Bone Marrow Transplantation最新文献

Tuberculosis (TB) is rare following hematopoietic cell transplantation (HCT). In this multinational retrospective study, we report the frequency, characteristics, and outcome of TB following HCT performed during 2000-2019. Fifty-two patients (35 (67%) males, 15 (29%) children) from 24 centers developed TB following allogeneic (n = 47) or autologous (n = 5) HCT; with the relative frequency of 0.21% and 0.025%, respectively. Forty (77%) were bacteriologically, 12 (23%) clinically confirmed. The median time from HCT to TB was 135 (range, 16-3225) days. Eighteen (35%) patients with extrapulmonary TB (mainly involving lymph nodes and liver/spleen) were significantly younger, developed TB shorter after HCT, more often had inherited underlying disease, and received immunosuppressive therapy at TB diagnosis as compared to pulmonary TB. Five (22%) of 23 patients with drug-susceptibility testing performed, were resistant to at least one anti-TB drug. Treatment success was achieved in 38/50 (76%) of treated patients. One-year overall survival reached 75.7% and the 1-year cumulative incidence of TB-associated death was 18.1%. Concluding, TB is a rare, albeit severe complication, which can develop any time after HCT, frequently involves extrapulmonary sites, and results in high mortality rates. High proportion of drug-resistant TB warrants routine susceptibility testing.

Autologous stem cell Transplant (ASCT)-related mortality (TRM) in AL amyloidosis remains elevated. AL amyloidosis patients (n = 1718) from 9 centers, transplanted 2003-2020 were included. Pre-ASCT variables of interest were assessed for association with day-100 all-cause mortality. A random forest (RF) classifier with 10-fold cross-validation assisted in variable selection. The final model was fitted using logistic regression. The median age at ASCT was 58 years. Day-100 TRM occurred in 75 patients (4.4%) with the predominant causes being shock, high-grade arrhythmia, and organ failure. Ten factors were associated with day-100 TRM on univariate analysis. RF classifier using these variables generated a model with an area under the curve (AUC) of 0.72 ± 0.12. To refine the model selection using importance hierarchy function, a 4-variable model [NT-proBNP/BNP, serum albumin, ECOG performance status (PS), and systolic blood pressure] was built with an AUC of 0.70 ± 0.12. Based on logistic regression coefficients, ECOG PS 2/3 was assigned two points while other adverse predictors 1-point each. The model score range was 0-5, with a day-100 TRM of 0.46%, 3.2%, 5.8%, and 14.5% for 0, 1, 2, and ≥3 points, respectively. This model to predict day-100 TRM in AL amyloidosis allows better-informed decision-making in this heterogeneous disease.

Patients with relapsed or refractory multiple myeloma (R/R-MM) are more susceptible to develop severe coronavirus disease 2019 (COVID-19) for their immunocompromised states. Despite good responses to B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T cell therapy, deficiencies in humoral immunity following CAR-T cell infusions can still cause life-threatening complications in these patients. We conducted a comparative study to delineate the clinical characteristics and outcomes between recipients of BCMA-targeted CAR-T cell therapy who contracted COVID-19 vs. unaffected counterparts. Advanced age (odds ratio [OR] = 1.367, 95% confidence interval [CI] = 1.017-1.838, P = 0.038) was a risk factor for developing severe COVID-19, while complete remission (CR) achieved by CAR-T cell therapy (OR = 0.012, 95% CI = 0.000-0.674, P = 0.032) was protective. Male sex (hazard ratio [HR] = 5.274, 95% CI = 1.584-17.562, P = 0.007) and CR achieved by CAR-T cell therapy (HR = 3.107, 95% CI = 1.025-9.418, P = 0.045) were protective factors associated with COVID-19 duration. CR achieved by CAR-T cell therapy (HR = 0.064, 95% CI = 0.007-0.589, P = 0.015) was also a protective factor for OS, while progression disease at the time of COVID-19 diagnosis (HR = 14.206, 95% CI = 1.555-129.819, P = 0.019) was regarded as a risk factor. Thus, older patients with R/R-MM and those who do not achieve CR after CAR-T cell therapy should be most protected from COVID-19 infection by the Omicron variant.

Acute graft-versus-host disease (aGvHD) remains a significant complication of allogeneic hematopoietic cell transplantation, with 40% of patients failing to respond to high-dose steroids. Ruxolitinib has become the standard treatment for steroid-refractory aGvHD (SR-GvHD), but its failure in approximately one-third of cases highlights the need for alternative therapies. Mesenchymal stromal cells (MSCs), known for their immunomodulatory properties, are suggested as a treatment option, but their role in SR-GvHD remains unclear. To better understand MSC therapy outcomes, the EBMT Cellular Therapy & Immunobiology Working Party conducted a survey of centers treating >20 SR-GvHD patients with MSCs between 2007 and 2020. Data from 313 patients were analyzed, revealing a 44.5% overall response rate at day 28. Responders at day 7 had a higher likelihood of maintaining responses by day 28. Using a landmark analysis, the overall survival at 12 months, conditional on being alive at day 28, was 39.2%. Survival at 12 months was 48.6% for responders, compared to 24.4% for non-responders. Despite manufacturing variabilities, MSCs produced by academic pharma appear effective in SR-GvHD, offering a viable treatment alternative for heavily pretreated patients. These findings support further investigation of MSCs to establish standardized protocols and validate their efficacy as third-line therapy for SR-GvHD.

Allogeneic hematopoietic cell transplantation (alloHCT) is an effective treatment for patients with relapsed/refractory peripheral T-cell lymphoma (PTCL), but the contribution of the conditioning regimen is still unclear. Here we present a retrospective single-center study using conditioning with intermediate-dose total body irradiation (TBI) and fludarabine for alloHCT in PTCL. Forty-seven patients underwent alloHCT for PTCL between 2010 and 2023 after conditioning with fludarabine and intermediate-dose TBI (8 Gy in 87% of the cases). In most patients alloHCT was administered as part of second-line therapy, in 22 (47%) patients after having been primary refractory, and 21 (45%) of the patients were chemoresistant at alloHCT. With a median follow-up of 5.5 years, 5-year progression-free survival (PFS), overall survival, relapse incidence, and non-relapse mortality were 61%, 65%, 24%, and 15%, respectively. The 5-year PFS of patients transplanted with stable disease and progressive disease was 57% and 26%, respectively. Of 11 relapses, only 2 (18%) occurred beyond 6 months post transplant, and no relapse was observed after onset of chronic graft-versus-host disease. AlloHCT with intermediate-dose TBI/fludarabine conditioning is associated with a favorable toxicity/efficacy profile and can provide durable survival in a substantial fraction of patients with PTCL including those with poorly controlled disease at transplant.

To validate the ability of the haematopoietic cell transplantation comorbidity index (HCT-CI) to predict the outcomes of patients with severe aplastic anaemia (SAA) receiving haploidentical haematopoietic stem cell transplantation (haplo-HSCT), we conducted a retrospective study including 530 SAA patients. Patients were stratified based on their HCT-CI scores into three distinct risk categories: low-risk (HCT-CI scores of 0, n = 343), intermediate-risk (HCT-CI scores of 1, n = 126), and high-risk groups (HCT-CI scores ≥ 2, n = 61). The 100-day platelet engraftment rate was significantly higher in the low-risk group compared to the intermediate-risk and high-risk groups (92.1% vs. 86.5% vs. 83.6%, P = 0.014). In addition, compared with the intermediate-risk and high-risk groups, the low-risk group demonstrated superior 5-year overall survival (OS, 91.8% vs. 83.3% vs. 70.1%, P < 0.001) and graft-versus-host disease-free/graft failure-free survival (GFFS, 80.1% vs. 71.3% vs. 63.6%, P = 0.009). Multivariate analysis revealed that elevated HCT-CI scores and previous antithymocyte globulin treatment were independent risk factors for OS, whereas elevated HCT-CI scores and donor age ≥ 40 years were correlated with worse GFFS. Consequently, the HCT-CI is associated with the clinical outcomes of SAA patients following haplo-HSCT, and it is imperative to closely monitor patients with a high comorbidity burden.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive and rare hematological malignancy with poor clinical outcomes. Stem cell transplantation helps to achieve long-term survival in adults. However, the benefit of haploidentical stem cell transplantation (HID-SCT) versus chemotherapy is unclear with BPDCN. We retrospectively analyzed 32 patients diagnosed with BPDCN including 15 who underwent HID-SCT and 17 who only received chemotherapy. The median age was 52 (range, 19-78) years. The ratio of male/female was 2.2. Skin, bone marrow and lymph node were the most three common sites of disease involvement. Compared with the chemotherapy group, patients in the HID-SCT group had significantly better progression-free survival (PFS; median, 7 months versus not reached, P < 0.001) and overall survival (OS; median, 13 months versus not reached, P < 0.001). The 4-year rates for PFS and OS in transplant patients were 74% (95% Confidence Interval [CI], 47, 100%) and 93% (79, 100%), respectively, compared to 0 in non-transplant patients. In conclusion, our results demonstrated HID-SCT could provide long-term remissions in BPDCN patients.