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Relapse is a major cause of treatment failure after allogeneic hematopoietic cell transplantation (allo-HCT) in myeloid malignancies. Additional strategies have been devised to further maximize the immunologic effect of allo-HCT, notably through maintenance therapy with hypomethylating agents such as 5-azacytidine (AZA). We conducted a single-center retrospective study to investigate the efficacy of AZA after allo-HCT for high-risk myeloid malignancies. All patients transplanted between Jan 2014 and Sept 2019 for high-risk acute myeloid leukemia (n = 123), myelodysplastic syndrome (n = 51), or chronic myelomonocytic leukemia (n = 11) were included. Patients who died, relapsed, or developed grade ≥ 2 acute graft-versus-host disease before day + 60 were excluded, as well as those who were eligible for anti-FMS-like tyrosine kinase 3 maintenance. Of the 185 included patients, 65 received AZA while 120 did not. Median age at transplant was 59 years; 51.9% of patients were males. The median follow-up was 24 months for both groups. Regarding main patient characteristics and transplantation modalities, the two groups were comparable. In multivariate analyses, there were no significant differences between the two groups in terms of 2-year cumulative incidence of relapse (HR = 1.19; 95% confidence interval (CI) 0.67-2.12; p = 0.55), overall survival (HR = 0.62; 95%CI 0.35-1.12; p = 0.12) and event-free survival (HR = 0.97; 95%CI 0.60-1.58; p = 0.91) rates. In conclusion, single-agent AZA does not appear to be an optimal drug for preventing post-transplant relapse in patients with high-risk myeloid malignancies. This study highlights the need for prospective studies of alternative therapies or combination approaches in the post-transplant setting.

Background Defibrotide is indicated for patients who develop severe sinusoidal obstructive syndrome following allogeneic hematopoietic cell transplantation (allo-HCT). Preclinical data suggested that defibrotide carries a prophylactic effect against acute graft-versus-host disease (aGVHD). Objective The purpose of this study was to investigate the effect of defibrotide on the incidence and severity of aGVHD. Methods This single-center retrospective study included all consecutive transplanted patients between January 2014 and December 2018. A propensity score based on 10 predefined confounders was used to estimate the effect of defibrotide on aGVHD via inverse probability of treatment weighting (IPTW). Results Of the 482 included patients, 64 received defibrotide (defibrotide group) and 418 did not (control group). Regarding main patient characteristics and transplantation modalities, the two groups were comparable, except for a predominance of men in the defibrotide group. The median age was 55 years (interquartile range [IQR]: 40-62). Patients received allo-HCT from HLA-matched related donor (28.6%), HLA-matched unrelated donor (50.8%), haplo-identical donor (13.4%), or mismatched unrelated donor (7.0%). Stem cell source was either bone marrow (49.6%) or peripheral blood (50.4%). After using IPTW, exposure to defibrotide was not significantly associated with occurrence of aGVHD (HR = 0.97; 95% CI 0.62-1.52; P = .9) or occurrence of severe aGVHD (HR = 1.89, 95% CI: 0.98-3.66; P = .058). Conclusion and Relevance Defibrotide does not seem to have a protective effect on aGVHD in patients undergoing allo-HCT. Based on what has been reported to date and on these results, defibrotide should not be considered for the prevention of aGVHD outside clinical trials.

International audience; BackgroundAllogeneic hematopoietic stem-cell transplantation (allo-HSCT) remains the best curative option for high-risk myelodysplastic syndrome . We retrospectively compared patient outcomes after allo-HSCT according to the intensity of the conditioning regimen.Patients and MethodsThree conditioning regimens were compared in 427 patients allografted for high-risk myelodysplastic syndrome: reduced-intensity conditioning (RIC), fludarabine (150-160 mg/m2) and busulfan (6.4 mg/kg); sequential FLAMSA-RIC, fludarabine, amsacrine, and aracytine followed by RIC; and myeloablative with reduced toxicity (RTC), fludarabine and busulfan (9.6 mg/kg or 12.8 mg/kg).ResultsThe patients in the 3 conditioning groups were different in regards to the number of treatment lines (P< .001), percentage of blasts in bone marrow (P< .001), and disease status at transplantation (P< .001). No significant differences in outcomes (overall survival, progression-free survival, nonrelapse mortality, relapse incidence, and graft versus host disease relapse-free survival) were observed between the 3 groups. Using propensity score analysis to overcome baseline imbalances, we compared 70 patients receiving FLAMSA-RIC to 260 patients receiving RIC, and compared 83 patients receiving RTC to 252 patients receiving RIC. The only factor influencing overall and progression-free survival was cytogenetic risk at transplantation. After the covariate adjustment using propensity score to reduce baseline imbalances, the only factor influencing overall and progression-free survival was still cytogenetic risk at transplantation.ConclusionOverall survival appears to be similar with the 3 conditioning regimens. The only factor influencing survival is cytogenetic risk at transplantation, suggesting that new promising drugs in the conditioning and/or early interventions after transplantation are needed to improve outcomes in these patients.

Ibrutinib, a first-class Bruton tyrosine kinase inhibitor, is known to be associated with adverse bleeding events and has been recently approved for the treatment of relapse Waldenström macroglobulinemia (WM). Here, we report the exhaustive clinical and biological follow-up of 2 patients treated by ibrutinib alone in the context of relapsed WM with an acquired von Willebrand syndrome (AVWS) complication. In two cases, ibrutinib has been shown to be quickly efficient and safe for treating both AVWS and its underlying condition the WM, without bleeding complications. Interestingly, ibrutinib treatment brings a rapid and extended over time normalization of von Willebrand factor clearance. These observations show that ibrutinib is a valuable therapeutic option in relapsed WM patients associated with AVWS and highlighting the need for further cohort studies with long-term follow-up of patients to confirm the efficacy and safety of a treatment by ibrutinib for WM patients with AVWS complication.

Letermovir is the first approved drug for cytomegalovirus (CMV) infection prophylaxis in adult CMV-positive patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Since CMV infection risk varies from patient to patient, we evaluated whether a risk-based strategy could be effective. All consecutive CMV-positive adult patients (median age: 56.0 years, IQR: 43.5-64.0) who underwent allo-HCT between 2015 and 2021 (n=316) were included. Letermovir was not used in Period 1 (2015-2017, n=186), whereas during Period 2 (2018-2021, n=130), letermovir was used in high-risk patients but not in low-risk patients, except in those receiving corticosteroids. In high-risk patients, the incidence of clinically significant CMV infection (csCMVi) in Period 2 was lower as compared to Period 1 (p0.001) by week 14: 10.5% (95% CI 4.6-19.2) vs 51.6% (41.0-61.3) and week 24: 16.9% (8.9-27.0) vs 52.7% (42.0-62.3), respectively. In low-risk patients, although only 28.6% of patients received letermovir in Period 2, csCMVi incidence was also significantly lower (p=0.003) by week 14: 7.9% (2.9-16.3) vs 29.0% (20.2-38.5) and week 24: 11.2% (4.9-20.5) vs 33.3% (23.9-43.0). Among low-risk patients who did not receive letermovir (n=45), 23 (51.1%) patients experienced transient positive CMV DNA without csCMVi by week 14, while it remained negative in 17 (37.8%) patients. In both risk groups, the two periods were comparable for CMV disease, overall survival, progression-free survival, relapse, and non-relapse mortality. We concluded that a risk-based strategy for letermovir use is an effective strategy which maintains the high efficacy of letermovir in high-risk patients but allows some low-risk patients not to use letermovir.

Background: Despite therapeutic progress, 10 to 30% of adult patients with primary mediastinal B cell lymphoma (PMBCL) are primary refractory or experience early relapse (R/R). Allogeneic stem cell transplantation (allo-HSCT) thus remains a potentially curative option in this setting. Material and Methods: In this multicenter retrospective study, the outcomes of 33 French and Belgian adult patients allo-transplanted for R/R PMBCL between January 1999 and December 2018, were examined. Results: At allo-HSCT time, patients had received a median of 3 treatment lines, 50% of them were in complete response, 40% in partial response and 10% had a progressive disease. Forty-two percent of the donors were siblings and 39% matched related. The median follow-up for alive patients was 78 months (3.5-157). Considering the whole cohort, 2-year overall survival (OS), progression free survival (PFS) and graft-versus-host disease-free/relapse-free survival (GRFS) were 48% (95%CI: 33-70), 47% (95%CI: 33-68) and 38.5% (95%CI: 25-60) respectively. Cumulative incidence of relapse and non-relapse mortality rates were respectively 34% (95%CI: 18-50) and 18% (95%CI: 7-34). Disease status at transplant was the only factor predicting survivals, patients with progressive disease showing significant lower 2-year 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). A plateau was observed for OS and PFS after 4 years with 10 patients alive after this date, suggesting that almost one third of the patients effectively salvaged and undergoing allo-SCT could be cured. Conclusion: This study indicates that allo-HSCT is a valid therapeutic option for R/R PMBCL, providing durable remissions.

Microtransplantation (MT) is based on injection of HLA-mismatched G-CSF mobilized hematopoietic stem cells, in combination with chemotherapy but without use of conditioning regimen nor immunosuppressive drugs. As a result, a transient microchimerism is induced without engraftment. Its efficacy relies both on host immune system stimulation (recipient versus tumor) and on a graft versus tumor effect. Data are scarce and concern mostly Asian patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (HR-MDS). In comparison to conventional treatment without MT, higher complete remission rates and longer disease free survival and overall survival have been reported. Safety seems acceptable. The most frequent adverse event is non-severe cytokine release syndrome. Risk of GVHD remains very low. Here, we summarize the published data and detail the practical aspects of the procedure. Current data are not strong enough to provide recommendations on indications. Nevertheless, it seems reasonable to propose MT to patients with AML or HR-MDS, regardless of age, presenting an indication for allogeneic stem cell transplantation but ineligible for it. MT is still under investigation and rather be proposed within clinical trials.

International audience; Introduction and motivation: Since the end of 2019, the COVID-19 pandemic has affected millions of people worldwide. With the rapid spread of this virus, an immense burden has fallen upon both healthcare and economic systems. As a consequence, there is an unprecedented urgency for researchers and scientific committees from all over the world to find an effective treatment and vaccine.Review structure: Many potential therapies are currently under investigation, with some, like Hydroxychloroquine, being authorized for emergency use in some countries. The crucial issue is now clearly to find the suitable treatment strategy for patients given comorbidities and the timeline of the illness. Vaccines are also under development and phase 1 clinical trials are rolling. Despite all efforts, no single drug or vaccine has yet been approved. In this review, we aim at presenting the proposed pathophysiological mechanisms of SARS-CoV-2 and to provide clinicians with a brief and solid overview of the current potential treatments classified according to their use at the three different currently proposed disease stages. In light of pathogenesis and proposed clinical classification, this review's purpose is to summarize and simplify the most important updates on the management and the potential treatment of this emergent disease.

In an effort to standardize hematopoietic stem cell allograft procedures, the Francophone bone marrow transplantation and Cell Therapy Society (SFGM-TC) organized the 9th Allograft Harmonization Practice Workshop in Lille in September 2018. The purpose of these workshops is to propose a consensual attitude to the centers that wish it. In this workshop, we discuss how to capture the cytogenetic and molecular abnormalities of acute leukaemias, myelomas, myelodysplasias, myeloproliferative syndromes and myelodysplastic/myeloproliferative syndromes in the database common to all European transplant centers called ProMISe and managed by the European Society for Blood and Marrow Transplantation (EBMT). The complexity of cytogenetic and molecular data makes it difficult to enter data into the ProMISe registry. This workshop proposes a tool for input assistance, in tabular form by pathology. The main recommendation for the karyotype remains that of the complex karyotype that must be entered in "Full caryotype". Concerning the molecular anomalies, it is necessary to enter all the items proposed by ProMISe. In reviewing all the sheets proposed by ProMise, we note the absence of some relevant elements that can be added later.

We performed a retrospective assessment of patient- and transplant-specific characteristics and outcomes for 4142 patients undergoing allogeneic haematopoietic cell transplant for myelofibrosis between 1995 and 2018 across 278 centres. Activity increased steadily across the four analysed eras (

Simple Summary Acute myeloid leukemia (AML) is the most frequent type of acute leukemia in adults. Allogeneic hematopoietic cell transplantation (allo-HCT) has been the only potentially curative treatment for the majority of patients. The ability of chimeric antigen receptor (CAR)-modified T-cell therapy directed against the CD19 antigen to induce durable remissions in patients with acute lymphoblastic leukemia (ALL) has provided optimism that this novel treatment paradigm can be extrapolated to AML. In this review, we provide an overview of candidate target antigens for CAR-T-cells in AML, an update on recent progress in preclinical and clinical development of investigational CAR-T-cell products, and discuss challenges for the clinical implementation of CAR-T-cell therapy in AML. Abstract Adoptive transfer of gene-engineered chimeric antigen receptor (CAR)-T-cells has emerged as a powerful immunotherapy for combating hematologic cancers. Several target antigens that are prevalently expressed on AML cells have undergone evaluation in preclinical CAR-T-cell testing. Attributes of an ‘ideal’ target antigen for CAR-T-cell therapy in AML include high-level expression on leukemic blasts and leukemic stem cells (LSCs), and absence on healthy tissues, normal hematopoietic stem and progenitor cells (HSPCs). In contrast to other blood cancer types, where CAR-T therapies are being similarly studied, only a rather small number of AML patients has received CAR-T-cell treatment in clinical trials, resulting in limited clinical experience for this therapeutic approach in AML. For curative AML treatment, abrogation of bulk blasts and LSCs is mandatory with the need for hematopoietic recovery after CAR-T administration. Herein, we provide a critical review of the current pipeline of candidate target antigens and corresponding CAR-T-cell products in AML, assess challenges for clinical translation and implementation in routine clinical practice, as well as perspectives for overcoming them.

OBJECTIVE Recipients of allogeneic hematopoietic stem cell transplantation (allo-HCT) with positive cytomegalovirus (CMV) serology are at increased risk of morbidity and mortality. The primary objective of this study was to assess the association between treated CMV infection and overall mortality within 1 year after allo-HCT in adult CMV-seropositive Recipients (R+). Secondary objectives included overall 5-year mortality after allo-HCT, risk factors for treated CMV infection, associations between treated CMV infection and allo-HCT complications and medical costs. METHODS A multicenter retrospective cohort study was conducted in adult CMV-seropositive recipients (R+) who underwent to allo-HCT between 1st January 2010 and 31st December 2014. RESULTS Five hundred seventy two CMV-seropositive patients (mean age, 50.2 years) undergoing allo-HCT between 2010 and 2014 were included; 55.9% of donors were CMV seropositive. CMV infection treated with antiviral therapy was reported in 227 patients (39.7%) after transplantation. One-year overall mortality was significantly increased in patients with treated CMV infections (hazard ratio, 1.86; 95% CI, 1.16-3.00; P = .011). Mean medical costs during the first post-HCT year were higher in patients with CMV infection (€46 853 vs €31 318; P

International audience; Motivation: COVID-19 is one of the most widely affecting pandemics. As for many respiratory viruses-caused diseases, diagnosis of COVID-19 relies on two main compartments: clinical and paraclinical diagnostic criteria. Rapid and accurate diagnosis is vital in such a pandemic. On one side, rapidity may enhance management effectiveness, while on the other, coupling efficiency and less costly procedures may permit more effective community-scale management.Methodology and main structure: In this review, we shed light on the most used and the most validated diagnostic tools. Furthermore, we intend to include few under-development techniques that may be potentially useful in this context. The practical intent of our work is to provide clinicians with a realistic summarized review of the essential elements in the applied paraclinical diagnosis of COVID-19.

Microtransplantation (MT) is based on injection of HLA-mismatched G-CSF mobilized hematopoietic stem cells, in combination with chemotherapy but without use of conditioning regimen nor immunosuppressive drugs. As a result, a transient microchimerism is induced without engraftment. Its efficacy relies both on host immune system stimulation (recipient versus tumor) and on a graft versus tumor effect. Data are scarce and concern mostly Asian patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (HR-MDS). In comparison to conventional treatment without MT, higher complete remission rates and longer disease free survival and overall survival have been reported. Safety seems acceptable. The most frequent adverse event is non-severe cytokine release syndrome. Risk of GVHD remains very low. Here, we summarize the published data and detail the practical aspects of the procedure. Current data are not strong enough to provide recommendations on indications. Nevertheless, it seems reasonable to propose MT to patients with AML or HR-MDS, regardless of age, presenting an indication for allogeneic stem cell transplantation but ineligible for it. MT is still under investigation and rather be proposed within clinical trials.

Introduction Les eruptions cutanees suite a une greffe de cellules hematopoietiques posent probleme de prise en charge et de diagnostic. En effet, la semiologie est souvent atypique et la biologie biaisee par l’immunodepression. Le diagnostic repose donc sur un faisceau d’arguments. Peu d’etudes se sont focalisees sur la caracterisation epidemiologique et semiologique des eruptions cutanees. Notre objectif etait d’etudier la frequence et decrire les eruptions cutanees au cours de la 1re annee de greffe. Materiel et methodes Nous avons realise une etude descriptive monocentrique retrospective dans le service de maladies du sang du CHU de Lille. Nous avons inclus l’ensemble des patients ayant beneficie d’une allogreffe entre le 1er janvier 2018 et le 31 decembre 2019. Un suivi d’un an etait realise apres la greffe sur la base de l’analyse du dossier medical informatise. Resultats Nous avons inclus 196 patients allogreffes dont les principales indications etaient : 41 syndromes myelodysplasiques (20,9 %) et 115 leucemies aigues (58,7 %). Au total, 89 patients (45,4 %) ont presente une eruption cutanee durant la premiere annee de greffe. Parmi ces patients, 70 (74,2 %) ont presente une GVH aigue, 6 (7 %) une toxicite a la chimiotherapie, 2 (2 %) une origine infectieuse, 4 (4 %) une GVH chronique et 1 (1 %) une toxidermie. Lors de l’eruption, la recherche d’une origine virale etait realisee chez 73 patients et 29 patients presentaient une PCR virale au moins positive (39,7 % des patients testes). La PCR EBV etait positive chez 10 patients (14,5 % des patients testes). Le traitement reposait surtout sur la corticotherapie systemique (n = 51, 58 %) ou sur les dermocorticoides (n = 45, 52 %). L’evolution etait generalement favorable sur le plan dermatologique (resolution des symptomes dans 66 cas (79,5 %). Un avis dermatologique etait sollicite pour 24 patients (27 %). Une biopsie etait realisee chez 11 patients (12,3 %) permettant de redresser le diagnostic vers une etiologie non evoquee dans 3 cas. Discussion Au total, pres de la moitie des patients vont presenter un episode d’eruption cutanee dans l’annee suivant la greffe (45,4 % de notre cohorte). Le diagnostic principalement retenu etait un episode de GVH aigue cutanee (74,2 %), comme decrit dans la litterature. Neanmoins, la frequence des toxidermies (1 %) et des infections (2 %) de notre cohorte apparait particulierement faible contrastant avec le taux de positivite des examens virologiques, particulierement concernant l’EBV. On notait une faible frequence des biopsies (12,3 %). Il y a donc un reel probleme diagnostique dans ces situations devant l’absence d’elements pathognomoniques. Cette etude a donc permis de mettre en evidence la frequence importante d’eruption cutanee chez les patients allogreffes justifiant la prise en charge pluridisciplinaire de ces patients fragiles avec une expertise dermatologique et hematologique conjointe.

INTRODUCTION: Myelodysplastic Syndrome (MDS) is a heterogenous disease which is almost incurable without an allogeneic hematopoietic cell transplantation (allo-HCT). Within the revised international scoring system (R-IPSS), MDS with poor and very poor cytogenetics have a much worse outcome after allo-HCT. The very poor cytogenetic subgroup refers to patients harboring more than 3 abnormalities and is therefore a highly heterogenous group. We have shown in acute myeloid leukemia (AML) that beyond complex karyotype, specific adverse cytogenetic features such as 7q abnormalities (abn7q), 5q abnormalities (abn5q), 17p abnormalities (abn17p) and monosomal karyotype (MK) worsen the outcomes after allo-HCT. We have therefore retrospectively reviewed MDS with very poor cytogenetics and studied the impact of adverse cytogenetic features on outcomes after transplant. METHODS: We selected MDS patients who underwent allo-HCT between 2001 and 2018 from a matched related or unrelated donor, for whom a full cytogenetic report was available in the EBMT registry. We then stratified them according to the presence of abn7q, abn5q, abn17p, MK and the number of abnormalities (≤5, 6-9 and ≥10). Graft-versus-host disease (GvHD) and relapse-free survival (GRFS) was defined as survival without grade II-IV acute GvHD, extensive chronic GvHD or relapse. RESULTS: A total of 154 patients were identified in the registry. One hundred twenty-three patients (81%) had MDS with excess of blasts and 4 (3%) had secondary AML. Median age was 59 years (interquartile range (IQR), 51-64) and the median follow-up was 38 months (95% confidence interval (CI), 34-60). The time from diagnosis to allo-HCT was a median of 6 months (IQR, 4-8). Two thirds of patients received a reduced-intensity conditioning regimen (N = 103, 67%) and 87 patients had a matched unrelated donor (57%). Almost all patients were in first complete remission at time of transplant (N= 149, 97%). Regarding specific cytogenetic features, 87 patients had abn7q (57%), 99 abn5q (64%), 59 abn17p (38%) and 120 MK (78%) with considerable overlap between groups. The 2-year overall survival (OS) and progression-free survival (PFS) was 34% (95% CI 26-42%) and 24% (95% CI 17-31%), respectively. The 2-year cumulative incidence of relapse and non-relapse mortality (NRM) was 59% (95% CI 51-67%) and 18% (95% CI 12-24%), respectively. The cumulative incidence of grade II-IV acute GvHD and chronic GvHD was 33% (95% CI 25-40%) and 44% (95% CI 36-53%) by day 100 and 2 years respectively. The 2-year GRFS was 12% (95% CI 6-17%). The presence of abn5q was associated with a significantly decreased PFS of 17% (95% CI 9-25%) versus 36% (95% CI 23-49%); p=0.05) and GRFS (6% (95% CI 1-11%) versus 23% (95% CI 11-34%); p=0.04). The presence of abn7q was associated with significantly increased NRM (25% (15-34%) versus 9% (2-16%); p=0.02) which did not translate into OS. There were no specific cytogenetic features that had an independent impact on the cumulative incidence of relapse, but age over 55 years did increase the relapse risk (65: 66% (95% CI 50-83%); p=0.03). A continuous effect was also observed (per decade increase: HR=1.24, 95%CI 1.02-1.52; p=0.03). Patients with an interval of more than 6 months from diagnosis to allo-HCT had almost double the OS (45% (95% CI 32-58%)) compared to patients with an interval less than 6 months (27% (95% CI 17-37%); p=0.04), however a continuous effect was not observed. CONCLUSION: MDS with very poor cytogenetics according to R-IPSS is a very bad group with dismal outcomes after allo-HCT. Within this high-risk group, specific adverse cytogenetic features such as the number of abnormalities, abn7q, abn5q, abn17p or MK did not stratify outcomes further, except for abn5q which was associated with a decreased PFS. Our results might be explained in part by the low number patients and by the over-representation of adverse features within this cohort. Despite that, advancing age was associated with increased relapse. Whilst allo-HCT remains the best therapeutic option for this very high-risk patient group, efforts should focus on post-transplant preemptive intervention strategies to prevent relapse. Disclosures Byrne: Incyte: Honoraria. Schroeder: Celgene: Honoraria, Other: Travel support, Research Funding. Blaise: Jazz Pharmaceuticals: Honoraria. Hayden: Jansen, Takeda: Other: Travel, Accomodation, Expenses; Amgen: Honoraria. Scheid: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria; Roche: Consultancy; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Yakoub-Agha: Jazz Pharmaceuticals: Honoraria.

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 .

Aim: Dynamic assessment of trends over time in patient- and transplant-specific characteristics and outcomes for patients undergoing 1st allogeneic haematopoietic cell transplant (allo-HCT) for Myelofibrosis (MF). Methods and Results: A total of 4142 MF patients were analysed who underwent allo-HCT between 1995-2018 (24-year period) across 278 centres based on data reported to the European Society for Blood and Marrow Transplantation. For analysis, 4 cohorts were considered based on year of allo-HCT: 60 years accounted for 8.7% of adults undergoing allo-HCT whereas for 2015-2018 this was 47%. Over time, increasing number of patients with a Karnofsky performance status (KPS) Conclusions: Despite a marked increase over this 24-year period in recipient age, RIC regimen utilisation and use of both URD and MMRD, this comprehensive analysis demonstrates stable OS and EFS rates. However, rates of GVHD have decreased over time, in particular extensive cGVHD. Further work is required to improve both the considerable NRM and relapse rates which remain significant. Disclosures McLornan: JAZZ PHARMA: Honoraria, Speakers Bureau; CELGENE: Honoraria, Speakers Bureau; NOVARTIS: Honoraria, Speakers Bureau. Platzbecker:Amgen: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Geron: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding. Chevallier:Incyte Corporation: Honoraria. Martínez-Lopez:Altum, Hosea: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Vivia Biotech: Honoraria; Amgen: Speakers Bureau; Takeda: Speakers Bureau; Roche: Speakers Bureau; Janssen: Speakers Bureau; Incyte: Research Funding, Speakers Bureau; Bristol Myers Squibb: Research Funding, Speakers Bureau; Novartis: Research Funding. Yakoub-Agha:Celgene: Honoraria; Jazz Pharmaceuticals: Honoraria; Novartis: Honoraria; Gilead/Kite: Honoraria, Other: travel support; Janssen: Honoraria.

International audience; Chimeric antigen receptor (CAR) T cells are a novel class of anti-cancer therapy in which autologous or allogeneic T cells are engineered to express a CAR targeting a membrane antigen. In Europe, tisagenlecleucel (Kymriah™) is approved for the treatment of refractory/relapsed acute lymphoblastic leukemia in children and young adults as well as relapsed/refractory diffuse large B-cell lymphoma, while axicabtagene ciloleucel (Yescarta™) is approved for the treatment of relapsed/refractory high-grade B-cell lymphoma and primary mediastinal B-cell lymphoma. Both agents are genetically engineered autologous T cells targeting CD19. These practical recommendations, prepared under the auspices of the European Society of Blood and Marrow Transplantation, relate to patient care and supply chain management under the following headings: patient eligibility, screening laboratory tests and imaging and work-up prior to leukapheresis, how to perform leukapheresis, bridging therapy, lymphodepleting conditioning, product receipt and thawing, infusion of CAR T cells, short-term complications including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, antibiotic prophylaxis, medium-term complications including cytopenias and B-cell aplasia, nursing and psychological support for patients, long-term follow-up, post-authorization safety surveillance, and regulatory issues. These recommendations are not prescriptive and are intended as guidance in the use of this novel therapeutic class.

Therapeutic options are limited for patients developing refractory sclerotic-type chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell transplantation. We previously showed that imatinib mesylate (IM) could be efficacious in this situation, although complete responses were uncommon (Magro L Blood 2009). We hypothesized that the combination of extracorporeal photopheresis (ECP) and IM could have synergistic effects to treat SR steroid-refractory cGVHD. While IM and ECP are separately used for the treatment of refractory cGVHD, the combination of both has never been investigated. We describe here the efficacy of the concurrent administration of IM with ECP in seven patients with refractory sclerotic-type cGVHD who had showed insufficient response to either IM or ECP. Seven consecutive patients (3 males and 4 females) with a median age of 46 years old, who received imatinib with concurrent ECP for refractory sclerotic-type cGVHD, were included. Patients were considered refractory if they were steroid-refractory or steroid-dependent. Four patients had previously showed insufficient partial response (PR) to IM, while three patients showed insufficient PR while receiving ECP. IM was started at 200 mg/day and increased to 400 mg/day if well-tolerated. ECP was initiated twice weekly then less frequently according to the patient’s individual treatment response. With a median follow-up of 56 months, the concurrent administration of IM with ECP deepened responses in all patients and induced durable complete responses (CR) in 4 (57%). Median time to best response was 4 months. Median duration of combination treatment was 42 months (range: 4–60). As of February 2018, 5 patients were still alive. Two patients died of myocardial infarction and one from relapse of a preexisting prostate cancer. The concurrent administration of IM with ECP led to complete and sustained responses in patients with refractory sclerotic-type cGVHD.

In an effort to standardize hematopoietic stem cell allograft procedures, the Francophone bone marrow transplantation and Cell Therapy Society (SFGM-TC) organized the 9th Allograft Harmonization Practice Workshop in Lille in September 2018. The purpose of these workshops is to propose a consensual attitude to the centers that wish it. In this workshop, we discuss how to capture the cytogenetic and molecular abnormalities of acute leukaemias, myelomas, myelodysplasias, myeloproliferative syndromes and myelodysplastic/myeloproliferative syndromes in the database common to all European transplant centers called ProMISe and managed by the European Society for Blood and Marrow Transplantation (EBMT). The complexity of cytogenetic and molecular data makes it difficult to enter data into the ProMISe registry. This workshop proposes a tool for input assistance, in tabular form by pathology. The main recommendation for the karyotype remains that of the complex karyotype that must be entered in "Full caryotype". Concerning the molecular anomalies, it is necessary to enter all the items proposed by ProMISe. In reviewing all the sheets proposed by ProMise, we note the absence of some relevant elements that can be added later.

Introduction: Response to conventional therapies for patients with T-cell prolymphocytic leukemia (T-PLL) is usually poor and is associated with short survival. The BCL-2 antagonist venetoclax was recently found to have some clinical activity in this disease (B Boidol et al., Blood, 2017); however, these early data suggest that this drug will not provide prolonged response when given as monotherapy. Several other drug classes have demonstrated preclinical activity in T-PLL, including HDAC inhibitors (HDACi), JAK/STAT inhibitors (JAK/STATi), and TCR pathway inhibitors (TCRi), particularly ITK inhibitors. To determine which drug(s) may be the optimal combination partner(s) for venetoclax in T-PLL, we utilized a functional approach known as BH3 profiling. This assay measures how close a cell is to the threshold of apoptosis ("priming") and identifies which anti-apoptotic proteins a cell depends on for survival. We also utilized a variant known as dynamic BH3 profiling (DBP) to measure early changes in pro-apoptotic signaling after various drug treatments. Methods: Clinically annotated primary T-PLL patient samples were obtained from the French Innovative Leukemia Organization network after informed consent. Peripheral blood mononuclear cells were isolated by Ficoll and viably frozen and later thawed for the experiments. Baseline BH3 profiling to measure cytochrome C (cyto-C) release was performed as per Ryan et al., Methods, 2013, and DBP as per Montero et al., Cell, 2015. Viability was assessed by AnnexinV/Hoechst staining. Ex vivo drug treatments included: BH3 mimetics (BCL-2i: venetoclax (VEN), MCL-1i: AZD5991, S63845), HDACi (belinostat = BEL), JAK/STATi (ruxolitinib = RUX) and TCRi (PRN694 = PRN). Protein expression was assessed by standard Western Blot. Primary CLL cells were used in some experiments as a comparator. To mimic the lymph node microenvironment, DBP and viability assays were performed in co-culture with the stromal cell line NK.tert. Tumoral DNA was also extracted, and we performed NGS on a panel of 29 genes, including ATM and TP53, as well as Sanger sequencing to assess for IL2R, JAK1, JAK3, STAT5B mutations. Statistical analyses were by unpaired and paired t-test with a two-tailed nominal p ≤ 0.05 considered as significant. Results: Samples were evaluated from 31 T-PLL patients. Baseline BH3 profiling revealed that, compared to CLL cells, T-PLL cells are less primed for apoptosis but have comparable dependency on MCL-1. BCL-2 dependency was found to be significantly lower in T-PLL than CLL (cyto-C release 48.8%; 62.7% p=0.0005), and to decrease further in the presence of stroma (Figure A, cyto-C release from 72.6% to 36.2%, p = 0.01). Consistent with our BH3 profiling results, the degree of BCL-2 dependency in T-PLL cells was strongly associated with the amount of apoptotic cell death induced by VEN (R2 -0.58, p=0.004), whereas MCL1 dependency was strongly associated with the cell death induced by the MCL1 inhibitors S63845 and AZD5991 (R2 -0.59, p=0.002 and R2 -0.68, p=0.0005 respectively, Figure B). We next performed DBP to assess the changes in apoptotic priming in T-PLL cells induced by HDACi, JAK/STATi and TCRi. To utilize doses similar to what can be achieved in patients, we assessed BEL 1mM, RUX 1mM and PRN 1mM. BEL and RUX increased overall T-PLL cell priming and BCL2 dependency (delta cyto-C release of 26.8%, p=0.004 and 14.8%, p=0.01 respectively Figure C), with no effect on MCL1 dependency. PRN had no significant effect on priming. Consistent with the DBP data, our viability assays showed that BEL and RUX induced significantly more cell death when combined with VEN compared to PRN (Figure D). Mutations in ATM, TP53, and JAK/STAT pathway genes were observed in cells from 35%, 6%, and 53% of patients, respectively, and did not impact the ex vivo activity of these drugs. Conclusion: We report the first data for BH3 profiling in T-PLL. We found that this disease is heterogeneously dependent on both BCL-2 and MCL-1, and that the lymph node microenvironment may decrease BCL-2 dependency. HDACi and JAK/STATi both enhance BCL-2 dependence, thereby sensitizing T-PLL cells to VEN. Ongoing studies will help further define the mechanism underlying these promising new combinations for T-PLL. Disclosures Herbaux: BMS: Honoraria; Gilead: Honoraria; Takeda: Honoraria; Abbvie: Honoraria; Janssen: Honoraria. Valentin:Roche: Other: Travel reimbursement; Abbvie Inc: Other: Travel reimbursement. Morschhauser:F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Bayer: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Staber:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda-Millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; MSD: Honoraria, Speakers Bureau. Davids:AbbVie, Astra-Zeneca, Genentech, Janssen, MEI, Pharmacyclics, Syros Pharmaceuticals, Verastem: Consultancy; Acerta Pharma, Ascentage Pharma, Genentech, MEI pharma, Pharmacyclics, Surface Oncology, TG Therapeutics, Verastem: Research Funding; AbbVie, Acerta Pharma, Adaptive, Biotechnologies, Astra-Zeneca, Genentech, Gilead Sciences, Janssen, Pharmacyclics, TG therapeutics: Membership on an entity's Board of Directors or advisory committees; Research to Practice: Honoraria.

Introduction: Systemic Light-chain amyloidosis (AL) is a clonal plasma-cell disorder, and has therefore benefited from the numerous therapeutic advances in multiple myeloma (MM). Nonetheless, outcome of refractory AL patients remains dire, especially in patients with severe end-organ damage. Daratumumab, a monoclonal antibody directed against CD38, has yielded significant results in MM, but data in AL, although promising, are scarce. Methods: Between November 2016 and July 2018, 15 relapsed or refractory patients with histologically proven AL from five different French centres from the Hauts-de-France region received ongoing daratumumab at the dose of 16 mg/kg, weekly for the first two cycles, twice a month from cycle 3-6, and monthly after cycle seven. All patients had, at least, previously received a proteasome inhibitor (PI) or immunomodulatory drug (IMiD). Efficacy and safety data were assessed retrospectively after required authorization (CNIL registration n°2197989). Results: Fifteen patients with a median number of previous lines of two [1-5] were included. Overall, the population was frail, with a median ECOG of one [range: 0 - 3], CIRS comorbidity score of 14 [8 - 27] and Charlson score of four [1 - 8]. Three of the patients had symptomatic MM according to International Myeloma Working Group criteria. All had elevated free light chains (mean 536 mg/L [38 - 1411]). The mean number of organ involved per patient was three [1-6]; 67% had evidence of cardiac involvement, including Mayo-Clinic stage III in all patients but one; 60% had kidney involvement, including two patients on chronic haemodialysis. Patients received a median of six cycles [1 - 17]. The overall haematological response was 73%, with at least a very good partial response (VGPR) in 33% of cases. Best haematological response was achieved after one cycle [1 - 10]. Eleven patients were evaluable for organ response, which was achieved in 36% of patients, after a median 3.5 cycles [3 - 5]. Infusion-related reactions occurred in 33% of patients, all were grade I-II. Infection occurred in 47% of patients, 60% being grade III or greater. At last follow-up, 67% of patients were still on daratumumab; two patients died, one from progressive disease and another from infection. Discussion: As previous results suggest, daratumumab yields promising results in relapsed AL patients in terms of both haematological and organ-response. Short-time to response is particularly striking in this study as it is a well-known determinant of outcome in AL. These results are particularly remarkable given the frailty and the severity of our population. Frailty indexes have long been used in haematology especially in MM where it is now established that an ECOG score ≥2 or a Charlson score ≥2 impairs overall survival. CIRS score has also been used in cancer patients, where the cut-off to predict mortality varies between 3-4 and 6-7 in chronic lymphocytic leukaemia and acute myeloid leukaemia, respectively. In our cohort, the median Charlson index was over two in 83% of patients and the CIRS was greater than six in all patients, emphasizing the frailty of this real-life AL-population. This may be explained by the extent of organ involvement and the multiple prior treatment received. All but one cardiac patients had Mayo stage III disease, 93% had two or more organs involved, and had dFLC>60mg/L at diagnosis. This indicates high-risk patients, who are less inclined to respond to treatment. Despite these high-risk characteristics, even with a short follow-up, we observed organ responses. As expected, the deeper the haematological response was, the more likely organ response was observed. Even though the general toxicity profile was favourable, the incidence of high-grade infection ought to be noted. Although it may be explained by a combination of factors (i.e. previous treatment, frailty, co-morbidities), infection could outweigh any benefit in terms of overall survival. Shorter treatment course, response or frailty-driven treatment strategies alongside prophylactic measures should therefore be evaluated prospectively in this high-risk population. Conclusion: Single agent daratumumab shows promising results, yielding rapid and deep haematological responses, with an acceptable safety profile, in a frail real-life AL population. Nonetheless, close attention should be paid in the future to infection and its relation to frailty in this specific group of patients. Disclosures Herbaux: Abbvie: Consultancy, Honoraria; Gilead Sciences, Inc.: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Facon:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees. Boyle:Janssen: Honoraria, Other: travel grants; Gilead: Honoraria, Other: travel grants; Amgen: Honoraria, Other: travel grants; La Fondation de Frace: Research Funding; Abbvie: Honoraria; Celgene: Honoraria, Other: travel grants; Takeda: Consultancy, Honoraria.

Development of echinocandin resistance in Candida krusei isolates following exposure to micafungin and caspofungin in a BM transplant unit

Objective To report the usefulness of three-dimensional (3D) ultrasonography for the assessment of parietal endometriosis. Design Case report. Setting Academic research hospital. Patient(s) A 35-year-old woman with a noncyclic, painful abdominal nodule near a caesarean delivery scar. Intervention(s) 3D ultrasonography and wide surgical resection with healthy margins. Main Outcome Measure(s) 3D ultrasonographic assessment of the endometriotic nodule. Result(s) We found that 3D ultrasonography offered a more specific description of parietal endometriosis with irregular and spiculated margins and depth infiltration as well as provided preoperative evaluation of volume measurements. Conclusion(s) Three-dimensional ultrasonography is a useful, noninvasive tool in extrapelvic endometriosis.

Introduction Chimerism analysis after allogeneic hematopoietic stem cells transplantation (HSCT) allows documentation and understanding of important clinical events such as engraftment, graft failure, and/or relapse. Few data are available on whether T-cell chimerism might be more informative than global chimerism. In this study, we focused on selective CD3+ T-cell chimerism and its interest to predict events after allogeneic HSCT. Methods This is a single center retrospective study. Only patients with a survival more than 3 months were included. Information concerning donors, recipients, conditioning regimen, graft harvesting and follow-up were collected in our center using prospective forms from Promise database. Evaluation of T-cell chimerism was performed on CD3+ blood cells after immunomagnetic sorting, by PCR-STR (short-tandem repeats) multiplex technique using 15 different markers. Analysis of the tandem repeat polymorphism was performed by sequencer and Genscan software (Applied Biosystem Inc.). Chimerism was evaluated in 2 ways: positive or negative, and % of recipient. An analysis with repeated measures was also performed to determine the utility of a positive measure of chimerism, independently of the date of sample after allograft, to predict a relapse. Results Between January 2006 and December 2011, 148 patients (pts) were admitted in our unit for allogeneic HSCT (32% with myeloablative conditioning and 68% with reduced conditioning). Median age was 54.3 years, 59 male, 89 female. Diagnosis included AML/MDS (n=77), ALL (n=23), Aplastic anemia (n=4), lymphoma and CLL (n=23), myeloma (n= 8) and myeloproliferative disorders (n=13). The donor was matched sibling (n=51), matched unrelated (10/10) (n=74) or mismatched unrelated (9/10)(n=23). Graft source was PBSC (n=97), BM (n=33) or CB (n=18). At transplant, 108 pts (73%) were in complete remission, 19 (13%) presented partial response and 21 (14%) have progressive disease. At time of analysis, median follow-up was 1.75 years. Median overall Survival (OS) was estimated at 2 years. Forty-seven pts (32%) presented relapse. Seventy pts (47%) are still alive. Main causes of death were HSCT related (n=38), relapse or progression (n=33) and other (n=7). Acute GVHD grade II-IV incidence was 32% (13.5% grade III-IV) and 58% for chronic GVHD. At day +30, 56% of pts presented a mixed T-cell chimerism with 36 (24.3%) pts with a chimerism higher than 25% recipient. At day +90, 41% have remained positive. For NRM, aGVHD and age were the only prognostic parameters statistically identified. For PFS, only T-cell chimerism with a positive 25% cut-off at D+30 was identified as a prognostic factor (p=.0017, HR(IC 95%) 2.52(1.39; 4.58). PFS was not reached if T-cell chimerism was inferior to 25% at D+30 versus 1.35 years (figure 1). The results were concordant in a subgroup analysis performed according to the myeloid or lymphoid neoplasia status. Otherwise, cGVHD incidence was higher if T-cell chimerism was less than 25% at D+30 (70% vs. 18%). Finally, the analysis with repeated measures confirmed that positive T-cell chimerism is strongly correlated with relapse (p=.001; HR (CI95%) 90.18(30.11; 270.13)). Conclusion After allogeneic HSCT, mixed T-cell chimerism higher than 25% at day +30 is strongly correlated with poor PFS, independently of source of cells, donors, intensity of conditioning, diagnosis or disease status at transplant. Considering this high-risk population, early intervention should probably be considered. Disclosures: No relevant conflicts of interest to declare.