Myriam Labopin

There are very limited data on treosulfan (Treo)-based conditioning before allogeneic hematopoietic stem cell transplantation (alloHSCT) in acute lymphoblastic leukemia. We aimed to compare fludarabine with Treo (FluTreo) or total body irradiation (FluTBI) in this setting. The final matched-pair analysis included ALL patients transplanted in complete remission after FluTreo (n = 153) or FluTBI (n = 431). The median patient age was 56.5 and 54.1 years, respectively. The allograft was derived from an unrelated (54.2% in FluTreo and 52% FluTBI group), matched sibling (30.7% and 32.5%) or haploidentical donor (15% and 15.5%). The incidence of acute graft-versus-host disease (GVHD) grade II-IV was 26.6% in the FluTreo and 30% in the FluTBI group (p = 0.43). The 2-year incidence of chronic GVHD was 33.5% and 40.7%, respectively (p = 0.23). The 2-year incidence of relapse and non-relapse mortality was 28.1% and 25.6% in the FluTreo and 25.1% and 20.4%, respectively, in the FluTBI group (p = 0.15 and p = 0.38). Leukemia-free survival and overall survival was 46.2% and 55% in the FluTreo and 54.5% and 61.3%, respectively, in the FluTBI group (p = 0.1 and p = 0.22). GVHD-free and relapse-free survival was 33.7% and 40.8%, respectively, in FluTreo and FluTBI patients (p = 0.06). In conclusion, there were no significant differences in transplant outcomes between the studied groups.

The optimal conditioning intensity for allogeneic hematopoietic stem cell transplantation (allo-HCT) in elderly acute myeloid leukemia (AML) remains elusive. We retrospectively analyzed 2900 AML patients aged ≥65 in complete remission who underwent allo-HCT from 2004 to 2021. Conditioning was classified as reduced-intensity conditioning (RIC: fludarabine with busulfan, melphalan, or treosulfan) or non-myeloablative (NMA: fludarabine with total body irradiation). Primary endpoints were overall survival (OS) and leukemia-free survival (LFS); secondary endpoints included non-relapse mortality (NRM), acute and chronic graft-versus-host disease (GVHD), and GVHD/relapse-free survival (GRFS). With follow-up censored to account for differences between arms, OS, LFS, and NRM at 2 years were similar between RIC and NMA on multivariable analysis. Peripheral blood stem cells (PBSC) were independently associated with superior OS (HR 0.67, p = 0.002) and LFS (HR 0.71, p = 0.008) versus bone marrow grafts. GRFS was equivalent between conditioning intensities, although RIC was associated with higher acute GVHD and NMA with higher extensive chronic GVHD. In exploratory analysis, OS and LFS were similar across RIC regimens (Flu/Bu2 as reference: Flu/Mel OS HR 0.91, p = 0.53; Flu/Treo OS HR 0.89, p = 0.42). In older AML patients in remission, RIC and NMA yield comparable survival and NRM; PBSC grafts may be associated with superior outcomes although this warrants validation.

Acute myeloid leukemia (AML) includes genetically defined subsets. In allogeneic hematopoietic cell transplantation (allo-HCT), the frequency and prognosis of gene-gene interactions may differ from those of patients treated with chemotherapy alone. In this study, adult patients (N = 952) with AML allografted between 2015 and 2023, with available next generation sequencing (NGS) at diagnosis were included. Most frequent mutations were DNMT3A (24%), FLT3-ITD (21%), NPM1 (21%), RUNX1 (16%), NRAS (16%), TET2 (14%), and IDH2 (12%). Multiple correspondence analysis identified distinct groups of co-occurring mutations. Outcome analysis was performed on 646 AML patients allografted in first complete remission (CR1). Six non-overlapping groups were constructed: 1) TP53 mutation (N = 47); 2) NPM1 mutation (N = 129); 3) FLT3-ITD and/or DNMT3A mutation (N = 128); 4) SRSF2 and/or ASXL1 and/or RUNX1 mutation (SAR group) (N = 132); 5) IDH1 and/or IDH2 and/or TET2 mutation (N = 43); and 6) all ten genes unmutated (N = 167). In multivariable analysis, TP53 mutation, adverse karyotype, and age negatively affected leukemia-free survival (LFS) and overall survival (OS). OS was additionally negatively affected when the ten genes were unmutated. Notably, outcomes were excellent for SAR mutations (2-year LFS 76%, OS 84%), indicating allo-HCT in CR1 can overcome their adverse risk at diagnosis.

Primary refractory acute myeloid leukemia (prAML) is a poor prognosis disease, with allogeneic hematopoietic stem cell transplantation (allo-HSCT) being the only potentially curative option. We retrospectively evaluated outcomes in 1574 adult prAML patients who underwent allo-HSCT from matched sibling donors (MSD), 10/10 or 9/10 unrelated donors (UD), or haploidentical donors between 2015 and 2020. Median follow-up was 24, 30, 38, and 24 months for MSD, UD 10/10, UD 9/10, and haploidentical transplants, respectively. MSD recipients were younger (median age 53 vs. 58–59 years in other groups, p < 0.001), had better performance status, and proceeded to transplant more quickly (3.8 months vs. >4 months in other groups, p = 0.004). In multivariate analysis, haploidentical HSCT was associated with inferior leukemia-free survival (LFS) and overall survival (OS) compared to other donor types. Additional negative predictors included adverse cytogenetics and longer time from diagnosis to transplant. Conversely, reduced-intensity conditioning and good performance status of the patient were associated with improved LFS. Disease progression remained the leading cause of transplant failure, underscoring the urgent need for more effective early post-transplant strategies.

Few studies analyzed the impact of bone marrow (BM) or peripheral blood stem cells (PBSC) on outcomes after haploidentical transplantation using post-cyclophosphamide (Haplo-PTCY). We analyzed 8854 adults with malignant disorders, given a first Haplo-PTCY. BM cells was used in 2914 and PBSC in 5940 patients. Multivariate models were built adjusting for the statistical differences between the 2 groups. Median follow-up time for survivors in the BM and PBSC groups were 48 and 30 months, respectively. Neutrophil Engraftment was observed in 92.4% of BM and 93.7% of PBSC recipients (p = 0.01). In a multivariate analysis, use of PBSC compared to BM, was associated with higher incidence of acute (HR:1.53; p < 0.0001) and chronic GVHD (HR:1.34; p < 10-3), increased non-relapse mortality (HR:1.22; p = 0.002), similar risk of relapse (HR:1.02; p = 0.79), and decreased overall survival (OS)(HR:1.13; p = 0.008); progression-free survival (PFS)(HR:1.11; p = 0.024) and GVHD-Relapse free survival (GRFS) (HR:1.2; p < 10–3). In conclusion, use of BM cells is associated with better outcomes compared to PBSC after Haplo-PTCY. Future studies should investigate better GVHD prophylaxis in the PBSC-Haplo-PTCY setting and the association of measured T-cell or other subpopulations of lymphocyte content in the PBSC graft.

Acute myeloid leukemia (AML) includes genetically defined subsets. In allogeneic hematopoietic cell transplantation (allo-HCT) setting, the frequency and prognosis of gene-gene interactions may differ from those of patients treated with chemotherapy alone. In this study, adult patients (N = 952) with AML allografted between 2015–2023, with available next generation sequencing (NGS) at diagnosis were included. The most frequent mutations were DNMT3A (24%), FLT3- ITD (21%), NPM1 (21%), RUNX1 (16%), NRAS (16%), TET2 (14%) , and IDH2 (12%). Multiple correspondence analysis identified distinct groups of co-occurring mutations. Outcome analysis was performed on 646 AML patients allografted in first complete remission (CR1). Six non-overlapping groups were constructed according to found groups and well-known clinical impact of NPM1 and TP53 mutations: 1) TP53 mutation; 2) NPM1 mutation; 3) FLT3 -ITD and/or DNMT3A mutation; 4) SRSF2 and/or ASXL1 and/or RUNX1 mutation (SAR group); 5) IDH1 and/or IDH2 and/or TET2 mutation; and 6) all ten genes unmutated. In multivariable analysis, TP53 mutation, adverse karyotype, and age negatively affected leukemia-free survival (LFS) and overall survival (OS). OS was additionally negatively affected when the ten genes were unmutated. Notably, outcomes were excellent for SAR mutations (2-year LFS 76%, OS 84%), indicating allo-HCT in CR1 can overcome their adverse risk at diagnosis.