International Journal of Hematology最新文献

The phase 3 DREAMM-8 (NCT04484623) trial assessed belantamab mafodotin + pomalidomide + dexamethasone (BPd) vs bortezomib + Pd (PVd) in lenalidomide-exposed patients with relapsed/refractory multiple myeloma (RRMM) and ≥ 1 prior therapy. Here, we present findings from Japanese patients (data cutoff: 27-May-24). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rate (ORR), duration of response (DoR), and safety. Overall, 21 patients were randomized 1:1 to BPd (N = 10) and PVd (N = 11). Median follow-up was 13.8 months (range 0.23-26.71). For BPd vs PVd, median PFS was not reached (NR; 95% CI 0.2-NR) vs 14.8 months (95% CI 1.9-NR; HR 0.53; 95% CI 0.1-2.8); ORR was 90% (9/10) vs 73% (8/11), including very good partial response or better in 70% (7/10) vs 36% (4/11); median DoR was NR vs 17.5 months. The safety profile was consistent with the global cohort. Ocular adverse events were more common with BPd vs PVd (90% [9/10] vs 9% [1/11]) and a majority were transient and reversible. While the sample size of this study is small, findings were aligned with the global cohort. BPd showed favorable efficacy compared with PVd, with a manageable safety profile in lenalidomide-exposed Japanese patients with RRMM.

Therapy-related myeloid neoplasms (t-MN) are an aggressive and heterogeneous group of myeloid disorders with no established guidelines for frontline treatment. This retrospective study of 53 consecutive t-MN patients at our institution evaluated the influence of clinical features, treatment approaches, and prognostic indicators on clinical outcomes of t-MN. The 1-year, 3-year, and 5-year overall survival (OS) rates were 61.0%, 50.0%, and 36.0%, respectively. Multivariate analysis revealed that age ≥ 60 (p = 0.009), TP53 (p = 0.040) and RAS mutations (p = 0.018) were associated with inferior OS. After induction therapy, patients who received a venetoclax-based regimen (venetoclax group) had an overall response rate (ORR) of 96.2%, compared with 63.6% in the chemotherapy group (p = 0.007). The venetoclax group tended to have better OS and DFS than the chemotherapy group (p = 0.052 and p = 0.078). Importantly, ORR rates and OS were higher in some subgroups of the venetoclax group, especially in patients over 60 years old and patients with intermediate/adverse risk. This study demonstrates the feasibility of venetoclax-based combination regimens for the treatment of t-MN and may influence decision-making for frontline therapy.

Primary mediastinal B-cell lymphoma (PMBCL) is a distinct subtype of large B-cell lymphoma characterized by 9p24.1 copy-number alterations and PD-1-mediated immune evasion. This profile confers high sensitivity to PD-1 inhibitors such as pembrolizumab. CD19-directed chimeric antigen receptor (CAR) T-cell therapies have shown benefit in relapsed or refractory (R/R) PMBCL, but their optimal role remains undefined. We retrospectively analyzed 31 patients with R/R B-cell lymphoma treated with lisocabtagene maraleucel (liso-cel), including four with PMBCL who received pembrolizumab prior to CAR-T. All four achieved remission before infusion, and three maintained durable complete responses (≥ 30 months). Toxicities were comparable to those in patients not treated with pembrolizumab, although one pembrolizumab-treated patient experienced fatal neurotoxicity. Favorable hematologic recovery and preserved T-cell counts at leukapheresis suggest that preceding PD-1 blockade did not compromise CAR-T manufacturing and may have enhanced T-cell fitness. These findings suggest that sequential PD-1 blockade followed by liso-cel is clinically feasible and may improve outcomes by leveraging the immune vulnerability of PMBCL. While prior studies have focused on axicabtagene ciloleucel, this report provides the first real-world data supporting the feasibility and potential benefit of this approach with liso-cel. Prospective studies are needed to confirm efficacy, safety, and optimal sequencing.

Previous studies have shown that the blood concentration of calcineurin inhibitors is related to the incidence of acute graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, its utility as an indicator for GVHD relapse prevention and graft-versus-tumor effect assessment has mostly been investigated in umbilical cord blood transplantation. We hypothesized that the simple area under the tacrolimus (TAC) concentration (AUTC) early after transplantation reflects TAC pharmacokinetics more accurately than the mean TAC concentration (MTC), and analyzed the relationship of AUTC with outcomes after unrelated allo-HSCT for myeloid malignancies. We set cut-off values of MTCs and AUTCs using receiver-operating-characteristic curves for each outcome. Patients with high MTC in week 3 (MTC 3) had a lower cumulative incidence of acute GVHD. High MTC 3 was associated with a higher relapse rate in univariate analysis, but was not significant in multivariate analysis. Meanwhile, high AUTC in week 3 (AUTC 3) was a predictor of relapse, worse relapse-free survival, and overall survival in both univariate and multivariate analysis. Development of acute GVHD was not associated with relapse. Therefore, AUTC 3 after unrelated allo-HSCT for myeloid malignancies may better reflect the relapse prevention effect of immunosuppression intensity than MTC or development of acute GVHD.

Introduction: Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) requires reliable vascular access for medication, transfusion, and blood sampling, which often involves painful venipuncture. This prospective study evaluated a novel dual peripherally inserted central venous catheter (PICC) technique to reduce venipuncture frequency in allo-HSCT recipients.

Methods: The study enrolled 29 allo-HSCT recipients. Each patient received two single-lumen PICCs: Catheter A for tacrolimus infusion and Catheter B, positioned distally, for blood sampling. Tacrolimus concentrations from Catheter B and venipuncture were compared using Bland-Altman analysis. Catheter-related adverse events were also evaluated to assess safety.

Results: PICC placement was successful in all patients. During 1378 catheter-days, one catheter-related bloodstream infection and one catheter occlusion occurred. Tacrolimus concentrations from PICC samples were strongly correlated with those of venipuncture samples (r = 0.93). Bland-Altman analysis showed good agreement, with a mean difference of 0.064 ng/mL, limits of agreement within ± 2.0 ng/mL, and no fixed bias.

Conclusion: Dual single-lumen PICCs provide a safe and accurate method for tacrolimus monitoring in allo-HSCT, and may improve patient experience by reducing the need for painful venipuncture. Further randomized-controlled trials are needed to confirm the benefits of this approach and assess its applicability to the monitoring of other therapeutic agents.

We retrospectively analyzed the effectiveness of posaconazole (tablet and infusion formulations) and its correlation with blood concentration in preventing invasive fungal infections (IFIs) in 360 patients who underwent allogeneic hematopoietic stem cell transplant (allo-HSCT) between 2010 and 2023. A total of 61 patients received posaconazole, 102 received micafungin, and 197 received fluconazole for primary prophylaxis. By day 100 post-transplant, the cumulative incidence of IFIs was significantly lower with posaconazole (5.0%) compared with fluconazole (14.4%) or micafungin (16.9%). Multivariate analysis showed that the risk of IFIs was significantly higher with fluconazole/micafungin than with posaconazole (hazard ratio 4.04, 95% CI 1.17-13.94, P = 0.027). This difference was most notable among patients with lymphoid malignancies (P = 0.053) and those undergoing repeat transplantation (P = 0.024). There were no significant differences in overall survival, non-relapse mortality, or mortality from IFI. Mean blood levels of posaconazole dropped to 0.57 μg/mL two weeks after allo-HSCT, coinciding with the observation of most IFIs in the posaconazole group shortly after transplant. Posaconazole appears to be more effective than fluconazole or micafungin as primary prophylaxis against IFIs in allo-HSCT recipients.

A 53-year-old woman experienced relapse of diffuse large B cell lymphoma (DLBCL) 16 years after achieving a first complete metabolic response (CMR). Despite initially being refractory to salvage chemotherapy, she achieved a second CMR and underwent umbilical cord blood transplantation (UCBT). On day 119 post-transplantation, she experienced a second relapse and received chimeric antigen receptor T (CAR T) cell therapy, achieving a third remission without cytokine release syndrome or graft-versus-host disease (GVHD). However, a third relapse occurred seven months after CAR T cell therapy. Epcoritamab treatment was initiated, resulting in CMR without severe complications. Subsequently, the patient underwent curative unrelated allogeneic peripheral blood hematopoietic stem cell transplantation (HSCT). She experienced no severe transplant-related complications, including serious GVHD or infections. She has remained in CMR for > 1 year after the second transplant. Epcoritamab appears to be an effective and safe treatment option for DLBCL relapse, even after both UCBT and CAR T cell therapy, suggesting that bridging therapy with epcoritamab followed by a second allogeneic HSCT may achieve long-term survival.

Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive disorder characterized by microthrombocytopenia, eczema, recurrent infections, and immune dysregulation, affecting approximately 1 in 100,000 live births. While the disorder was historically fatal in early childhood, advances in hematopoietic stem cell transplantation (HSCT), gene therapy, and supportive care have improved survival, though morbidity remains high. Mutations in the WAS gene disrupt the WAS protein (WASp), which is essential for actin cytoskeleton dynamics, thereby impairing immune cell function. Over 466 mutations correlate with disease severity, from severe classic WAS to milder X-linked thrombocytopenia (XLT). Supportive therapies manage symptoms, while HSCT offers a cure for severe cases. Gene therapy has emerged as a promising alternative, with early gamma-retroviral trials showing efficacy but also a risk of leukemogenesis. Third-generation lentiviral vectors with self-inactivating LTRs (long terminal repeats) demonstrate improved safety and immune restoration in clinical trials. This review evaluates the evolution of gene therapy for WAS, from early trials to emerging genome editing approaches, assessing their efficacy, safety, and potential to transform clinical outcomes.

This study compared dasatinib and imatinib in adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). Using pooled data from three JALSG prospective trials (Ph + ALL202, Ph + ALL208, Ph + ALL213), we analyzed outcomes for 206 patients aged 15-64 years treated with dasatinib (n = 74) or imatinib (n = 132) in combination with chemotherapy. We applied propensity score matching (1:1) and inverse probability of treatment weighting to minimize selection bias and balance baseline characteristics. Dasatinib plus chemotherapy was associated with significantly higher complete molecular response rates after induction therapy compared with imatinib. In the propensity score-matched cohort (n = 68 patients per group), 3-year event-free survival (EFS) was significantly higher with dasatinib (73 vs. 49%, P = 0.01), as was 3-year overall survival (OS) (85 vs. 60%, P = 0.004). Multivariate analysis, incorporating allogeneic stem cell transplantation in first complete remission as a covariate, confirmed that dasatinib had an independent favorable prognostic impact on EFS (hazard ratio [HR], 0.54; P = 0.02) and OS (HR, 0.39; P = 0.003). Although the 3-year cumulative incidence of relapse tended to be lower with dasatinib (18 vs. 40%, P = 0.07), non-relapse mortality was comparable between groups (8.8 vs. 12%, P = 0.33). This analysis demonstrates improved survival with dasatinib-based therapy in adult Ph + ALL, informing tyrosine kinase inhibitor selection in treatment planning.