Bone Marrow Transplantation最新文献

Methodological advancements now allow older adults with AML to receive allografts although conflicting data exist regarding relative outcomes across age groups and benefits of different conditioning intensities. We retrospectively analyzed 495 adults aged 60-64 (n = 184), 65-69 (n = 189), or ≥70 (n = 122) allografted for AML in remission at our institution from 2006 to 2023. There were no significant differences in relapse or relapse-free survival (RFS) among the 3 age cohorts after multivariable adjustment. Patients aged ≥70 years had higher non-relapse mortality (NRM) than those aged ≥60-64 (P = 0.022) but their overall survival (OS) was only statistically non-significantly shorter (P = 0.11). There was an important interplay between age, conditioning intensity, and outcomes. Relative to age 60-64, age ≥70 years was associated with a higher risk of relapse (hazard ratio [HR] = 3.47; P = 0.012) and NRM (HR = 3.88; P = 0.001) with reduced intensity conditioning (RIC), leading to shorter RFS (HR = 3.79; P < 0.001) and OS (HR = 3.46; P < 0.001), while no such associations were found with nonmyeloablative (NMA) conditioning. Underlying, patients aged 60-64 and 65-69, but not those aged ≥70, had a significantly lower relapse risk with RIC relative to NMA conditioning, whereas NRM risks increased across all age cohorts. Our findings support allografting for adults ≥70 with AML in remission, especially with NMA conditioning.

Hematopoietic stem cell transplantation (HSCT) is an established treatment for selected patients with inborn errors of metabolism. In this first report from the PDWP-SBTMO, we included 105 patients transplanted between 1988 and 2021 across six Brazilian HSCT centers. The most prevalent diseases were X-linked adrenoleukodystrophy (n = 61) and mucopolysaccharidosis (type I n = 20; type II n = 10), with a median age at HSCT of 8.7 years and 2.1 years, respectively. Most conditioning regimens were myeloablative and busulfan-based. With a median follow-up of 6.7 years, the 5-years overall survival (OS) was 75% (95% CI, 0.65-0.82) with a superior 5-years OS for those transplanted after 2010 (87% vs. 63%, p = 0.01). Higher risk of death was associated with the use of haploidentical donor (HR8.86, p 0.021), unrelated cord blood (HR 8.76, p 0.005), unrelated donor (HR 5.91, p 0.02), and for HSCT performed before 2010 (HR 4.16, p = 0.0015). The CI of acute GVHD was 24.8%, while chronic GVHD was 9.5%. Major causes of death were infections (n = 8), GVHD (n = 6), and neurologic progression (n = 3). Despite improvements in transplant outcomes since 2011, challenges persist, emphasizing the need for early diagnosis, timely transplantation and expanding HSCT centers with expertise in the field.

The accessibility of CAR-T cells in centralized production models faces significant challenges, primarily stemming from logistical complexities and prohibitive costs. However, European Regulation EC No. 1394/2007 introduced a pivotal provision known as the hospital exemption. This exemption enables academic institutions to produce ATMPs, including autologous CAR-T cells, under GMP conditions tailored to specific needs. In response to this regulatory framework, our work group has launched a guideline initiative. This endeavor aims to bolster academic CAR T-cell manufacturing by implementing strategic workshops that serve a dual purpose: standardizing production processes and ensuring both efficacy and safety standards are met. This inaugural focused on delineating criteria for the release of fresh CAR-T cell batches. Key emphases included thorough product characterization, stringent safety and potency evaluations. These criteria are essential for compliance with regulatory mandates and aligning with industry best practices. Notably, the release of initial CAR T-cell batches will be facilitated through provisional certification, with final certification contingent upon the acquisition of comprehensive analytical control results. This procedural framework adheres to methodologies endorsed by the SFGM-TC and the EBMT. Such adherence underscores a commitment to harmonizing practices across academic manufacturing facilities, thus fortifying the accessibility, efficacy, and safety of point-of-care units.

The poor outcome of TP53 alteration has been reported in myelodysplastic syndrome (MDS) patients. However, the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in TP53 alteration patients remains debated. Previous studies showed that TP53 mutations had no effect on the prognosis of patients with acute leukemia after haploidentical HSCT (haplo-HSCT). The effect of haplo-HSCT on MDS patients with TP53 alterations remains to be further elucidated. We aimed to reveal the role of TP53 alterations in the prognosis of MDS patients undergoing allo-HSCT, especially haplo-HSCT. 261 MDS patients with known TP53 status were enrolled, including thirty-seven patients with TP53 mutation/deletion (TP53mut/del). TP53mut/del patients showed a worse rate of 2-year cumulative incidence of relapse (CIR) and 2-year disease-free survival (DFS) than TP53 wild type (TP53wt) patients (46.2% vs 17.0%, P < 0.001; 41.8% vs 68.9, P < 0.001) after allo-HSCT, even for those with haplo-HSCT (CIR: P < 0.001; DFS: P = 0.002). However, the prognostic effect of TP53 alteration on overall survival (OS) was not observed in patients with haplo-HSCT (66.7% vs 75.2%, P = 0.108). Positivity of post-transplantation measurable residual disease (post-MRD) and time from diagnosis to transplantation were independent risk factors for MDS patients. TP53 alterations do not affect OS in patients undergoing haplo-HSCT requires further validation.

Umbilical cord blood transplantation (CBT) is accepted as an effective treatment for acute myeloid leukemia (AML), and reduced-intensity conditioning (RIC), rather than myeloablative conditioning (MAC) regimens allowed elderly patients to be treated safely. However, appropriate intensities of conditioning regimens are still unclear, especially for middle-aged patients. To compare outcomes after RIC and MAC regimens, we analyzed AML patients aged 16 years or older in the Japanese registry database, who underwent single cord unit CBT between 2010-2019. Median ages of the RIC group (n = 1353) and the MAC group (n = 2101) were 59 and 51 years (P < 0.001), respectively. 5-year overall survival (OS) after MAC was superior to that of RIC (38.3% vs 27.7%, P < 0.001) with lower incidence of relapse (33.9% vs 37.4%, P = 0.029) and better neutrophil engraftment (84.7% vs 75.9%, P < 0.001). Detailed subgroup analysis revealed that age at transplantation is the most important factor affecting 5-year OS in RIC and MAC. This analysis identified a threshold of 55 years, beyond which the superiority of MAC disappeared, irrespective of other factors such as disease status or performance status. In conclusion, RIC may be preferable for patients aged 56 or older in CBT for AML due to higher potential toxicities.

Transplant-associated thrombotic microangiopathy (TA-TMA) is an increasingly recognized complication in hematopoietic cell transplantation (HCT). Given the rarity of prospective pediatric studies on TA-TMA, this study aimed to evaluate the incidence, survival outcomes, and risk factors for predicting early the development of TA-TMA in a pediatric population following allogeneic HCT. We conducted a prospective analysis of 173 pediatric patients to evaluate the incidence, survival outcome, and risk factors of TA-TMA. The cumulative incidence of TA-TMA at one-year post-HCT was 4.7% (95% CI, 2.2-8.6%). Patients with TA-TMA showed significantly poorer 1-year overall survival (OS) rate, 50.0% ± 17.7% compared to 85.4% ± 2.8% in those without TA-TMA (p = 0.008). Additionally, the non-relapse mortality (NRM) rate was higher in the TA-TMA group at 12.5% (95% CI, 3.7-55.8%) versus 7.0% (95% CI, 2.8-10.1%) (p = 0.598). A urine protein/creatinine ratio ≥ 1 mg/mg on day 30 post-HCT was significantly associated with TA-TMA occurrence (adjusted HR, 9.5; [95% CI], 1.28-70.39; p = 0.028). This study showed the significantly unfavorable clinical outcomes associated with TA-TMA in pediatric patients and emphasized the importance of early identification of patients at risk. Further research is needed to explore additional strategies for early detection and intervention to improve outcomes.