Bone Marrow Transplantation最新文献

Central nervous system lymphomas (CNSL) are a heterogeneous group of generally aggressive tumors whose prognosis varies significantly, being more favorable in patients with primary disease and poorer in those with secondary lymphoma. Current treatments typically involve intensive chemotherapy followed by consolidation with autologous stem cell transplantation or whole-brain radiotherapy. However, if the disease relapses, there is no established standard of care. The recent approval of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy for systemic B-cell lymphomas has shifted the treatment landscape for previously incurable patients. Even though this therapy was initially underexplored in the setting of CNSL due to safety and efficacy concerns, it could offer a new therapeutic avenue for these patients. In this review, we will provide a concise overview of the current treatment strategies for CNSL, highlighting their key limitations, including relapse rates and long-term toxicity. Following this, we will explore the most important studies and clinical trials on CNSL, focusing on recent advancements in anti-CD19 CAR T-cell therapy. This comprehensive analysis will offer insights into the successes and challenges of treating CNSL effectively.

Ruxolitinib has been approved for the treatment of adults and pediatric patients ≥12 years with steroid refractory graft-versus-host disease (GvHD). However, real-life studies are needed to confirm the results of clinical trials and further assess its efficacy in special populations. We performed a descriptive, retrospective, multi-center study of 352 adults and 42 pediatric patients treated with ruxolitinib for steroid-refractory acute or chronic GvHD. Among 119 and 233 adult patients with acute and chronic GvHD, overall response rate (ORR) was 58.8% (CR 33.6%) and 65.7% (CR 18.5%), respectively. Corticosteroids were withdrawn in 59.2% and 40.1%, and ruxolitinib in 47.2% and 34.8% in the acute and chronic groups of responders. Among 29 and 13 pediatric patients with acute and chronic GvHD, ORR was 82.7% (CR 51.7%) and 100% (CR 23%), respectively. Among responder patients, corticosteroids were withdrawn in 72.7% and 50%, and ruxolitinib in 75% and 30.7% in both groups respectively. Ruxolitinib in the real world setting, showed similar results as compared to clinical trials. Its efficacy is maintained in subsequent lines of treatment. In the pediatric population, the data are more favorable. In the long-term follow-up, corticosteroids, ruxolitinib and other inmunosuppressive drugs could be eliminated in a remarkably proportion of patients.

Bloodstream infections (BSI) are frequent complications after allogeneic hematopoietic cell transplant (HCT). This study reports data on pre-engraftment BSI in years 2016-2021 and analyses changes in incidence, aetiology, resistance and mortality compared with two previous periods (2004-2009 and 2010-2015). In years 2004-2021, 1364 patients received HCT. De-escalation strategy for empirical antibiotic therapy was introduced in 2011. In 381 patients from years 2016-2021, the incidence of pre-engraftment BSI was 37.8%. Independent predictors of BSI were older age, AML/MDS and active disease. In 1364 patients, the incidence of BSI increased from 22% in period 1 to 38% in period 3 (p = 0.008), particularly gram-negative BSI: from 10.1% to 19.7% (p = 0.001). Among gram-negatives, resistance to third-generation cephalosporins remained stable (40.2% in period 3), while resistance to carbapenems and fluoroquinolones decreased (respectively, 12.6% and 59.8% in period 3). Seven and 30-day mortality after the first BSI decreased, respectively, from 11% in period 1 to 1.4% in period 3 and from 20.5% to 4.9% (p < 0.001 for both). Less recent transplant period was the only factor associated with higher mortality (p = 0.001). Incidence of pre-engraftment BSI is high and increased overtime, particularly for gram-negatives. Resistance rates remained stable, and mortality decreased overtime, documenting improvements in the BSI management.

The endothelial activation and stress index (EASIX) score, calculated as [lactate dehydrogenase (LDH; U/L) × serum creatinine (mg/dL)]/platelets (10e9/L)], has been shown to be predictive of nonrelapse mortality (NRM) and endothelial complications in adults receiving allogeneic stem cell transplantation (allo-HSCT); however, definitive results are lacking for children. We retrospectively evaluated consecutive paediatric allo-HSCT recipients and calculated the log2 EASIX score every day from admission to day +35. In 167 allo-HSCT recipients, the EASIX score increased from before conditioning (-0.79) to a maximum score on day +20 (2.23). In multivariate analysis, the EASIX score at day +7 was an independent predictor of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) (OR 1.52; 95% CI, 1.08-2.13; p = 0.017) and NRM (OR 1.68; 95% CI 1.16-2.42; p = 0.006). At several time points between day +0 and day +14, the EASIX score was independently associated with NRM, with the strongest predictive power being observed on day +12 (OR 3.05; 95% CI, 1.53-6.10; p = 0.002). Age correlated linearly with the EASIX score at all analysed time points, but score prediction was confirmed even when age was added to the multivariate model, indicating that age was not a confounding factor in the observed associations. The EASIX score determined shortly after transplantation can be further explored as a predictor of SOS/VOD and NRM in paediatric allo-HSCT recipients.

Identifying patients who may benefit from autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma is crucial, especially in the era of effective induction and consolidation strategies. We analyzed data from 12763 patients enrolled in the German Registry for Hematopoietic Stem Cell Transplantation and Cell Therapy (DRST), distinguishing those who underwent single (n = 8736) or tandem ASCT (n = 4027) from 1998 to 2021. Our findings show that the median age at first ASCT increased over time, while the use of tandem ASCT declined. The shift in treatment practices coincided with higher rates of complete response (CR) post-induction therapy. Significantly improved overall survival and event-free survival over time were observed across all age groups, especially in older patients, but not in patients under 40. Tandem ASCT showed benefits for patients who did not achieve CR after initial ASCT. However, patients with ISS III and renal impairment had poorer outcomes with tandem ASCT. In conclusion, while ASCT remains an important anti-myeloma tool, careful patient selection for tandem ASCT is essential, particularly avoiding its use in patients with ISS III and renal impairment, older age, and those already achieving CR after initial ASCT.

Patients with TP53-mutated myelodysplastic neoplasms (MDS) have unfavorable prognoses; the benefit of cytoreductive treatment before hematopoietic stem cell transplantation (HSCT) is debated. We retrospectively analyzed 284 MDS patients undergoing allogeneic HSCT; among which 49 had TP53 mutation, with 38 receiving cytoreduction and 11 treated exclusively with best supportive care (BSC) before transplantation. Regardless of TP53 allelic state, patients with mutated-TP53 had a lower overall survival rate and higher relapse rate than those with wild-type TP53 (P < 0.001, P = 0.002, respectively). Among the TP53-mutated cohort, the 2-year overall survival rate in the cytoreduction group was comparable to that in the BSC group (34.6% vs. 45.5%, P = 0.53), and no other prognostic benefit was observed as well (all P < 0.05). Moreover, no prognostic difference was found among the chemotherapy subgroup, hypomethylating agent subgroup, and BSC subgroup (all P > 0.05). Patients in the pre-HSCT measurable residual disease (MRD) negative subgroup, pre-HSCT MRD-positive subgroup, and BSC subgroup exhibited similar prognoses (all P > 0.05). Multivariate analyses showed that pre-HSCT cytoreduction was not associated with post-transplant survival (all P > 0.05). In conclusion, TP53-mutated MDS patients have poor post-HSCT outcomes; compared to BSC, pre-HSCT cytoreduction doesn't improve prognosis, even in those with MRD negative before transplantation.