Abstract: Iron overload after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with oxidative stress and adverse outcomes. Although deferasirox reduces ferritin, its effect on survival remains incompletely characterized. We conducted a prospective observational study across 7 French centers, enrolling 41 patients with acute myeloid leukemia or myelodysplastic syndromes who initiated deferasirox 6 months after allo-HSCT. Eligibility required complete remission, iron overload (ferritin level >1000 μg/L), and preserved organ function. Outcomes were compared with propensity score–matched controls (1:2) from the SFGM-TC registry. End points were overall survival (OS), progression-free survival (PFS), transplant-related mortality (TRM), relapse, and safety. Analyses employed exact matching, inverse probability of treatment weighting (IPTW), and multivariable Cox models. Ferritin level decreased from 1700 μg/L to <1000 μg/L by 18 months. Across analytic methods, deferasirox was associated with a reduced hazard of progression or death (PFS: hazard ratio [HR], 0.41-0.44) and a reduced hazard of mortality (OS: HR, 0.28-0.43). TRM was significantly reduced in propensity score matching and Cox models (HR, 0.21), whereas the IPTW analysis yielded a comparable point estimate (HR, 0.24) that did not reach the significance threshold (P = .063). The probability of relapse (estimated via cumulative incidence of relapse) did not differ significantly. Adverse events were predominantly renal and manageable. Initiating deferasirox 6 months after allo-HSCT was associated with sustained ferritin reduction, a reduced hazard of progression or death (PFS), lower TRM, and a favorable although nonsignificant hazard of mortality (OS), with acceptable safety. These findings support deferasirox as a feasible posttransplant intervention, warranting confirmation in randomized trials.

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative option for many hematologic malignancies, yet transplant-related toxicity and relapse continue to constrain long-term benefit. Prognostic tools based on clinical variables alone show limited transportability across centers. We hypothesized that integrating immunogenetic architecture, captured by HLA Evolutionary Divergence (HED), into machine-learning survival models would improve prediction of graft-versus-host disease–free/relapse-free survival (GRFS). We developed SMART, a time-dependent framework that estimates dynamic GRFS probabilities after allo-HCT. We analyzed 16,028 adults transplanted between 2010–2022. Model development used the French SFGM-TC registry (N = 13,979), split into training (N = 9,840) and held-out test (N = 4,139) sets. Random survival forests, XGBoost-Cox, and elastic-net Cox models were trained using 9 clinical predictors, with or without 10 recipient/donor locus-specific HED features (19 predictors total) and externally evaluated in 616 patients from five U.S. centers with complete data. Across algorithms, discrimination for this composite endpoint was modest (c-index < 0.60), but the addition of HED consistently improved performance and enabled reproducible stratification into low-, intermediate-, and high-risk groups based on the cumulative hazard score. Model-based simulations uncovered a non-linear (U-shaped) association between total HED and GRFS, with optimal outcomes at intermediate HED levels (~ 75th percentile). In haploidentical transplantation (N = 2,056), outcomes were maximized when donor and recipient HED were concordant (“match like with like”). In 9/10 mismatched unrelated donors (N = 1,326), HLA-B mismatches showed the greatest HED sensitivity. Integrating immunogenetics with clinical data improves GRFS risk modeling and supports HED as an actionable feature for donor selection and pre-transplant risk stratification. SMART is available for research use.

Allogeneic stem-cell transplantation (allo-SCT) is met with increased toxicity and relapse in elderly patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The nonmyeloablative conditioning (NMAC) regimen combining 2GyTBI, fludarabine, and cyclophosphamide (FluCyTBI) with post-transplant cyclophosphamide (PTCy) has been described as well adapted to AML/MDS patients aged ≥70yo in the haplo-identical setting. PTCy has then been implemented as basis for GVHD prophylaxis in allo-SCT with unrelated donors (UD). We here report our experience with a single FluCyTBI+PTCy platform for both haplo and UD allo-SCT in older AML or high-risk MDS patients. We retrospectively analyzed 203 patients transplanted at our center between 2015 and 2024. Median age at transplant was 69. Donors were haplo, mismatched UD, and matched UD in 64%, 18% and 18% of patients, respectively. Day+100 grade III-IV acute GVHD (aGVHD) and 3-y moderate/severe chronic GVHD (cGVHD) rates were 8% and 18%. Donor age ≥35yo was predictive of increased aGVHD III-IV and female-to-male sex-mismatch was associated with increased moderate/severe cGVHD. 3-y NRM rate was 15%. 3-y OS was 62%, with only monosomal karyotype predicting worse survival. FluCyTBI+PTCy is safe and produces promising outcomes in both haplo and UD settings. Beyond HLA-matching, non-HLA donor-related factors constitute critical determinants of patient outcome.

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative option for secondary acute myeloid leukemia (sAML). Post-transplant cyclophosphamide has improved graft-versus-host disease (GVHD) prophylaxis, enabling the broader use of alternative donors. For patients lacking a human leukocyte antigen (HLA)-matched donor, haploidentical donor (Haplo) or 9/10 HLA mismatched unrelated donor (MMUD) HSCTs are widely used, yet their relative effectiveness in sAML is uncertain. We retrospectively compared outcomes after Haplo versus MMUD HSCT in adults with sAML in first complete remission transplanted between 2010 and 2022. Among 711 patients, 602 received Haplo and 109 MMUD grafts. Patient and transplant characteristics differed between cohorts, including donor age, conditioning intensity, graft source, and transplant year. Neutrophil recovery was faster after MMUD transplantation, while platelet recovery was comparable. Rates of acute and chronic GVHD, relapse incidence, non-relapse mortality, overall survival, leukemia-free survival, and GVHD-free/relapse-free survival were similar. Reduced intensity conditioning lowered acute GVHD risk, while peripheral blood grafts increased chronic GVHD. Lower Karnofsky score, older age and adverse-risk cytogenetics were adverse prognostic factors. Haplo and MMUD transplantation demonstrated comparable efficacy and safety with post-transplant cyclophosphamide, supporting both approaches as viable alternatives in the absence of an HLA-matched donor.

CHRONOS is a multicenter, retrospective, cohort study involving acute graft-versus-host disease (aGvHD) adult patients with gastrointestinal (GI) symptoms, steroid- and ruxolitinib refractory, who initiated third-line therapy between 30 May 2019 and 30 September 2024. Primary endpoints were all-organ overall response rate (ORR) and GI-specific ORR (GI-ORR) around 28 days after treatment initiation. Secondary endpoints included duration of response, real-world progression-free survival (rwPFS) of underlying malignancy, and overall survival (OS). Fifty-nine patients from 16 sites in Europe were included. On Day 28, ORR was 36% (95% CI: 24-49%), GI-ORR was 37% (95% CI: 25-51%); 29% (95% CI: 11-49%) of responders lost response within 30 days, and 52% (95% CI: 29-72%) within 90 days. Median rwPFS and median OS were both 86 days (95% CI: 54-128 days). Median OS was higher in responders than in non-responders (186 versus 45 days). Over the 12-month follow-up period, 41 patients died, mainly due to aGvHD progression (n = 25), and infectious complications (n = 9). Within 3 months, Grade ≥ 2 infectious events occurred in 51% of patients; Grade 3-4 thrombocytopenia and neutropenia in 64% and 32%, respectively. These findings demonstrate limited effectiveness of third-line therapy in this cohort of steroid- and ruxolitinib-refractory aGvHD patients with GI symptoms.

The growing burden of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) among aging populations underscores the critical need for tailored treatment strategies for elderly patients. While allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only potentially curative option for eligible patients, its application in older adults is fraught with significant challenges. This review explores recent advancements in optimizing allo-HSCT for elderly patients with AML and MDS. Key considerations include assessing patient fitness, predicting transplant outcomes, refining conditioning regimens, and designing personalized treatment strategies. Optimizing the comprehensive management of elderly patients across the pre-transplant, transplant, and post-transplant phases is expected to broaden access to allo-HSCT and enhance its curative potential.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is an established treatment for peripheral T-cell lymphoma (PTCL), particularly for patients with relapsed/refractory (r/r) disease. We aimed to retrieve novel information on the role of histology, disease status prior to transplantation, and donor choice for patients with PTCL not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic lymphoma kinase (ALK)-negative ALCL. We compared imaging by computed tomography (CT) or positron emission tomography (PET) for defining disease status prior to allo-SCT. Eligible were adult patients with PTCL-NOS, AITL, and ALK-negative ALCL undergoing allo-SCT between 2010 and 2022 and reported to EBMT. 1958 patients underwent allo-SCT. Of patients with known number of prior lines of therapies (n = 1310), 301 (23

BACKGROUND:Autologous haematopoietic cell transplantation (auto-HCT) is the recommended treatment for chemosensitive relapsed Hodgkin lymphoma, while allogeneic haematopoietic cell transplantation (allo-HCT) is indicated for patients who had unsuccessful auto-HCT. The introduction of novel therapeutic agents, alongside advances in donor selection, conditioning regimens, and graft-versus-host disease prophylaxis, might improve post-transplantation outcomes, however supporting data remain limited. We aimed to evaluate changes in post-transplantation outcomes over the period 2010-22, and to identify predictors of these outcomes. METHODS:We conducted a retrospective, registry-based cohort study of patients aged 18 years or older with relapsed or refractory classical Hodgkin lymphoma undergoing first auto-HCT or first allo-HCT between Jan 1, 2010, and Dec 31, 2022, registered with the European Society for Blood and Marrow Transplantation (EBMT), with data from more than 600 transplantation centres, across 53 countries, reporting all HCTs and yearly follow-ups. Patients who received allo-HCT for relapse after auto-HCT were included but tandem transplantations were excluded. For allo-HCT, we included patients who received grafts from matched related donors, mismatched related donors, and unrelated donors. The primary endpoints were overall survival and progression-free survival, which were assessed with the Kaplan-Meier method at 2 years and 5 years after HCT. Multivariate analyses were performed using the Cox proportional-hazards regression model to identify predictive factors. FINDINGS:We identified 22 047 patients who received a first transplantation for relapsed or refractory Hodgkin lymphoma, after excluding 1324 patients with missing follow-up data and 1225 patients with nodular lymphocyte predominant Hodgkin lymphoma, 19 498 patients were retained: 15 648 received auto-HCT (6772 [43%] were female and 8839 [57%] were male, data were missing for 37 patients); median age at HCT was 35 years [IQR 27-47]; median follow-up was 2·4 years [IQR 2·3-2·5]), and 3850 received allo-HCT (1572 [41%] female and 2273 [59%] were male, data were missing for five patients; median age at HCT 32 years [IQR 26-42]; median follow-up was 3·9 years [IQR 3·8-4·1]). For auto-HCT, from years 2010-14 to years 2019-22, the 2-year progression-free survival increased from 63% (95% CI 62-65) to 73% (71-74) and overall survival increased from 85% (95% CI 84-86) to 93% (91-94). Partial response (hazard ratio [HR] 1·92 [95% CI 1·74-2·11]) or stable or progressive disease (2·45 [2·17-2·76]) at transplantation negatively affected progression-free survival. For allo-HCT, from years 2010-14 to years 2019-22, the 2-year progression-free survival, and overall survival, increased from 44% (95% CI 41-46) to 62% (58-66), and from 66% (63-68) to 72% (68-75), respectively. Partial response (HR 1·58 [95% CI 1·39-1·78]) or stable/progressive disease (2·28 [2·02-2·58]) at transplantation negatively affected progression-free survival. INTERPRETATION:To our knowledge, this is the largest study on HCT for Hodgkin lymphoma in recent years, and our findings that outcomes after auto-HCT and allo-HCT improved over time provide relevant information that could set the basis for prospective trials or additional studies. FUNDING:None.

We investigated whether machine learning (ML) could enhance exposure and survival prediction, refine target exposures and customise the initial dosage of high-dose (HD) busulfan in patients undergoing a conditioning regimen for bone marrow transplantation. Using retrospective data from 71 adult patients with HD busulfan, ML models were developed to predict drug clearance, area under the curve (AUC), optimal starting dose and one-year survival. Model’s performance was evaluated using the area under the curve (AUC)-ROC, the area under the curve (AUC)-PR, sensitivity, specificity, RMSE, and SHAP value interpretation. Random Forest models integrating albuminemia, GFR, bilirubin, cumulative AUC, and peak concentrations improved exposure prediction over pharmacokinetic modelling (AUC-ROC: 0.80 vs. 0.56). Patients with low albumin levels and Busulfan AUC above 66 mg/L·h had shorter survival times, whereas other could tolerate exposure levels of up to 90.5 mg/L·h. A busulfan clearance model was developed to estimate the AUC prior to the initial dose, and this could outperform standard mg/kg dosing. ML-guided dosing would have reduced the dose for patients overexposed with mg/kg dosing and conversely increased starting dose for those underexposed with standard dosing. Therefore, implementing such ML models to support PK-guided dosing could improve both target exposure and dosing with HD Busulfan.

Allogeneic hematopoietic cell transplantation (HSCT) remains the only curative treatment in patients with myelodysplastic syndrome (MDS). However, due to the transplant-related toxicity, the benefit of HSCT over other non-cellular therapy is restricted to patients at high risk of disease progression. We analyzed outcomes of MDS patients undergoing HSCT in the last 2 decades to determine whether outcomes have improved over time and identify which variables influence such outcomes. MDS patients recorded in the EBMT registry, transplanted from all allogeneic donors (unrelated cord blood donor (UCB), or an HLA-matched or mismatched donor) between 2000 and 2022, were included but those transformed to Acute Myeloid Leukemia before transplant were excluded. Overall survival (OS), relapse-free survival (RFS), relapse, non-relapse mortality (NRM) were analyzed in non-overlapping 5-year cohorts defined by year of HSCT (2000-2004, 2005-2009, 2010-2013, 2014-2017 and 2018-2022). The Kaplan-Meier estimator was used for OS, and RFS and the log-rank test was used to compare differences between groups. The crude cumulative incidence estimator and Gray's test were used for competing events. Multivariable analyses (MVA) were performed using Cox proportional hazards models, including interaction terms between baseline variables and calendar period of HSCT. Overall, 18,710 patients were included in the analysis. Median age at transplant increased from 49.7 years in the earliest period (2000-2004) to 61.5 years in the most recent analyzed period (2018-2022). The majority of patients were transplanted for MDS with excess blasts (MDS-EB) (62%) with a stable proportion over time. 4-year OS, RFS, NRM improved over time and were 44% (95% CI: 42-47), 39% (95% CI: 36-41), and 35% (95% CI: 32-37) during 2000-2004 and 53% (95% CI: 51-55), 47% (95% CI: 45-48) and 24% (95% CI: 23-25) in the most recent period, respectively. The 4-year cumulative incidence of relapse did not significantly change over time being 26% across all groups. In the MVA for OS, compared to the use of an HLA matched donor (MRD), the hazard ratios (HR) were 1.42 (95% CI's in all parentheses 1.30-1.54) for a mismatched related donor (MMRD), 1.05 (1.00-1.11) for matched unrelated donor (MUD), 1.30 (1.21-1.39) for mismatched unrelated donor (MMUD), and 1.69 (1.46-1.95) for UCB. Other variables influencing OS were older age at HSCT [HR: 1.18 per 10 years older (1.15-1.20)], male recipient sex [HR: 1.10 (1.04-1.15)], lower Karnofsky score [80 versus (vs) ≥90:1.32 (1.26-1.39); <80, HR: 1.75 (1.51-2.03)], higher comorbidity score [intermediate vs low: 1.10 (1.03-1.18), high, HR: 1.26 (1.19-1.35)], positive CMV serology in the patient [HR: 1.19 (1.13-1.25)], male recipient / female donor, HR vs other donor- recipient sex combinations: 1.09 (1.02-1.14), HSCT whilst not in CR vs CR [HR: 1.15 (1.09-1.22)], and poorer cytogenetic risk [intermediate vs good or very good risk IPSS-R, HR: 1.17 (1.08-1.26), poor, HR: 1.36 (1.24-1.49), very poor, HR: 1.91 (1.78-2.05)]. These factors were similarly associated with RFS. All variables that impacted OS and -RFS also impacted NRM. While a reduced intensity regimen decreased the risk of NRM [HR compared to myeloablative: 0.84 (0.79-0.90), this was counterbalanced with an increased risk of relapse (HR 1.22 (1.13-1.30)]. Despite the inclusion of these factors in the survival models, a significant association between the latest HSCT time group and better OS, RFS, NRM and relapse was noticed. Moreover, the association of some of these variables and outcome after HSCT improved over time. For instance, the risk of poorer OS and RFS for MMRD, MMUD and UCB compared to MRD improved over time albeit remaining significant (RFS HR during 2000-2004 for MMRD was 1.61 (1.14-2.27), MMUD was 1.47 (1.20-1.81), UCB was 2.89 (1.66-5.03) and had changed to 1.19 (1.05-1.34), 1.16 (1.01-1.32) and 1.53 (1.07-2.17), respectively in the 2018-2022 period). Altogether, our data over two decades show that despite increasing recipient age, the OS, RFS and NRM after MDS HSCT have progressively improved. Risk factors associated with outcome are also evolving, possibly due to progress in averting complications and transplant platforms.

In higher risk myelofibrosis patients, the only treatment able to improve survival and cure the disease is allogeneic hematopoietic stem cell (HSCT). However, not all potential candidates have a donor and it has been reported that transplantation from an HLA-mismatched donor gives disappointing results as compared to transplantation from an HLA matched donor. In this phase 2 trial (registered at clinicaltrial.com as NCT04728490), transplantation from an haplo-identical donor was proposed in patients without an HLA matched donor using fludarabine 30mg/m2/day (D) for 5 days – treosulfan 10g/m2/D for 3 days– thiotepa 5 mg/kg for one day– post-translant cyclophosphamide 50 mg/kg ion day +3 and day +5 (PTCY) -ciclosporine and mycophenolate mofetil plateform. The trial was sponsored by Hôpital Saint-Louis, APHP, Paris, France, with the financial support of MEDAC pharmaceutical and the scientific support and network of the French Society of Cellular Therapy (SFGM-TC). We conducted a single-arm phase 2 clinical trial to demonstrate that using an haplo-identical related donor will increase the relapse and rejection-free survival post-HSCT as compared to an historical cohort of patients received 9/10 HLA matched unrelated donor. Our hypothesis was that 1-year relapse and rejection-free survival could reach 55% instead of 30%. Using a 2-sided, one-sample log-rank test, with 90% statistical power and a 5% significance level, 28 patients had to be included. Secondary objectives were incidence of acute and chronic GVHD, hematological recovery, relapse, non-relapse mortality, severe infections and overall survival. Inclusion criteria were age 18-70 years, myelofibrosis, and at least two of the following characteristics: constitutional symptoms, hemoglobin level < 10g/dl, thrombocytopenia < 100G/L, peripheral blast > 1%, white blood cell (WBC) count > 25 G/L, poor cytogenetics (+8; -7/7q-;i(17q);-5;5q-;12p-;inv(3);11q23, and ECOG < 3. Follow-up was scheduled for 12 months and amended later to 24 months after transplantation. Results presented here are at one year endpoint. We included 29 patients in 15 French centres, one of whom did not receive the transplantation due to a fatal haemorrhage. Further analyses were based on the 28 transplanted patients; all patients are followed > 12 months, 3 patients are still followed-up on July 2025 to reach the 24th month. Median age at inclusion was 65 years (IQR: 58-67), 19 (68%) were men, 11 (39%) had general symptoms, 10 (36%) were transfusion dependant, 21 (75%) had hemoglobin level < 10 g/dl, 13 (46%) had platelet count < 100 G/L, 13 (46%) had peripheral blast >1%, 7 (25%) had WBC count >25 G/L, and 3/16 had a complex cytogenetic. 15 patients had grade 2 fibrosis, 12 grade 3 (and one unknown). Hematopoietic stem Cell Transplantation-Comorbidity Index was 0-1 in 20 (71%) patients and 2 or more in 8 (29%) patients. Among the 25 patients with NGS tested, 15(62%), 5 (21%) and one (4%) had JAK2V617F, CALR, and MPL mutation, respectively. Other genes frequently altered were ASXL1 (71%), TET2 (29%), EZH2 (25%) and RUNX1 (21%). Eighteen patients had primary myelofibrosis, 10 had secondary myelofibrosis. All the 28 patients received peripheral blood stem cells from their donor and cells were cryopreserved in 10 (36%) in the context of COVID-19 pandemia. One-year relapse and rejection-free survival was 64.3% (95%CI: 48.8-84.7), significantly above the historical rate of 35% in transplantation from a 9/10 unrelated donor. Cumulative incidence of grade 2-4 and grade 3-4 acute GVHD were 64.3% (95%CI: 43-79.4) and 25% (95%CI:10.8-42.2); 11 patients developed chronic GVHD, with 1-year cumulative incidence estimated at 39.3% (95%CI, 21.1-57.1). Cumulative incidence of neutrophils recovery on day 60 was 85.7% (95%CI: 63.9-94.8), and that of platelet recovery was 67.9% (46.4-82.2). One patient relapsed after HSCT, and 10 patients died due to viral pneumonia (SARS-COV-2, n=1 or influenza, n=1), multi-organ failure without documented infection (n=2), graft rejection/non engraftment (n=2), and acute GVHD (n=4). One-year overall survival was 67.9% (95%CI: 52.6 – 87.6). One-year non-relapse mortality (NRM) was 32.1% (95%CI: 15.8 – 49.7). In conclusion, the primary endpoint of one-year relapse and rejection -free survival was achieved. However, the NRM is the first cause of failure, mainly due to acute GVHD, MOF and infections justifying further investigations to reduce early toxicity.

IntroductionAcute myeloid leukemia (AML) is a rare haematological cancer with poor 5-years overall survival (OS) and high relapse rate. Leukemic cells are sensitive to Natural Killer (NK) cell mediated killing. However, NK cells are highly impaired in AML, which promote AML immune escape from NK cell immune surveillance. We made the first report of CD56neg CD16+ NK cells expansion in AML. This unconventional subset has been reported to expand in some chronic viral infections. Although it is unclear whether CD56neg NK cells expansion mechanism is common across diseases, it seems more relevant than ever to further investigate this subset, representing a potential therapeutic target.MethodsWe used PBMCs from AML patients and HV to perform mass cytometry, spectral flow cytometry, bulk RNA-seq and in vitro assays in order to better characterize CD56neg CD16+ NK cells that expand in AML.ResultsWe confirmed that CD56neg CD16+ NK cells represent a unique NK cell subset coexpressing Eomes and T-bet. CD56neg CD16+ NK cells could recover CD56 expression in vitro where they displayed unaltered NK cell functions. We previously demonstrated that CD56neg CD16+ NK cells expansion at diagnosis was associated with adverse clinical outcome in AML. Here, we validated our findings in a validation cohort of N=38 AML patients. AML patients with CD56neg CD16+ NK cells expansion at diagnosis had decreased overall survival (HR[CI95]=5.5[1.2-24.5], p=0.0251) and relapse-free survival (HR[CI95]=13.1[1.9-87.5], p=0.0079) compared to AML patients without expansion after 36 months follow-up. RNA-seq unveiled that CD56neg CD16+ NK cells were mature circulating NK cells with functional capacities. Upon expansion, CD56neg CD16+ NK cells from AML patients showed altered proteomic phenotype, with increased frequency of terminally mature CD56neg CD16+ NK cells expressing TIGIT along with decreased frequency of Siglec-7+ CD56neg CD16+ NK cells.DiscussionTaken together, our results suggest that we could harness CD56neg CD16+ NK cells cytotoxic potential in vitro to restore NK cell anti-tumor response in AML patients with CD56neg CD16+ NK cells expansion and improve patients’ prognosis. To conclude, CD56neg CD16+ NK cells represent a relevant target for future NK-cell-based immunotherapies in AML.

Background There are very scarce data regarding the outcome of elderly patients with acute lymphoblastic leukemia (ALL) who received allogeneic hematopoietic stem cell transplantation (alloHSCT) as consolidation therapy in 1rst or higher complete remission (CR). Most studies evaluating the benefit of alloHSCT in ALL include both young and elderly populations. Thus, the optimal conditioning regimen still need to be determined in a frail population represented by patients over 60 years old. In addition, total body irradiation (TBI) dose is of first importance, as prior reports demonstrated its potential higher anti-leukemic effect. We here present the outcome of ALL patients older than 59 years from the Société Francophone de Greffe de Moelle et Thérapie Cellulaire (SFGM-TC) registry. Method This is a retrospective study. The primary outcome was overall survival (OS). Secondary outcomes were progression free survival (PFS), non-relapse mortality (NRM), relapse incidence (RI), acute Graft-versus-host disease (aGvHD) grade II-IV, chronic GvHD, neutrophil engraftment and GvHD-free relapse-free survival (GRFS). Competing risks analyses were performed to analyze NRM with competing event relapse, and aGvHD grade II-IV, chronic GvHD and neutrophil engraftment with competing events relapse and death. Univariable analyses were performed using the log-rang test for OS and PFS, while Gray's test was used for cumulative incidence (CI). Multivariable analyses were performed using the Cox proportional hazards regression model including age, ALL subtype, time from diagnosis to alloHSCT, disease status at alloHSCT, donor to patient CMV status, donor to patient sex, ATG use, myeloablative conditioning (MAC), TBI use. Results A total of 316 patients ≥ 60 years old transplanted for ALL from 2012 to 2022 in 36 participating centers were included in this study. Patient's characteristics are described in Table 1. With a median follow up of 34.5 months (IQR 29.5-38.8), 3-year OS was 46% (95% CI 40-53%) (Figure 1A) with only the disease status at transplant impacting negatively OS, 53% (95% CI 46-60%) in CR1, 32% (95% CI 21-49%) in CR2, 29% (95% CI 13-63%) in advanced disease, p=0.002 and the ALL subtype, 59% (95% CI 51-68%) in Ph+ ALL, 40% (95% CI 29-54%) in Ph- ALL, 34% (95% CI 20-55%) in T-ALL, 20% (95% CI 9-42%) in other/NA, p<0.001. 3-year PFS was 41% (95% CI 35-48%) (Figure 1B) with the disease status at transplant impacting negatively, 49% (95% CI 42-57%) in CR1, 26% (95% CI 16-42%) in CR2, 22% (95% CI 9-58%) in advanced disease, p<0.001, the ALL subtype, 51% (95% CI 42-61%) in Ph+ ALL, 41% (95% CI 31-54%) in Ph- ALL, 21% (95% CI 10-41%) in T-ALL, 21% (95% CI11-43%) in other/NA, p<0.001, year of HSCT worse < 2018, p=0.007, CMV -/- worse, p=0.033, absence of TBI worse, p=0.018. 3-year NRM was 23% (95% CI 18-28%) (Figure 1C) and none of the factors impacted it. 3-year RI was 36% (95% CI 31-42%) (Figure 1D) with the disease status at transplant impacting negatively, 29% (95% CI 23-36%) in CR1, 50% (95% CI 35-63%) in CR2, 56% (95% CI 26-77%) in advanced disease, p=0.0042, the ALL subtype, 26% (95% CI 19-34%) in Ph+ ALL, 43% (95% CI 31-54%) in Ph- ALL, 57% (95% CI 38-73%) in T-ALL, 42% (95% CI 25-59%) in other/NA, p=0.0064, year of HSCT worse < 2018, p=0.0216, CMV -/- worse, p<0.001, absence of TBI worse, p=0.0069, MRD worse, p=0.0111. 3-year GRFS was 30% (95% CI 25-37%) with the disease status at transplant impacting negatively, 35% (95% CI 28-43%) in CR1, 22% (95% CI 13-37%) in CR2, 23% (95% CI 9-59%) in advanced disease, p=0.029, the ALL subtype, 37% (95% CI 30-47%) in Ph+ ALL, 33% (95% CI 23-46%) in Ph- ALL, 15% (95% CI 7-32%) in T-ALL, 17% (95% CI 8-38%) in other/NA, p=0.0029, year of HSCT worse < 2018, p<0.001. CI of aGVHD grade II-IV was 33% (95% CI 28-38%), grade III-IV 11% (95% CI 8-15%), cGVHD 35% (95% CI30-41%), extensive cGVHD 21% (95% CI 16-26%).Multivariable analyses confirmed a worse OS and PFS for advanced disease, with a HR of 1.79 (95% CI 1.22-2.64), p=0.00322 and ALL subtype with a HR for other than Ph+ ALL of 1.99 (95%CI 1.42-2.79). Conclusion: This study suggests that alloHSCT is a reasonable option for elderly ALL patients without any impact of age but advanced disease and ALL subtype other than Ph+ ALL negatively influenced the outcome.