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International audience; Whether to choose Haploidentical (Haplo) or one-antigen mismatched unrelated donor (1Ag-MMUD) hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PTCy) remains an unanswered question. We compared PTCy- Haplo-HCT to PTCy-1Ag-MMUD-HCT for acute myeloid leukemia (AML) in complete remission (three groups: 1Ag-MMUD using peripheral blood (1Ag-MMUD-PB; n = 155); Haplo using bone marrow (Haplo-BM; n = 647) or peripheral blood (Haplo-PB; n = 949)). Haplo-BM and Haplo-PB had a higher non-relapse mortality (NRM) compared to 1Ag-MMUD-PB (HR 2.28, 95% CI 1.23-4.24, p

The Idelalisib treatment prior to allogeneic stem cell transplantation for patients with chronic lymphocytic leukemia: a report from the EBMT chronic malignancies working party, written by Johannes Schetelig, Patrice Chevallier, Michel van Gelder, Jennifer Hoek, Olivier Hermine, Ronjon Chakraverty, Paul Browne, Noel Milpied, Michele Malagola, Gerard Socié, Julio Delgado, Eric Deconinck, Ghandi Damaj, Sebastian Maury, Dietrich Beelen, Stéphanie Nguyen Quoc, Paneesha Shankara, Arne Brecht, Jiri Mayer, Mathilde Hunault-Berger, Jörg Bittenbring, Catherine Thieblemont, Stéphane Lepretre, Henning Baldauf, Liesbeth C. de Wreede, Olivier Tournilhac, Ibrahim Yakoub-Agha, Nicolaus Kröger, Peter Dreger was originally published Online First without Open Access. After publication in volume 56, issue 3, page 605–613 the author decided to opt for Open Choice and to make the article an Open Access publication. Therefore, the copyright of the article has been changed to © The Author(s) 2020 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0. Open access funding enabled and organized by Projekt DEAL. Korrektur zu 10.1038/s41409-020-01069-w

Allogeneic stem cell transplantation (allo-SCT) represents the most beneficial treatment for patients with active relapsed/refractory (R/R) hematologic malignancies. Recently, sequential regimens combining debulking chemotherapy followed by reduced-intensity conditioning (RIC) have shown encouraging results for these patients. In this retrospective study, we report the extended results of a sequential regimen of clofarabine, cytosine arabinoside, and RIC in 131 adults with active R/R myeloid disease at transplant. Conditioning consisted of clofarabine (30 mg/m2/day) and cytosine arabinoside (1 g/m2/day) for 5 days, followed, after a rest of 3 days, by an RIC combining cyclophosphamide (60 mg/kg) for 1 day, iv busulfan (3.2 mg/kg/day) for 2 days, and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Between 2007 and 2016, 131 patients (males n = 75, median age: 52.6 years) were identified from the SFGM-TC registry. There were 111 acute myeloid leukemia (AML) patients and 20 cases with myelodysplastic or myeloproliferative syndrome. Status at transplant was known for all but 4 patients and was primary refractory (n = 81) and 1st or 2nd relapse (n = 46). All patients received allo-SCT from a matched donor (sibling n = 64, unrelated n = 67). Engraftment was observed in 105/122 (86%) evaluable cases and 63% of the patients achieved complete remission (CR) after transplant. The 1-year overall survival, disease-free survival, relapse incidence, non-relapse mortality, and graft-versus-host disease-free/relapse-free survival were 39.2%, 28.1%, 41.0%, 30.8%, and 22.2%, respectively. This study confirms that this sequential clofarabine-based regimen provides a high CR rate in this critical population, although relapse remains a matter of concern.

Background: There are currently few data on the outcome of acute myeloid leukemia (AML) in adolescents and young adults (AYAs) after allogeneic HSCT. The aim of this study is to describe the outcome and its specific risk factors for children, AYAs and adults after a first allogeneic HSCT for AML. Methods: In this retrospective study, we compared the outcome of AML patients receiving a first allogeneic HSCT between 2005 and 2017 according to their age at transplantation’s time: children (Results: With a median follow-up of 4.37 years (min-max 0.18 – 14.73 years), the probability of 2 year-overall survival (OS) was 71.4% in children, 61.1% in AYAs and 62.9% in adults (p=0.0009 for intergroup difference). Both relapse and non-relapse mortality (NRM) Cumulative Incidence (CI) estimated at 2 years were different between the age groups (30.8% for children, 35.2% for AYAs and 29.4% for adults - p=0.0254, and 7.0% for children, 10.6% for AYAs and 14.2% for adults, pConclusion: Age is an independent risk factor for NRM and extensive chronic GVHD. This study suggests that AYAs AML patients should be treated with chemotherapy-based MAC regimen and bone marrow as stem cells source.

International audience; No abstract available

Allogeneic hematopoietic stem cell transplantation (HSCT) remains a potentially curative and useful strategy in high-risk relapsing chronic lymphocytic leukemia (CLL). Minimal residual disease (MRD) assessment at 12 months (M12) post-HSCT is predictive of relapse. This phase II study aimed to achieve M12 MRD negativity (MRDneg) using an MRD-driven immune-intervention (Md-PII) algorithm based on serial flow-cytometry blood MRD, involving cyclosporine tapering followed in case of failure by donor lymphocytes infusions. Patients had high-risk CLL according to the 2006 European Society for Blood and Marrow Transplantation consensus, in complete or partial response with lymphadenopathy

International audience

CAR-T Cells have opened new doors for cellular immunotherapies and provides new therapeutic options for patients with refractory B-cell malignancies, B-cell acute lymphoblastic leukemia and diffuse large B-cel lymphoma. CAR-T Cells have benefited from an accelerated approval procedure in many countries. Indeed, The French health authorities have approved the specialties Tisacel ® and Axicel ®, but additional data including the use of CAR-T Cells in real life were also mandatory. In regard to the scientific interest of the project, LYSA-LYSARC committed itself to prospectively and retrospectively collect information on patients eligible for CAR-T Cells as required by French health authorities. Other academic cooperating groups (GRAALL, IFM, SFCE, FILO and the scientific society SFGM-TC) were associated to this initiative which aims to build a nationwide CAR-T Cells devoted registry, so-called DESCART (Dispositif d'Enregistrement et Suivi des patients traités par CAR-T cells). DESCAR-T is a real-life multicentric registry set up in French sites qualified for CAR-T Cells treatment. DESCAR-T objective is to describe the use of CAR-T Cells in real life. All paediatric and adult patients with hematological malignancy fulfilling CAR-T Cells approval criteria and for whom a CAR-T Cells therapy has been discussed are included from 1 July 2018. Clinical data are directly collected from medical records and patients are treated according to the centers' routine practices. One of the distinctive features of DESCAR-T is its link with HTA for CAR-T Cells s reimbursement by the French public health system. DESCAR-T is the first national registry promoted by an academic group allowing centralized data collection for both academic and HTA/health authorities' purposes.

Prognosis of patients with graft failure is dismal, and retransplantation is the sole option for long-term survival. To address the interest of haploidentical transplantation as a salvage option in this context, we analyzed data from 24 patients with graft failure or loss retransplanted with a haploidentical donor who received post-transplant cyclophosphamide (PTCy) as graft-versus-host disease prophylaxis (GVHD). Fludarabine-based reduced-intensity conditioning was used in 23 patients and the Baltimore regimen in 14 patients. The median delay between previous and salvage transplantation for graft failure was 63 days (range, 39 to 98). In addition to PTCy, all patients received cyclosporine, and 22 patients also received mycophenolate mofetil for GVHD prophylaxis. With a median follow-up of 353 days (range, 16 to 2010), 1-year overall survival (OS) was 56% (95% confidence interval, 38% to 81%). Transplant complications accounted for 80% of deaths. The cumulative incidence of neutrophil engraftment at day +30 was 79%. Cumulative incidence of grades II to IV acute GVHD at day 100 was 14%, and 1-year cumulative incidence of chronic GVHD was 31%. One-year cumulative incidence of relapse was 13%. Stem cell source did not impact on engraftment, GVHD, relapse, or OS. Salvage haploidentical transplant with PTCy for rescuing graft failure patients leads to an acceptable 1-year OS and might be a valid option in this poor situation.

Immunotherapy with chimeric antigen receptor engineered-T cells (CAR-T) has revolutionized the landscape of treatment of relapsed or refractory B-cell. However, the use of autologous T cells has limitations: variable quality of collected effector T cells, duration of the process sometimes incompatible with uncontrolled hemopathy, limited number of available CAR cells, sometimes fatal toxicities, extremely high cost. Natural Killer (NK) cells are an interesting alternative to T cells. NK cells are very powerful cytotoxic effectors that have demonstrated an anti-tumor effect after haploidentical hematopoietic stem cells transplantation or in adoptive cell therapy against a number of solid or hematological tumors. Mainly, they can be used in allogeneic situations without causing major toxic side effects. The sources of NK cells are multiple: cell line, cord blood, peripheral blood, induced pluripotent stem cells. Recent advances in manufacturing engineered CAR-NK cells make it possible to promote antibody-dependent cell-mediated cytotoxicity (ADCC), as well as the activation and persistence of these cells, notably via the cytokine Il-15. The majority of the reports on CAR-NK cells concern pre-clinical or early clinical trials. However, the many advantages of "off-the-shelf" allogeneic CAR-NK cells provide great potential in cancer treatments.

CAR-T cells represent a new anti-tumor immunotherapy which has shown its clinical efficacy in B-cell malignancies. The results of clinical trials carried out in this context have shown that certain immunological characteristics of patients before (at the time of apheresis) and after the administration of the treatment, or of the CAR-T cells themselves, are correlated with the response to the treatment or to its toxicity. However, to date, there are no recommendations on the immunological monitoring of patients treated in real life. The objectives of this workshop were to determine, based on data from the literature and the experience of the centers, the immunological analyses to be carried out in patients treated with CAR-T cells. The recommendations relate to the characterization of the patient's immune cells at the time of apheresis, the characterization of the injected CAR-T cells, as well as the monitoring of the CAR-T cells and other parameters of immune reconstitution in the patient after administration of the treatment. Harmonization of practices will allow clinical-biological correlation studies to be carried out in patients treated in real life with the aim of identifying factors predictive of response and toxicity. Such data could have a major medico-economic impact by making it possible to identify the patients who will optimally benefit from these expensive treatments.

A multistage model instructed by a large dataset (knowledge bank [KB] algorithm) has recently been developed to improve outcome predictions and tailor therapeutic decisions, including hematopoietic stem cell transplantation (HSCT) in acute myeloid leukemia (AML). We assessed the performance of the KB in guiding HSCT decisions in first complete remission (CR1) in 656 AML patients younger than 60 years from the ALFA-0702 trial (NCT00932412). KB predictions of overall survival (OS) were superior to those of European LeukemiaNet (ELN) 2017 risk stratification (C-index, 68.9 vs 63.0). Among patients reaching CR1, HSCT in CR1, as a time-dependent covariate, was detrimental in those with favorable ELN 2017 risk and those with negative NPM1 minimal residual disease (MRD; interaction tests, P = .01 and P = .02, respectively). Using KB simulations of survival at 5 years in a scenario without HSCT in CR1 (KB score), we identified, in a similar time-dependent analysis, a significant interaction between KB score and HSCT, with HSCT in CR1 being detrimental only in patients with a good prognosis based on KB simulations (KB score ≥40; interaction test, P = .01). We could finally integrate ELN 2017, NPM1 MRD, and KB scores to sort 545 CR1 patients into 278 (51.0%) HSCT candidates and 267 (49.0%) chemotherapy-only candidates. In both time-dependent and 6-month landmark analyses, HSCT significantly improved OS in HSCT candidates, whereas it significantly shortened OS in chemotherapy-only candidates. Integrating KB predictions with ELN 2017 and MRD may thus represent a promising approach to optimize HSCT timing in younger AML patients.

Background There are currently few data on the outcome of acute myeloid leukemia (AML) in adolescents after allogeneic HSCT. The aim of this study is to describe the outcome and its specific risk factors for children, adolescents and young adults after a first allogeneic HSCT for AML. Methods In this retrospective study, we compared the outcome of AML patients receiving a first allogeneic HSCT between 2005 and 2017 according to their age at transplantation’s time: children (n = 564), adolescent and post-adolescent (APA) patients (15–25 years, n = 647) and young adults (26–40 years; n = 1434). Results With a median follow-up of 4.37 years (min–max 0.18–14.73 years), the probability of 2-year overall survival (OS) was 71.4% in children, 61.1% in APA patients and 62.9% in young adults (p = 0.0009 for intergroup difference). Both relapse and non-relapse mortality (NRM) Cumulative Incidence (CI) estimated at 2 years were different between the age groups (30.8% for children, 35.2% for APA patients and 29.4% for young adults—p = 0.0254, and 7.0% for children, 10.6% for APA patients and 14.2% for young adults, p p Conclusion Age is an independent risk factor for NRM and extensive chronic GVHD. This study suggests that APA patients with AML could be beneficially treated with a chemotherapy-based MAC regimen and bone marrow as a stem cells source.

International audience; The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organises annual workshops in an attempt to harmonise clinical practices among different francophone transplantation centres. The SFGM-TC harmonisation workshops aim at establishing practical guidelines, on the one hand, from data from the literature and international recommendations and, on the other hand, by consensus in the absence of formally proven data. The sexual and emotional life of allogeneic hematopoietic stem cells transplanted (HSCT) patients is often very impacted and remains a subject relatively little addressed by patients and caregivers. This article is an update from a previous workshop and is accompanied by a patient booklet, which will be included in the post allograft follow-up workbook published by the SFGM-TC. The purpose of these two documents is to facilitate discussions between patients and caregivers on the subject and to present proposals for follow-up and tools to better manage the sexual and emotional life of allotransplanted patients.

In order to identify cytomegalovirus (CMV)-seropositive patients who are at risk of developing CMV infection following first allogeneic hematopoietic cell transplantation (allo-HCT), we built up a scoring system based on patient/donor characteristics and transplantation modalities. To this end, 3690 consecutive patients were chronologically divided into a derivation cohort (2010-2012, n = 2180) and a validation cohort (2013-2014, n = 1490). Haploidentical donors were excluded. The incidence of first clinically significant CMV infection (CMV disease or CMV viremia leading to preemptive treatment) at 1, 3, and 6 months in the derivation cohort was 13.8%, 38.5%, and 39.6%, respectively. CMV-seropositive donor, unrelated donor (HLA matched 10/10 or HLA mismatched 9/10), myeloablative conditioning, total body irradiation, antithymocyte globulin, and mycophenolate mofetil significantly and independently affected the incidence of 3-month infection. These six factors were selected to build up the prognostic model. Four risk groups were defined: low, intermediate-low, intermediate-high, and high-risk categories, with a 3-month predicted incidence of first clinically significant CMV infection in the derivation cohort of 22.2%, 31.1%, 45.4%, and 56.9%, respectively. This score represents a framework for the evaluation of patients who are at risk of developing clinically significant CMV infection following allo-HCT. Prospective studies using this score may be of benefit in assessing the value of anti-CMV prophylaxis in well-defined patient cohorts.

International audience; We report the results of the French Temporary Authorization of Use (ATU) compassionate program of letermovir for primary prophylaxis conducted in 21 transplant centers. Patients were CMV seropositive allogeneic hematopoietic cell transplantation recipients and at high risk for CMV infection. Primary prophylaxis was defined as initiation of letermovir between day 0 and day +28 post-transplant. Between November 2017 and January 2019, 96 patients with a median age of 56 years received letermovir and follow-up data were available for 78 patients. The median time from transplant to letermovir initiation was 4 days, and the median duration of exposure to letermovir was 78 days, with 57 patients still on treatment at the cutoff date. Letermovir was temporarily discontinued in 4 patients (5.1%) and stopped in 39 patients (50.0%), in most cases due to planned end of treatment (n = 16, 20.5%). Fifteen patients (19.2%) each presented one positive CMV PCR, in median 13 days after letermovir initiation. Clinically significant CMV infection was reported in 5 patients (6.4%). No CMV disease was reported. At least one adverse drug reaction was reported for 12 patients (15.4%). In this early access program, letermovir was effective with comparable results of the phase 3 study with a low rate of clinically significant CMV infection, including in patients who were at high-risk for CMV infection.

BackgroundPeripheral T cell lymphomas form a heterogeneous group with a usually dismal prognostic. The place of allogeneic stem cell transplantation to treat PTCL is debated.MethodsWe retrospectively analyzed the overall survival (OS), event-free survival (EFS), relapse, and transplant-related mortality (TRM) and associated variables in 285 adults with non-primary cutaneous PTCL (PCTL-NOS (39%), angioimmunoblastic T cell lymphomas (29%), anaplastic T cell lymphomas (15%), and other subtypes (17%)), who received alloSCT in 34 centers between 2006 and 2014.ResultsAlloSCT was given as part of front-line therapy (n= 138) to 93 patients in first complete response (CR) and 45 in first partial response (PR), and of salvage therapy (n= 147) to 116 patients for second or more CR/PR and 31 for progressive disease. Reduced-intensity conditioning (RIC) was given to 172 patients (62%), while 107 (38%) received myeloablative conditioning (MAC). The median follow-up was 72.4 months. The 2- and 4-year OS were 65% and 59%, respectively, and the cumulative incidence of relapse was 18% after 1 year and 19% after 2 years. TRM was 21% at 1 year, 24% after 2 years, and 28% after 4 years. In multivariate analysis, grade III–IV acute GvHD (HR = 2.57, 95% CI 1.53–4.31;p= 0.00036), low Karnofsky score < 80% (HR = 5.14, 95% CI 2.02–13.06;p= 0.00058), and progressive disease status before transplant (HR = 2.21, 95% CI 1.25–3.89;p =0.0062) were significantly associated with a reduced OS.ConclusionsThe data demonstrate in the largest retrospective cohort of non-cutaneous PTCL so far reported that alloSCT after RIC or MAC is an effective strategy, even in chemoresistant patients.

The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organises annual workshops in an attempt to harmonise clinical practices among different francophone transplantation centres. The SFGM-TC harmonisation workshops aim at establishing practical guidelines, on the one hand, from data from the literature and international recommendations and, on the other hand, by consensus in the absence of formally proven data. The sexual and emotional life of allogeneic hematopoietic stem cells transplanted (HSCT) patients is often very impacted and remains a subject relatively little addressed by patients and caregivers. This article is an update from a previous workshop and is accompanied by a patient booklet, which will be included in the post allograft follow-up workbook published by the SFGM-TC. The purpose of these two documents is to facilitate discussions between patients and caregivers on the subject and to present proposals for follow-up and tools to better manage the sexual and emotional life of allotransplanted patients.

International audience

[Objectives] The aim of this study was to compare the effect of the intensity of conditioning approaches used in allogeneic transplantation in myeloma—reduced intensity conditioning (RIC), non‐myeloablative (NMA), myeloablative conditioning (MAC) or Auto‐AlloHCT—on outcomes in patients who had had a prior autologous transplant., [Methods] A retrospective analysis of the EBMT database (1991‐2012) was performed., [Results] A total of 344 patients aged between 40 and 60 years at the time of alloHCT were identified: 169 RIC, 69 NMA, 65 MAC and 41 Auto‐Allo transplants. At a median follow‐up of 54 months, the probabilities of overall survival (OS) at 5 years were 39% (95% CI 31%‐47%), 45% (95% CI 32%‐57%), 19% (95% CI 6%‐32%) and 34% (95% CI 17%‐51%), respectively. Status at allogeneic HCT other than CR or PR conferred a 70% higher risk of death and a 40% higher risk of relapse. OS was markedly lower in the MAC group (P = .004). MAC alloHCT was associated with a higher risk of death than RIC alloHCT until 2002 (HR = 4.1, P < .001) but not after 2002 (HR = 1.2, P = .276)., [Conclusion] From 1991 to 2002, MAC was associated with poorer OS. Between 2003 and 2012, there were no significant differences in outcomes based on these different approaches.

Persisting severe thrombocytopenia more than 6 weeks after allogeneic stem cell transplantation is a common problem associated with adverse prognosis. Peffault de Latour et al report the results of the first trial of the thrombopoietin mimetic, romiplostim, in this setting, demonstrating recovery of platelet counts in 18 of 24 patients.

International audience; Haploidentical hematopoietic stem cell transplantation has been growing steadily since 2012. The SFGM-TC has twice published guidelines concerning T-cell repleted haploidentical grafts with high dose cyclophosphamide post-transplantation. The 2013 workshop recommended using the non-myeloablative Baltimore protocol with bone marrow and developed prospective protocols to evaluate these transplantations. The 2015 workshop reported improved results of reduced conditioning regimens in Hodgkin's lymphoma and intensive conditioning in myeloid hemopathies, and a similar outcome with 10/10 HLA matched donor with the same disease-risk score thus raising the question of the qualifier "alternative" for haploidentical transplants. The current work concerns the criteria for selecting the donor. The main criterion remains the absence of anti-HLA antibodies directed against the donor present in the recipient sera (DSA - Donor Specific Antibodies). In case of DSA and in the absence of an alternative donor, desensitization protocols exist. The other criteria are impossible to prioritize: age, sex, CMV, and blood type. The degree of relatedness and the number of HLA incompatibilities do not seem to be a criterion of choice. The 'ideal' donor would be a young man, CMV-matched, without major ABO incompatibility with a marrow transplant. There is insufficient data for the KIR-ligand and NIMA/NIPA mismatch. Peripheral stem cell grafts appear to yield more acute GVHD than bone marrow grafts after intensive conditioning, but with comparable survival rates. Based on the literature review, the comparison of haploidentical with unrelated donors encourages inclusion in existing national protocols randomizing these different donors.

Isocitrate dehydrogenase (IDH) 1 and 2 mutations occur in 20% of acute myeloid leukemia (AML). Patients with AML carrying IDH1-2 mutations have a similar prognosis compared to patients without these mutations (DiNardo et al, AM J H, 2015). However, the impact of IDH1-2 mutations on patients with AML undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT) is not well known. In this study, we investigate the prognostic impact of IDH1-2 mutational status on AML patients undergoing alloHCT in complete remission (CR). In this retrospective registry-based analysis, we identified 710 consecutive adult patients (46.2% female; median age: 58.5 years [range, 18-78]) with AML undergoing allo-HCT in CR between 2015 and 2019 at 85 EBMT participating centers. Cord blood, ex-vivo graft manipulated transplants, and patients with favorable cytogenetics were excluded. Median follow-up was 15 months [95% CI 13.4-16.6]. Patients were categorized based on IDH1-2 mutational status, with 300 (42%) mutated and 410 (58%) wild type. Six hundred and fifty-two (92%) and 58 (8%) patients had de novo and secondary AML, respectively, and 141 (20%) patients had poor-risk cytogenetics. IDH1-2 mutation was positively correlated with NPM1 mutation (40% in IDH1-2 mutated vs 27% in wild type, p=0.0001) and more frequently encountered in middle-aged patients (p=0.01). No correlation was noted between IDH1-2 and FLT3 mutation or other patient characteristics. Minimal residual disease (MRD) data was available for 344 patients, 53% of which were MRD-negative at transplant in both groups. Six hundred and twenty-three (88%) and 87 (12%) patients were in first and second CR at time of transplant, respectively. Patients received grafts from a matched sibling (24%), unrelated (62%), or haploidentical (14%) donor, and myeloablative conditioning (MAC) was used in 42%. Ninety-three percent of the patients received peripheral blood as the stem cell source. At day 180, the cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was significantly lower in IDH1-2 mutated compared to wild-type patients (22% vs 33%, p=0.002). No differences in chronic GVHD rates were noted between the 2 groups (39% vs 40%, p=0.87). The 2-year cumulative relapse incidence (RI) was significantly lower and the GVHD-free, relapse-free survival (GRFS) was also improved in IDH1-2 mutated compared to wild-type patients (14.4% vs 27%, p=0.001 and 47% vs 39%, p=0.006, respectively). This led to an improved leukemia-free survival (LFS) in IDH1-2 patients (69% vs 59%, p=0.01), however, it did not translate into an overall survival (OS) difference. No significant difference was noted in non-relapse mortality (NRM) between the 2 groups (17% vs 14.2%, p=0.26). These findings were confirmed in multivariate analysis. In fact, IDH1-2 mutation was associated with significant improvement in RI (hazard ratio [HR]=0.4 [95%CI 0.25-0.64], p=0.0001), LFS (HR=0.7 [95%CI 0.51-0.95], p=0.022), aGVHD II-IV (HR=0.63 [95%CI 0.45-0.87], p=0.005) and GRFS (HR=0.69 [95%CI 0.54-0.89], p=0.004). Conversely, the presence of adverse cytogenetics and undergoing allo-SCT in second CR increased the RI (HR=2.29 [95%CI 1.46-3.61], p=0.0003 and HR=2.84 [95%CI 1.64-4.91], p=0.0002, respectively) and were associated with a shorter LFS (HR=1.67 [95%CI 1.18-2.36], p=0.004 and HR=1.61 [95%CI 1.06-2.44], p=0.025) while reduced intensity (RIC) conditioning had a worse impact on OS compared to MAC (HR=1.56 [95%CI 1.07-2.29], p=0.022). Additionally, in the subgroup of patients with available MRD data, MRD positivity at transplant significantly increased RI (HR=2.15 [95%CI 1.09-4.23], p=0.027) with no impact on survival. In conclusion, our data suggest that the presence of IDH1-2 mutations acts as an independent prognostic factor and is associated with improved outcome in patients with AML in CR undergoing allo-HCT. Indeed, patients with IDH1-2 mutations had significantly lower rates of RI and aGVHD, which translated into improved LFS and GRFS. Nevertheless, patients with MRD positivity at time of transplant had significantly increased RI. Further studies investigating allo-HCT outcomes in IDH1-2 mutated patients with AML in the era of IDH inhibitors (both in the pre- and post-transplant setting) would help to further define the impact of these mutations in this setting and thus optimize an individualized treatment approach. Disclosures Labopin: Jazz Pharmaceuticals: Honoraria. Esteve: Abbvie: Consultancy; Pfizer: Consultancy; Astellas: Consultancy; Novartis: Research Funding; Novartis: Consultancy, Research Funding; Bristol Myers Squibb/Celgene: Consultancy; Jazz: Consultancy. Kröger: Novartis: Research Funding; Riemser: Honoraria, Research Funding; Sanofi: Honoraria; Neovii: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Gilead/Kite: Honoraria; Celgene: Honoraria, Research Funding; AOP Pharma: Honoraria. Blaise: Jazz Pharmaceuticals: Honoraria. Socie: Alexion: Research Funding. Ganser: Jazz Pharmaceuticals: Honoraria; Novartis: Honoraria; Celgene: Honoraria. Yakoub-Agha: Jazz Pharmaceuticals: Honoraria. Bazarbachi: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Hikma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees.

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative therapy in patients with primary or secondary myelofibrosis. Ruxolitinib, a JAK-inhibitor, has been approved in myelofibrosis patients and is effective to alleviate symptoms of the disease in a substantial proportion of patients. In a French phase 2 study, the use of ruxolitinib as a bridge to HSCT was followed by a high transplantation rate, with one third of patients presenting clinical improvement before HSCT (partial response or spleen size reduction) (BMT 2021, Robin et al). The aim of the current study is to compare post-transplantation outcomes between patients who received ruxolitinib before HSCT and those who did not. Methods: This retrospective study includes patients with primary or secondary myelofibrosis registered in the SFGM-TC registry including patients from France, Belgium and Switzerland. Patients who received HSCT between July 2010 and December 2019 with available information regarding ruxolitinib treatment were included. The impact of ruxolitinib was analyzed by multivariable Cox regression and a propensity score. Results: 305 patients could be included, of whom 143 received ruxolitinib prior to HSCT (RuxoG). All patient characteristics are given in RuxoG followed by no ruxolitinib group (noRuxo). The diagnosis before HSCT was primary myelofibrosis (83% vs 75%), secondary myelofibrosis (13% vs 19%) or transformed into AML (4% vs 6%). Karnofsky score at transplant was < 70% in 9% and 11%. In RuxoG. median age was older (60.29 vs. 58.75, p=0.069) and delay from diagnosis longer (20.42 vs 13.26 months, p=0.040). RuxoG patients had less frequently anemia < 10 g/dl (84% vs 98%, p=0.027) or thrombocytopenia < 50 G/L (22% vs 32%, p=0.066) and presented more frequently splenomegaly or pre-graft splenectomy (83% vs 63%, p=0.0007). DIPSS score was well balanced in both groups, being high or intermediate-2 in 100 patients (79% vs 86%, p=0.23), from the 235 patients with available data. Myeloablative conditioning regimen was used in 16% vs 26% (p=0.049), and conditioning regimen consisted of on fludarabine-busulfan in 33% vs 61%, fludarabine-melphalan in 47% vs 22% or other in 20% vs 16% (p Conclusion: Patients who received ruxolitinib before HSCT were at higher risk of acute GVHD and post-transplant mortality, but this was not observed in patients responding to ruxolitinib and it does not translate into higher risk of chronic GVHD. Main hypotheses to explain these finding could be: 1) specific disease, patient or transplant characteristics in RuxoG; 2) the longer delay to transplantation or 3) a specific effect of ruxolitinib. This study suggests that myelofibrosis patients responding to ruxolitinib should have the transplant without waiting disease progression. Figure 1 Figure 1. Disclosures Forcade: Novartis: Other: travel grant. Loschi: AbbVie: Ended employment in the past 24 months, Honoraria; CELGENE/BMS: Honoraria; Gilead: Ended employment in the past 24 months, Honoraria; Novartis: Ended employment in the past 24 months, Honoraria; Servier: Ended employment in the past 24 months, Honoraria; MSD: Honoraria. Duléry: Takeda Gilead Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Robin: NEOVII MEDAC NOVARTIS: Research Funding.

Introduction: Primary mediastinal B cells lymphoma (PMBCL) is a rare subtype of aggressive non Hodgkin lymphoma (NHL). Despite therapeutic progresses, 10 to 30% of PMBCL patients are primary refractory or experience early relapses (R/R). Despite Autologous hematopoietic cell transplantation (auto-HCT) after bridging therapy or new therapies such as PD-1 inhibitors or CAR-T cells, R/R PMBL patients have a very poor outcome. Allogeneic stem cell transplantation (allo-HCT) is thus a potentially curative treatment for patients who relapsed after salvage therapies. Only limited data have been published about allo-SCT in R/R PMBCL (Herrera A. F, BBMT 2019). In the present study conducted on behalf the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) and the lymphoma study association (LYSA) group, we investigated the outcomes of allo-transplanted adult R/R PMBCL. Methods This multicenter retrospective study included all adult R/R PMBCL patients reported to the SFGM-TC and who underwent an allo-HCT between 1999 and 2018. Data have been obtained through ProMISe (internet-based system shared by all European transplantation centers) and completed by consulting the medical files of the LYSA group centers. All patients have given signed informed consent. Results Thirty-three patients with R/R PMBCL from 19 French (n=29) and 3 Belgium (n=4) centers were included. The median age at transplant was 33 y (18-61), with a predominance of female patients (58%). Majority of patients had a low HCT-CI score [0 = 9/17 (53%), data missing in 16 patients]. Seventy-six percent of patients had an IPI score between 1 and 2 and Ann Harbor score was ≥ 3 in 56.6% at diagnosis. Median number of treatment lines before allo-HCT was 3 (1-6). All patients received poly-chemotherapies with anthracyclines and anti-CD20 as first-line therapy. Most sixty-one percent of patients had previously undergone auto-HCT and one patient received CAR-T before allo-HCT. Forty one percent of patients were primary refractory. At time of transplant, 50% of patients were in complete response, 40% in partial response, and 10% had a progressive disease. Conditioning regimen was reduced intensity regimen in 63%. Stem cell source was PBSC in 88%. Donors were sibling in 42% or matched related donor in 39%. An alternative donor was chosen in 18%. GVHD prophylaxis included antithymocyte globulin in 61%, and calcineurin inhibitor in 97%. Median follow up was 78 months (3.5-157). Considering the whole cohort, 2y OS, DFS, NRM, and cumulative incidence of relapse were 48% (95%CI: 33-70), 60% (95%CI: 44-82), 18% (95%CI: 7-34), and 34% (95%CI: 18-50) respectively. Cumulative incidences of day 100 grade I-II and III-IV acute GVHD 36% and 0%, respectively. Cumulative incidence was 32% among whom 33% had an extensive cGVHD. Patients with progressive disease at transplantation had worst 2y PFS and OS (PFS: HR: 6.12, 95%CI: 1.32-28.31, p=0.02 and OS: HR: 7.04, 95%CI: 1.52-32.75, p=0.013). Conclusion: To our knowledge, this is the largest published study evaluating outcomes of allo-HCT for R/R PMBCL. Although this is a retrospective study with a limited number of patients, the outcomes suggest that allo-HCT is a therapeutic option providing durable remissions for patients with R/R PMBCL. Introduction: Primary mediastinal B cells lymphoma (PMBCL) is a rare subtype of aggressive non Hodgkin lymphoma (NHL). Despite therapeutic progresses, 10 to 30% of PMBCL patients are primary refractory or experience early relapses (R/R). Despite Autologous hematopoietic cell transplantation (auto-HCT) after bridging therapy or new therapies such as PD-1 inhibitors or CAR-T cells, R/R PMBL patients have a very poor outcome. Allogeneic stem cell transplantation (allo-HCT) is thus a potentially curative treatment for patients who relapsed after salvage therapies. Only limited data have been published about allo-SCT in R/R PMBCL (Herrera A. F, BBMT 2019). In the present study conducted on behalf the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) and the lymphoma study association (LYSA) group, we investigated the outcomes of allo-transplanted adult R/R PMBCL. Methods This multicenter retrospective study included all adult R/R PMBCL patients reported to the SFGM-TC and who underwent an allo-HCT between 1999 and 2018. Data have been obtained through ProMISe (internet-based system shared by all European transplantation centers) and completed by consulting the medical files of the LYSA group centers. All patients have given signed informed consent. Results Thirty-three patients with R/R PMBCL from 19 French (n=29) and 3 Belgium (n=4) centers were included. The median age at transplant was 33 y (18-61), with a predominance of female patients (58%). Majority of patients had a low HCT-CI score [0 = 9/17 (53%), data missing in 16 patients]. Seventy-six percent of patients had an IPI score between 1 and 2 and Ann Harbor score was ≥ 3 in 56.6% at diagnosis. Median number of treatment lines before allo-HCT was 3 (1-6). All patients received poly-chemotherapies with anthracyclines and anti-CD20 as first-line therapy. Most sixty-one percent of patients had previously undergone auto-HCT and one patient received CAR-T before allo-HCT. Forty one percent of patients were primary refractory. At time of transplant, 50% of patients were in complete response, 40% in partial response, and 10% had a progressive disease. Conditioning regimen was reduced intensity regimen in 63%. Stem cell source was PBSC in 88%. Donors were sibling in 42% or matched related donor in 39%. An alternative donor was chosen in 18%. GVHD prophylaxis included antithymocyte globulin in 61%, and calcineurin inhibitor in 97%. Median follow up was 78 months (3.5-157). Considering the whole cohort, 2y OS, DFS, NRM, and cumulative incidence of relapse were 48% (95%CI: 33-70), 60% (95%CI: 44-82), 18% (95%CI: 7-34), and 34% (95%CI: 18-50) respectively. Cumulative incidences of day 100 grade I-II and III-IV acute GVHD 36% and 0%, respectively. Cumulative incidence was 32% among whom 33% had an extensive cGVHD. Patients with progressive disease at transplantation had worst 2y PFS and OS (PFS: HR: 6.12, 95%CI: 1.32-28.31, p=0.02 and OS: HR: 7.04, 95%CI: 1.52-32.75, p=0.013). Conclusion: To our knowledge, this is the largest published study evaluating outcomes of allo-HCT for R/R PMBCL. Although this is a retrospective study with a limited number of patients, the outcomes suggest that allo-HCT is a therapeutic option providing durable remissions for patients with R/R PMBCL. Disclosures Sibon: Abbvie: Consultancy; Takeda: Consultancy; iQone: Consultancy; Roche: Consultancy; Janssen: Consultancy. Loschi: AbbVie: Ended employment in the past 24 months, Honoraria; CELGENE/BMS: Honoraria; Gilead: Ended employment in the past 24 months, Honoraria; Novartis: Ended employment in the past 24 months, Honoraria; Servier: Ended employment in the past 24 months, Honoraria; MSD: Honoraria. Dulery: Novartis: Honoraria; Takeda: Consultancy; Gilead: Other: Travel support and registration fees for scientific meetings .

Given the poor prognosis of relapsed/refractory myeloid malignancies, the concept of sequential conditioning before allogeneic hematopoietic stem cell transplantation (allo-HSCT) has proven to be an effective approach. We sought to evaluate a sequential scheme combining fludarabine, amsacrine, and cytarabine (FLAMSA) for cytoreduction, followed by reduced-intensity conditioning with busulfan and melphalan (FLAMSA-BuMel), which was designed to be suitable for both HLA-matched and haploidentical HSCT. This single-center retrospective study included 36 adult patients with high-risk myeloid malignancies who underwent allo-HSCT from HLA-matched (n = 19) or haploidentical (n = 17) donors. Along with the standard prophylaxis for graft-versus-host disease (GVHD), patients with a haploidentical donor received post-transplantation high-dose cyclophosphamide. A post-transplantation consolidation treatment with low-dose 5-azacytidine and prophylactic donor lymphocyte infusions was provided whenever possible. Thirty patients (83%) achieved complete remission on day +30. With a median follow-up of 30.0 months, the 2-year overall survival was 89% in the HLA-matched group versus 34% in the haploidentical group (P = .0018). The 2-year disease-free survival in these 2 groups was 68% and 34%, respectively (P = .013). At 2 years, the probability of relapse was 32% and 20%, respectively, and nonrelapse mortality was 0% and 58%, respectively (P = .0003). The leading cause of death was relapse in the HLA-matched group (3 of 19) and hemorrhagic events (5 of 17) in the haploidentical group, favored by significantly delayed platelet reconstitution and a severe GVHD context. These data confirm the feasibility of FLAMSA-BuMel as a sequential conditioning in allo-HSCT for high-risk myeloid malignancies. The use of bone marrow as the preferred graft source might reduce the incidence of acute GVHD and nonrelapse mortality in the haploidentical transplantation setting.

Despite great improvements in the outcome of patients with lymphoma, some may still relapse or present with primary refractory disease. In these situations, allogeneic hematopoietic cell transplantation is a potentially curative option, this is true particularly in the case of after autologous stem cell transplantation if remission can be achieved. Recently, novel agents such as anti-PD1 and BTK inhibitors have started to challenge the use of allogeneic hematopoietic cell transplantation for relapsed or refractory lymphoma. During the 2016 annual workshop of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), we performed a comprehensive review of the literature published in the last 10 years and established guidelines to clarify the indications and transplant modalities in this setting. This section specifically reports on our conclusions regarding diffuse large B cell lymphoma.

Despite great improvements in the outcome of patients with lymphoma, some may still relapse or present with primary refractory disease. In these situations, allogeneic haematopoietic cell transplantation (allo-HCT) is a potentially curative option, in particular in the case of relapse after autologous stem cell transplantation. Recently, novel agents such as anti-PD1 and BTK inhibitors have started to challenge the use of allo-HCT for relapsed or refractory lymphoma. During the 2016 annual workshop of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), we performed a comprehensive review of the literature published in the last 10 years and established guidelines to clarify the indications and transplant modalities in this setting. This manuscript reports on general considerations regarding allo-HCT for lymphoma and elaborates on the use of alternative donors in this setting.

Despite great improvements in the outcome of patients with lymphoma, some may still relapse or present with primary refractory disease. In these situations, allogeneic haematopoietic cell transplantation is a potentially curative option, in particular in the case of relapse after autologous stem cell transplantation. Recently, novel agents such as anti-PD1 and BTK inhibitors have started to challenge the use of allogeneic haematopoietic cell transplantation for relapsed or refractory lymphoma. During the 2016 annual workshop of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), we performed a comprehensive review of the literature published in the last 10 years and established guidelines to clarify the indications and transplant modalities in this setting. This manuscript specifically reports on our conclusions regarding Hodgkin's lymphoma as well as rarer entities, such as T cell lymphomas.

Despite great improvements in the outcome of patients with lymphoma, some may still relapse or present with primary refractory disease. In these situations, allogeneic hematopoietic cell transplantation is a potentially curative option, this is true particularly the case of relapse after autologous stem cell transplantation. Recently, novel agents such as anti-PD1 and BTK inhibitors have started to challenge the use of allogeneic hematopoietic cell transplantation for relapsed or refractory lymphoma. During the 2016 annual workshop of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), we performed a comprehensive review of the literature published in the last 10 years and established guidelines to clarify the indications and transplant modalities in this setting. This paper specifically reports on our conclusions regarding indolent lymphomas, mainly follicular lymphoma and chronic lymphocytic leukemia.

To the editor: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare form of acute myeloid leukemia (AML) that has been recognized as a distinct entity in the 2008 World Health Organization classification of hematopoietic tumors.[1][1] BPDCN is characterized by frequent skin and bone

Chronic GvHD-related keratoconjunctivitis sicca (cGvHD-related KCS) can significantly alter the quality of life of patients after allogeneic hematopoietic stem cell transplantation. The aim of this work was to assess the efficacy and tolerability of scleral lenses to treat severe cGvHD-related KCS. In this retrospective, multicenter study, we included 60 consecutive patients diagnosed with cGvHD-related KCS and fitted with scleral lenses. Patients were evaluated at baseline and at 2 months with the following tests: the Ocular Surface Disease Index (OSDI) to assess quality of life, the Oxford score to grade corneal damage and the logarithm of minimal angle of resolution (Log MAR) scale to determine visual acuity. We observed improvement in quality of life in 58 patients (97%). All parameters improved at 2 months. We observed significant differences at 2 months compared with baseline for the mean OSDI (86 versus 30, respectively, P

Resume L’allogreffe de cellules souches hematopoietiques constitue en soi un parfait exemple d’immunotherapie. Ses effets positifs sont lies a la reaction du greffon contre la tumeur, malheureusement souvent associee a la toxicite de la reaction du greffon contre l’hote. Si les mecanismes de ces deux reactions restent imparfaitement connus, certaines modalites de traitements associes ou certains choix therapeutiques peuvent modifier cette reaction immunologique. Il est ainsi devenu possible de la moduler. Dans ce contexte, le choix des donneurs, du type de conditionnement, du type de greffon ou encore l’utilisation de reinjection de cellules du donneur apres la transplantation sont autant d’outils ou de variables qui peuvent optimiser au mieux la procedure. Cet article a pour objectif de presenter l’ensemble de ces parametres en fonction des donnees actuelles.

Haploidentical hematopoietic stem cell transplantation (HSCT) is being increasingly used due to improvement of the transplantation procedures allowing a reduction of graft-versus-host-disease (GVHD) and of transplant-related mortality (TRM). Such improvements have been particularly observed after administration of T-replete HSCT graft associated to an in vivo T cell depletion by the administration of high-doses of cyclophosphamide (HD-Cy) after transplantation. Here, we have analyzed the results of haplo-identical T replete HSC transplants, in particular, when performed with post-transplant HD-Cy in order to provide recommendations for the clinical practice. Criteria of choice for a haploidentical donor by priority order are absence of donor-specific antibodies (DSA) and to prioritize: CMV seronegative recipient/donor couples, ABO matching in case of deserythrocytation, male donor for a male recipient, the youngest donor. There is no clear argument in favor of the use of bone marrow versus peripheral blood stem cells (PBSC) after non myeloablative conditioning regimen, while after ablative conditioning PBSC seem to be associated with higher risks of GVHD without obvious impact on survival. Results of haploidentical HSCT, confirmed by several groups, are interesting in lymphomas (in particular Hodgkin disease) and for acute leukemia. Outcomes of patients rely on age, disease status at transplant and conditioning intensity. At equivalent disease risk, results of haploidentical HSCT seem comparable to those of HLA matched HSCT, raising the question of the classification of such transplants as alternatives. In all cases, we recommend to include patients in prospective clinical trials.

The use of autologous haematopoietic stem cell transplantation (AHSCT) in autoimmune disease (AD) patients has increased progressively worldwide. We retrospectively analysed the long-term outcome of AHSCT for AD reported to the French Society for Bone Marrow Transplantation and Cellular Therapy (SFGM-TC). All French AD patients (≥ 18 years at transplant) with a first AHSCT between 1997 and 2013 were included. Primary data were derived from the European Society for Blood and Marrow Transplantation (EBMT) registry, and additional data were obtained through a specific questionnaire designed for the study. Primary end-point was overall survival (OS). Secondary end points were progression-free survival (PFS) and non-relapse mortality (NRM). Ninety-four AD patients were included, of whom 71% suffered from rheumatologic diseases (n = 67, including 56 systemic sclerosis (SSc)), 16% from neurological disease (n = 15, including 14 multiple sclerosis (MS)) and 13% from various other AD (n = 12). After a median (interquartile range, IQR) follow-up of 83 months (38–130), OS at 5 and 10 years were 77% (95% CI 68.5–86.2) and 64% (95% CI 51.7–76.3), and for PFS 51% (95% CI 40.4–61.6) and 44% (95% CI 32.8–55.3), respectively. Overall, NRM was 8.7% (95% CI 4.0–15.5) at day 100, 9.8% (95% CI 4.8–16.9) at 5 years and 13.6% (95% CI 6.9–22.5) at 10 years. This first SFGM-TC retrospective report shows long-term benefit of AHSCT in AD patients with acceptable toxicity.

Introduction. Allogeneic stem cell transplantation (SCT) can be curative for those with high-risk or recurrent hematologic cancers including T-cell non-Hodgkin's lymphoma (TCL). For patients lacking an HLA-matched related donor, donor sources such as haplo-identical (Haplo) relatives or cord blood (UCB) represent reasonable alternatives. There is currently little data on the outcome of TCL patients undergoing alternative donor transplantation. The Société Francophone de Greffe de Moelle et de Transplantation Cellulaire (SFGM-TC) conducted this study to evaluate the outcome of recipients of alternate donor allo-SCT for TCL. Methods. 95 patients with non epidermotropic TCL, transplanted between 2003 and 2017, reported to ProMISE (Project Manager Internet Server), an internet-based system shared by 36 Francophone transplantation centers, were reviewed. Comparisons of outcome after transplants from different donors (Haplo, n=41 vs UCB, n=54) were performed with regard to overall survival (OS), non-relapse mortality (NRM), relapse and acute/chronic graft-versus-host disease (aGVHD/cGVHD) incidence. Results. Patients' characteristics are detailed in Table 1. Median age at HSCT was 42.5 (range, 3.6 - 68) years, with an older cohort for the Haplo group (50.7 vs 33.6 for UCB, p< .001). Except for the median year of transplantation (median year 2017 for Haplo vs 2010 for UCB,) and the myeloablative regimen (22% for Haplo vs 48% for UCB, p .009), both Haplo and UCB groups were comparable concerning interval from diagnosis to HSCT, donor/recipient CMV status, sex and ABO mismatch. Patients received a median of 2 (range, 1-5 for Haplo; 1-6 for UCB) therapeutic lines. Twenty-eight (10 in Haplo vs 18 in UCB, p NS) underwent auto- or allo-SCT prior to Haplo or UCB-HSCT. Median time to engraftment was shorter (19 vs 25 days, p .025) in Haplo recipients. According to donor type, no differences were found in univariate analysis for the CI of grade II-IV aGVHD (35% vs 35%, p .88) and cGVHD (30% vs 28%, p .49). Median follow-up was 24 months and 47 months for Haplo and UCB recipients, respectively (p .004). At 12 months, OS was 71% and 50% (p .033), progression-free survival (PFS) 63% and 44% (p .045) and NMR 7% and 26% (p .014) in HSCT from Haplo and UCB, respectively. Relapse incidence was similar following HSCT from Haplo and UCB (32% vs 31%). Conclusion. Based on these first results, our study suggests that Haplo-HSCT is a strategy achieving prolonged survival as compared to UCB donors, due to less toxicity and similar incidence of relapse. An analysis of influencing factors will be further detailed. Figure Disclosures Blaise: Jazz Pharmaceuticals: Honoraria; Pierre Fabre medicaments: Honoraria; Molmed: Consultancy, Honoraria; Sanofi: Honoraria. Socie:Alexion: Consultancy. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding. Robin:Novartis Neovii: Research Funding.

Purpose We developed a prognostic scoring system to evaluate the prognosis of myelodysplastic syndrome (MDS) patients surviving more than 100 days allogeneic hematopoietic cell transplantation after (allo-HCT). Patients and methods We performed a landmark analysis on a derivation cohort of 393 cases to identify prognostic factors for 3-year overall survival. Potential predictor variables included demographic and clinical data, transplantation modalities and early post-transplant complications. The scoring system was tested against a validation cohort which included 391 patients. Results Complications occurring before day 100 such as relapse [HR = 6.7; 95%CI, 4.5-10.0] (4 points), lack of platelet recovery [HR, 3.6; 95%CI, 2.2-5.8] (2 points), grade-II acute GVHD [HR = 1.7; 95%CI, 1.2-2.5] (1 point) and grade-III/IV [HR = 2.6; 95%CI, 1.8 -3.8] (2 points) were the only independent predictors of 3-year OS. The 3-year OS associated with low (0), intermediate (1-3) and high (≥4) risk scores was respectively 70%, 46% and 6%. The model performed consistently in both cohorts, with good calibration. Conclusion This post-transplant scoring system is a powerful predictor of outcome after allo-HCT for MDS, and can provide useful guidance for clinicians. Additional studies are required to evaluate this scoring system for other hematologic malignancies.

Intravascular hemolysis in Paroxysmal nocturnal hemoglobinuria (PNH) can effectively be controlled with eculizumab, a humanized monoclonal antibody that binds complement protein C5. We report here a retrospective comparison study between 123 patients treated with eculizumab in the recent period (>2005) and 191 historical controls (from the French registry). Overall survival (OS) at 6 years was 92% (95%CI, 87 to 98) in the eculizumab cohort versus 80% (95%CI 70 to 91) in historical controls diagnosed after 1985 (HR 0.38 [0.15 to 0.94], P = 0.037). There were significantly fewer thrombotic events (TEs) in the group of patients treated with eculizumab (4% [1-10]) as compared to the historical cohort (27% [20-34]). However, we found that TEs may still occur after the initiation of eculizumab treatment and that previous TEs still have a negative impact on survival. Evolutions to myelodysplastic syndrome or acute leukemia were similar in both cohorts. There was less evolution to aplastic anemia in the treatment group. In multivariate analysis, absence of a previous TE and treatment with eculizumab were associated with a better OS. Treatment with eculizumab improves overall survival in classic PNH patients without increasing the risk of clonal evolution.

Antithymocyte globulins (ATG) plus cyclosporine (CSA) is the gold standard immunosuppressive treatment (IST) for patients with aplastic anemia. A prospective randomized trial showed in 2011 that hATG was superior to rabbit ATG for first-line treatment of severe AA. The French Health Agency (ANSM) permitted a patient-named authorization for temporary use (ATU) program of hATG (ATGAM, Pfizer) in patients with AA in 2011 since commercial access to hATG is not approved. We took advantage of this program to analyze the outcomes of 465 patients who received antithymocyte globulins (ATGAM) plus CSA as first line treatment (n = 379; 81.5%), or for refractory (n = 26) or relapsed disease (n = 33), from September 2011 to March 2017. In the entire cohort one year, 72% of the patients had partial and 13% had complete response, with worse response for patients with severe AA and a longer interval between diagnosis and IST (more than 6 months). Severe adverse events were mainly linked to infections (24%), hemorrhages (6%), and elevated liver function tests (5%). Overall at 12 months, 9.7% of patients required second line IST and 15.6% received transplantation. Fifty-five patients died during the study mainly because of infections (53%). Factors predicting independently worse survival were age over 40 years, neutrophils less than 0.5 × 109 /L, male gender and longer delay between diagnosis and hATG (>6 months period). This study does illustrate the results of ATGAM with CSA in a true-life perspective and confirms ATGAM as standard of care IST to treat patients with AA not eligible for HSCT.