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We analysed long-term outcome of patients receiving haematopoietic allogeneic stem cell transplantation (allo-HSCT) as a first transplant for high-risk Hodgkin lymphoma (HL). One hundred and ninety patients were included in this study, 63% of them had previously received brentuximab vedotin and/or checkpoint inhibitors. Seventy patients (37%) received an unrelated donor allo-HSCT, 99 (51%) had myeloablative conditioning (MAC) and 60% had in vivo T-cell/depleted grafts (TCD). The 100-day cumulative incidence (CI) of grade II-IV acute graft-versus-host disease (GVHD) was 25% and the 3-year CI of chronic GVHD was 38%. The 3-year CI of non-relapse mortality (NRM) and relapse rate were 21% and 38% respectively. After a median follow-up of 58 months, 3-year overall survival (OS) and progression-free survival (PFS) were 58% and 41% respectively. Multivariate analysis showed that, in comparison to reduced-intensity conditioning regimens with or without TCD, MAC using TCD had similar NRM and a lower risk of relapse leading to significantly better OS and PFS. MAC without TCD was associated with higher NRM and worse survival outcomes. These results suggest that in patients with high-risk HL and candidates of allo-HSCT, a MAC strategy with TCD might be the best option.

International audience; Background: Immunoglobulin replacement therapy is recommended in case of severe hypogammaglobulinemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the supposed increased risk of infection in case of hypogammaglobulinemia has not been confirmed in allo-HSCT. In this study, we assessed the relationship between the gamma globulin level and the risk of infection during the 100 days following the allo-HSCT.Methods: We gathered the weekly laboratory tests from day 7 to day 100 of 76 allograft patients, giving a total of 1 044 tests. 130 infections were documented clinically, by imaging, or microbiologically.Results: Average gamma globulin levels between D-7 and D100 did not differ between patients with or without infection (642 ± 232 and 671 ± 246 mg/dL, respectively, P = .65). Gamma globulin level

Because of the persistently high rates of relapse of patients with high-risk acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) following allogeneic hematopoietic stem cell transplantation (allo-HSCT), post-transplantation maintenance therapy has been proposed. We previously initiated a Phase II trial in which epigenetic therapy was combined with immunotherapy in an attempt to reduce disease relapse. In that study, low-dose azacitidine (AZA) and escalating doses of donor lymphocyte infusion (DLI) were given as post-allo-HSCT maintenance treatment. In the present study, we retrospectively analyze a larger cohort of patients receiving post-transplantation maintenance therapy and provide updates on some patients of the earlier study. The objectives of the present study were to analyze the cumulative incidence of relapse (CIR), overall survival (OS), and progression-free survival (PFS) and the incidence of acute and chronic graft-versus-host disease (GVHD) of patients with high-risk AML or MDS receiving post-transplantation maintenance treatment with AZA with or without DLI. We retrospectively analyzed 77 patients (54 with AML, 23 with MDS) considered at high risk based on either their genomic or clinical status at transplantation. Following allogeneic transplantation, they received at least 1 cycle of prophylactic or preemptive low-dose AZA with or without escalating doses of DLI to prevent disease relapse. Almost one-half of the patients (47%) were able to receive the full 12 cycles of scheduled AZA, and a majority (79%) received at least 1 DLI. With a median follow-up of 24 months, 19 patients (25%; 16 with AML, 3 with MDS) relapsed, at a median of 9.8 months (range, 4 to 58.6 months), giving a 22% CIR at 24 months. OS and PFS at 24 months were 70.8% and 68.3%, respectively. The cumulative incidences of grade II-IV acute GVHD and chronic GVHD were 27.4% and 45%, respectively. Only a minority of patients (11%) required delayed administration of AZA. These findings confirm that AZA-DLI maintenance is both tolerable and effective in reducing the risk of post-transplantation relapse.

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Introduction Citrulline, a non-essential amino acid produced exclusively by enterocytes in the small intestine and involved in the synthesis of L-arginine, is not metabolized by the liver. Therefore citrulline serum concentration is highly correlated with functional enterocyte mass, and decreases with digestive toxicity induced by conditioning therapy (radiotherapy and/or chemotherapy) for hematopoietic stem cell transplantation (HSCT) . Acute Graft-versus-host disease (GvHD), one of the major complications of HSCT, is correlated to conditioning-induced gut barrier damage and may be predicted by pre-transplant serum citrulline level (Rashidi, BBMT 2018). It could be interesting to know whether citrulline kinetics could also represent a biomarker for conditioning toxicity, non-relapse mortality (NRM), and GvHD. The aim of this study is thus to define group-based trajectory modeling, to identify clusters of individual serum citrulline kinetics in the early phase of allogeneic HCST, and to test whether these unsupervised trajectories were correlated with these early complications. Materials and Methods Serum citrulline was quantified by liquid chromatography in blood samples collected from consecutive patients who received an allogeneic HSCT in our institution between July 2014 and November 2019. These samples were drawn at different time-points: pre-transplant (D-7, D-3); day of transplant (D0), and post-transplant (D7, D15, D21). Distinct trajectories were identified for serum citrulline by using the semiparametric mixture model described by Nagin (Nagin, Stat Methods Med Res 2018). Results Among 161 patients (pts) included in the study, with a median age of 53 years (17-72), 98 pts (60.9%) received a reduced-intensity conditioning (RIC), 36 pts (22.4%) reduced-toxicity conditioning (RTC), 18 pts (11.1 %) sequential conditioning, and 9 pts (5.6%) myeloablative conditioning (MAC). Donor were identical sibling (22%), matched unrelated donor (52%) and haploidentical sibling (25%). Graft source was peripheral blood mononuclear cells in 144 pts (89.4%) and bone marrow in 17 pts (10.6%) respectively. HCT-CI score was low, intermediate and high-risk in 38%, 32%, and 30% of pts respectively. Disease-Risk Index (DRI) was low/intermediate in 111 pts (69%) and high/very-high in 50 pts (31%). With a median follow up of 29.1 month, 3-year overall survival (OS), disease-free survival (DFS), and NRM rates were 64.5%, 58.3%, and 18.9%, respectively. The median number of citrulline samples per patient was 7 [3-16]. Median citrulline concentrations before conditioning and at D-3, D0, D7 and D15 were statistically different during RIC, RTC, MAC, and sequential conditioning (p In the whole cohort, 3 citrulline trajectories were determined in an unsupervised method. Patients belonging to these 3 trajectories were different according to intensity of conditioning received with lower citrulline trajectories during MAC and sequential conditioning (p After restricting the analysis to pts who received RIC conditioning (n=98), higher pre-HSCT citrulline concentrations were associated with a lower NRM (p=0.042). Unsupervised analysis in this setting individualized 4 clusters of individual trajectories (figure 1), that did neither distinguish age (p=0.28), DRI (p=0.87), HCT-CI score (p=0.81) nor the incidence of acute (p=0.6) or chronic (p=0.4) GvHD. However, the lowest citrulline trajectory contained significantly more haploidentical transplantations (p=0.004) and less pts who received antithymocyte globulin for GvHD prophylaxis (p=0.005). Interestingly in this RIC cohort, cumulative incidence of NRM at 12 months was 23%, 21%, 8%, and 0% respectively according to the 4 citrulline trajectories (figure 2). Conclusion In patients receiving allogeneic HSCT, the variation of serum citrulline concentrations depends on the intensity of the conditioning regimen. In patients who received RIC conditioning, lower plasma citrulline trajectories are associated with higher NRM. In this setting, citrulline may be an attractive biomarker for predicting conditioning toxicity and NRM. Disclosures Hunault: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Diachi: Membership on an entity's Board of Directors or advisory committees; Jansen: Honoraria; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Thepot:astellas: Honoraria; novartis: Honoraria; sanofi: Honoraria; celgene: Honoraria.

Introduction: Pre-transplant comorbidities, which may impact the success of allogeneic stem cell transplantation (AlloSCT) can be appreciated through 3 different scoring systems. The Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) allows to predict non-relapse mortality (NRM) and survival (Sorror, Blood 2005). Its prognostic value was further augmented by the addition of donor age (< vs ≥40 yo) (Comorbidity/Age index, C/AI, Sorror, JCO 2014) then of pre-transplant ferritin (< or >2500 µg/L) and albumin (3.5g/dL) serum levels as well as platelet count (< vs >100 109/L) (Augmented Comorbidity/Age index, AC/AI, Elsawy, BBMT 2019). The performance of these 3 scores has not been evaluated in haploASCT using post-transplant cyclophosphamide (PTCY), a procedure in constant expansion worldwide. Material and Methods: We studied retrospectively the impact on non-relapse mortality (NRM), overall (OS) and disease-free (DFS) survival of the 3 comorbidity scores on a cohort of 223 patients (pts) having received a haploSCT with PTCY. All pts had pre-transplant ferritin and albumin levels and platelet counts available. These parameters were evaluated at the time of the pre-transplant check-up or just before conditioning (median from transplant: 20 days, range: 4-49). Results: Pts were recruited in 4 French centers (Nantes n=127; Angers n=45; Besançon n=29, Brest n=22). They had received haploSCT between October 2013 and January 2020. There were 136 males and 87 females with a median age of 55 yo (16-71, >40 years n=172). The majority of pts had a myeloid disease (n=157) and received a reduced intensity regimen (n=161, myeloablative n=30; sequential n=32). Respectively, 132 and 91 pts had low/intermediate and high/very-high Disease-Risk Index (DRI). All pts received PTCY, cyclosporine and mycophenolate mofetyl as graft versus host disease (GVHD) prophylaxis. Donors had a median age of 40.8 years (19.4-71.7). Median HCT-CI, C/AI and AC/AI scores were 2 (0-8), 3 (0-9) and 3 (0-11), respectively. The HCT-CI score was 5 in 110, 83 and 30 pts, respectively, while the AC/AI score was With a median follow-up for alive patients of 35.6 months (6-77), 3-year OS, DFS and NRM were 47.8+3%, 46+3% and 29.4+6%, respectively. In univariate analysis, better 3-year OS and DFS were associated with lymphoid diseases (OS: 60.4+6% vs 42.3+4%, p=0.02; DFS: 56.2+6% vs 41.6+4%, p=0.04), low/intermediate DRI (OS: 59.1+4% vs 30.1+7%, p3.5g/dL 50.1+4%, p=0.03; 3.5g/dL 47.4+3%, p=0.05). OS and DFS were not impacted by ferritin levels, platelet count, recipient age, gender, nor any of the 3 comorbidity scores. A lower 3-year NRM was observed in younger pts ( In multivariate analysis, each comorbidity score was compared to DRI, donor and patient age, type of disease and pre-transplant albumin levels. DRI and donor age remained associated with OS and DFS. This was also the case for recipient age, except when considering a high C/AI index score. Finally, an older age of recipients and donors remained associated with higher NRM. Conclusion: HCT-CI, C/AI and AC/AI do not to predict survivals nor NRM in haploSCT with PTCY, suggesting that pre-transplant comorbidities should not be a contra-indication to this procedure. As donor age is the only factor predicting survivals and NRM in this series, while multiple donors are generally available in the haploSCT setting, the selection of a younger donor should be the rule whenever possible for all patients. Disclosures Hunault: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Diachi: Membership on an entity's Board of Directors or advisory committees; Jansen: Honoraria; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Deconinck:ImmunoGen: Consultancy, Research Funding; Stemline: Consultancy. Thepot:astellas: Honoraria; novartis: Honoraria; sanofi: Honoraria; celgene: Honoraria. Le Gouill:Loxo Oncology at Lilly: Consultancy; Roche Genentech, Janssen-Cilag and Abbvie, Celgene, Jazz pharmaceutical, Gilead-kite, Loxo, Daiichi-Sankyo and Servier: Honoraria. Chevallier:Incyte Corporation: Honoraria.

Introduction: The prognosis of older patients treated for acute myeloid leukemia (AML) relies on cytogenetic/molecular classifications as well as their ability to tolerate intensive induction therapy for which comorbidities have an important impact. A prognostic model has been elaborated to incorporate these two variables, cytogenetic/molecular risk and comorbidities evaluated by the Hematopoietic Cell Transplantation - Comorbidity Index (HCT-CI) (Sorror et al. 2017). The AML-composite model (AML-CM), which also incorporates hypoalbuminemia and high LDH levels at diagnosis, has been recently updated to incorporate the new European LeukemiaNet (ELN) 2017 classification (Sorror et al. 2019). In this study, we aimed to confirm the predictive impact of the revised AML-CM in an independent cohort and to explore which parameters were the most relevant for predicting early mortality and relapse. Patients and Methods: All patients (pts) older than 60 years diagnosed with AML who received intensive induction therapy in our department between 2004 and 2017 were included. Patients with acute promyelocytic leukemia were excluded. They received induction therapy with idarubicin 8 mg/m2 for 5 days and cytarabine 100 mg/m2 for 7 days with or without lomustine 200 mg/m2 on day 1. Patients in first complete remission (CR1) were to receive six consolidation courses with idarubicin 8 mg/m2 for one day and cytarabine 100 mg/m2 for 5 days and maintenance therapy with oral methotrexate and mercaptopurine. The HCT-CI and the revised AML-CM were calculated as previously described (Sorror et al. 2005; Sorror et al. 2019) using individual patient medical records. Early mortality was defined as death within one month after the start of induction therapy. The ELN 2017 classification, the HCT-CI, and the revised AML-CM were considered to determine which parameters - comorbidities or cytogenetic/molecular risk - were associated with each outcome. Results: Ninety-nine pts were included in the study with a median age of 66 years-old (range: 60 - 82). Twenty-seven pts (27%) had secondary AML (prior solid tumor requiring chemotherapy and/or radiation therapy in 11 pts and prior hematological malignancy in 16 patients). According to the ELN 2017 classification, 24 (24%) were favorable, 53 (54%) were intermediate, and 22 (22%) were adverse. The most frequent comorbidities included liver disease (30 pts, low/moderate, 5 pts, severe), previous cancer (22 pts), and arrythmia (22 pts). Thus, 13 (13%), 25 (25%), 44 (45%), and 17 (17%) pts had a revised AML-CM score of 1-4, 5-6, 7-9, and >10, respectively. 78 pts (79%) achieved CR1, with 10 early deaths (10%) due to toxicity (early mortality) and 11 induction failures (11%). Fifteen pts received allogeneic SCT. 54 (55%) relapsed, and 72 (73%) died with a median follow-up of 18 months (range: 0 - 167). Both the HCT-CI and the AML-CM were associated with increased early mortality (OR: 1.4, 95% CI: 1 - 1.8, p=0.03 for HCT-CI and OR: 1.3, 95% CI: 1-1.7, p=0.03 for AML-CM) whereas the ELN 2017 classification had no impact. The predictive value of the AML-CM for early mortality was not superior to the HCT-CI (area under the curve - AUC: 0.76, p=0.01, and 0.76, p=0.01, respectively). The risk of relapse was only associated with an unfavorable ELN 2017 classification (OR: 8.8, 95% CI: 1.1 - 70, p=0.04). It was the most predictive parameter for relapse, in comparison to the HCT-CI and the revised AML-CM, but this did not reach statistical significance (AUC: 0.62, p=0.08). The AML-CM clearly distinguishes 4 groups with different prognosis (Figure, p 10, respectively (OR: 1.4, 95% CI: 1.2 - 1.8, p Conclusion: The revised AML-CM is an effective tool for predicting overall survival in older pts with AML receiving intensive induction therapy. It is a better prognostic system compared to the HCT-CI and the ELN 2017 classification as it combines the evaluation of comorbidities, which predicts early mortality, and cytogenetic/molecular risk, which predicts relapse. Figure Disclosures Orvain: Novartis: Honoraria; Incyte: Honoraria.