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International audience; In the absence of an HLA matched familial donor, a search for an unrelated donor or cord blood unit is initiated through worldwide registries. Although a first look-up on available HLA information of donors in the "book" at BMDW (Bone Marrow Donor Worldwide) can provide a good estimation of the number of compatible donors, the variety of resolution typing levels requires confirmatory typing (CT) which are expensive and time consuming. In order to help recipient centers in their work. The French donor registry (France Greffe de Moelle/Agence de la Biomedecine) has recently developed a software program called "EasyMatch(R)" that uses haplotype frequencies to compute the likelihood of phenotypic match in donors according to various typing resolution levels. The goal of our study is to report a single monocentric user-experience with EasyMatch(R), demonstrating that its routine use reduced the cost and the delay of the donor search in our center, allowing the definition of a new strategy to search compatible unrelated donors. The strategy was first established on a retrospective cohort of 217 recipients (185 adults and 32 children=before score) and then validated on a prospective cohort of 171 recipients (160 adults and 11 children=after score). For all patients, we calculated the delay between the registration day and the donor identification day, and the number of CT requested to the donor centre. Considering both groups, we could observe a significant decrease of the number of CT from 8 to 2 (p\textless0,001), and a significant decrease of the median delay to identify a suitable donor from 43 to 31days (p\textless0.0001). EasyMatch(R) estimates the number of potentially identical donors, but doesn't foresee availability of the donors. It provides us an easy tracking of mismatches, an estimation of the number of potential donors, the selection of population following ethnic origin of patients and a high prediction when probability is high or low. It affords a new approach of donor search in our daily work and improves the efficiency in the great challenge of the compatible donor identification

Background: Reduced-intensity conditioning (RIC) regimens have led to a dramatic reduction of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The concept of RIC is to deliver adequate immunosuppression with manageable graft-versus-host disease (GVHD) and the eventual development of a potent graft-versus-leukemia effect. Nevertheless, GVHD prophylaxis remains a challenging task after allo-HSCT. While the combination of cyclosporine A (CsA) and a short course of methotrexate (Mtx) after transplantation is considered as the gold standard for GVHD prophylaxis after conventional myeloablative allo-HSCT from HLA-identical siblings, there is no consensus on the optimal preventive GVHD prophylaxis after RIC allo-HSCT. On the other hand, recent and ongoing studies are evaluating a promising GVHD prophylaxis strategy using post-transplantation cyclophosphamide (PTCy). The aim of this study is to evaluate the impact of different GVHD prophylaxis used after RIC allo-HSCT in patients receiving peripheral blood stem cells (PBSC) from unrelated donors for hematological malignancies. Patients and methods: We evaluated 127 consecutive patients with hematological malignancies who received RIC allo-HSCT and were followed in our center between January 2008 and January 2016; 74 (58%) were males, median age was 58 years (range: 18-70), 52 (41%) had acute myeloid leukemia, 36 (28%) myelodysplastic syndrome, 12 (10%) myeloproliferative syndrome, 9 (7%) Non-Hodgkin lymphoma, 9 (7%) chronic lymphocytic leukemia, 6 (5%) multiple myeloma and 3 (2%) chronic myeloid leukemia. At transplantation, 65 (51%) patients were in complete response (CR) or chronic phase (CP). RIC regimen consisted on fludarabine, intermediate doses of IV busulfan and anti-thymocyte golbulins (ATG) (Thymoblobulin) in 56 (44%) patients and a sequential FLAMSA regimen in 71 (56%) patients and who also received similar doses of ATG (Thymoglobulin). PBSC donors were 10/10 HLA matched in 81 (64%) patients and 9/10 HLA mismatched in 46 (36%) patients. Patients were divided according to GVHD prophylaxis into 3 groups: group 1 consisted on CsA alone with 23 (18%) patients, group 2 include patients who received either CsA + mycophenolate mofetil (MMF), n= 64 (50%) or CsA + Mtx, n= 20 (16%) or CsA + cyclophosphamide n= 5 (4%), and group 3 included patients receiving CsA + MMF + tacrolimus n= 15 (12%) patients. Results: After transplantation, all patients in group 1 engrafted after a median of 17 (3-25) days, 81/89 (91%) engrafted in group 2 after a median of 17 (5-58) days and 14/15 (94%) engrafted in group 3 after a median of 16 (9-24) days. We did not observe any significant impact of the type of GVHD prophylaxis on the 100-day incidence of grade II to IV acute GVHD, which occurred in 6/15 (40%), 34/81 (42%) and 7/14 (50%) for the groups 1, 2 and 3 respectively (p=0.18). Grade III-IV acute GVHD occurred in 3 (20%), 24 (29%) and 5 (33%) in the three groups respectively (p=0.11). Similarly, cumulative incidence of 1 year chronic GVHD was not different between groups 1, 2 and 3 reaching 46%, 43% and 46% respectively (p=0.6) among them 3/15 (20%), 18 (22%) and 3/14 (21%) patients had an extensive form. After a median follow-up of 22 months for surviving patients, although there was no significant difference between the three groups in terms of non-relapse mortality, we observed more infection-related mortality with 45% and 83% in groups 2 and 3 respectively compared to 47% in group 1. The cumulative incidence of relapse at 2 years was 22%, 31 and 26% for the three groups respectively (p=0.23). Overall survival rates at two years were 43%, 31% and 44 % for groups 1, 2 and 3 respectively (p=0.42). The multivariate analysis taking into account the type of disease, donor HLA matching, disease status at transplantation, type of RIC and the type of prophylaxis, showed that the incidence of acute GVHD was influenced only by the use of FLAMSA regimen from mismatched donors, HR= 2.2 [1.3-3.1], p=0.05 which had also the same impact on the occurrence of chronic GVHD. Conclusion: Despite its limitations and the need for prospective randomized studies, the results of our study suggest that in the RIC allo-HSCT from unrelated donors, the different GVHD prophylaxis associations lead to similar GVHD outcomes. Patients with more immunosuppressive drugs had a higher incidence of infection-related mortality and in which PTCy could be a better option. Disclosures Nicolini: BMS: Consultancy, Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Anti–human leukocyte antigen (HLA) antibodies are associated with several complications in solid organ transplantations, but their impact after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not yet well defined. To evaluate the relevance of anti-HLA antibodies, we have retrospectively analyzed 107 peripheral blood allo-HSCTs after reduced-intensity conditioning regimen between 2005 and 2010. Acute myeloid leukemia and multiple myeloma were the most frequent malignancies in the cohort. The detection of anti-HLA antibodies was systematically performed in all patients before transplantation. Anti-HLA antibodies were present in 24 patients (22%). There was no significant impact of anti-HLA antibodies on engraftment, incidence of relapse, and incidence of acute graft-vs-host disease. The presence of anti-HLA antibodies was associated with significantly worse overall survival ( p = 0.006) and event-free survival ( p = 0.024) after stratification on sex. The 3-year probability of overall survival was 34% without anti-HLA antibodies and 16% in their presence. Patients with anti-HLA antibodies had a higher transplant-related mortality associated with life-threatening vascular complications. Our study supports that anti-HLA antibodies should be tested and considered as an important impacting factor for transplantation outcomes after reduced-intensity conditioning allo-HSCT. We recommend its consideration before allo-HSCT in the donor–recipient selection parameters.

Abstract 3520 Background: CLL remains incurable with standard therapies. Myeloablative allogeneic SCT (allo-HSCT) is still associated with high TRM and few late relapses. Recently, the major focus of transplantation in CLL has been with reduced-intensity conditioning (RIC) allo-HSCT, which is applicable to the more elderly patient population and which attempts to exploit the graft-versus-leukemia (GVL) effect that was proved in CLL Objective: To evaluate the efficacy and toxicity a RIC regimen including fludarabine and total body irradiation (TBI) with the introduction of rituximab for allo-HSCT in patients with a CLL stage B or C diagnosis. Materials and methods: This prospective study included adult CLL patients with age 70%). Donors were mobilized by G-CSF and in case of collection failure, bone marrow aspiration was authorized. The conditioning included: rituximab 375mg/m2 on day -5, fludarabine 30 mg/m2 from day-4 to day-2, TBI 2grays (6-7 cGrays/minute) on day 0 and rituximab 500mg/m2 on day1 and day8. GVHD prophylaxis used cyclosporine A (IV 3mg/kg/day) from day-2 and mycomofetil fenolate oral (2g/day) from day 1. Results: Between April 2003 and December 2008, 40 patients were included, 34 (85%) males and 6 females with a median age of 54 years (35-65), 38 (95%) were in B stage at diagnosis and 2 in stage C. Among 23 explored for cytogenetics, 8 were abnormal (3 del17, 1 trisomy12, 1 t(8-11) & 1 del13). Before transplantation, 17 patients received 2 lines treatment, 10 three lines, 5 four lines, and 8>4. Only 1 patient received a previous auto-HSCT. Among 18 explored for Matutes status, 1 was in score 1, 1 in score 2, 3 in score 3, 5 in score 4 & 9 in score 5. At time of allograft, 7 (17%) patients were in complete response (CR), 29 (73%) in partial response (PR) and 4 (10%) M). For ABO matching, 68% were compatible, 19% major incomp. & 13% minor incopm. The median interval diagnosis-allo-HSCT was 58 months (6-177). Median CD34+ number was 7.64 (3.1-18.7). Seven (17%) patients did not receive rituximab during conditioning because the protocol did not include it at the beginning and has been amended later. Thirty-nine (98%) patients engrafted with a median time to neutrophils recovery of 20 days (11-70), 79% of patients reached a total donor chimerism at day 90. Seventeen patients developed aGVHD grade ≥II (8 grII, 8 grIII & 1 grIV) with a cumulative incidence at 3 months of 44% (36-52). The cumulative incidence of cGVHD was, at 12 months: 29% (21-36) for limited and extensive; at 18 months: 32% (24-40) limited and 42% (34-50) extensive. After a median follow-up of 28 months (3-71), the median OS was not reached with 3 and 5-years probability of 55%(41-74). The median time of EFS was 30 months (15 - 70) with a 5-years probability of 46%(33-66). The cumulative incidence of relapse at 1 and 3 years was 17% (11-23) and 22% (15-29) respectively. The cumulative incidence TRM at 1 and 3 years was 10% (5-15) and 27% (20-35) respectively. At the last follow-up, 17 patients died, 6 due to relapse and 11 due to TRM. We noticed a high severe infection rate (56%) and 4% of deaths related only to infection. The univariate analysis showed a positive trend of rituximab on OS and relapse, and a significant protective effect on aGVHD>=2 (p=0.02). The multivariate analysis studying age, interval diagnosis-allo-HSCT, ABO and sex matching, disease status at allo-HSCT, CD34+ number, and rituximab, showed a positive significant impact of this last factor (rituximab) on OS and EFS [HR=0.1 [0-0.6] p=0.02 & HR=0.1[0-0.4] p=0.035 respectively]. Conclusion: We showed interesting results in terms of OS, relapse and TRM in patients with advanced CLL after Fludarabine/TBI allo-HSCT. The introduction of rituximab allowed a better outcome especially a significant reduction of incidence and severity of acute GVHD. Nevertheless there was still a high incidence of cGVHD, already known following the Fludarabine/TBI conditioning, leading us to propose either to increase the number of rituximab injections after allo-HSCT, or to test Fludarabine/busilvex/ATG associated to rituximab. Download : Download high-res image (109KB) Download : Download full-size image Disclosures: No relevant conflicts of interest to declare.

Abstract 2371 Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) appears to offer a potential advantage in terms of event free survival (EFS) and overall survival (OS) in patients with acute leukemia (AL) with bad prognostic factors. The main issue is to find a donor; usually, a patient has 30% chance to find an HLA identical sibling donor (SD) and approximately 40% chance to find a suitable unrelated donor (UD) from international registries. Unfortunately, 40% of registered patients relapse or die before finding a donor. Aim: Our objective was to evaluate the outcome (OS & EFS) in AL patients, whether they had an HLA identical SD, an UD or no donor (ND) after registration on France Greffe de Moelle (FGM) registry, either transplanted later or not. Our secondary objective was to evaluate the impact of interval between, diagnosis and allo-HSCT, donor finding and allo-HSCT, interval registration-allo-HSCT, on OS and EFS. Methods: We have analyzed 251 AL patients diagnosed between January 2000 and December 2008, for whom a search for a donor was initiated for a required allo-HSCT. There were 117 (47%) males and 134 females with a median age at diagnosis of 40 years [16-66], 177 (71%) were AML (prognosis according to cytogenetics & molecular markers: 59 were good, 97 poor and 21 not done) 75 were ALL (prognosis according to cytogenetics & molecular markers: 33 were good, 16 poor and 26 not done). Seventy six (30%) patients had an available SD and received allo-HSCT within a median time of 3.5 months (0.5 – 43) (59 AML & 17 ALL), and 38 (15%) with SD but were not transplanted due to early relapse and/or death. For patients with no available SD, a registration on FGM registry was done. One hundred thirty seven patients were registered after a median interval of 2.3 months (0.4-135) from diagnosis, 33 (13%) patients (24 AML & 9 ALL) did not find any donor, have not been transplanted and they received the standard of care. One hundred and four (41%) patients (62 AML & 42ALL) found an UD or cord blood cell (CBC) unit after a median registration time of 1.6 months (0.3 – 26): 86 with UD of which only 60 have been transplanted within a median time of 2.3 months (0.4 – 14), 18 with CBU of which only 17 were transplanted. Among transplanted patients, 113 (74%) were in complete response (CR) at transplantation, and 40 were in less than CR. Fifty (33%) received peripheral blood (PBSC) (23 UD & 27 SD), 86 (57%) received bone marrow (BM) (37 UD & 49 SD) and 17 (10%) CBC units. For conditioning, 56 (37%) were reduced intensity (29 SD & 27 UD) and 96 standard (47SD & 50 UD). For HLA, there were 45 HLA 10/10, (27BM & 18 PBSC), 14 HLA 9/10 (9BM 5PBSC) 1 HLA 8/10 (BM) and for CBC 14 HLA 4/6 and 3 HLA 5/6. Results: After a median follow-up of 25 months (0.2- 234), the median OS was 78 months (51 – 133) for transplanted patients with SD (3years OS: 68%), it was 33 months (27 – 47) for transplanted patients with UD (3years OS: 44%), 21 months (15 – 37) for not transplanted patients with available SD or UD (3years OS: 34%) and finally it was 31 months (23-221) for patients with ND (3years OS: 45%). The median EFS for the same groups was 38 months (23 – 133), 24 months (17 – 36), 15 months (11-24) and 23 months (14 – 48) respectively. The only factors negatively affecting OS in multivariate analysis (studying age, sex, AL type, cytogenetics, donor or no donor, transplanted or not, UD or SD) were age and allo-transplanted from UD. When adjusting only on transplanted patients, taking into account in addition to previous factors, the time between diagnosis-registration, time between registration-allo-HSCT, disease status at allo-HSCT, stem cell source, conditioning; three significant factors affected OS: disease status ( Conclusion: The results of our first analysis seemed surprising regarding our knowledge of outcome in allo-HSCT from SD and UD, which led us to investigate on unusual interfering factors. We have explored the relation between the interval diagnosis-registration for a donor search and the interval registration-allo-HSCT that appeared as major factors affecting survival in UD allo-HSCT settings. Disclosures: No relevant conflicts of interest to declare.

Abstract 4549 Introduction Patients with high risk AML have poor outcomes. However, the only approach with curative potential remains allogeneic HSCT. With the aim to improve the effect of allogeneic HSCT by sequential use of chemotherapy, RIC regimen and pDLI, we are currently conducting a prospective pilot study for high risk AML. High risk AML was defined by unfavorable cytogenetics, adverse molecular abnormality, secondary AML, and AML requiring 2 induction courses to obtain CR1. After identification of a HLA 10/10 donor, patients are received the sequential regimen consisted of fludarabine (30mg/m2/d), Ara-c (2g/m2/d) and amsacrine (100mg/m2/d) (FLAMSA) chemotherapy for 4 days. After 3 days of rest, RIC regimen consisted of 4 Gy TBI, cyclophosphamide for 2 days (40 mg/kg in case of matched related donors, and 60 mg/kg for unrelated or mismatched donors), and ATG (5mg/kg total dose) (German regimen) or Busulfan 3.2mg/kg/d during 4 days followed by ATG (5mg/kg total dose) (French regimen). The modified regimen has been established after our results in refractory AML patients (ASH 2011, poster 1957). Prophylactic donor lymphocyte transfusion was given from day +120 in patients who were not receiving immunosuppression and were free of GvHD. Our objective is to include 20 patients and to compare with a control cohort of patients with the same high risk AML treated according to the conventional strategy during the same period. Results Between August 2010 and November 2011, we have included 12 consecutive patients in first complete response who underwent an allogeneic HSCT after sequential FLAMSA-RIC regimen with a median follow-up of 12 months (range [7–22]). Nine patients were < 55 years old (median age: 54 [28–64]), 7 patients had an unrelated donor and 5 patients had a related donor. The stem cell source was PBSC for 11 patients and two cord blood unit for 1 patient. Before FLAMSA-RIC regimen, 3 patients had received two induction courses to obtain CR1. All patients had adverse cytogenetics or molecular abnormalities and 1 patient had a secondary AML. At the last follow-up, 6 patients (50%) are alive in CR. (Figure 1.) Four patients (33.3%) died in remission. The cause of death was infection for 2 patients, aGvHD for 1 patient and graft failure for 1 patient. Only one patient died from relapse 6 months after transplantation. Five patients (41.6%) experienced aGvHD and 2 patients (16.6%) had an extensive cGvHD including the patient who has been transplanted with 2 cord blood unit. Six patients (75%) in a group of 8 patients aged > 45 years experienced complications (infection (n=3) and GvHD (n=3)). One patient (25%) from a group of 4 patients aged < 45 years had infectious complication after transplantation. Prophylactic donor lymphocyte transfusion was given in 6 patients, the causes of no administration were GvHD for 2 patients, cord blood unit as stem cell source for 1 patient and 3 patients were dead before 120 days after transplantation. From the 6 patients who had received pDLI, 5 patients are alive in CR and 1 patient died from GvHD. Conclusion The FLAMSA-RIC regimen before allogeneic HSCT is a new approach for high risk AML. Between 2012 January and 2012 July, 8 additionnal patients have been included and the results for the whole study will be communicated later. Our primary results are promising especially for young patients (< 45 years) who seem to better profit from this sequential FLAMSA-RIC regimen. Disclosures: Nicolini: Novartis, Bristol Myers-Squibb, Pfizer, ARIAD, and Teva: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Abstract 3111 Cord blood transplantation (CB-T) is increasingly used as a treatment alternative for hematological malignancies. The use of double CB-T has leaded to interesting results in adult patients. We retrospectively evaluated 31 patients, 19 males and 12 females with a median age of 36 years (range: 20–63) who received double CB-T for hematological malignancies at our institution between 2005 and 2011. There were 15 AML, 9 ALL, 2 CML, 1 Hodgkin disease, 1 NHL, 1 MM and 1 MDS; at transplantation, 18 (58%) were in CR, 5 (16%) in PR and 8 (26%) in relapse, 16 patients received a myeloablative conditioning and 15 a reduced intensity one. Different characteristics of both CB units (CBU) are described in Table 1. When considering matching variables between the 2 CBUs and the recipient, for sex matching: in 10 cases, CBUs were both matched with the recipient, in 1 case both mismatched and in 20 cases, only 1 CBU was mismatched with recipient. For ABO compatibility, in 7 cases, CBUs were both compatible with the recipient, in 13 cases both were incompatible and in 1 case, only one was incompatible. For HLA matching, in 18 cases, both CBUs were 4/6 with the recipient and in 13 cases, only one CBU was 5/6. When considering HLA matching between the 2 CBUs, there were 7 with 3/6 HLA matching, 17 with 4/6, 6 with 5/6 and 1 with 6/6. After transplantation, 25 (81%) patients engrafted among them, 6 had mixed chimerism (presence of the 2 CBUs) and 19 had one dominant CBU. Non-engrafted patients were in relapse or progressive disease and received RIC before allo-HSCT. There were 13 patients who developed acute GVHD ≥2 (8 grade III-IV) and 6 chronic GVHD (3 limited and 3 extensive). After a median follow-up of 6.5 months (range: 1–54), the median OS was not reached with a 1 year probability of 58% (95%CI: 42–80), only 3 patients relapsed. The cumulative incidence of transplant related mortality (TRM) was 37% (95%CI: 28–46). A multivariate model that studied the different matching possibilities (sex, ABO and HLA) between the 2 CBUs together and then between the 2 CBUs with the recipient combined to CNT and CD34 cells number, showed that only the sex matching between the 3 partners can determine the dominant CBU later (p=0.04). In multivariate analysis taking into account pre-transplant and the matching variables, no factor impacted the engraftment while factors that impacted on OS were age [HR=1.1 (1.03–1.25), p=0.01], disease status at HSCT [relapse, HR=8.7 (1.4–52), p=0.01] and TNC number [ HR=0.99 (0.98–1), p=0.02]. Age and TNC number also had a significant impact on TRM [HR=1.12 (1.02–1.23), p=0.01 and HR=0.99 (0.98–1), p=0.003]. In conclusion, we did not find any impact of the different matching variables between the 2 CBUs either together or with the recipient on different transplantation outcomes. Nevertheless, sex matching between the 3 partners seems to play a role in the determination of the dominant CBU later and its installation in the recipient. Disclosures: No relevant conflicts of interest to declare.

Abstract 4093 Introduction: Relapse remains a major cause of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with hematological diseases. During the last decade, many improvements have been achieved in the understanding of the disease- and patient-related conditions in order to obtain the optimal allogeneic effect but the relapse is still representative which leaded to the development of different chemo- and immuno-therapy strategies. Aims: To evaluate at a first time the different pre- and post-transplantation factors impacting the relapse occurrence after allo-HSCT, and at a second time, to evaluate factors impact the survival post-relapse including the different treatment options. Material and methods: We have retrospectively studied the occurrence of relapse in 345 patients, 198 (57%) males and 147 (43%) females with a median age of 43 years (range17–66) who received allo-HSCT at our institution for hematological malignancies between years 2000 and 2011; 205 (59%) from siblings donors and 140 (41%) form unrelated donors. At transplantation, there were 148 (43%) patients in first complete response or first chronic phase (CR1/CP1), 66 (19%) in CR2/CP2 and 131 (38%) < CR2/CP2. Two hundred and six (60%) patients received a full intensity conditioning and 139 (40%) a reduced intensity one. The different patients and transplantations characteristics are detailed in Table 1. Results: After HSCT, 336 (97%) patients engrafted. The cumulative incidence of acute GVHD≥2 at 3 months was 35% (95%CI 32–37); the cumulative incidence of extensive and limited chronic GVHD at one year was the same 15% (95%CI 13–17). After a median follow-up of 11.4 months (range 4–129), the median overall survival (OS) for the whole population was 19 months (range 12–33) with a 2-years probability of 47% (95%CI 42–53). Eighty eight (25.5%) patients relapsed with a cumulative incidence at one and two years of 19% (95%CI 17–21) and 22% (95%CI 20–24) respectively. Characteristics of relapsed patients are described in Table 1. After relapse, 65 (74%) patients were treated [21 (32%) received donor lymphocyte infusion (DLI) alone, 21 (32%) chemotherapy alone, 14 (22%) DLI + chemotherapy and 9 (14%) received other treatment] and 23 (26%) were not treated due to deadly relapse. The median OS from relapse was 4 months (range 3–5) and the one year probability of OS in patients who relapsed was 21% (95%CI 14–31). The multivariate analysis studying the impact of different variables on the occurrence of relapse showed a negative impact of disease status [ Conclusion: We showed that relapse after allo-HSCT in hematological malignancies is still a significant issue, disease status at HSCT and CMV matching worsen its occurrence while cGVHD can be protective. Survival rate after relapse is still very low reflecting the difficulty to find an optimal treatment, disease status at transplantation seem to have a long term effect while the use of DLI with or without chemotherapy can offer better results. In addition to the new chemotherapy molecules, immunotherapy should be used in order to enhance the graft-versus-leukemia effect not only after relapse, but also early in presence of a minimal residual disease. Disclosures: No relevant conflicts of interest to declare.

Abstract 4481 Introduction: HLA matching has been demonstrated to play a major role in the different outcomes of allogeneic hematopoietic transplantation (allo-HSCT) in patients with hematological malignancies. When searching for an unrelated donor the commonly evaluated HLA loci are -A, -B, ± -C, -DRB1 and DQB1. The 2 loci DRB3 and DRB4 have never been taken into account and never been evaluated. Aims: To evaluate the impact of HLA-DRB3 and -DRB4 on the different unrelated allo-HSCT outcomes especially in case of mismatch presence on these loci. Material and methods: We have of 30 patients (study group) who received unrelated allo-HSCT with a HLA-DRB3 or HLA-DRB4 mismatched donor and we compared their outcomes to outcomes of a matched control group of 30 patients with the same characteristics except for the DRB3 or DRB4 donor mismatching. In the study group, there were 16 males and 14 females with a median age of 45 years (25–62), 18 patients had AML, 6 ALL, 2 MDS, 2 multiple myeloma (MM), 1 CML and 1 NHL. Fifteen patients received a myeloablative conditioning and 15 received a reduced intensity one (RIC). At transplantation, 16 patients were in CR, 4 in PR and 10 in relapse; 15 patients received PBSC and 15 BM. There were 16 patients with 10/10 HLA identical donor among them 11 had a DRB3 mismatch and 5 had a DRB4 mismatch. There were 14 patients with 9/10 HLA identical donor among them 9 had a DRB3 mismatch (mismatched: 3 on HLA-A, 1HLA-B, 4 HLA-C and 1 on HLA-DQB1) and 5 had a DRB4 mismatch (mismatched: 1 on HLA-A, 1HLA-B, 1 HLA-C and 2 on HLA-DQB1). In the control group, there were 16 males and 14 females with a median age of 46 years (25–64), 18 patients had AML, 6 ALL, 3 MM, 1 CML and 2 NHL. Fifteen patients received a myeloablative conditioning and 15 received a RIC. At transplantation, 22 patients were in CR, 1 in PR and 7 in relapse; 15 patients received PBSC and 15 received BM. There were 16 patients with 10/10 HLA identical donor and 14 patients with 9/10 HLA identical donor (mismatched: 6 on HLA-A, 3 HLA-B, 4 HLA-C and 1 on HLA-DQB1) all patients in the control group were matched for HLA-DRB3 and –DRB4. Results: After HSCT, 27 (90%) patients in the study group engrafted while 29 (96%) engrafted in the control group. The cumulative incidence of acute GVHD≥2 at 3 months was 37% (28–46) and 30% (22–39) for the study and control groups respectively, with a same cumulative incidence of chronic GVHD at one year of 20% (12–28). At day 90 post HSCT, 17 (63%) patients in the study group were in CR and 25 (86%) in CR in the control group. After a median follow-up of 5 months (0.2–46) and 13 months (0.5–60) for study and control groups respectively, the median overall survival (OS) was 7 months (3–32) and 21 months (11-NR) with a 2-years probability of 25% (12–51) and 41% (25–69) respectively; the median time of progression-free survival (PFS) was 3 months (0.2–46) and 10 months (1–60) with a 2-years probability of 16% (6–42) and 37% (21–63) respectively. The cumulative incidence of relapse at 1 year was the same for the two groups with 30% (22–39); the cumulative incidence of transplant related mortality (TRM) at 3 months and 1 year were 17% (10–24) vs. 3% (0–7) and 37% (28–46) vs. 10% (5–16) for study and control groups respectively. The multivariate analysis that studied age, type of disease, matched or mismatched HLA, with or without DRB3 or DRB4 mismatch, disease status at transplantation and type of conditioning showed a significant worse OS in 9/10 mismatched patients with or without a DRB3 or DRB4 mismatch (HR=5.3; [1.6–18] p=0.006); 10/10 matched patients with a DRB3 or DRB4 mismatch (HR=3.9; [1.2–12] p=0.02) and patients not in CR at transplantation (HR= 4.4; [1.6–12] p=0.004); similarly, the same groups had a worse PFS while patients not in CR or with a DRB3 or DRB4 mismatch showed a worse TRM in multivariate analysis, (HR=6; [1.5–24] p= 0.02) and (HR=3.5; [1.02–12] p=0.04) respectively. Conclusion: We demonstrated that the HLA-DRB3 or DRB4 matching donor is relevant for OS and TRM of patients who undergo allo-HSCT from unrelated donor either in the 10/10 or 9/10 HLA matching settings. Moreover, in view of the important impact of these loci mismatches, we recommend its consideration in the unrelated donor selection setting particularly in the 10/10 HLA unrelated donors. Since the evaluation of these loci is not widely done within HLA laboratories, we suggest conducting a large prospective study in order to validate its impact on unrelated allo-HSCT outcomes. Disclosures: No relevant conflicts of interest to declare.

Abstract 3087 Introduction Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only potential to cure wide types of hematological diseases. A patient has 30% of chance to find a HLA-identical sibling donor while the rest of patients should find an alternative unrelated donor. The use of 10/10 HLA matched unrelated transplants has been used as a main alternative and with its unavailability, when available, a 9/10 HLA mismatched unrelated transplant has been used. The outcome of this last mismatched transplant is not very clear and its use according to patient and disease conditions has not been well defined yet. Aims To evaluate the outcome of allo-HSCT from 9/10 HLA mismatched unrelated donors compared to those from 10/10 HLA identical unrelated donors and siblings; and to define which category of patients can benefit the more in each alternative. Material and methods We have retrospectively studied the outcome of 213 patients who received allo-HSCT for different hematological malignancies, 121 (57%) from HLA identical siblings, 63 (29%) from 10/10 HLA identical unrelated donors and 29 (14%) from 9/10 HLA mismatched unrelated donors treated during the same period of time between 2006 and 2011 at our institution. In the mismatched group, 12 patients had the mismatch at HLA-A locus, 7 at the HLA-B, 7 at the HLA-C and 3 at the HLA-DQ. Characteristics between the 3 groups were comparable except for: disease type between the 2 unrelated groups, sex-matching, CMV-matching and ABO-matching. The different characteristics are detailed in Table 1. Results After HSCT, engraftment was significantly lower in the 9/10 HLA group (90%) than in the 10/10 HLA group (95%) than in the sibling group (99%), (p=0.03); the cumulative incidence of acute GVHD ≥2 at 3 months was 32% (23–41), 20% (15–26) and 27% (23–32) respectively; the cumulative incidence of extensive chronic GVHD at one year was 21% (13–30), 9% (5–13) and 17% (14–21) for the 3 groups respectively. After a median follow-up of 8 months (0–54) in the 9/10 HLA group, 10 months (0–60) in the 10/10 HLA group and 18 months in the siblings group, the median overall survival (OS) was 10 months (5–21), 18 months (11-NR) and 60 months (31-NR) respectively with a 2-years probability of 19% (8–44), 43% (31–59) and 63% (54–74) respectively. There was a higher but not significant relapse incidence at one year in the 9/10 HLA group compared to other groups while the transplant related mortality was significantly higher with a cumulative incidence at 1 year of 45% (35–55), (p Conclusion We showed that allo-HSCT from 9/10 HLA mismatched unrelated donors have a significantly worse OS than those from matched unrelated donors and siblings; this was mainly due to an increased TRM in this group. Patients in first CR or CP could benefit the more from matched or 9/10 unrelated allo-HSCT while the use of transplants from 9/10 HLA unrelated donors in patients not in CR1 or CP1 should be limited to clinical trials. In view of these results, we should consider and evaluate the use of cord blood as an alternative source of transplant according to patient and disease conditions. Disclosures: No relevant conflicts of interest to declare.

Abstract 2038 Introduction: Anti-HLA antibodies are associated with several complications in solid organ transplantations but their impact after allogeneic hematopoietic stem cell transplantation (HSCT) is not very well defined yet. Patients and methods: To evaluate the relevance of anti-HLA antibodies, we have retrospectively analyzed 107 peripheral blood allogeneic HSCT after reduced-intensity conditioning (RIC) regimen between 2005 and 2010. Acute myeloid leukaemia (n=52,48.5%) and multiple myeloma (n=18,17%) were the most common diagnosis in the cohort. The detection of anti-HLA antibodies was systematically performed in all patients before transplantation. Results: We found in 24 patients (22%) the presence of anti-HLA antibodies. There was no association between the presence of anti-HLA antibodies and engraftment, incidence of relapse or acute GvHD. The presence of anti-HLA antibodies was associated with worse survival in univariate analysis (HR 2.04; [95%CI,1.21–3.44], p=0.0056) and in multivariate analysis (HR 2.63; [95%CI, 1.32–5.25], p=0.006). The 3-year probability of OS was 34% (95%CI, 24–49) without anti-HLA antibodies and 16% (95%CI, 6–41) in their presence (Figure 1). The other significant factors on survival were the disease status at transplantation, the age, minor and major ABO incompatibilities between donor and recipient, the sex-mismatching and the CMV status. Moreover, the positive anti-HLA antibodies group showed a trend of higher TRM in univariate analysis (p=0.07) and in multivariate analysis (HR= 1.9; [95%CI, 0.94 – 3.9], p=0.076). The TRM at 3 years after transplantation were 31% (95%CI, 26–37) without anti-HLA antibodies and 46% (95%CI, 36–57) in their presence (figure 2). The causes of the pejorative effect of the anti-HLA antibodies were not defined yet but we observed microangiopathy associated with vascular endothelium damage which could be related to the presence of anti-HLA antibodies. Conclusion: Our study suggests that anti-HLA antibodies should be tested and considered as an important prognostic factor for transplant outcomes after RIC HSCT. Disclosures: No relevant conflicts of interest to declare.

Abstract 1957 Introduction: The FLAMSA sequential chemotherapy regimen followed by RIC for allo-HSCT and prophylactic donor lymphocyte transfusion (pDLT) was introduced a few years ago as a salvage therapy for patients with refractory or high risk AML/MDS. This retrospective analysis aimed to assess the outcome of 40 patients with refractory or high risk AML/MDS who received a salvage FLAMSA sequential chemotherapy (including a subgroup of patients who received a modified FLAMSA regimen incorporating Busulfan instead of total-body irradiation (TBI)). Patients and methods: This series included 30 males and 10 females with a median age of 52 years (range, 32–66) treated in 2 transplant centres in France. Diseases characteristics were as follow: progressive or refractory disease after rescue treatment for first relapse (n=21), early relapse without any further salvage therapy (n=4), and primary induction failure (PIF; n=4). The series also included 7 patients with high risk MDS (IPSS ≥ 1.5), and another 4 patients in first CR but having a very poor prognosis based on cytogenetics features (CR group hereinafter). According to cytogenetics and molecular markers, 12 patients were classified in the “standard risk” cytogenetics risk group, while 21 patients had an unfavourable/poor profile. Data were not available for 7 patients. The FLAMSA regimen included Fludarabine (30 mg/m2/d), cytarabine (2 g/m2/d) and amsacrine (100mg/m2/d) from day −12 to day −9. In addition, priming with G-CSF once daily was done in 12 patients. After 3 days of rest, a RIC regimen was administered. In 28 patients, the RIC regimen included 4 Gy. TBI, ATG 5 mg/kg total dose, and cyclophosphamide (40 mg/kg in case of matched related donors, and 60 mg/kg for unrelated or mismatched donors). In the remaining 12 patients, TBI was replaced by I.V. Busulfan 3.2 mg/kg/d for 4 days. Per protocol, pDLT was planned to be given from day +120 in patients who were not receiving immunosuppression and were free of GvHD. Eighteen patients were transplanted using an HLA identical sibling donor, and 22 received transplant from an unrelated donor (14 matched 10/10 and 8 mismatched 9/10). Results: After allo-HSCT, 39 patients (97.5%) engrafted. In the CR group (n=4), after a median follow-up of 5 months (range, 3–31) all patients were still alive in CR at last follow-up. In the remaining 36 patients, 9 patients developed acute GVHD ≥2 with a cumulative incidence at 3 months of 18% (95%CI, 10–26). At day 90 post HSCT, 23 (64%) patients could achieve hematological CR, and 14 of the 23 remained in CR at last follow-up. After a median follow-up of 6 months (range, 1–60), the 2-years probability of OS was 30% (95%CI, 17–52), and the 2-years probability of PFS was 29% (95%CI, 17–50). The cumulative incidence of disease progression at 1 year was 25% (95%CI, 18–33). Interestingly, none of the patients who received Busulfan instead of TBI as part of the RIC, relapsed. The cumulative incidence of TRM at 3 months and 1 year were 14% (95%CI, 8–20) and 22% (95%CI, 15–29), respectively. In the multivariate analysis (taking into account all relevant parameters such as priming with G-CSF, conditioning with or without TBI, related or unrelated donors, HLA matching and number of previous treatment lines), there was a significantly worsened PFS in patients who received transplant from a mismatched donor (HR=3.6; [95%CI, 1.3–10] p=0.01; below Figure). Also, when considering disease relapse, there was a highly significant impact of the type of RIC regimen (in favour of a FLAMSA regimen without TBI (p Conclusion: Despite its limitations, results from this analysis confirm that a FLAMSA sequential chemotherapy regimen followed by RIC and allo-HSCT is a valid salvage therapy for patients with refractory or high risk AML/MDS. This study shows that HLA mismatched donors should be avoided in FLAMSA regimen. Moreover a modified FLAMSA regimen incorporating I.V. Busulfan instead of TBI is likely to allow better long-term disease control, warranting prospective evaluation. Disclosures: No relevant conflicts of interest to declare.

Abstract 3520 Background: CLL remains incurable with standard therapies. Myeloablative allogeneic SCT (allo-HSCT) is still associated with high TRM and few late relapses. Recently, the major focus of transplantation in CLL has been with reduced-intensity conditioning (RIC) allo-HSCT, which is applicable to the more elderly patient population and which attempts to exploit the graft-versus-leukemia (GVL) effect that was proved in CLL Objective: To evaluate the efficacy and toxicity a RIC regimen including fludarabine and total body irradiation (TBI) with the introduction of rituximab for allo-HSCT in patients with a CLL stage B or C diagnosis. Materials and methods: This prospective study included adult CLL patients with age < 65 years in stage B or C in response after a salvage treatment either following at least 2 treatment lines (1 including fludarabine) or after a progressive disease after auto-HSCT, having a HLA identical sibling donor and a good performance status (Karnfosky >70%). Donors were mobilized by G-CSF and in case of collection failure, bone marrow aspiration was authorized. The conditioning included: rituximab 375mg/m2 on day -5, fludarabine 30 mg/m2 from day-4 to day-2, TBI 2grays (6-7 cGrays/minute) on day 0 and rituximab 500mg/m2 on day1 and day8. GVHD prophylaxis used cyclosporine A (IV 3mg/kg/day) from day-2 and mycomofetil fenolate oral (2g/day) from day 1. Results: Between April 2003 and December 2008, 40 patients were included, 34 (85%) males and 6 females with a median age of 54 years (35-65), 38 (95%) were in B stage at diagnosis and 2 in stage C. Among 23 explored for cytogenetics, 8 were abnormal (3 del17, 1 trisomy12, 1 t(8-11) & 1 del13). Before transplantation, 17 patients received 2 lines treatment, 10 three lines, 5 four lines, and 8>4. Only 1 patient received a previous auto-HSCT. Among 18 explored for Matutes status, 1 was in score 1, 1 in score 2, 3 in score 3, 5 in score 4 & 9 in score 5. At time of allograft, 7 (17%) patients were in complete response (CR), 29 (73%) in partial response (PR) and 4 (10%) < PR. For sex-matching, 59% were mismatched (27%of them were F>M). For ABO matching, 68% were compatible, 19% major incomp. & 13% minor incopm. The median interval diagnosis-allo-HSCT was 58 months (6-177). Median CD34+ number was 7.64 (3.1-18.7). Seven (17%) patients did not receive rituximab during conditioning because the protocol did not include it at the beginning and has been amended later. Thirty-nine (98%) patients engrafted with a median time to neutrophils recovery of 20 days (11-70), 79% of patients reached a total donor chimerism at day 90. Seventeen patients developed aGVHD grade ≥II (8 grII, 8 grIII & 1 grIV) with a cumulative incidence at 3 months of 44% (36-52). The cumulative incidence of cGVHD was, at 12 months: 29% (21-36) for limited and extensive; at 18 months: 32% (24-40) limited and 42% (34-50) extensive. After a median follow-up of 28 months (3-71), the median OS was not reached with 3 and 5-years probability of 55%(41-74). The median time of EFS was 30 months (15 - 70) with a 5-years probability of 46%(33-66). The cumulative incidence of relapse at 1 and 3 years was 17% (11-23) and 22% (15-29) respectively. The cumulative incidence TRM at 1 and 3 years was 10% (5-15) and 27% (20-35) respectively. At the last follow-up, 17 patients died, 6 due to relapse and 11 due to TRM. We noticed a high severe infection rate (56%) and 4% of deaths related only to infection. The univariate analysis showed a positive trend of rituximab on OS and relapse, and a significant protective effect on aGVHD>=2 (p=0.02). The multivariate analysis studying age, interval diagnosis-allo-HSCT, ABO and sex matching, disease status at allo-HSCT, CD34+ number, and rituximab, showed a positive significant impact of this last factor (rituximab) on OS and EFS [HR=0.1 [0-0.6] p=0.02 & HR=0.1[0-0.4] p=0.035 respectively]. Conclusion: We showed interesting results in terms of OS, relapse and TRM in patients with advanced CLL after Fludarabine/TBI allo-HSCT. The introduction of rituximab allowed a better outcome especially a significant reduction of incidence and severity of acute GVHD. Nevertheless there was still a high incidence of cGVHD, already known following the Fludarabine/TBI conditioning, leading us to propose either to increase the number of rituximab injections after allo-HSCT, or to test Fludarabine/busilvex/ATG associated to rituximab. Disclosures: No relevant conflicts of interest to declare.

Abstract 2353 Background: The key point in allogeneic hematopoietic stem cell transplantation (allo-HSCT) is to find the optimal balance between the graft-versus-host disease (GVHD) and the graft-versus-leukemia (GVL) effect particularly in the unrelated HSCT settings, without forgetting the important role of conditioning. Objective: To evaluate the toxicity and efficacy of a new reduced intensity conditioning regimen including Treosulfan, followed by allo-HSCT from a 10/10 HLA identical unrelated donor. Materials and Methods: This prospective study included adult patients presenting a hematological malignancy in need of allo-HSCT using a 10/10 HLA identical unrelated donor. Accepted diagnoses were: CML in 1st chronic phase (CP) resistant to imatinib, in 2nd CP or in complete remission (CR) after blast crisis. Multiple myeloma (MM) or chronic lymphocytic leukemia (CLL) in stage B or C in response after relapse post-auto-HSCT. Acute lymphocytic or myeloid leukemia (ALL, AML) patients in CR1 at high risk or The conditioning included: Treosulfan 12g/m2/day intra-venous (day-6 to day-4), fludarabine 30mg/m2/day intra-venous (day-6 to day -2) and ATG 2.5 mg/kg/day (day-2 to day-1). GVHD prophylaxis used cyclosporine A oral (5mg/kg/day) or iv. (3mg/kg/day) from day-1. Peripheral stem cells after mobilization by G-CSF were used as HSC source. Results: Between February 2005 and July 2009, 56 patients were included in 5 different French centers, 30 (54%) males and 26 females with a median age of 57 years (18-65.5). There were 38 (68%) myeloproliferative disorders [29 AML (14 in CR1, 14 CR2 & 1 2 lines. For sex-matching, 49% of patients were sex-mismatched (half of them were F>M). For CMV, 43% were -/-, 25% +/+, 28% +/− and 1% -/+. For ABO matching, 52% were compatible, 24% major incomp. & 24% minor incopm. The median time between diagnosis and allograft was 15 months (4-168). The median number of infused CD34+ cells was 6.5 × 106/Kg(1-17.2) Fifty-four (96%) patients engrafted with a median time to neutrophils (>0.5G/l), and platelets (>50G/l) recovery of 16 days (4-86), 11 (4-82) respectively. Seventeen patients developed aGVHD grade ≥II (8 grade II, 2 grade III & 7 grade IV) with a cumulative incidence at 3 months of 31% (25-38). The cumulative incidence of cGVHD was, at 12 months: 32% (25-39) limited and 6% (2-10) extensive; at 18 months: 34% (27-47) limited and 8% (5-12) extensive. After a median follow-up of 13 months (1-57), the median overall survival (OS) was not reached with a 3 years probability of 52% (38-71). The median time of event free survival (EFS) was 15 months (8 - 57) with a 3-years probability of 47% (35-64). The cumulative incidence of relapse at 3 years was 25% (19-31) and the cumulative incidence of transplant-related mortality (TRM) at 12, 18 and 36 months was 20% (16-27), 23% (16-29) (same at 18 & 36 months) respectively. At the last follow-up, 22 patients died, 7 due to relapse and 15 due to TRM (5 pneumonia, 4 GVHD, 1 secondary malignancy and 6 other causes). We showed in a univariate analysis a higher 3-years OS of patients in CR1 (65%) compared to those Conclusion: We showed very promising results in terms of OS, relapse and TRM with an impressive GVL effect, in heavily pre-treated patients and transplanted using unrelated donors. Treosulfan appears to be a good choice for conditioning especially with a better outcome in AML patients in CR1. Disclosures: No relevant conflicts of interest to declare.

Abstract 4678 Improvement of survival in AML patients remains an important objective to achieve; recently better therapeutic strategies were defined according to the stratification of different markers. According to cytogenetics and molecular markers we determined 2 groups of patients: a good prognosis group for patients who had good cytogenetics [inv 16 and t (8, 21)]and intermediate 1 (normal cytogenetics associated to either NMP1+ with ITD- or CEBPα +ITD-) and a poor prognosis group for patients classified as in intermediate 2 (normal cytogenetics associated to other molecular markers) and unfavourable cytogenetics. To see if allogeneic hematopoietic stem cell transplantation had an impact on these groups, we studied 78 patients who underwent an allogeneic HSCT for AML and for whom we had cytogenetics and molecular markers. There were 73 de novo and 5 secondary AML, FAB classification showed 9 M0, 11 M1, 15 M2, 8 M4, 24 M5, 3 M6, 1M7, 7 patients were unclassified. Regarding cytogenetics and molecular markers: 6 were in favourable, 29 in intermediate and 38 in unfavourable group and we found 5 Flt3 mutated, 22 Flt3 ITD+, 4 MLL mutated, 13 Hoxa9 mutated, 10 Evi1 mutated, 34 Wt1 mutated and 17 NMP mutated. Using the new classification, 11 patients were in the good prognosis group and 61 in the poor prognosis group (6 patients have not been classified due to cytogenetics failure and/or missing data of molecular markers). At transplant, 42 patients were in CR1, 22 in > CR1 and 14 in progressive disease, 49 received a myelo-ablative and 29 a non myelo-ablative conditioning. As HSC source, 27 received PBSC, 46 bone marrow and 5 cord blood cells. At the last follow-up, 28 have relapsed, 38 patients are alive (36 in CR and 2 in relapse) and 40 died. With a median follow-up of 32 months, the 3-years overall survival was 45%±12 with no significant impact of age, FAB classification, kind of AML (de novo vs secondary), HSC source (PBSC vs BM), Flt3, MLL, HoxA9, NMP and WT1 mutations. We found a difference of survival but not reaching the significance for Flt3 ITD [27.5% ±20 (mutated)vs 52% ±12 (non mutated), p=0.09] and a significant difference of survival for Evi1 [48.5%±14 (non mutated) vs 22.5% ±26 (mutated), p=0.04]. We also showed a difference of survival not reaching the significance according to cytogenetics with 83%±30 for favourable, 53%±20 for intermesiate and 28%±16 for unfavourable although we observed a very significant difference of OS according to the new prognosis classification between the good prognosis group with 81%±24 and the poor prognosis group with 38%±14 (p=0.04). In addition, we found a significant better survival for patients in 1st CR (60%±16) vs > CR1 (31%±22) or in progressive disease (24%±22)(p=0.009) and a significant difference of survival according to conditioning with 54%±16 for myelo-abative vs 11%±18 for RIC ( p CR1 at transplant. The multivariate analysis showed a significant impact on OS of the new prognosis classification [HR=3.62 [95%CI 2.89-4.35] (p=0.03)], disease status at transplant [HR=151 [95%CI 1.28-1.74] (p=0.07)], kind of conditioning [HR=0.32 [95%CI 0-0.7] (p=0.003)], Evi1 [HR=0.33[95%CI 0-0.8] (p=0.02)] and Flt3 ITD [HR=0.43 [95%CI 0.07-0.78] (p=0.02)]. This study showed the importance of the new prognosis classification in terms of OS for AML and allogeneic HSCT did not erase the impact of this parameter, the OS after allogeneic HSCT remains very poor for patients having Evi1 mutation and Flt3ITD for whom it is fundamental to propose new strategy of allogeneic HSCT in 1st CR as for example allotransplant after FLAMSA regimen or haplo-identical allogeneic HSCT. Disclosures: No relevant conflicts of interest to declare.

Abstract 4124 We reported our experience on the antifungal prophylaxis by posaconazole in patients with acute myeloblastic leukaemia (AML) who were exposed to induction chemotherapy. To validate the benefit of an antifungal prophylaxis in this kind of population, we conducted a prospective study giving posaconazole (200mg per os x 3/24h) to all AML patients hospitalized for induction in the period 2007-2008 (group I) and to compare the observed results (incidence of severe invasive aspergillosis and overall survival) with a control group (group II) which was represented by all AML patients hospitalized for induction during the period 2006-2007 and who did not received any antifungal prophylaxis. There was in total 143 AML patients and after matching on age, gender, FAB classification and molecular markers, we got 121 patients (59 males and 62 females with a median age of 55 years): 55 patients in group I and 66 patients in group II. There were 91 AML de novo and 30 secondary AML, 18 patients had good cytogenetic markers, 43 intermediate and 58 poor (2 non evaluated). According to cytogenetics plus molecular markers, we distinguished 2 groups: a good prognostic group (n=29) associating favourable cytogenetics and intermediate 1 (normal cytogenetics+ Flt3 ITD, CEBPA,NMP1) and a poor prognosis group (n=75) with unfavourable cytogenetics and intermediate 2 (17 patients were not determined). As induction chemotherapy, patients received different combinations according to protocols, age and AML characteristics. The median interval between AML diagnosis and hospitalization was 0 day (-41 – +7), 92 patients (76%) were placed in laminar air flow rooms. After induction, 100 patients achieved a CR and 2 patients died during induction period. The median duration of aplasia and of hospitalization were 28 days (7 – 91) and 37 days (22 – 101) respectively. There was no significant difference for all the above characteristics between group I and group II. Concerning posaconazole prophylaxis, the treatment was started the 1st day of chemotherapy with a median duration of 27 days (8-94): 35 patients (64%) received their prophylaxis until their discharge, 7 (13%) discontinued due to toxicity [hepatic (n=3), renal (n=1), transfer to intensive care unit (n=3)] and 13 (23%) switched to another fungal treatment because of IA suspicion (n=5), probable IA (n=2) and invasive candidosis (n=5). Results At Day32 post induction, we observed 2 probable IA (3.6%) in group I and 8 IA [possible (n=4) + probable IA (n=4)] (12%) in group II (p = 0.085). The cumulative incidence of IA in group I and II was: at day 100, 7.27% vs 15.5%, at 1 year 12.72% vs 22.72% and at 18 months 14.54% vs 24.24% respectively. The Kaplan-Myer analysis on time to death from any cause at Day 100, showed a significant survival benefit in favour of the Pozaconazole group (group I) over the control group (group II) (p=0.0023) (figure1), this difference was also significant when we adjusted the analysis only on deaths caused by IA (figure2). After a median follow-up of 8.6 months, the probability of overall survival was 92.3% at day 100, 83.5% at 6 months, 70% at 1 year, 58% at 18 months and 36% at 2 years with a significant difference between groups I and II(p=0.02). At the last follow-up, 39 patients died in the group II and 10 in the group I. Concerning the other risk factors, the multivariate analysis showed a significant impact on long term OS of age [HR= 0.103 (0.02 – 0.5) (p= 0.00029) ], cytogenetics [HR=2.524 (1.172-5.44) (p=0.0018)] and response to induction [HR=7.73 (3.579-16.7) (p=1.9e-7)]. Conclusion We showed a very important impact of anti-fungal prophylaxis in patients undergoing chemotherapy for AML especially for invasive aspergillosis, which is a risk factor to take into account in addition to age, cytogenetics and response to treatment. Disclosures: No relevant conflicts of interest to declare.

Abstract 4336 Introduction for patients in search of an unrelated donor for haematopoietic stem cell transplantation (HSCT), a 10/10 allele-matched donor represents the best option; for a CMV- patient, a CMV- donor is generally preferred to a CMV+ donor due to low risk of CMV infection when both donor and patients are CMV-, however it is not known at the present how the CMV serological status affects transplant outcome compared to patient-donor HLA matching, and this is particularly true when more than one donor is available. The aim of the present study is to analyze the effect of CMV matching with respect to HLA matching on HSCT outcome, in patients who are CMV-. Methods CMV-patients who underwent a HSCT from an unrelated donor between 1st Jan 2000 and 31st Mar 2009 at our Institution were included in the analysis. Patients receiving HSC from cord blood were excluded. Evaluation of overall survival (OS), progression-free survival (PFS), non-relapse mortality (NRM) and acute graft-versus-host disease (GvHD) were performed with Kaplan-Meier method or cumulative incidence analysis; comparisons among groups were performed using log-rank test. Data about most relevant patients' and donors' factors (patients' age, gender matching, AB0 incompatibility, diagnosis, disease status at HSCT, CMV matching, HLA matching, HSCT conditioning, use of ATG, TBI, source of HSCs) were collected and included in a multivariate Cox regression analysis: the relative impact of CMV and HLA matching on HSCT outcomes were expressed as hazard ratio (HR) together with the 95% confidence interval (CI), after adjustment for the above mentioned factors. Results sixty-six patients were eligible for the analysis, median age was 35 (16-64), diagnoses were acute leukemia (n=33: n=23 CR1 and n=10 CR2 or more), MDS (n=8), multiple myeloma (n=8), non Hodgkin's lymphoma (n=6), CML (n=5: n=2 chronic phase, n=3 acceleterated or acute phase), myeloproliferative syndrome other than CML (n=3), aplastic anemia (n=1), CLL (n=1), Hodgkin's lymphoma (n=1). A high-resolution 10/10 HLA matching was present in 55 (83%) HSCTs while one mismatch (9/10-matched donor) was present in 11 (17%) HSCTs: n=8 at HLA-A, n= 3 at HLA-C. All recipients were CMV-. Donors were CMV- in 40 of 55 (73%) 10/10-matched pairs and in 6 of 11 (54%) 9/10-matched pairs. Median follow-up was 225 days (range: 82-2014). In univariate analysis, no significant survival differences were detected among patients with HLA matched and mismatched donors (1y-OS= 42% and 20% respectively, p=0.23) or with CMV- and CMV+ donors (1y-OS= 34% and 48% respectively, p=0.26); no significant differences in occurrence of grade 2-4, grade 3-4 acute GvHD or PFS were observed as well. However, a significantly increased probability of NRM was seen when a HLA mismatched donor was present (1y-NRM= 80% vs 33%, p=0.03); this was not the case of CMV serological status (p=0.31). Multivariate analysis for NRM showed a HR = 5.22 (95% CI: 1.47-18.56) with p= 0.01 for HLA mismatched vs. matched and HR = 0.72 (95% CI: 0.23-2.24) with p= 0.57 for CMV mismatched vs. matched. Conclusion these results confirm that HLA matching is critical in determining the incidence of NRM and should continue to be preferred to CMV matching in CMV seronegative patients undergoing HSCT from an unrelated donor. However, a larger, multicenter analysis could better clarify this issue and help to define the relative importance of HLA matching vs. CMV serology in this setting of patients. Disclosures: No relevant conflicts of interest to declare.

This retrospective analysis concerned 374 patients (pts) who underwent an allogeneic HSCT for CLL reported to the EBMT registry. There were 282 males (75%) and 92 females with a median age of 53 years (24–69). The interval between diagnosis and transplantation was 53 months (3–308). Forty-five pts (12%) have received a previous HSCT. At transplant, 302 among 323 evaluated patients had a good performance status (PS) (93%), 51 pts were in CR (14%), 163 in PR (45.5%), 39 in SD (11.5%) and 105 in PD (29%) among 353 evaluated patients. Two hundred and ninety-two pts received a standard (Std) and 82 a reduced intensity conditioning regimen (RIC); 314 pts received PBSC, 55 BM and 5 cord blood cells from 202 HLA siblings (Sib), 2 mismatched related donors and 170 unrelated donors (UD). There were 136 (36%) sex-mismatched (90 F/M and 46 M/F), 150 pairs (40%) had an ABO incompatibility (61 minor, 99 major) and for CMV: 80 pairs were +, 148− and 112 mixed. After transplantation, 359 pts engrafted, 201 pts developed an AGVHD (gr I: 76, gr II : 79, gr III: 30 and gr IV:16) and 153 presented a cGVHD (75 limited and 78 extensive). At day 100 after transplant, the cumulative incidence of AGVHD for the total population was 17% (13–22) for gr I, 31% (26–36) for gr ≥ II. [Sib: 19% (13–25) gr I and 27% (21–34) gr ≥ II; UD: 16% (9–22) gr I and 38% (29–47) gr ≥ II]. Results concerning the cumulative incidence of AGVHD according to HLA typing and kind of conditioning are shown in Table I. At 1 year after transplant for the total population, the cumulative incidence of limited and extensive cGVHD were 15 % (6–24) and 29.5% (18–41) for Std; 18.6 (13–24) and 18% (13–23) for RIC respectively. With a median follow up of 38 months, the probability of 3-year and 5-year overall survival (OS) and disease-free survival (DFS) for the total group were 56% (51–62) and 47.4 % (42–53); 49 % (43–56) and 42% (36–48.5) respectively. We observed a significant difference concerning 5-year OS according to the pretransplant disease status [CR: 73% (60–89), PR: 57% (48–68) and PD: 35% (26–46)] (p Table 1: cumulative incidence of AGVHD, NRM and RM according to HLA typing and kind of conditioning Figure Figure 1. Probability of OS for Standard conditioning group and RIC group Figure 1. Probability of OS for Standard conditioning group and RIC group