Didier Blaise

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a potentially curative treatment for high-risk acute myeloid leukemia (AML), and outcomes are strongly influenced by disease status at transplantation. In transplants using conventional graft-versus-host disease (GVHD) prophylaxis, outcomes also depend on the number of induction courses required to achieve first complete remission (CR1); however, this has not been evaluated in patients receiving post-transplant cyclophosphamide (PTCy). We retrospectively analyzed 677 adult AML patients transplanted in CR1 between 2012 and 2022 using PTCy-based GVHD prophylaxis. Outcomes were compared between patients achieving CR1 after one induction course ( n = 518) and those requiring two courses ( n = 159). Baseline characteristics, donor type, conditioning intensity, graft source, engraftment, and rates of acute and chronic GVHD were comparable between groups. Patients requiring two inductions had a higher 2-year cumulative incidence of relapse (27% vs. 19.3%; HR 1.75, p = 0.003). However, no significant differences were observed in 2-year overall survival (62.8% vs. 69%), leukemia-free survival (61.1% vs. 65%), GVHD-free/relapse-free survival (46.3% vs. 50.4%), or non-relapse mortality (11.9% vs. 15.7%). In AML patients receiving alloHSCT with PTCy, outcomes were largely similar regardless of whether CR1 was achieved after one or two-induction courses, with relapse incidence being higher in patients requiring 2 inductions.

Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is a potentially curative strategy for acute myeloid leukemia (AML), but the impact of HLA disparity in the era of posttransplant cyclophosphamide (PTCy) and reduced‐toxicity conditioning remains unclear. We performed an EBMT registry study including 275 adult AML patients in first complete remission undergoing first allo‐HSCT between 2012 and 2023 using a uniform platform of treosulfan‐based conditioning and PTCy. Among them, 206 received haploidentical grafts and 69 underwent 9/10 mismatched unrelated donor (MMUD) transplantation. Median follow‐up was 2.5 years. At 2 years, overall survival was 73.1% after haploidentical transplantation and 71.6% after MMUD transplantation ( p = 0.96). Leukemia‐free survival at 1 year was 66.3% and 65.2%, respectively ( p = 0.76). Relapse incidence (17.1% vs. 18.7%, p = 0.84) and nonrelapse mortality (16.6% vs. 16.1%, p = 0.86) were comparable between groups. Rates of Grade II–IV and Grade III–IV acute GVHD were similar, whereas chronic GVHD was higher after haploidentical transplantation (36.4% vs. 12.7%, p = 0.001), without differences in extensive forms. In multivariable analyses, donor type was not associated with overall survival, leukemia‐free survival, relapse incidence, or nonrelapse mortality. Increasing age adversely affected outcomes, while Karnofsky performance status ≥ 90 and reduced‐intensity conditioning were associated with improved survival. These findings suggest that, within a treosulfan–PTCy platform, major transplant outcomes are comparable between donor types, although haploidentical transplantation was associated with a higher incidence of chronic GVHD.

Allogeneic hematopoietic cell transplantation (allo-HCT) can cure acute leukemia, but relapse and non-relapse mortality restrict its success. Existing models focus on single prognostic areas and are not designed to predict leukemia-free survival (LFS), the outcome that best reflects allo-HCT’s curative intent. In this large retrospective cohort of allografted AL patients ( N = 24,317), we combined key pre-transplant patient, disease, and treatment factors into a practical holistic H-score to predict post–allo-HCT LFS. Component weights were derived from Cox-regression hazard ratios in a training cohort ( N = 19,029). The model was validated in a geographically split testing cohort (N = 4760), with outcomes assessed using Kaplan-Meier analysis and multivariate Cox models. In the overall cohort ( N = 24,317), 2-year overall survival and LFS were 64% and 56%, respectively. The H-score stratified patients into four risk groups, with 2-year LFS ranging from 66.2% in the low-risk group to 32.0% in the very high-risk group. The H-score was the strongest independent predictor of LFS ( p < 0.0001), outperforming individual indices and offering more refined risk stratification. The H-score was also an independent predictor of overall survival, relapse, and non-relapse mortality. While individual prediction is limited, the H-score aids patient counseling and provides a useful baseline for comparing new transplant treatments.

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.

We report a pooled analysis of real-world data of adult patients from two European registries of defibrotide use (DEFIFrance and EBMT Post-Authorization Safety Study [EBMT PASS]) to provide insights into the duration of defibrotide therapy to achieve resolution of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) symptoms by severity. Overall, 275 defibrotide-treated adults with VOD/SOS post-hematopoietic cell transplantation (HCT) were included (severe VOD/SOS, n = 215; nonsevere VOD/SOS, n = 60). Median time from the start of defibrotide treatment to VOD/SOS resolution was 18.5 and 16.5 days in patients with severe and nonsevere VOD/SOS, respectively. Among patients with VOD/SOS resolution, symptoms resolved after >21 days in 31% (n = 40/128) and 32% (n = 14/44) with severe and nonsevere VOD/SOS, respectively. In all patients with VOD/SOS resolution independent of severity (n = 174), the Kaplan-Meier-estimated survival at Day 100 post-HCT was 82% (95% confidence interval [CI]: 75%, 87%); this was 78% (95% CI: 70%, 84%) and 91% (95% CI: 78%, 96%) in patients with severe and nonsevere VOD/SOS, respectively. Serious treatment-emergent adverse events of interest occurred in 31% of patients with VOD/SOS resolution. This pooled analysis supports the utility of defibrotide treatment for VOD/SOS and highlights that treatment may often need to be continued beyond 21 days to achieve resolution.