients (45%) receivedmyeloablativeconditioning (MAC) and reduced intensity conditioning (RIC), respectively. The main stem cell source was peripheral blood (81%). In vivo T-cell depleted (TCD) methods were used in 665 patients (50%). Median time from diagnosis to transplant was 5.1 months (range 2-387 months) while the median follow-up duration was 35.5 months (range 8-174 months). Results Engraftment occurred in 96.3%, 69.7% and 30.3% had full and mixed donorchimerism, respectively. At 2 year post-transplant, the cumulative incidence (CI) of acute GVHD grade II-IV and grade III-IV was 26.3% and 8.4%, respectively, whereas CI of chronic GVHD was 30.9% with extensive chronic GVHD 17.8%. Leukemia free survival (LFS), overall survival (OS), CI of relapse, non-relapse mortality (NRM) at 2 years for the whole group was 31.3%, 36.8%, 51.1% and 17.6%, respectively, while 2-year GVHD-free, relapse-free survival (GRFS) was 19.8%. LFS, OS, GRFS, CI of relapse and NRM at 2 years for patients transplanted in CR1 was 38.4%, 44.5%, 23.8%, 46% and 15.7%, respectively. For patients with active disease these outcomes were 14.6%, 18.5%, 9.6%, 63.5% and 21.9%, respectively (Figure A, B). Patients ages 40-60 years transplanted in CR1 with MAC demonstrated lower relapse (40.2% vs. 51% with RIC, p=0.005), offset by a higher NRM (18.2% vs 9.8% RIC, p=0.037), associated with higher incidence of acute GVHD, and a non-significant difference in LFS (Figure C, D). In multivariable analysis (MVA) for the entire group, advanced age, transplantation in active disease, secondary AML and presence of deletion or monosomy 5 or 7 predicted poor LFS and OS. All of these factors as well as year of transplant (before 2010) also predicted poor GRFS, while conditioning intensity (MAC vs RIC) and donor type did not influence survival outcomes. Prognostic factors for relapse were age, secondary AML, active disease at transplant and presence of deletion or monosomy 5, while prognostic factors for NRM were older age, active disease, use of a mismatched unrelated donor and deletion or monosomy 7. Conclusions In this largest analysis of complex karyotypes AML patients, relapse remains the most common cause of treatment failure with 45% for patients in CR1 and 63.5% for patients not in remission relapsing after transplant. The only modifiable factorsat this time are performing transplantation in CR1 as soon as the donor is available. Control of GVHD might allow younger patients receiving MAC to have a lower NRM and improved LFS. Novel approaches are needed to decrease relapse rate and improve survival in these patients. Table Multivariable analysis for patients with CK AML. Table. Multivariable analysis for patients with CK AML. Figure A. CI of relapse for all patients and patients in CR; B. LFS for all patients and patients in CR; C. CI of relapse for patients age 40-60 years in CR with MAC, RIC; D. LFS for patients age 40-60 years in CR with MAC, RIC. Figure. A. CI of relapse for all patients and patients in CR; B. LFS for all patients and patients in CR; C. CI of relapse for patients age 40-60 years in CR with MAC, RIC; D. LFS for patients age 40-60 years in CR with MAC, RIC. Disclosures Ciurea: Cyto-Sen Therapeutics: Equity Ownership; Spectrum Pharmaceuticals: Other: Advisory Board. Champlin:Ziopharm Oncology: Equity Ownership, Patents & Royalties; Intrexon: Equity Ownership, Patents & Royalties.

Secondary acute myeloid leukemia (sAML) is a very heterogeneous group of disease derived from myelodysplasia, chronic myeloproliferative disorders or after exposure to chemotherapy and or radiation therapy (therapy related AML) or due to exposure to environmental carcinogens. sAML has traditionally been considered a devastating disease with inferior outcomes compared to de novo AML, affecting a vulnerable population of heavily pretreated, especially older patients. Allogeneic hematopoietic stem cell transplantation (HCT) is the only potential curative therapy and usually considered in patients with low comorbidities and transplant related risk score. However, relapse is the most frequent cause of failure after HCT, occurring in more than 50% of the patients. No systematic large analysis of HCT for sAML is available to study the risk factors and outcome. Therefore, the EBMT Acute Leukemia Working Party has performed a retrospective registry study on patients with sAML (n=4256) undergoing HCT. Patients who underwent HLA-identical sibling (n=2290) or unrelated donor (n=1966) peripheral blood (n=3781) or bone marrow transplantation (n=475) from 2000 to 2013 are included in the study. All unrelated donors were Human Leucocyte Antigens (HLA)-matched (10/10) (n=1532) or one locus mismatched (9/10) (n=434). 1901 (45%) patients received ablative (MAC) and 2355 (55%) reduced-intensity conditioning (RIC) regimen. Median age at transplant was 56 years, IQR 48-63 (MAC 51, IQR 42-58; RIC 60, IQR 54-64). Median time from diagnosis of sAML to HCT was 6.2 months, IQR 4.1-12.0 (MAC 5.6, IQR 3.8-9.7; RIC 7.0, IQR 4.4-14.12; p Two year cumulative incidence of relapse (RI) and non-relapse mortality (NRM) were 33% (95% CI, 32-35%) and 25% (95% CI, 24-27%), respectively. The Kaplan-Meier estimate of overall survival (OS) and leukemia-free survival (LFS) at 2 years were 46% (95% CI, 44-48%) and 41% (95% CI, 39-43%), respectively. Acute GVHD (grade II-IV) occurred in 1043 (26%) patients. The 2-year cumulative incidence of chronic GVHD was 54% (95% CI, 51-56). Two year OS, LFS, RI and NRM of MAC and RIC groups were 48% (95% CI, 46-50) vs. 44% (95% CI, 42-47), p=0.06, 44% (95% CI, 41-46) vs. 39% (95% CI, 37-41), p=0.003, 30% (95% CI, 28-32) vs. 36% (95% CI, 34-38), p In multivariate analysis adjusted for variable with different distribution between groups, the type of conditioning (RIC vs. MAC) had no impact on OS and LFS, however RIC group had higher RI (HR, 1.3, 95% CI 1.12-1.44, p=0.0001) and lower NRM (HR 0.8, 95% CI 0.72-0.96, p=0.01). Older age at HCT was an independent adverse prognostic factor for OS, LFS and NRM. Time from diagnosis to HCT had no impact on transplant outcome. Patients receiving PB grafts had superior OS (HR 0.84, 95% CI 0.73-0.97, p=0.01), LFS (HR 0.85, 95% CI 0.74-0.97, p=0.02) and lower RI (HR 0.83, 95% CI 0.70-0.99, p=0.049) compared with BM. Patients in remission and receiving HCT from HLA-identical siblings were independently associated better outcome. In summary, our registry study in the largest cohort of patients studied so far receiving HCT for secondary AML, demonstrated that about 45% of patients with secondary AML can attain long term survival after HCT. Patients receiving ablative regimens were associated with lower relapse risk and patients in remission had superior survival. Patients receiving PB grafts were associated potent graft-versus leukemia effects with decreased relapse risk and improved survival. Post- transplant pre-emptive therapy to decrease relapse risk might improve outcome further in these high risk populations. Disclosures Niederwieser: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Glass:Roche, MSD, Takeda, Riemser, Ctilifesciences: Honoraria, Research Funding. Esteve:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Schmid:Janssen Cilag: Other: Travel grand; Neovii: Consultancy.

Because information on management and outcome of AML relapse after allogeneic hematopoietic stem cell transplantation (HSCT) with reduced intensity conditioning (RIC) is scarce, a retrospective registry study was performed by the Acute Leukemia Working Party of EBMT. Among 2815 RIC transplants performed for AML in complete remission (CR) between 1999 and 2008, cumulative incidence of relapse was 32% ± 1%. Relapsed patients (263) were included into a detailed analysis of risk factors for overall survival (OS) and building of a prognostic score. CR was reinduced in 32%; remission duration after transplantation was the only prognostic factor for response (P = .003). Estimated 2-year OS from relapse was 14%, thereby resembling results of AML relapse after standard conditioning. Among variables available at the time of relapse, remission after HSCT > 5 months (hazard ratio [HR] = 0.50, 95% confidence interval [CI], 0.37-0.67, P < .001), bone marrow blasts less than 27% (HR = 0.53, 95% CI, 0.40-0.72, P < .001), and absence of acute GVHD after HSCT (HR = 0.67, 95% CI, 0.49-0.93, P = .017) were associated with better OS. Based on these factors, 3 prognostic groups could be discriminated, showing OS of 32% ± 7%, 19% ± 4%, and 4% ± 2% at 2 years (P < .0001). Long-term survival was achieved almost exclusively after successful induction of CR by cytoreductive therapy, followed either by donor lymphocyte infusion or second HSCT for consolidation.

Treatment options for adults with primary refractory acute myeloid leukaemia (PREF AML) are extremely limited. Although sibling allogeneic stem cell transplantation can result in long-term survival, most patients lack a matched family donor and are destined to die of refractory disease. Greater availability of unrelated donors and improvements in supportive care have increased the proportion of patients with PREF AML in whom allografting is technically feasible, but the outcome of unrelated donor transplantation in this population has not been studied. We therefore analysed overall survival in 168 patients with PREF AML, who underwent unrelated donor transplantation between 1994 and 2006. The 5-year overall survival for the whole group was 22%. In multivariate analysis, fewer than three courses of induction chemotherapy, a lower percentage of bone marrow blasts at transplant and patient cytomegalovirus seropositivity were associated with improved survival. This allowed the development of a scoring system that identified four groups with survival rates between 44±11% and 0%. This study demonstrates an important role for unrelated donor transplantation in the management of selected patients with PREF AML and confirms the importance of initiating an urgent unrelated donor search in patients with no matched sibling donor, who fail to respond to induction chemotherapy.

T cell–depleted haploidentical hematopoietic stem cell transplantation (haploHSCT) is an option to treat children with very high-risk acute lymphoblastic leukemia (ALL) lacking an HLA-identical donor. We analyzed 127 children with ALL who underwent haploHSCT in first (n = 22), second (n = 48), or third (n = 32), complete remission or in relapse (n = 25). The 5-year leukemia-free survival (LFS) was 30%, 34%, 22%, and 0%, respectively. A risk-factor analysis was performed for patients who underwent transplantation in remission (n = 102). Five-year nonrelapse mortality (NRM), relapse incidence (RI), and LFS were 37%, 36%, and 27%, respectively. A trend of improved LFS rate and decreased RI was observed for children given a graft with higher number of CD34+ cells (adjusted P = .09 and P = .07, respectively). In a multivariate analysis, haploHSCT performed in larger centers (performing ≥ 231 allotransplantations in the studied period) was associated with improved LFS rate and decreased RI (adjusted P = .01 and P = .04, respectively), adjusting for different patient-, disease-, and transplant-related factors such as number of previous autotransplantations, cytomegalovirus serology status, type of T-cell depletion, and use of total body irradiation and antithymocyte globulin. In conclusion, higher CD34+ cell dose and better patient selection may improve outcomes of children with ALL who undergo a haploHSCT. Transplant centers initiating programs on haploHSCT for children may collaborate with more experienced centers.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an alternative treatment to patients with high-risk acute leukemia lacking a human leukocyte antigen-matched donor. We analyzed 173 adults with acute myeloid leukemia (AML) and 93 with acute lymphoblastic leukemia (ALL) who received a haplo-HSCT in Europe. All grafts were T cell–depleted peripheral blood progenitor cells from a direct family or other related donor. At transplantation, there were 25 patients with AML in CR1 (complete remission 1), 61 in more than or equal to CR2, and 87 in nonremission, and 24 with ALL in CR1, 37 in more than or equal to CR2, and 32 in nonremission. Median follow-up was 47 months in AML and 29 months in the ALL groups. Engraftment was observed in 91% of the patients. Leukemia-free survival at 2 years was 48% plus or minus 10%, 21% plus or minus 5%, and 1% for patients with AML undergoing transplantation in CR1, more than or equal to CR2, and nonremission, and 13% plus or minus 7%, 30% plus or minus 8%, and 7% plus or minus 5% in ALL patients, respectively. In conclusion, haplo-HSCT can be an alternative option for the treatment of high-risk acute leukemia patients in remission, lacking a human leukocyte antigen-matched donor.

Allogeneic stem cell transplantation using an HLA identical sibling donor has the capacity to produce long term disease free survival in a significant number of patients with primary refractory acute myeloid leukaemia (AML). The increased availability of volunteer unrelated donors has resulted in allogeneic transplantation becoming a realistic option in large numbers of patients lacking a sibling donor. However the outcome of patients with primary refractory AML after unrelated donor transplantation has not been systematically examined before. We have therefore studied the outcome of 186 adults with primary refractory AML who underwent an unrelated donor transplant from 1995 to 2006. All patients were refractory to induction chemotherapy having received a mean of 2.2 courses of chemotherapy (range 1 to 6). Cytogenetic status at diagnosis is available in 96 patients: 3 patients had good risk cytogenetics, 60 intermediate risk and 33 adverse risk cytogenetics by MRC criteria. The median interval from diagnosis to transplant was 4.2 months (range 2–6 months). 141 patients underwent transplantation from a 6/6 matched unrelated donor and 45 from a mismatched unrelated donor. 150 patients were transplanted using GCSF mobilised peripheral blood stem cells. 136 patients were transplanted using a myeloablative conditioning (MAC) regimen. 50 patients were transplanted using a reduced intensity conditioning (RIC) regimen of whom 30 received a low dose TBI based regimen. 137 patients achieved a complete remission (CR) post-transplant. The 2 year overall survival for the whole group was 31% and 43% for patients who achieved a CR post-transplant. The day 100 non-relapse mortality was 16% (19% for MAC allografts v 9% for RIC allografts). In univariate analysis time to transplant (

Introduction: Previous trials have shown that autologous stem cell transplantation (ASCT) is superior to conventional chemotherapy in terms of remission rate and PFS in younger MM patients. Concerns about toxicity and potential efficacy of ASCT in older MM patients lead most centers to limit ASCT indications to patients aged Patients and Methods: We prospectively analyzed the outcomes of 56 consecutive MM patients who had received ASCT between September 2012 and September 2014 in 6 institutions in France (protocol ClinicalTrials.gov Identifier: NCT01671826). Patients were newly diagnosed MM. For induction therapy, all patients received a bortezomib-based induction regimen (VD, VTD, VCD, or VRD, 4 to 6 cycles) according to center's local guidelines. Mobilization was performed with G-CSF or G-CSF+cyclophosphamide and plerixafor whenever needed. High-dose chemotherapy consisted of either 140 mg/m2 or 200 mg/m2 Melphalan. A short two months consolidation phase post ASCT was allowed (lenalidomide-dexamethasone, VD, VTD, VCD or VRD). No maintenance treatment was given. Response, disease progression and relapse were defined according to the IMWG uniform response criteria. All patients signed an informed consent form according to the EBMT guidelines. Results: At time of diagnosis, median age was 67 (range, 64-74) years with 23% of patients being >70 years. There were 30 males and 26 females. The immunoglobulin subtype was IgG (n=29), IgA (n=15), light chain (n=10), other (n=2). The Salmon and Durie stage was III in 89% of cases (n=47), and the ISS score was I (n=18; 35%), II (n=19; 37%), III (n=14; 27%). Patients had high risk cytogenetics features (t(4;14) and/or del17p) in 9 cases (16%). 10% of patients had a serum creatinine level >176 micromol/L. None of the patients underwent hemodialysis. The Sorror comorbidity score was 0 (34), 1 (6), 2 (2), 3 (6), 6 (1), unknown (7). The median age at time of ASCT was 68 years, and the median time from diagnosis to ASCT was 5 months. In an intention to treat analysis, out of 56 patients, 6 patients could not proceed to ASCT because of an early infectious death (n=1), serious comorbidity (n=2), disease refractoriness to induction (n=1), and failure to collect an adequate PBSC graft (n=2). A median of 5.31x106/Kg CD34+ cells could be collected. Disease status at time of ASCT was: CR (n=12; 24%), VGPR (n=19; 38%), PR (n=17; 34%), and SD/non-responding (n=2; 4%). The conditioning regimen consisted of 140mg/m² melphalan in 18 cases (36%) and 200mg/m2 in 32 patients (64%). Moreover, 4 patients (8%) received a tandem ASCT. The median time for neutrophils and platelets engraftment was 12 days. The day-100 post ASCT non-relapse mortality was 0% and the 2-year NRM was 4.2% (95% CI:[0.3-18.3]). The overall response rate at day 100 was 96% (CR: 34%, VGPR: 47%, PR: 15%, SD/non-responsive: 4%). At 3 months post ASCT, 82% patients were able to receive the planned post ASCT consolidation treatment. After a median follow-up of 12 months, the estimated progression-free (PFS) and overall survival (OS) rates at 2 years were 76% (95%CI: [61.6-94.1]) and 88% (95%CI: [76.7-100]), respectively. The incidences of infectious complications post ASCT, and response rates were comparable between the two melphalan dose levels (p=0.28). However, in the univariate analysis, the 200 mg/m2 melphalan conditioning group showed a better OS rate compared to the 140 mg/m2 group (1-year OS: 100% vs. 67%; p=0.012). Conclusion: These prospective multicenter results indicate that ASCT is a safe and effective treatment modality for elderly, but fit MM patients at the era of novel induction agents. Of note, patients above age 70 did not experience a worse prognosis. Thus, age per se should not be used as an exclusion criterion for ASCT. Longer follow-up data will be presented, but these results already set the frame for a randomized comparison to the non-transplant approaches in this patients' subgroup. Disclosures Garderet: Bristol-Myers Squibb: Consultancy. Touzeau:AbbVie: Research Funding. Stoppa:Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria. Karlin:Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria; Amgen: Honoraria; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees. Moreau:Celgene, Janssen, Takeda, Novartis, Amgen: Membership on an entity's Board of Directors or advisory committees.

Introduction: The response rate (partial remission and better) of pomalidomide and low dose dexamethasone in myeloma patients who received prior lenalidomide and bortezomib was 34% (Richardson P, Blood 2011, 118; abs 634). In order to increase the response rate of a pomalidomide based therapy, investigators commonly add oral weekly cyclophosphamide to pomalidomide and dexamethasone (PCD). We conducted a retrospective, single institution, study to analyse the efficacy and toxicity of the PCD combination for relapse/refractory patients. Patients / Methods: Patients had relapsed/refractory myeloma. They received pomalidomide 4 mg PO D1-21, dexamethasone 40 mg PO D1-4 and D15-19 (20mg if older than 75 years) or 40 mg once a week and oral cyclophosphamide 300 mg on D1, 8, 15, 22 of a 28 days cycle. Treatment was given as a bridge to transplantation or until progression. Granulocyte colony stimulating factor support was allowed. Thrombosis and infectious prophylaxis were recommended. Responses were assessed per the IMWG criteria. Results: Twenty patients were analyzed. The median age was 57 (range= 42 -76) years, and 9 were males (45 %). The immunoglobulin subtype was IgG 19, IgA 1. At diagnosis, the SD stage was I (73%) and II (27 %) and 5 missing values. The ISS score was I (50 %), II (30 %), III (20 %). The disease characteristics before PCD were: bone disease in 13 patients (93%, with 6 missing values), median calcemia was 2.3 micromol/L (range= 2.1- 2.6), hemoglobin was 11g/dL (range= 8-14), platelets were 178 000/mm3 (range=7-361), 10 % had a creatinine level >176 micromol/L (no hemodialysis was performed), elevated lactate dehydrogenase (> 470 IU) in 5 cases (25 %), elevated C-reactive protein (> 5 IU), for 6 patients (40%, 5 missing values). The median time from diagnosis to current therapy was 4 years (range= 1-16 years). The median number of prior therapies was 4 (range= 2-6). Prior treatments were chemotherapy (9), thalidomide (10), lenalidomide (20), bortezomib (19), autologous stem cell transplantation (ASCT) (10), double ASCT (1). Five patients were bortezomib refractory and 4 were lenalidomide refractory. The median number of administered cycles was 4 (2-12). The confirmed response rate (more than PR) was 63 % and the median number of cycles to response 3 (range=1-9). The number of responders after the first cycle was 8/19 (42 %). The type of best response were: CR: 1 (5%), VGPR: 3 (16%), PR: 8 (42%), SD: 4 (21%), PD: 3 (16%). With a follow-up of 8.5 months, the median PFS at 1 year is 80.7 % (95% CI: [63.2-100]). Patients without relapse at follow-up are 13 (65%). The causes of PCD withdrawal are: scheduled ASCT (6, 46%), toxicity (3, 23%), disease progression (4, 31%). The treatments after PCD failure were ASCT (4, 21 %), IMiDs (7, 37 %), other (10, 53 %). Response (≥PR) to salvage treatment post PCD was 60 %. At the last follow-up, the status was n=19 alive, and 1 patient lost to follow up. Toxicity was mostly neutropenia (50 %) and one patient had pulmonary aspergillosis. Conclusion: Toxicities were manageable and the PCD regimen had evidence of preliminary efficacy. Almost half of the patients could proceed to salvage ASCT. The IFM is currently conducting a phase II study analyzing the role of PCD for relapsing patients who were initially treated with bortezomib lenalidomide dex and had an ASCT upfront or delayed (IFM 2009/DFCI trial). Disclosures Garderet: Bristol-Myers Squibb: Consultancy.

Allogeneic hematopoietic stem cell transplantation (HSCT) offers a potential cure for a variety of hematological malignancies. Patients without an HLA matched sibling donor can turn to unrelated donor registries to identify a suitably HLA matched donor. In the case where a fully HLA-A, -B, -C, -DRB1 and -DQB1 (10/10) matched donor is unavailable, there are often multiple 9/10 matched donors to select from. However, the prioritization and identification of permissive HLA mismatches in the 9/10 matched setting have proven elusive. Fetal exposure to non-inherited maternal antigens (NIMA) imparts lifelong immune modulating effects leading to tolerance to these antigens. Prior studies have found that matching for non-inherited maternal antigens (NIMA) can lead to lower rates of acute graft versus host disease (aGVHD) and lower treatment-related mortality (TRM) in cord blood HSCT (J.J. van Rood et al., Blood 2002; J. J. van Rood et al., PNAS, 2009; V. Rocha et al., BBMT, 2012). Patients undergoing mismatched HSCT with adult unrelated donors could benefit from NIMA matching by introducing maternal HLA testing during confirmatory typing of the donor and using NIMA matching as a criterion for mismatched donor selection. This joint EBMT-CIBMTR retrospective analysis was designed to evaluate the influence of NIMA matching in HSCT with mismatched adult unrelated donors. Matching criteria were based on HLA-A, -B, -C, -DRB1, -DQB1 at high resolution. Included donor-recipient pairs had 5 loci HLA typing and a minimum of one year follow-up recorded at EBMT or CIBMTR and donors were registered with DKMS German Bone Marrow Donor Center. To obtain maternal HLA typing information, DKMS contacted the respective donors by mail to inform about the study and to provide detailed information, a buccal swab kit and an informed consent form to the donor's mother that the donor could send on. SBT-based HLA typing was performed at the DKMS Life Science Lab, Dresden, Germany once signed informed consent and samples were received. A total of 1735 donors were contacted and maternal samples could be retrieved for 803 cases (46%). A total of 50 NIMA matches (6%) were found reflecting the rate expected from previous studies. Multivariate analyses were performed using Cox proportional hazards models adjusting for significant co-variates for overall survival (OS), disease free survival (DFS), relapse, TRM and acute and chronic GVHD comparing NIMA matched to NIMA mismatched cases. The final analysis population was restricted to 9/10 matched cases (N=452) transplanted for acute myeloid leukemia (N=307) and acute lymphoblastic leukemia (N=145) using myeloablative (N=307) or reduced intensity (N=145) conditioning from 1999-2013. The NIMA matched (N=32) and mismatched (N=420) groups were well balanced for all disease, patient, transplant and donor characteristics. The groups differed by mismatched HLA locus with the NIMA matched group skewed towards more HLA-C mismatches (66% vs. 35%). Univariate analyses did not find any significant differences between the NIMA matched and mismatched groups for any outcomes. TRM rates were similar between the groups at 1 year with 23% (95% CI: 10-40%) and 23% (95% CI: 19-28%) in the NIMA matched and mismatched groups, respectively. No significant associations were observed in multivariate analyses of the NIMA matched versus mismatched groups (Table). In contrast to prior studies of NIMA matched HSCT, no significant associations were found between NIMA matching and any outcomes. However, our findings may be due to the fact that the current study was underpowered to detect the expected difference in TRM observed in prior studies. Investigation on a larger cohort or a prospective trial would be needed. We thank Carlheinz Müller from the German unrelated donor registry ZKRD for providing additional HLA information and the donors and their mothers for their cooperation in this study. Table. Multivariate analysis results of NIMA matched versus mismatched (used as reference) HSCT Table 1.OutcomeHR95% CIp-valueOS0.890.54-1.480.653DFS0.880.53-1.430.598TRM0.740.35-1.600.447Relapse0.890.45-1.750.737aGVHD II-IV0.970.53-1.800.935aGVHD III-IV0.590.19-1.910.382cGVHD1.770.99-3.160.053 Disclosures Lee: Bristol-Myers Squibb: Consultancy; Kadmon: Consultancy. Nagler:Biokine LTD: Consultancy.

Results of reduced intensity conditioning regimen (RIC) in the HLA identical haematopoietic stem cell transplantation (HSCT) setting have not been compared to those after myeloablative (MA) regimen HSCT in patients with acute myeloblastic leukaemia (AML) over 50 years of age. With this aim, outcomes of 315 RIC were compared with 407 MA HSCT recipients. The majority of RIC was fludarabine-based regimen associated to busulphan (BU) (53%) or low-dose total body irradiation (24%). Multivariate analyses of outcomes were used adjusting for differences between both groups. The median follow-up was 13 months. Cytogenetics, FAB classification, WBC count at diagnosis and status of the disease at transplant were not statistically different between the two groups. However, RIC patients were older, transplanted more recently, and more frequently with peripheral blood allogeneic stem cells as compared to MA recipients. In multivariate analysis, acute GVHD (II-IV) and transplant-related mortality were significantly decreased (P=0.01 and P

Relapsed AML after allogeneic SCT has a poor prognosis. So far, no standard therapy could be defined. Donor lymphocyte transfusion (DLT) has been effective in a minority, however, no data is available to identify patients who will benefit from the procedure. Neither, the outcome of patients treated with or without DLT have been compared. We retrospectively evaluated overall survival (OS) of 489 adults with de novo AML in hematological relapse after SCT, receiving DLT (n=190) or not (n=299). DLT and noDLTgroups were well balanced in terms of patient age (median:37y in both groups), donor age, cytogenetics (good:5vs7%, intermediate:83vs79%, poor:12%vs14%), WBC at diagnosis, donor type (geno-id:71vs72%, MUD:18% both, mismatched:11vs10%), status at transplantation (CR1:38vs41%, CR2:13vs15%, advanced:49vs44%), conditioning, source of stem cells, and time from transplant to relapse (5vs4.5 months). However, DLT patients had a median of 39% BM blasts, as compared to 54% for the noDLT group (p=0.03). Follow-up was 32 and 30 months. Within the DLT group, chemotherapy was additionally given in 130 cases. Nevertheless, only 33% of patients received DLT in CR or aplasia, 67% had measurable disease. AGvHD developed in 41% of patients following DLT. CR and PR were achieved in 31.1% and 4.8% of DLT patients. In a multivariate analysis, younger patient age ( 5 months) from transplant to relapse (HR=7.74,p=0.002) were associated with better OS after DLT. When comparing the outcome of patients receiving or not DLT, OS at 2 years was 10±1% for the entire cohort, 18±3% for DLT and 6±1% for noDLT (p5 months) from transplant to relapse (HR=2.40, p

Item does not contain fulltext De novo erythroleukemia (EL) is a rare disease. Reported median survival are poor and vary from 4 to 14 months. The value of hematopoietic stem cell transplantation (HSCT) for EL is unknown. This EBMT registry study reports on the largest series of patients with EL treated with HSCT in first complete remission-103 autologous and 104 HLA identical sibling allogeneic HSCT. Outcome and identification of prognostic factors for each type of transplantation were evaluated. For autologous HSCT, outcome at 5 years showed a leukemia-free survival (LFS) of 26% +/- 5%, a relapse incidence (RI) of 70% +/- 6%, and a transplant-related mortality (TRM) of 13% +/- 4%. By multivariate analysis, the only prognostic factor was age. For allogeneic HSCT, outcome at 5 years showed an LFS of 57% +/- 5%, an RI of 21% +/- 5%, and a TRM of 27% +/- 5%. By multivariate analysis, prognostic factors were graft-versus-host disease and age. This study represents the largest series of de novo EL treated with HSCT and shows that allogeneic HSCT is by far the most effective treatment.

International audience; Retroviral genomes consist of two identical RNA molecules joined non-covalently near their 5'-ends. Recently, we showed that an imperfect autocomplementary sequence, located in the L3 domain, plays an essential role in avian sarcoma-leukosis virus (ASLV) RNA dimerization in vitro. This sequence can adopt a stem-loop structure and is involved in ASLV replication. Here, we found that in the absence of nucleocapsid protein, RNA transcripts of avian leukosis virus (ALV) were able to form two types of dimers in vitro that differ in their stability: a loose dimer, formed at a physiological temperature, and a tight dimer, formed at a high temperature. A mutational analysis was performed to define the features of these dimers. The results of this analysis unambiguously confirm that the two L3 stem-loops interact directly in both types of dimers. A loop-loop interaction is the main linkage in the loose dimer. In contrast, in the tight dimer, the stem and the loop of the L3 hairpin form an extended duplex. Surprisingly, we also found that the dimerization properties defined for our ALV strain (type SR-A) differ from those found in other ASLV strains.

Background Allo-HSCT has been shown to increase survival and improve cure in acute leukemia (AL). However, this procedure is accompanied by high rates of morbidity and mortality. Several risk scores based on conventional statistical methods may aid decision regarding whom and how to perform allo-HSCT, but these methods carry inherent limitations, which may lead to sub-optimal candidate selection. Machine learning (ML) is a field in computer science stemming from artificial intelligence and is part of the data mining approach for data analysis. ML algorithms are commonly applied in technological and commercial settings. They allow for coping with complex data scenarios and thus may be suitable for outcome prediction in allo-HSCT. With this background, and using a ML prediction method- the alternating decision tree (ADT) algorithm, we developed an interpretable model for overall mortality (OM) and treatment-related mortality (TRM) at day +100 after allo-HSCT in AL. Patients and Methods 28,995 adult allo-HSCT recipients from the registry of the ALWP of EBMT were analyzed. Twenty two variables were available including year of transplant (range, 2000-2011), diagnosis (Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia), disease status, Karnofsky performance status, conditioning regimen (myeloablative or reduced- intensity conditioning), graft type (peripheral blood, bone marrow or cord blood), donor and recipient HLA compatibility, CMV serostatus, GVHD prophylaxis regimens, etc. Per study definitions, the primary outcomes to be predicted were OM and TRM at day +100 days after allo-HSCT. The complete dataset was split into 3 sets: training set (n=11,600), testing set (n=8,688) and validation set (n=8,707). The ADT prediction model was tested and optimized according to the first 2 subgroups and validated on the last one. Output from the ADT model, included variables selection with assigned scores in a tree-based structure and area under the ROC curve (AUC), a measure for model discrimination Results Each of the ADT models selected 12 out 22 variables for prediction of OM and TRM at day +100. Ten variables were mutual for both prediction models, although different weights were assigned. These included: age, diagnosis, disease status, Karnofsky performance status (all at time of transplant), donor-recipient HLA-matching, number of transplants in each center per year, year of transplant, conditioning regimen and the donor's and patient's CMV serostatus. Variables selected exclusively by the OM prediction model were graft type and donor-patient CMV serostatus match, whereas the TRM model selected time from diagnosis to transplant and donor-recipient sex match. Applying the models on the validation set yielded AUCs of 0.701 (95% confidence interval [CI] 0.691-0.710) for OM prediction and 0.67 (95% [CI] 0.66-0.68) for TRM. The ADT prediction models assigned scores correlating with patient outcome. Patients in each of the validation sets were grouped according to their score range and the prediction success. A Higher score was correlated with higher rate of the measured outcome in both models (figure 1 and figure 2). Conclusions We present two new models, based on the ADT ML algorithm, for prediction of OM and TRM at day +100 after allo-HSCT. The models are robust as they rely on a high number of samples and a large validation set. As shown in the figures, higher scores correlated with a poorer outcome, reaching more than 50% mortality for a score range of 5.76-7 in the OM prediction model. The AUC performance measure was better for OM than TRM, possibly due to a higher event rate in former, making it easier to predict. Improving the predictive ability will probably necessitate evaluation of more variables, as the limitation of the maximal predictive performance is most likely in the information gained from the variables and not from the sample size or algorithm used. This is currently under progress, especially combination with other risk scores linked to comorbidities. In summary, our models can aid candidate selection for allo-HSCT, by providing a measurable score that correlates with transplant success. Disclosures: Schmid: Novartis: Honoraria, Research Funding, travel grant Other; Roche: travel grant, travel grant Other; MSD: Honoraria.

Abstract 4139 The prognosis of patients with AML harboring the FlT3 ITD is known to be poor in those patients treated with chemotherapy alone. However, it remains uncertain whether this abnormality has also an impact on outcome following high dose intensification and autologous stem cell transplantation (ASCT). We addressed this question using the EBMT data base: we initially reported on a total of 134 patients in 2010 (Blood 2010, 3356a). Following further queries, we have now extended our study to a total of 357 patients with AML autografted in CR1 between January 2000 to December 2009, and in whom the information on the presence or the absence of FlT3ITD was available. 258 (136 with a normal karyotype) patients were ITD negative and 99 (63 with a normal karyotype) were ITD positive. 96% of the patients received peripheral blood as a source of stem cells. The median follow up was 30 m. (range, 1–118). Patients who were ITD positive had higher white cell counts at diagnosis (54 vs. 12.5 109/L; p In the univariate analysis, Leukemia-Free Survival (LFS) at 3 years was significantly lower in patients who were ITD positive (34±5% vs. 52±4%; p=0.001) and the relapse incidence was higher (58±5% vs. 42±4%; p=0.002). The Non-Relapse Mortality (NRM) rate was similar (8±3% vs. 6±1%; p= 0.7). By multivariate analysis, the only unfavorable prognostic factors for outcome were failure to achieve CR with more than one induction course (slow remitters), and the presence of an ITD, which were associated with higher relapse incidence (p= 0.006; p=0.03) and lower LFS (p=0.05; p=0.005). In this series, it was interesting to observe that the only group with a significantly lower LFS in univariate analysis, was the group of patients who were FlT3ITD positive without NPM1 mutation (23±11% vs. 56±6% for FLT3ITD negative/NPM non-mutated, 46±8% for FLT3ITD negative/NPM mutated and 48±13% for FLT3ITD positive /NPM mutated; p=0.03). We conclude that in the context of autografting for AML in CR1, the presence of a FLT3ITD is an unfavorable prognostic factor only in less than 50% of the patients corresponding to those with the absence of a NPM1 mutation. This study helps to better define the population of patients with AML that would benefit most from intensification with autologous stem cell transplantation. Disclosures: No relevant conflicts of interest to declare.

Abstract 3004FN2 Clofarabine (CLO), a second generation purine analogue, has demonstrated an efficient anti-leukemia activity while showing a favorable toxicity profile. The aim of our study was to analyse the results of CLO as part of the conditioning regimen prior to allo-SCT for the treatment of patients with AML or ALL. This retrospective multicenter report assessed the outcome of 90 patients who received a clofarabine-containing conditioning regimen allogeneic stem cell transplantation (allo-SCT) for AML (n=69) or ALL (n=21) between November 2006 and September 2010 and reported on the EBMT registry. The median age was 42 years (range: 18–69) at transplant. The majority of patients presented with an active disease at transplant (CR1 n=8; CR2 n=16, active disease n=66). All patients had received a CLO-containing conditioning regimen (RIC n=88; MAC n=2) with the following combinations: CLO/TBI n=27; CLO/Busulfan n=10; CLO/Busulfan/ATG n=32; CLO/others drugs n=21. With a median follow-up of 14 months (range: 1–45), 2-years OS, LFS, relapse incidence, non-relapse mortality (NRM) and chronic GVHD were 28+-5%, 23+-5%, 41+-6%, 35+-5% and 38+-7%, respectively. When comparing AML and ALL patients, OS and LFS were significantly higher for AML patients (OS: 35+-6% vs 0%, p Disclosures: No relevant conflicts of interest to declare.

Abstract 3501 Acute myeloid leukemia (AML) with translocation t(6;9)(p23;q34)/DEK-NUP214(CAN) rearrangement (t(6;9) AML) is a rare but well-characterized entity, associated to a poor prognosis. In this regard, a possible benefit of allogeneic hematopoietic stem-cell transplantation (alloHSCT) has been suggested, based on small series of patients. To investigate the potential role of alloHSCT for the management of t(6;9) AML we analyzed the outcome of patients with this AML subtype submitted to alloHSCT and reported to the ALWP, and compared it to other well-defined cytogenetic categories. Overall, we identified 74 patients (median age: 38, 18–65; 51% male) diagnosed with t(6;9) AML allografted since 1988 (median year of transplant: 2004). Most transplants were performed in complete response (CR1=56, 76%; CR2=8, 11%), whereas only a minority were performed in advanced phase (primary refractory, n=5; relapse, n=5). Donor was an HLA-identical sibling in 43 transplants (58%), and a matched unrelated donor in 24 (32%). Conditioning regimen consisted of a myeloablative regimen in most patients (n=61, 82%), and source of stem-cells was peripheral blood in 41 (55%) and bone marrow in 32 (43%). After a median follow-up of 51 months, 3-year leukemia-free survival (LFS), relapse incidence (RI), and non-relapse mortality (NRM) for patients allografted in CR1 was 51±7%, 19±6%, and 30±7%, respectively, whereas LFS for patients transplanted in other disease status was only 16±10% (p Disclosures: No relevant conflicts of interest to declare.

The cell source for autologous stem cell transplantation has shifted since 1994 from bone marrow (BM) to peripheral blood (PB). However, no study has compared outcomes. We analyzed 2165 adults with acute myelocytic leukemia (AML) and 1545 adults with acute lymphocytic leukemia (ALL) in first complete remission (CR1) who received autografts (AML: 1607 PB and 558 BM, ALL: 1126 PB and 416 BM) from 1994 to 2006. AML: Relative to the time of CR1, PB transplants were performed earlier than BM transplants. Since a poorer outcome was associated with a shorter interval from CR1 to PB transplantation, patients were divided into three groups: BM, early PB (≤ 80 days after CR1) and late PB transplants. BM recipients were younger, and more received total body irradiation. In multivariate analysis, transplant-related mortality was not different among groups, but relapse incidence (RI) was higher for early PB (p = .0006) and late PB (p = .01) compared to BM (56 ± 3%,.46 ± 2%, 39 ± 2% respectively). Earlier PB (p= .02) and later PB transplants (p= .06) were associated with a lower three year LFS rate than marrow (36± 3%, 46 ± 2%, 52± 2% respectively). ALL:: In multi variate analysis the only poor prognostic factors were a high white cell count at diagnosis and cytogenetics (presence of the Phi/bcr-abl). The RI and LFS at 2 years were identical in patients receiving BM and PB ( 45 ± 3% vs 47 ± 2% and 47 ± 3% vs 46 ± 2% respectively) In conclusion, in AML patients autografted in CR1 but not in ALL, risk of relapse was lower with BM than with PB, independent of the CR1 to transplantation interval.

Patients with acute myelocytic leukaemia (AML) with core binding factor mutations (CBF), bearing abnormalities of chromosome 16 or t(8;21) are classified as good risk with chemotherapy regimens including high dose cytosine arabinoside and are not subjected to hemopoietic stem cell transplantation (HSC) front line. However there are limited data from old studies indicating good outcome following HSC, autografting in particular, and there has been recently some concern about higher than expected relapse incidence following conventional chemotherapy in this patient population. From January 1990 to December 2004, a total of 325 adult patients were reported to the EBMT Acute Leukemia registry as receiving a transplant in first remission (CR1). Of these, 159 had an inversion 16, including 124 with no additional chromosome abnormality and 35 with other abnormalities. 166 had a t(8;21) translocation, as the only chromosome abnormality in 106 and associated to other abnormalities in 60. 64 patients with inv 16 and 81 patients with t(8;21) received a geno-identical allograft. 95 patients with inv 16 and 85 patients with t(8;21) translocation received an autograft. In patients with inv 16, following allogeneic and autologous transplantation respectively, the LFS were 59 ± 7% and 66 ± 5% (p=0.5), the RI 27 ± 6% and 32 ± 4% (p=0.45) and the TRM 14 ± 4% and 2 ± 2% (p=0.003). The LFS was significantly higher after January 2001. Female patients had a significantly lower incidence of relapse and a higher LFS. The existence of additional chromosome abnormalities not only did not worsen the prognosis but was associated with less relapses (12±5% vs 34 ± 4%, p= 0.01), and a better LFS (78 ± 7% vs 59 ± 5%, p=0.04). In patients with t(8;21), following allogeneic and autologous transplantation respectively, the LFS were 60 ± 5% and 66 ± 5% (p=0.69), the RI 15 ± 2% and 28 ± 3% (p=0.03) and the TRM 24 ± 3% and 6 ± 1% (p=0.003). Younger age and a lower white cell count at diagnosis were associated with a lower TRM and a better LFS.There was no difference in outcome between female and male patients. Following autologous transplantation as compared to allogeneic, the TRM was significantly lower and the relapse incidence significantly higher. For all adult CBF AML, the LFS did not differ between autologous and allogeneic transplants. Although the reasons why these patients were transplanted are unclear, considering the low TRM of autologous stem cell transplantation and the possibility to monitor in vivo purging by molecular biology, the data support the inclusion of ASCT in the front line treatment of CBF AML and suggest that a randomized prospective trial comparing high dose ARA-C and ASCT would be of interest.

Abstract 1975 Background: Among patients with AML with normal cytogenetics (CN-AML), the presence or absence of the NPM1 mutation (NPM1mut) and the FLT3 internal tandem duplication (FLT3-ITD) allows to define molecular subgroups, which proved to influence leukemia-free survival (LFS) both after chemotherapy and allo-SCT (Schlenk, NEJM 2008, Brunet, JCO 2012). Hence, the genotypes are currently used as “disease risk” criteria, especially to define indication for allo-SCT in CR1. The influence of these markers on overall survival (OS) after allo-SCT has not been evaluated so far. Methods: An EBMT registry-based analysis included adults fulfilling the following criteria: CN-AML, peripheral blood stem cell or bone marrow allo-SCT in CR1 between 2006 and 2011, using matched-related (MRD) or matched unrelated donor (MUD), and detailed information on the mutational status of NPM1 and FLT3-ITD being available. OS, LFS, relapse incidence (RI) and non-relapse mortality (NRM) were calculated according to molecular subgroups. Further, a multivariate Cox model for risk factors was applied, including the following, predefined variables: Age (<> median), white blood cell counts at diagnosis, time from diagnosis to CR1, donor type (MRD versus MUD), conditioning regimen (reduced versus standard) and presence or absence of NPM1mut and FLT3-ITD. Results: 366 patients (median age: 49.5 years, range 18.0–70.6; 49% males, MRD in 54%) were included. Median time from diagnosis to CR1 was 45 days (range: 7–181), and median time from CR1 to allo-SCT was 109 days (range: 11–308). Median follow-up from allo-SCT was 12 months (range: 1–61). The Kaplan-Meier estimates of 2-year OS and LFS for the entire cohort were 69±3% and 62±3%, the cumulative incidence of relapse and NRM were 23±2% and 14±2%. Presence of an NPM1mut had no influence on LFS or OS. In contrast, presence of an FLT3-ITD was strongly associated with increased RI (p=0.0004), and decreased LFS (p=0.004) and OS (p=0.0007). Results at 2 years from allo-SCT (% +/− SD) according to molecular subgroups are shown in the table below (mut, mutated, WT, wild type): In the multivariate Cox model, age above the median of 49.5 years was the only factor associated with increased NRM (HR= 3.15, 95%CI: 1.27–7.82, p=0.01), whereas FLT3-ITD was the only factor that correlated with RI (HR=2.80; 95%CI; 1.26–6.20, p=0.01). Both older age and presence of FLT3-ITD were significantly associated with inferior LFS (HR=1.73, 95%CI: 1.03–2.91, p=0.04 for age, HR=2.03, 95%CI: 1.13–3.65, p=0.02 for FLT3-ITD) and, most importantly, with decreased OS (HR=2.29; 95%CI: 1.27–4.15, p=0.006 for age, and HR=2,75; 95%CI: 1.41–5.34, p=0.003 for FLT3-ITD). The latter data allowed the development of a scoring system, identifying three prognostic groups with 2-year survival rates of 42+/−7% (patients with both older age and FLT3-ITD), 66+/−4% (older age or FLT3-ITD) and 74+/−7% (younger age and FLT3-ITDneg, p Conclusion: We conclude that older age and FLT3-ITD are major risk factors for OS after allo-SCT in CN-AML patients in CR1, independently from other factors such as donor type, intensity of the conditioning, or NPM1 mutational status. Disclosures: Schmid: Novartis Germany: Honoraria, Research Funding; Fresenius Germany: Honoraria, travel grants, travel grants Other; Roche Germany: Honoraria, travel grants, travel grants Other; Pfizer: Travel Grants, Travel Grants Other; MSD Pharma: Honoraria, Travel grants Other; Cellgene: travel grants, travel grants Other. Attal:celgene: Membership on an entity's Board of Directors or advisory committees; janssen: Membership on an entity's Board of Directors or advisory committees.

Abstract 650 The Seattle group previously reported that the adapted Charlson CI (Sorror-CI) was useful for predicting NRM and survival in patients undergoing allo-SCT. However, the value of this CI index is still under considerable debate, since the cohort used by Sorror et al. (Blood 2005; 106:2912-9) included a large age range, a wide variety of diseases, with both myeloablative and RIC transplants. On the other hand, toxicities and NRM prediction is most likely needed in elderly and medically infirm patients who are increasingly offered RIC allo-SCT. Therefore, the current study was designed to test the performance of this CI and its association with outcomes among a cohort of 345 patients (i) aged >50 y.; (ii) diagnosed with a single disease entity, AML in CR1, and (iii) who underwent a RIC allo-SCT reported to the EBMT registry between 1999 and 2006. In this series, the median year of allo-SCT was 2004, and the median age was 58 y. (range, 50-76). 32% of patients needed more than one induction course to achieve CR1. A fludarabine-based RIC regimen was used in 64% of patients, while 31% of patients received low-dose TBI as part of their RIC, and 6% received other non-specified RIC regimens. 76% of the patients received allo-SCT from an HLA-matched sibling donor. Based on score calculated with hazard ratios (HR) estimated on the population studied, 161 patients (47%) had a CI score of 0, 96 patients (29%) had a score of 1, and 49 (14%) had a CI score of 2. The remaining 39 patients (11%) had CI scores of 3 or more. In this cohort, 2 years overall and leukemia-free survival rates were 64±3% and 54±3% and the 2 years relapse and -NRM cumulative incidences were 32±2%, and 15±2% respectively. The 2 years NRM incidences according to comorbidities score 0, 1, 2 and 3+ were 9±2%, 15±4%, 18±5% and 31±7%, respectively. In multivariate models (adjusted for recipient age, donor type, use of TBI or not, and cytogenetics risk group) comorbidities such as moderate active liver disease, obesity, prior history of renal dysfunction, and prior history of severe liver disease were associated with the highest HRs for 2 years NRM (varying from 2.11 to 2.76) and 2 years cumulative incidences of NRM varying from 22% to 44%, whereas previous solid tumor, diabetes, rheumatologic abnormalities, moderate pulmonary diseases, cardiac abnormalities (other than arrhythmia and valve disease) were associated with the lowest HRs (varying from 0.2 to 1.0) with 2 years cumulative incidences of NRM varying from 5 to 17%. Results from this large study performed in a single disease entity and homogeneous allo-SCT setting, suggest that the hematopoietic cell transplantation-specific CI is a simple, informative and useful tool for capturing pre-transplant comorbidities, and for predicting NRM after RIC allo-SCT for AML in CR1 in patients aged >50 y. Such index may be used for clinical trials and patient counselling before RIC allo-SCT. Disclosures: No relevant conflicts of interest to declare.

Increasing numbers of patients are receiving reduced intensity conditioning regimen allogeneic hematopoietic stem cell transplantation. We hypothesized that the use of bone marrow graft might decrease the risk of graft-versus-host disease compared to peripheral blood after reduced intensity conditioning regimens without compromising graft-versus-leukemia effects. Patients who underwent reduced intensity conditioning regimen allogeneic hematopoietic stem cell transplantation from 2000 to 2012 for acute leukemia, and who were reported to the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation were included in the study. Eight hundred and thirty-seven patients receiving bone marrow grafts were compared with 9011 peripheral blood transplant recipients after reduced intensity conditioning regimen. Median follow up of surviving patients was 27 months. Cumulative incidence of engraftment (neutrophil >= 0.5x10(9) /L at day 60) was lower in bone marrow recipients: 88% versus 95% (P