Annals of Hematology最新文献

The clinical success of FLT3 inhibitors has led to their steadily increasing use in the treatment of acute myeloid leukemia (AML), both in the relapsed/refractory setting and as post-transplant maintenance. Despite their expanding application, there is currently no guidance on the optimal duration of therapy or the feasibility of discontinuation. In the maintenance context, current practice is largely based on trial protocols with predefined treatment periods, yet relapses after cessation have been documented. Similarly, in the relapsed/refractory setting, the management of long-term responders to FLT3-directed monotherapy lacks evidence-based guidance.We report two cases of FLT3-ITD AML patients with relapse after discontinuation of prolonged FLT3 inhibitor therapy, despite sustained remission prior to withdrawal. As such scenarios remain insufficiently characterized in the literature, these case vignettes are presented to highlight the unresolved challenge of defining the appropriate duration of FLT3 inhibitor therapy and to underscore the need for systematic evaluation to establish evidence-based strategies for safe discontinuation or extended administration.

β-thalassemia is an inherited blood disorder with long-term associated complications. The purpose of this study was to evaluate the clinical significance of the lncRNA-HBBP1 and lncRNA-XIST expression profiles in the diagnosis of β-thalassemia patients. One hundred children patients with β-thalassemia participated in this case-control study: 50 patients diagnosed as Beta Thalassemia Major (β-TM) and 50 patients diagnosed as Beta Thalassemia Intermedia (β-TI) groups. Furthermore, there were 50 children as healthy control group. Assessment of both genes' expression was performed by RT-qPCR. The findings displayed that both lncRNA-HBBP1 and lncRNA-XIST were highly expressed within the β-TM group than in the β-TI and the control groups (P < 0.001 for both). The lncRNA-HBBP1 and lncRNA-XIST expression were significantly higher in β-thalassemia patients presented with jaundice, thalassemia facies, or organomegaly (p < 0.001 for all). In addition, lncRNA-XIST expression was significantly higher in β-thalassemia patients with splenectomy (p = 0.002). Spearman correlation revealed that the expression of both genes was significantly correlated with HbF % in β-TM and β-TI groups (p < 0.001 for both). Based on the ROC curve analysis, the sensitivity of lncRNA-HBBP1 and lncRNA-XIST for discriminating the β-TM group from the β-TI group was 82% and 80%, respectively. Collectively, the examined lncRNAs could offer novel biomarkers for β-thalassemia disorder once confirmed in extensive upcoming investigations.

Epcoritamab, a CD3xCD20 bispecific antibody, resulted in deep, durable responses with a manageable safety profile in patients with relapsed/refractory large B-cell lymphoma (LBCL) in EPCORE^® NHL-1 (NCT03625037). We report results from a 3-year follow-up. Adults with relapsed/refractory LBCL received epcoritamab until progressive disease or unacceptable toxicity. The primary endpoint was overall response rate (ORR). Median age was 64.0 years, 39% of patients received prior CAR T-cell treatment, and 75% were refractory to ≥ 2 consecutive lines of treatment. As of May 3, 2024 (median follow-up 37.1 months [range, 0.3-45.5]), ORR was 59% and complete response (CR) rate 41% by investigator assessment. Median duration of response was 20.8 months (95% confidence interval [CI], 13.0-32.0). Median duration of CR was 36.1 months (20.2-not reached [NR]); the longest ongoing CR was > 43 months. Median progression-free survival was 4.2 months (95% CI, 2.8-5.5) in all patients and 37.3 months (26.0-NR) in patients with CR. Median overall survival was 18.5 months (95% CI, 11.7-27.7) in all patients and NR in patients with CR. Of 119 patients evaluable for minimal residual disease (MRD) assessments, 54 (45%) were MRD-negative at any time during the study. Most common adverse events were cytokine release syndrome (51%), fatigue (25%), and pyrexia (25%), with no new safety signals. Grade 1, 2, and 3 infections occurred in 23%, 34%, and 24% of patients, respectively. The durability of responses and prolonged survival in complete responders suggest long-term disease-free survival with epcoritamab in these patients with relapsed/refractory LBCL.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative treatment for aplastic anemia (AA). For patients lacking a matched sibling donor (MSD) or matched unrelated donor (MUD), haploidentical HSCT (haplo-HSCT) has become an alternative with comparable efficacy. However, donor-specific anti-HLA antibodies (DSAs) remain the principal barrier. In this study, we compared transplant outcomes in DSA-positive recipients after desensitization with plasma exchange (PE) combined with anti-B-cell therapy. Between January 2019 and December 2023, we enrolled 30 DSA-positive AA patients who underwent haplo-HSCT at our center. All received a desensitization regimen combining PE with anti-B-cell agents. By propensity-score matching (1:2 ratio, caliper 0.02), we additionally enrolled 60 DSA-negative controls matched for key clinical variables to compare therapeutic efficacy and long-term outcomes between the two groups. This study enrolled 90 AA patients who underwent haplo-HSCT: 30 were DSA-positive and 60 were DSA-negative. Baseline characteristics were comparable between the two groups. After desensitization with PE combined with anti-B-cell agents, the DSA-positive group achieved outcomes equivalent to those of the DSA-negative group. Specifically, EBV reactivation (46.7% vs. 68.3%; P = 0.002) was significantly better in the DSA-positive group. Engraftment, aGVHD, Effacacy, OS, and GRFS rates were similar between two groups. However, the risk of cGVHD remains higher in the DSA-positive group (40% vs. 12%; P = 0.009). For DSA-positive AA patients who are candidates for haplo-HSCT and for whom no DSA-negative donor can be identified, desensitization with PE combined with anti-B-cell agents represents an established strategy to improve transplant outcomes; nevertheless, close surveillance for cGVHD is warranted after transplantation.