International Journal of Hematology最新文献

Purpose: This study investigated the correlation between plasma biomarker levels and post-transplant complications of allo-HSCT in children. The biomarkers analyzed were sST2, REG3α, TNFR1, IL-6, and IL-8.

Methods: From January 1, 2019 to October 30, 2024, specimens from 157 patients were collected at aGVHD onset or when aGVHD was clinically presumed to be likely to occur.

Results: Patients with aGVHD and intestinal aGVHD had significantly elevated sST2 levels. Patients with grade III/IV aGVHD had significantly higher sST2 and REG3α levels than patients with grade I/II aGVHD. OS and NRM differed significantly between patients with high sST2 and REG3α indexes (sST2 ≥ 124,090 pg/ml and REG3α ≥ 17,176 pg/ml) and those with low sST2 and REG3α indexes (P < 0.05). Univariate logistic regression analysis indicated that aGVHD, SOS, and TA-TMA were correlated with elevated sST2 and REG3α levels. Multivariate logistic regression analysis indicated that grade III/IV aGVHD was significantly associated with elevated sST2 and REG3α levels (each P = 0.003).

Conclusions: Elevated sST2 and REG3α can reflect the occurrence and severity of aGVHD. Acute GVHD, SOS, and TA-TMA can all lead to fluctuations in sST2 and REG3α levels, and warrant further study.

Although several studies suggest that higher busulfan exposure is associated with neurotoxicity, research on the relevance of pharmacokinetic parameters is limited. The aim of this study was to explore the impact of busulfan area under the concentration-time curve (AUC) on the development of neurological complications in children and adolescents receiving busulfan-containing conditioning regimens. Patients aged 0-20 years who received a busulfan-based regimen at our hospital between June 2017 and May 2024 were analyzed. The primary outcome measure was the incidence of neurological complications within 7 days of starting busulfan. A total of 36 consecutive patients were analyzed. Median busulfan AUC across 96 h (AUC96) was 86.3 (interquartile range 73.6-100.8) mg × h/L. Overall, 13 (36%) patients developed neurological complications, including 2 patients with grade 3 seizures. The AUC96 cut-off value was set at 80.0 mg × h/L (sensitivity 85%, specificity 57%, area under the receiver-operating characteristic curve 0.71). A higher incidence of neurological complications was observed in the AUC96 > 80.0 mg × h/L group than in the AUC96 ≤ 80.0 mg × h/L group (50% vs. 14%, P = 0.033). These results suggest that a higher busulfan AUC96 may be associated with an increased risk of neurological complications.

Background: Hearing loss is a recognized permanent consequence (PC) of Langerhans cell histiocytosis (LCH). However, its characteristics and association with central nervous system (CNS)-related PCs remain unclear.

Procedure: This study retrospectively analyzed the data of 317 pediatric patients with multisystem or multifocal bone LCH enrolled in the Japan LCH Study Group -96 or -02 trial.

Results: Hearing loss was identified in nine patients (2.8%), a lower incidence than previously reported. It was significantly associated with ear lesions, but not with craniofacial bone involvement at the time of diagnosis. Detailed information was available for seven patients: Three had sensorineural hearing loss, and four had mixed-type hearing loss without hearing improvement. At the last follow-up, hearing loss was unilateral in six cases and bilateral in one, with severity ranging from moderate (n = 1) to severe (n = 2) and profound (n = 4). CNS-PCs were found in five patients and were significantly associated with hearing loss (p = 0.018). One patient without ear lesions developed progressive sensorineural hearing loss due to neurodegeneration (ND).

Conclusions: Patients with hearing loss should be closely monitored for CNS-PCs, and those with LCH-associated ND should be carefully monitored for the development of sensorineural hearing loss.

TAFRO syndrome is a rare systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly. Its pathogenesis remains elusive, and its non-specific symptoms overlap with idiopathic multicentric Castleman disease, complicating its management. This report discusses two cases of TAFRO syndrome resistant to conventional treatments, including corticosteroids, tocilizumab, and rituximab. Both patients showed significant clinical improvement after treatment with ruxolitinib, a JAK-STAT pathway inhibitor. The first patient was a 55-year-old man who showed clinical improvement with ruxolitinib after the failure of multiple lines of treatment, including corticosteroids, tocilizumab, rituximab, and cyclosporin A. The second was another 55-year-old man who experienced disease relapse 18 months after initial treatment but responded rapidly to ruxolitinib. These cases highlight the potential role of ruxolitinib as a therapeutic option for refractory TAFRO syndrome. In addition, Epstein-Barr virus (EBV) DNA was detected in the serum of the first patient, making this the first report to demonstrate the effectiveness of ruxolitinib in EBV-associated TAFRO syndrome. These findings highlight the need for further studies to confirm the efficacy of ruxolitinib in such cases and elucidate the pathophysiological mechanisms underlying TAFRO syndrome, which could guide future therapeutic strategies.

Background: The CD3xCD20 bispecific antibody epcoritamab demonstrated deep, durable responses with manageable safety in relapsed/refractory (R/R) follicular lymphoma (FL) in EPCORE NHL-3 (phase 1/2; NCT04542824). This analysis evaluated 3-year follow-up outcomes in Japanese patients.

Methods: Adults with CD20 + FL and ≥ 2 prior lines of therapy (LOTs) received subcutaneous epcoritamab (0.16/0.8-mg step-up doses; 48-mg full doses) until disease progression or death. The primary endpoint was overall response rate (ORR).

Results: Twenty-one patients received epcoritamab (median age: 65 years; median prior LOTs: 4; 57.1% double refractory; 57.1% progressed within 24 months of any first-line treatment). At a median follow-up of 35 months, the ORR was 95.2% and the complete response (CR) rate was 76.2%. Median duration of response, duration of CR, progression-free survival, and overall survival were not reached. At 3 years, 66.7% and 93.3% of complete responders remained progression-free and alive, respectively. Minimal residual disease negativity was achieved in 88.9% (16/18) of evaluable patients. Common treatment-emergent adverse events included cytokine release syndrome (90.5%) and injection-site reaction (71.4%), all predominantly grade 1-2 and occurring in early treatment cycles, and none fatal.

Conclusions: Epcoritamab monotherapy provided durable long-term remission with favorable safety in Japanese patients with R/R FL over 3 years of follow-up.

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.