International Journal of Hematology最新文献

Viruses induce approximately 12% of human cancers, including lymphomas. In the case of T/NK cell neoplasms, human T-cell leukemia virus type I (HTLV-1) causes adult T-cell leukemia-lymphoma (ATL), and Epstein-Barr virus (EBV) is associated with extranodal NK/T-cell lymphoma (ENKTCL) and chronic active Epstein-Barr virus disease (CAEBV). Common mechanisms for lymphoma development have been proposed. Viral genes, such as tax and HTLV-1 bZIP factor (HBZ) of HTLV-1, and latent membrane protein 1 (LMP1) and BamHI A rightward transcript microRNA (miRNA-BART) of EBV, contribute to host immune evasion and modulation of host signaling pathways, resulting in the persistence of viral-infected cells. This viral strategy is closely associated with oncogenesis. Furthermore, the long-term survival of infected cells leads to the accumulation of somatic mutations and aberrant epigenetic alterations. These events eventually lead to ATL, ENKTCL, and the lymphoma-like subset of CAEBV. Interrupting these common oncogenic mechanisms is a promising therapeutic strategy for viral-driven lymphomas with poor prognoses.

Tagraxofusp (TAG), a first-in-class CD123-targeted therapy, is a recombinant fusion protein of human interleukin-3 conjugated to a truncated diphtheria toxin payload. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive orphan hematologic cancer with a poor prognosis, and is derived from plasmacytoid dendritic cells that overexpress interleukin-3 receptor subunit alpha (IL3RA or CD123). This open-label phase I/II study evaluated the efficacy and safety of TAG in 11 Japanese BPDCN patients, of whom seven were treatment-naïve (TN) and four had relapsed/refractory (R/R) disease. In the phase I portion, seven patients (five TN, two R/R) were treated, and no dose-limiting toxicity was observed, with 12 μg/kg/day tolerated. In the phase II portion, four patients (two TN, two R/R) were treated. Among the seven TN BPDCN patients, the rate of complete response (CR) + clinical CR (CRc: CR with minimal residual skin abnormality) was 57.1% (90% confidence interval [CI], 22.5-87.1), and the lower limit of the 90% CI (22.5%) exceeded the pre-specified threshold of 10%. Common adverse events included increased alanine aminotransferase (81.8%) and aspartate aminotransferase (72.7%), hypoalbuminemia, hypokalemia, and capillary leak syndrome (54.5%). The results indicate that TAG was effective and had a manageable safety profile in Japanese BPDCN patients.

Monosomal karyotype (MK) comprises chromosomal abnormalities defined as either one single autosomal monosomy with structural abnormalities (MK1) or two or more distinct autosomal monosomies (MK2). MK is a predictive factor for extremely poor prognosis in patients with acute myeloid leukemia (AML), and not all patients are eligible for allogeneic hematopoietic cell transplantation (HCT). Using registry data from the Japan Society for Transplantation and Cellular Therapy, we retrospectively analyzed 892 AML patients with MK who underwent initial HCT between 2000 and 2017. The median follow-up among surviving patients was 3.1 years (range, 0.1-13.8 years). The 3-year overall survival (OS) rate was 26% for the 284 MK1 patients, which was significantly higher than the 10% observed in the 608 MK2 patients (P < 0.001). Multivariate analysis showed that MK subtype, disease status at time of HCT, patient age at HCT, sex, performance status, and year of HCT significantly affected OS. Notably, MK1 was associated with better OS than MK2 in both patients in complete remission (CR) and non-CR patients. Molecular pathogenesis may be different between MK1 and MK2, and further investigation is required to gain biological insight into the impact of MK subtype on post-HCT outcomes.

Background: Cutaneous T-cell lymphoma (CTCL) is a rare malignancy with limited data available from the Middle East. This study evaluated the clinical characteristics, treatment patterns, and outcomes of CTCL patients treated in Kuwait.

Methods: This was a retrospective review of all adult patients diagnosed between February 2021 and March 2024. Data included demographics, staging, treatment modalities, and outcomes. Kaplan-Meier analysis was used to evaluate progression-free survival (PFS) and overall survival (OS).

Results: The study included 86 patients. The mean age at diagnosis was 44 years (range: 16-80), and 84% of patients presented with early-stage disease (IA-IIA). NB-UVB phototherapy was the most common treatment for early-stage disease, while brentuximab vedotin was frequently used for advanced diseases. Median OS was 30 months in patients with advanced disease and not reached in those with early-stage disease (p = 0.003). Median PFS was 22 months overall, and significantly longer in early-stage than advanced disease (50 vs. 15 months, p = 0.009). Advanced stage, blood involvement, and elevated LDH were significant predictors of worse PFS.

Conclusion: This study provides the first real-world analysis of CTCL outcomes in Kuwait. The findings underscore the importance of early detection and the role of novel therapies in disease management.

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.