BACKGROUND:Although posttransplant cyclophosphamide (PT-Cy) is currently widely used to prevent graft-vs-host disease after allogeneic hematopoietic stem cell transplantation (alloHSCT), concerns remain regarding its cardiotoxicity. The aim in this study was to assess the association between early cardiotoxicity occurring within the first 100 days posttransplant and PT-Cy. METHODS:We conducted a monocentric retrospective observational study including all consecutive patients who underwent alloHSCT at Saint Louis University Hospital between July 2011 and July 2023. The primary endpoint was a composite of early cardiotoxicity, including cardiovascular death, heart failure (HF), myocarditis, pericardial disease, cardiac arrhythmias, and acute arterial events. Propensity-score matching was performed to balance characteristics between patients who received posttransplant PT-Cy and those who did not. Predictors of early cardiotoxicity were analyzed using Fine and Gray subdistribution hazard models. RESULTS:Among 1381 patients, 143 (10%) experienced early cardiotoxicity within 100 days posttransplant. The most frequent events were HF (53%), cardiac arrhythmias (20%), and pericardial disease (19%). Age (subdistribution hazard ratio [sHR] 1.01, 95% confidence interval [CI] 1.00-1.03, P = 0.028), prior HF (sHR 2.02, 95% CI 1.04-3.93, P = 0.037), prior cancer therapy-related cardiac dysfunction (sHR 4.24, 95% CI 2.05-8.78, P < 0.001), hypertension (sHR 1.54, 95% CI 1.00-2.36, P = 0.047), and PT-Cy (sHR 1.62, 95% CI 1.07-2.44, P = 0.022) were independently associated with early cardiotoxicity. After 1:1 propensity-score matching, the administration of PT-Cy remained associated with cardiotoxicity (HR 2.00, 95% CI 1.05-3.80, P = 0.035). CONCLUSIONS:The administration of PT-Cy was independently associated with an increased risk of early cardiotoxicity, particularly HF. These results underscore the need for early cardiovascular risk assessment and tailored surveillance, particularly in patients receiving PT-Cy.

We compared the presence of additional chromosomal abnormalities (ACAs, n = 345) with a referent group with no ACAs (n = 169) (noACAs) in patients with Ph+ ALL receiving TKI before transplantation. The groups did not differ significantly in age, gender, or interval from diagnosis to transplantation. More patients with ACAs received PB grafts (86.4% vs. 78.1%, p = 0.03), while more patients in the noACAs group received myeloablative conditioning (87% vs. 75.9%, p = 0.003). Day 30 ANC (≥109/L) was 97.9% vs. 98.2%, and day 60 platelet count (≥20 × 109/L) was 93.9% vs. 95.5%. Day 100 acute GVHD grades II-IV was 26.4% vs. 31%, and of grades III-IV was 8.6% vs. 9.7%. 4-year chronic GVHD was 40.5% vs. 39.9%, and the proportion of extensive chronic GVHD was 19.3% vs. 20.1%. 4-year NRM was 13.1% vs. 13.5%, and 4-year RI was 19.2% vs. 21.1%; 4-year LFS and OS were 67.7% vs. 65.4% and 76.3% vs. 78.5%. 4-year GRFS was 48.5% vs. 45%, respectively. In multivariable analysis, having ACAs and the number of ACAs did not significantly affect transplant outcomes. Administration of a TKI upfront, followed by transplantation, may overcome the poor prognostic influence of ACAs in Ph+ ALL.

Introduction La drépanocytose affecte 30 000 personnes en France. Environ 700 patients ont bénéficié d’une allogreffe de cellules souches hématopoïétiques entre 1988 et 2022, principalement des enfants, mais actuellement, la procédure est de plus en plus souvent proposée à l’âge adulte. Les particularités médicales et psychologiques des patients nécessitent une prise en charge spécifique. Méthodes Nous nous sommes appuyées sur la revue de la littérature et l’expérience des équipes, conformément à la méthodologie habituelle recommandée dans les ateliers d’harmonisation de la SFGM-TC. Nous nous sommes focalisées sur l’évaluation pré-greffe, la préparation transfusionnelle, la préservation de la fertilité, le suivi médical post-greffe, le suivi psychologique et la prise en charge de la douleur. Résultats La greffe pour drépanocytose nécessite une évaluation complète des atteintes d’organe et de la faisabilité transfusionnelle en pré et post-greffe, impliquant une étroite collaboration interdisciplinaire. Les techniques de préservation de la fertilité doivent être adaptées au type de conditionnement et à l’âge du patient. La persistance en post-greffe de douleurs mimant les crises vaso-occlusives, malgré la normalisation des paramètres biologiques, est un phénomène actuellement bien documenté, dont la prise en charge est complexe mais nécessaire, avec une sensibilisation des équipes à ce phénomène. La période post-greffe et l’expérience de la guérison somatique sont souvent marquées par une perte de repères et un mal-être psychique nécessitant une prise en charge spécifique personnalisée. Conclusion Une collaboration interdisciplinaire, une préparation méticuleuse et un suivi à long terme sont indispensables pour améliorer les résultats des greffes chez les patients drépanocytaires ainsi que leur bien-être global. Une meilleure sensibilisation des équipes et l’implication des patients experts sont également recommandées.

Letermovir (LMV), a CMV-specific terminase inhibitor, is recommended for cytomegalovirus (CMV) prophylaxis in CMV-seropositive allogeneic hematopoietic stem cell transplant (alloHSCT) recipients. The association between low-level CMV DNAemia during prophylaxis and the emergence of mutations in CMV terminase complex genes remains unclear. We retrospectively analyzed 127 alloHSCT recipients at Saint-Louis Hospital, Paris, receiving LMV prophylaxis (108 primary, 24 secondary, and 5 both). Weekly CMV DNAemia monitoring was performed, and samples with viral loads ≥ 3 log IU/mL underwent whole-genome next-generation sequencing to detect mutations in terminase complex genes. During LMV prophylaxis, CMV DNAemia was detected in 31.5% of primary and 62.5% of secondary prophylaxis patients; however, viral loads ≥ 3 log IU/mL remained low in both groups (8.3%). The frequency of polymorphisms in terminase complex genes increased 2.5-fold during prophylaxis compared with pre-prophylaxis, and then decreased 3.0-fold after prophylaxis withdrawal. Confirmed LMV resistance was found in two patients, representing 1.6% of all patients and 18.2% of those with CMV DNAemia ≥ 3 log IU/mL. Two additional patients harbored mutations at resistance-associated positions in UL56 and UL89, totaling 36% of patients with viral loads ≥ 3 log IU/mL displaying mutations at known resistance sites. Clinically significant CMV infections were successfully managed with preemptive therapies. This study confirms the efficacy of LMV prophylaxis and demonstrates that LMV exerts selective pressure on the terminase complex, increasing the risk of resistance when CMV DNA levels exceed 3 log IU/mL, underscoring the importance of timely consideration of alternative antiviral therapies when CMV replication persists.

INTRODUCTION:Sickle cell disease affects approximately 30,000 people in France. Between 1988 and 2022, 700 patients underwent allogeneic hematopoietic stem cell transplantation (HSCT), mainly children, but the procedure is increasingly offered to adults. The medical and psychological complexities of transplantation in this population require specific attention to optimize care. METHODS:Our work was based on a literature review and team experience, following the standard methodology of the SFGM-TC. Our focus was on pre-transplant evaluation, transfusion preparation, fertility preservation, post-transplant medical follow-up, psychological support, and pain management. RESULTS:Transplantation for sickle cell disease requires comprehensive assessment of organ damage, transfusion preparation, and close interdisciplinary collaboration. Fertility is a major concern, with tailored protocols based on the patient's sex and age. Post-transplant pain, often complex, necessitates multidisciplinary follow-up and team awareness. Psychologically, the post-transplant transition is marked by a loss of bearings, requiring personalized psychological support. CONCLUSION:Interdisciplinary collaboration, meticulous preparation, and long-term follow-up are essential to improving transplant outcomes in sickle cell patients. Enhanced team awareness and the involvement of expert patients are also recommended.

ABSTRACT:The Group for Research in Adult Acute Lymphoblastic Leukemia (GRAALL)-2014 trial evaluated an intensive, age-adapted protocol for adults aged 18 to 59 years with Philadelphia chromosome negative acute lymphoblastic leukemia. The trial was motivated by findings from the previous GRAALL-2005 study, which reported excessive toxicity from pediatric-inspired therapy in older patients and no added benefit from allogeneic hematopoietic stem cell transplantation (allo-HSCT) among those with an early favorable response to treatment. Thus, the GRAALL-2014 protocol aimed to reduce treatment-related toxicity in patients aged ≥45 years and to limit allo-HSCT to patients with poor measurable residual disease (MRD) responses. A total of 743 patients were included, and outcomes were compared with those of GRAALL-2005 trial. The GRAALL-2014 study demonstrated reduced early mortality and higher complete remission rates in patients aged ≥45 years. MRD-guided transplantation decisions reduced allo-HSCT indications by ∼50%. Although older patients experienced a higher cumulative incidence of relapse, no significant difference in disease-free survival (DFS) was observed compared with historical cohorts across age subgroups. The overall 4-year DFS was 57.1% (95% confidence interval [CI], 53.4-61.1). Notably, 4-year overall survival improved significantly, from 65.5% (95% CI, 61.7-69.8) to 71.7% (95% CI, 67.7-76.0) in younger patients (P = .031) and from 49.6% (95% CI, 43.5-56.5) to 59.5% (95% CI, 53.5-66.3) in older patients (P = .011). These findings highlight the value of individualized treatment strategies that balance efficacy and safety. Future studies should investigate the integration of immunotherapy to further reduce treatment intensity and improve outcomes. This trial was registered at www.clinicaltrials.gov as #NCT02617004 and #NCT02619630.

Management of cerebral vasculopathy in sickle cell anemia (SCA) includes standard-care, that is, chronic transfusion (CT) or hydroxyurea, and hematopoietic cell transplantation (HCT). DREPAGREFFE-1 (December 2010/June 2013), a French multicenter trial, was the first prospective trial comparing standard-care to match sibling donor (MSD)-HCT in 67 (35F/32M) SCA children (5-15 year) on CT for abnormal time-averaged mean maximum velocities (TAMMV ≥ 200 cm/s). Seven had a stroke history. We reported that MSD-HCT reduced the highest TAMMVs at 1- and 3-year (p < 0.001) and improved quality of life (QoL) for physical and school functioning. In stroke-free patients, the 3-year stenosis score was lower (p = 0.010). Nevertheless, no significant difference was observed for silent cerebral infarcts (SCI) and cognitive performance. This prompted us to initiate DREPAGREFFE-2 to reevaluate the outcomes at 10 years (September 2022/August 2024) with the same 67 SCA children. No death or stroke occurred in either arm. No rejection or chronic-GvHD arose in the MSD-HCT group (n = 32). In the standard-care group (n = 35), 16 were on hydroxyurea, and 16 on CT at Year 10, and 3 received haploidentical-HCT. After MSD-HCT, the QoL was better, even for social functioning, and the number of hospitalizations, hospitalized days (p < 0.001), and crises (p = 0.001) was lower than on standard-care. In stroke-free patients, stenosis (p = 0.027) and SCI scores (p = 0.041) decreased significantly more after MSD-HCT than on standard-care; working memory (p = 0.016) and processing speed (p = 0.011) improved significantly after MSD-HCT, but worsened on standard-care. These effects were not previously detected with shorter follow-up. This supports earlier consideration of HCT for SCA children with MSD to preserve neurologic function and QoL for a more productive future.

Abstract Hematopoietic stem cell transplantation (HSCT) remains the only curative option for sickle cell disease (SCD), but its use in adolescents and adults is limited by toxicity concerns. We evaluated the risk–benefit profile of HSCT in this population through a comparative analysis of transplant versus nontransplant strategies. HSCT was analyzed as a time‐dependent variable in consecutive adolescents and adults with an indication for transplantation who were referred for HSCT counseling. At the last follow‐up, patients had either undergone HSCT or not. HSCT procedures involved matched related donor (MRD) transplants after myeloablative or non‐myeloablative conditioning, and haploidentical transplants after reduced‐intensity conditioning. The primary endpoints were overall survival (OS) and composite event‐free survival (cEFS), calculated from the initial consultation. Events included death, grade III–IV acute or moderate‐to‐severe chronic graft‐versus‐host disease (GVHD), graft rejection, overt stroke, third hospitalized painful crises within two years, acute chest syndrome (ACS), delayed hemolytic transfusion reaction, or initiation of new SCD modifying therapy. Ninety‐four patients were included (median follow‐up: 2.9 years), of whom 58 underwent HSCT. The 2‐year OS was 98% with HSCT versus (vs.) 97% without HSCT (P = 0.55). cEFS was significantly higher post‐transplant (72% vs. 28%, P < 0.0001), with marked reduction in painful crises and ACS. Among patients who underwent transplantation, the 2‐year rejection‐free survival from the time of transplant was 91% for MRD and 82% for haploidentical HSCT (P = 0.40). HSCT substantially improves cEFS without excess short‐term mortality, supporting its broader use in adolescents and adults with SCD, particularly when an MRD is available.

AIMS:Patients undergoing allogeneic haematopoietic stem cell transplantation (alloHSCT) are at increased risk of cardiovascular complications; however, comprehensive data on these risks in large cohorts remain limited. This study aims to identify predictors of cardiovascular events in a large cohort of alloHSCT patients. METHODS AND RESULTS:We conducted a retrospective monocentric study including all consecutive patients aged 15 years and older with haematologic malignancies who underwent alloHSCT between 2011 and 2020. Data were extracted from electronic medical records, including demographic, clinical, and transplant-specific variables. The primary composite outcome was cardiotoxicity including cardiovascular death, heart failure (HF), rhythm/conduction disorders, acute arterial events, venous thromboembolism (VTE), and myopericarditis. Predictors of cardiotoxicity were analysed using Cox proportional hazards regression and Fine-and-Gray models. Among 1027 patients recruited (age 45 ± 16 years, 62% male), 30% experienced cardiotoxicity after a median (interquartile range, IQR) follow-up of 4 (1-7) years. The median (IQR) time to the first event was 8 months (3-17). In multivariable analysis, independent predictors for early events (≤100 days) were age, hypertension, history of HF, cancer therapy-related cardiac dysfunction (CTRCD), and high-dose administration of cyclophosphamide (≥100 mg/kg). For late events (>100 days), independent predictors were age, hypertension, history of VTE, atrial fibrillation/flutter, history of HF, CTRCD, previous liposomal anthracycline exposure, and high-risk haematopoietic cell transplantation-comorbidity index (HCT-CI) score category. CONCLUSION:Our study identifies independent predictors of early and late cardiotoxicity, including demographic data, cardiovascular risk factors, history of cardiovascular disease, and oncologic history. REGISTRATION:EBMT registry: CNIL 2093819.

Background: (Ph+) is the most common cytogenetic abnormality in adults with ALL. Additional chromosomal abnormalities (ACA) are found in about 60%-70% of patients (pts) with Ph+ ALL. Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment paradigm in Ph+ ALL. Allogeneic transplantation (HSCT) is still the standard of care in Ph+ ALL-eligible pts in CR1. Data are conflicting regarding the impact of ACA and complex karyotype (CK) on outcomes of Ph+ ALL pts undergoing HSCT while in CR1 in the TKI era. Methods:The study aimed to assess the impact of ACA and CK on HSCT outcomes of Ph+ ALL pts that received a TKI and underwent first HSCT while in CR1 between 2010-2022. Pts needed to have full karyotyping data, including Ph as an abnormality. Outcomes were LFS, OS, GVHD-free relapse-free survival (GRFS), RI, and NRM. The impact of ACA was evaluated by comparing the presence of ACA (1 ACA, 2-3 ACA, or ≥4 ACA) to the referent group with no ACA (noACA). Results: 514 Ph+ pts were included: with ACA (n=345); without ACA (n=169). Of the 345 pts with ACA, 109 had 1 ACA, 100 had 2-3 ACA, and 136 had > 4 ACA. 210 pts had at least one monosomy, most frequently monosomy 7 (n=63). 101 pts had at least one trisomy. Twelve pts had 11q23 translocations. IKZF1 mutations were observed in 8.7% and 7.7% of pts with and without ACA, respectively. The presence of ACA was associated with a higher rate of MRD-negativity pre HSCT (56.2% vs. 46.5%, p=0.04). Median follow-up was 4.2 years (95% CI, 3.9-4.7). Median year of transplant was 2018 IQR, 2015-2020), with no significant difference between the groups (p=0.27). Median age was 42.6 years (IQR, 31.7-53.5), and 54.5% were male. The groups (ACA vs. noACA) did not differ significantly in terms of age, gender, and interval from diagnosis to HSCT. In the ACA and noACA groups, donors were matched siblings in 32.5% vs. 28.4%, unrelated in 37.1% vs. 27.2%, or haploidentical in 28.7% vs. 40.2%, respectively. More pts with ACA received PB grafts compared to the noACA group (86.4% vs. 78.1%, p=0.03). Pt CMV seropositivity was more frequent in the ACA than in the noACA group (70.5% vs. 57.2%, p=0.009). The use of myeloablative conditioning was more frequent in noACA than in ACA pts (87% vs. 75.9%, p=0.003), with TBI-based being the most frequent conditioning in both groups (51.9% vs. 40.2%). Post-transplant cyclophosphamide was administered to 12.9% vs. 14.8%, respectively (p=0.55). Day 30 absolute neutrophil count (>109/L) was 97.9 % vs. 98.2 % and day 60 platelet count (>20x109/L) was 93.9 % vs. 95.5%, for the ACA and noACA groups, respectively. The incidence of day 100 acute (a) GVHD grades II-IV was 26.4% vs. 31% and of grades; III-IV was 8.6% vs. 9.7%, respectively. 4-year incidence of chronic (c) GVHD was 40.5 % vs. 39.9 % and of extensive cGVHD was 19.3% vs. 20.1 %. 4-year NRM was 13.1 % vs. 13. 5%, and 4-year RI was 19.2 % vs. 21.1 %, respectively. The 4-year LFS and overall survival rates were 67.7% vs. 65.4 % and 76.3% vs. 78.5%, respectively. 4-year GRFS was 48.5% vs. 45%, respectively. In multivariate analysis, having ACA and the number of ACAs did not affect transplant outcomes significantly. Compared to noACA, hazard ratios for LFS were 0.93, 0.90, and 1.06 for 1 ACA, 2-3 ACA, and ≥4 ACA, respectively. Year of HSCT and age were poor prognostic factors for NRM, LFS, and OS. Year of HSCT was also a poor prognostic factor for RI, GRFS, and total and extensive cGVHD. Greater than 6 months from diagnosis to HSCT was a negative prognostic factor for NRM, LFS, OS, GRFS, and aGVHD II-IV. MRD-positivity pre-HSCT was a poor prognostic factor for LFS, OS, and NRM. A mismatched related donor was associated with lower RI and higher NRM. An unrelated donor was associated with higher NRM and aGVHD II-IV, while reduced intensity conditioning was associated with a lower incidence of aGVHD II-IV. Female-to-male donor was associated with a higher incidence of total cGVHD. Conclusions: In this registry-based retrospective analysis of Ph+ ALL pts receiving a TKI and subsequent HSCT, no significant differences were observed in transplantation outcomes between pts with or without ACA, including those with additional CK. Notably, achieving MRD-negativity pre HSCT was significantly higher in pts with ACA. These data may indicate that the administration of a TKI upfront, followed by HSCT, may overcome the poor prognosis influence of the ACA, including CK in Ph+ ALL.

Context. The outcome of adolescents and young adults (AYA) aged 15 to 25 with cancer has improved, with five-year survival rates now exceeding 85%. However, disease progression remains the leading cause of death in this population. AYAs face unique challenges that require tailored oncologic, psychosocial, and supportive care approaches. Palliative care, aimed at improving the quality of life for patients with life-threatening illnesses, is crucial in this context. Although data remain limited in the field, some evidence suggests palliative care may enhance end-of-life (EOL) care in this population. This study aimed to describe EOL care practices in AYA with hematologic malignancies receiving palliative care. Patients and methods. We conducted a retrospective, single-center descriptive study including patients who (1) died between January 2020 and July 2025, (2) received care for hematologic diseases in the AYA unit at Saint Louis Hospital and (3) had a collegially validated palliative care decision documented in the medical record. Data was extracted from medical records. The primary objective was to assess EOL care using the HI-EOL (High Intensity-EOL) and the MI-EOL (most Invasive-EOL) scores as previously described. Secondary objectives included characterization of the patient population, description of EOL management, with a specific focus on transfusion practices. Results. A total of 38 patients were included. Most had acute leukemia (n=34, 90%), the remaining had lymphoma (n=4, 10%). Median age at diagnosis was 17 years (range: 10-26), and 20 years at death (15-30). Patients received a median of 3 lines of therapy (1-7). Four patients (10%) were refractory to first-line therapy. Twenty-four patients (63%) underwent hematopoietic stem cell transplantation (HSCT), 11 (29%) received CAR T-cell. Most patients (n=32, 84%) were refractory to the last treatment. Disease progression was the main reason for transitioning to palliative care (n=33, 87%), which also represented the leading cause of death (n= 32, 84%). Other conditions indicating palliative care transition were complications of allo-HST (n=3, 8%), infectious complication (n=1) and deterioration of general condition (n=1). The median time from palliative care decision to death was 26.5 days (2-180) and from the last chemotherapy to death was 37.5 days (1-278). Ten patients (26%) received chemotherapy after the documented palliative care decision. A majority of patients were seen by the mobile palliative care team (n=24, 63%) with a median time of 7 days (0-51) after the palliative care decision. Sixteen patients (42%) met at least one HI-EOL criterion. All received chemotherapy within the 14 days before death, which was the only criteria of the HI-EOL score in our cohort. Two patients underwent cardiopulmonary resuscitation, thus meeting one MI-EOL criterion. Among the patients evaluated by the mobile palliative team, 16 out of 24 (67%) had no HI-EOL criteria, compared to 6 out of 14 (43%) who were not (p=0.198). Twenty-seven patients (73%) received at least one transfusion of red blood cells (RBC) and 33 (89%) a transfusion of platelets during the last month of their life. Notably, 24 patients (65%) had a platelet transfusion and 12 (32%) a RBC transfusion during the final five days of life. Among the patients who expressed a preference for the place of death (n=19, 50%), 12 (63%) wished to die at home. However, only five patients (13.2%) died at home, while the majority (n=27, 71%) died in the AYA unit. Three patients died in their local hospital. 1 in a specialized palliative care unit and 1 in an intensive care unit.Discussion. This study highlights several challenges in EOL care of AYAs with hematologic malignancies. The late integration of palliative care, often within the final weeks of life, may reflect the aggressive nature of these diseases, and/or the clinical reluctance to transition from curative to palliative intent. While involvement of the mobile palliative care team appeared to be associated with lower EOL care intensity, the limited sample size precludes definitive conclusions. Importantly, barriers such as limited access to transfusion support outside the hospital and the lack of dedicated AYA palliative services hinder the ability to respect patient preferences for EOL care, particularly home death. Improving collaboration between hematologists and palliative care specialists is essential to optimize EOL care in this vulnerable population.

BACKGROUND:After allogeneic hematopoietic stem cell transplantation (alloHSCT), the HAS recommends transfusing red blood cells (RBCs) matched for Rh ("Rhesus") phenotypes, and the EFS recommends respecting both donor and recipient Rh phenotypes. We previously reported a 10.3% allo-immunization rate in 58 Rh-incompatible alloHSCT recipients transfused in the donor phenotype: none was directed against the mismatched donor Rh antigens. STUDY DESIGN AND METHODS:In this single-center retrospective study, we investigated the incidence of allo-immunization to RBC antigens during the first year after alloHSCT in 264 patients with partial donor/recipient Rh matching, and transfused from alloHSCT with RBCs expressing at least one donor Rh antigen absent from the recipient. RESULTS:Six patients had a positive RBC antibody screening test (allo-immunization rate: 2.3%). In five cases, the antibodies were unrelated to the transfusion strategy. One patient presented a temporary anti-C, possibly related to the transfusion strategy, occurring in a context of immune hemolytic anemia. DISCUSSION:Our findings indicate that the transfusion of RBC in the donor Rh phenotype is associated with a low rate of immunization to RBC antigens. These results question the current transfusion guidelines in alloHSCT recipients, aiming to limit the use of short-supply RBCs phenotypes.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been a cornerstone in the treatment of adult acute lymphoblastic leukemia (ALL). Its indications have evolved with the adoption of pediatric-inspired protocols, refined risk stratification based on minimal residual disease (MRD), the identification of high-risk genetic subtypes, and the emergence of novel immunotherapies. Agents such as blinatumomab and inotuzumab ozogamicin can induce deep remissions and increasingly challenge traditional transplant algorithms. Chimeric antigen receptor T cell (CAR T-cell) therapies further reshape post-relapse strategies, while advances in conditioning regimens and donor selection have broadened allo-HSCT applicability. Current evidence supports allo-HSCT in patients with high-risk features or persistent MRD, though its benefit is increasingly debated in MRD-negative responders. This review synthesizes evolving data on indications, timing, modalities, and outcomes of allo-HSCT in adult ALL and highlights the need for personalized, MRD and genomics-guided approaches to optimize cure while minimizing transplant-related risks in the immunotherapy era.

Conditioning regimen prior to hematopoietic stem cell transplantation have an impact on patient fertility through the use of gonadal irradiation and/or bifunctional alkylating agents. Their impact on fertility depends mainly on the dose used and, in women, on age at the time of treatment. All patients should benefit before treatment from a consultation informing them of the potential impact on fertility and of fertility preservation techniques. In the absence of contraindications, the major toxicity of myeloablative conditioning regimen justifies fertility preservation. There are few data concerning fertility after reduced-intensity conditioning. Despite lower theoretical gonadotoxicity, we also recommend fertility preservation, if possible before transplantation. The fertility preservation techniques used depend on the patient's age, pathology and conditioning. In the event of subsequent use of harvested gonadal tissue in the context of acute leukemia or aggressive lymphoma, it is advisable to assess the risk of reintroduction of tumor cells. Finally, it is recommended to assess gonadal function after transplant, especially after reduced conditioning. If there is persistent residual gonadal function, post-treatment fertility preservation should be discuss.