Bone Marrow Transplantation最新文献

Thrombocytopenia following an allogeneic hematopoietic cell transplant (allo-HCT) is a potentially serious complication, and the efficacy of eltrombopag, a thrombopoietin receptor agonist, in this context is unclear due to inconsistent findings. Additionally, other post-allograft outcomes in eltrombopag treated patients such as transfusion independence, overall survival (OS), and non-relapse mortality have not been systematically reviewed. The aim of this systematic review/meta-analysis (SR/MA) is to evaluate the efficacy of eltrombopag in allo-HCT-induced thrombocytopenia by analyzing data from 16 eligible studies. Pooled rate of response for platelets counts achieving >30 × 10⁹/L and >50 × 10⁹/L were 72% and 56%, respectively. When evaluating the composite endpoint of platelets response and transfusion independence, pooled rates for >30 × 10⁹/L and >50 × 10⁹/L plus transfusion independence were 47% and 56%, respectively. Pooled OS, bleeding-related mortality and mortality from GVHD/infection were 68%, 6%, and 19%, respectively. These findings show that eltrombopag is an effective treatment of allo-HCT-induced thrombocytopenia. Optimal dose and duration of treatment remain to be determined in a large prospective study. Results of this SR/MA suggest a beneficial effect of eltrombopag for thrombocytopenia after allo-HCT. These results could represent the benchmark to be used for future prospective and comparative studies to better understand the benefit of this intervention.

Autologous hematopoietic cell transplantation (autoHCT) remains a therapeutic option for multiple myeloma (MM) at relapse. We retrospectively analyzed 650 patients who underwent delayed (n = 335) or salvage (n = 315) autoHCT at a single center from 2006-2023. Median age was 61.4 years; 22% were Black, and 21% had high-risk cytogenetics. Forty-nine percent received >3 prior therapy lines, and 33% were lenalidomide-refractory. Non-relapse mortality was 3% at day 100 and 4% at 1 year. Median progression-free survival (mPFS) was 17.5 months and median overall survival (mOS) 47.3 months, with no significant difference between delayed and salvage autoHCT (mPFS 16.3 vs. 19.1 months; mOS 43.2 vs. 50.8 months). In salvage autoHCT, transplant ≥24 months after first autoHCT was associated with superior outcomes (mPFS 20.6 vs. 8.4 months; mOS 54.6 vs. 12.5 months; p < 0.001). Multivariable analysis identified adverse factors for PFS and OS including high-risk cytogenetics, R-ISS stage II-III, lenalidomide- or carfilzomib-refractory disease, anti-CD38 antibody non-exposure, and >3 prior therapy lines; achieving CR post-transplant and receiving maintenance predicted improved outcomes. This largest single-center cohort demonstrates delayed or salvage autoHCT is feasible and effective, particularly for patients with prolonged first remissions, and provides a benchmark for emerging therapies in relapsed/refractory MM.

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.

We retrospectively analyzed data from the EBMT registry on patients with pretransplant comorbidities associated with cardiovascular risk. Patients who underwent first allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first complete remission between 2010 and 2022 from unrelated donors using post-transplant cyclophosphamide (ptCy) or anti-thymocyte globulin (ATG)-based graft-versus-host disease prophylaxis with a history of cardiac disease, arrhythmia, diabetes, obesity or cerebrovascular disease according to the HCT-specific comorbidity index were included. We performed a matched-pair analysis using a propensity score. After matching, 432 patients were included: 313 in the ATG group and 119 in the ptCy group. At 2 years, overall survival was 67.5% (95% CI 61-73.2) and 68.6% (95% CI 56.7-77.8); leukemia-free survival was 60.4% (95% CI 53.8-66.4) and 62.6% (95% CI 50.4-72.6); relapse incidence was 22.1% (95% CI 17-27.7) and 23.2% (95% CI 14.3-33.4); non-relapse mortality was 17.5% (95% CI 13.1-22.4) and 14.1% (95% CI 7.5-22.8), respectively. In conclusion, our study suggests that the use of ptCY for GVHD prophylaxis in patients with preexisting comorbidities associated with cardiovascular risk yields long-term outcomes comparable to those observed with ATG-based approaches.

The interplay between graft-versus-host disease (aGVHD) and the graft-versus-leukemia (GVL) effect in children with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (HSCT) remains complex. This EBMT Pediatric Diseases Working Party (PDWP) retrospective analysis of 2374 pediatric AML patients evaluated the impact of aGVHD on relapse incidence (RI), non-relapse mortality (NRM), overall survival (OS), and leukemia-free survival (LFS). Grade III/IV aGVHD significantly reduced RI (HR: 0.61, p = 0.01) while significantly increasing NRM (HR: 4.51, p < 0.001), offsetting any benefits in OS and LFS. Grade II aGVHD increased NRM (HR: 2.07, p = 0.002) without affecting RI or OS, while grade I aGVHD had no significant impact on these outcomes. Patients with Grade II or higher aGVHD were at greater risk of both chronic (c)GvHD (HR: 1.98 for Grade II; HR: 4.33 for Grade III/IV, p < 0.001) and extensive cGVHD (HR: 2.52 for Grade II; HR: 4.91 for Grade III/IV, p < 0.001). These findings highlight the challenge of mitigating NRM while preserving the GVL effect to optimize disease control and long-term survival in pediatric AML. This study provides critical insights for refining post-transplant strategies in this population.

We evaluated the influence of donor type in 3006 adults with adverse-risk cytogenetic acute myeloid leukemia (AML) in first complete remission undergoing allogeneic hematopoietic cell transplantation (HCT). Donor types included matched sibling (MSD), matched unrelated (MUD), mismatched unrelated (MMUD), and haploidentical donors. At 2 years, leukemia-free survival, overall survival (OS), and graft-versus-host disease (GVHD)-free/relapse-free survival were 47%, 55%, and 36%. Compared with MSD, OS was inferior with MUD (HR 1.36; 95% CI, 1.1-1.67), MMUD (HR 1.4; 95% CI, 1.07-1.83), and haploidentical grafts (HR 1.33; 95% CI, 1.02-1.73). Haploidentical was associated with lower relapse risk (HR 0.72; 95% CI, 0.53-0.97), but higher non-relapse mortality (NRM) (HR 3.85; 95% CI, 2.44-6.08). All alternative donors showed higher rates of grade II-IV acute GVHD. In 702 patients receiving post-transplant cyclophosphamide (PTCy), survival differences attenuated. However, haploidentical and MMUD showed higher risk of grade III-IV acute GVHD (HR 2.61; 95% CI, 1.04-6.54 and HR 3.74; 95% CI, 1.14-12.24), and haploidentical had increased NRM (HR 3.22; 95% CI, 1.23-8.44), without significant relapse. Findings support safety of alternative donors and reinforce MSD as preferred choice in adverse-risk AML. PTCy mitigates but does not eliminate the risk of donor mismatch.