International Journal of Hematology最新文献

The GVH3001 study assessed the efficacy and safety of ibrutinib in Japanese patients with steroid-dependent or -refractory chronic graft-versus-host disease (cGVHD). However, the effects of ibrutinib on lung function and reduction in corticosteroid dose, which is a measurable factor associated with improved quality of life, could not be adequately assessed in patients who initially presented with lung involvement. This post hoc analysis aimed to evaluate temporal changes in daily corticosteroid dose, as well as effectiveness outcomes based on lung function and symptom burden (percent predicted forced expiratory volume in 1 s [%FEV₁] and Lee cGVHD Symptom Scale lung subscale score, respectively) in the subgroup of patients with cGVHD who had lung involvement at baseline. Seven of the 19 patients in the GVH3001 study had lung involvement at baseline. The daily corticosteroid dose for cGVHD decreased in five of these patients, and %FEV₁ remained relatively stable in two patients but increased to > 80% in one patient. Lee cGVHD Symptom Scale scores were relatively stable throughout the study in patients with lung involvement. Ibrutinib may allow corticosteroid dose reduction without worsening lung function or increasing symptom burden in previously treated patients with cGVHD and associated lung involvement.

T cell-replete haploidentical hematopoietic stem cell transplantation (TCR-haplo-HSCT) is a potentially curative therapy for pediatric intractable hematological malignancies due to its graft-versus-leukemia efficacy. This single-center cohort study examined the effects of graft composition (T cell type and dose) on pediatric TCR-haplo-HSCT outcomes in 32 children with relapsed/intractable hematological malignancies. Graft T cell composition was classified using flow cytometry. High graft CD8⁺ T cell doses reduced disease relapse and improved overall survival and event-free survival, but did not increase transplant-related mortality and the incidence of grade III/IV acute graft-versus-host disease. Doses of grafted CD3⁺, CD4⁺, and CD34⁺ T cells did not affect patient outcomes. Children with differing event-free survival times were divided by a graft CD8⁺ T cell dose cut-off of 2.03 × 10⁸ kg^-1. These findings revealed that grafted CD8⁺ T cells improved the graft-versus-leukemia effect of pediatric TCR-haplo-HSCT without increasing the risk of transplant-related mortality.

After recent advances in sequencing technologies led to the discovery of novel genes associated with predisposition to hematological malignancies, studies have now shown that myeloid neoplasms associated with germline variants are more common than previously estimated. Based on these findings, myeloid neoplasms with germline predisposition have emerged as a unique category in the recent World Health Organization classification of Haematolymphoid Tumors. Clonal hematopoiesis is common in healthy individuals, particularly in older people. In patients with germline predisposition to hematological malignancies, clonal hematopoiesis is frequently observed at younger ages and is often associated with unique disease-specific driver mutations, some of which are hypothesized to compensate for the inherited defect. This review summarizes recent findings on clonal hematopoiesis in cancer predisposition syndromes.

Due to the poor prognosis of adult T-cell leukemia/lymphoma (ATL), new treatments are urgently needed, especially for elderly patients with aggressive ATL. The anti-CCR4 antibody drug mogamulizumab (MOG) has been approved for the treatment of untreated ATL. To analyze the impact of MOG on elderly patients, we conducted a retrospective analysis of patients aged 70 years and older with aggressive ATL diagnosed at our institution between 2015 and 2021. Among 32 patients, including those who received best supportive care, the median survival time (MST) and 2-year overall survival (OS) rate were 14.6 months (range, 0.0-83.7), and 34.7% [95% confidence interval (CI), 18.2-51.9], respectively, which were better than outcomes in our previous study. The MST and 2-year OS for patients treated with MOG-containing chemotherapy were 18.1 months (range, 4.0-83.7) and 45.0% (95%CI, 23.1-64.7), respectively, demonstrating clear improvement. Adverse events observed with MOG-containing treatment, such as myelosuppression and skin rash, were similar to those reported previously. Univariate analysis identified comorbidity as a predictor of poor outcomes, but not intensity of MOG-containing treatment, suggesting a different mechanism of action than that of classical chemotherapy. Our study suggests that MOG-containing treatments are an option for elderly patients with ATL.

Sutimlimab, a complement inhibitor, has recently been approved in Japan for treating cold agglutinin disease (CAD). We report the safety and efficacy of sutimlimab in Japanese patients with CAD who completed a global phase 3 clinical trial (CARDINAL/CADENZA: 26-week treatment with 1-2 years of open-label extension [OLE] periods) and subsequently participated in the Japanese OLE study. Patients with a recent history of blood transfusion (CARDINAL, n = 3) and those without (CADENZA, n = 4) were analyzed (71.4% female; median [range] baseline age: 70 [46-83] years). For CARDINAL/CADENZA, the treatment duration (median [range]) was 140.9 (104.9-157.3) weeks, and the cessation period was 70 (61-133) weeks. For the Japanese OLE study, the treatment duration was 47.1 (15.1-49.1) weeks. Three (42.9%) patients experienced treatment-related and treatment-emergent adverse events (TEAEs): injection site erythema, cystitis bacterial, viral infection, and blood pressure increased during CARDINAL/CADENZA. One (14.3%) patient experienced one treatment-related TEAE (urinary tract infection) during the Japanese OLE study. One patient died of renal failure, considered unrelated to sutimlimab, that was exacerbated by hepatorenal syndrome due to liver cirrhosis and bacterial peritonitis, in addition to CKD. Hemoglobin and bilirubin levels improved during treatment but deteriorated after withdrawal and recovered on retreatment. Sutimlimab was well tolerated over a median of 3.8 years, with no new safety concerns identified during retreatment.

Introduction: The recently developed platelet aggregation technique based on low-angle light scattering (LaSca) in diluted platelet-rich plasma (PRP) requires only a small sample volume and provides information about platelet aggregation and shape change. This study aimed to investigate the influence of preanalytical and analytical variables and to validate the method in a real-life pediatric hematology hospital setting.

Methods: Platelet aggregation was induced by ADP in diluted PRP in the presence of 2 mM calcium at 23 °C. The study included healthy adults (n = 30), healthy children (n = 20), and pediatric patients with suspected or diagnosed platelet function abnormalities (n = 25).

Results: The assay parameters were stable for at least 3 h after isolation of PRP and were sensitive to plasma dilution in the range of 2-8%. The initial aggregation velocity was significantly reduced in pediatric patients compared with healthy children (p < 0.05). ADP-induced light transmission amplitude was moderately correlated with LaSca amplitude of aggregation in healthy children (p = 0.52, p < 0.05) but not in pediatric patients.

Conclusions: We standardized the protocol for platelet aggregation assessment by LaSca and characterized the influence of preanalytical and analytical variables on it.

We report the first large-scale retrospective cohort study on adolescent and young adult (AYA) polycythemia vera (PV) and essential thrombocythemia (ET) in Japan, a subgroup analysis using Japanese multicenter registry data (JSH-MPN-R18). This study included patients with PV (n = 31) or ET (n = 141) aged 20 to 39 years at the initial visit. Hemorrhage-free survival (HFS) was better in AYA ET than in non-AYA ET (5-year HFS: 100% vs. 88.6%, p < 0.01), which might be attributed to differences in antithrombotic treatment rates between AYA and non-AYA patients. Although thrombosis-free survival did not differ statistically, the percentage of venous thrombotic events (TEs) among total TEs was higher in AYA compared to non-AYA PV and ET in Japan (26.0% vs. 6.0%, p < 0.01), but much lower than figures reported in European or US cohorts. Cytoreductive therapy (CRT) was administered to 25.8% of AYA patients with PV and 43.3% of AYA patients with ET, and the reason was usually unrelated to high risk of thrombosis. These results could be used to develop a more appropriate strategy for managing PV and ET in the Japanese AYA population.

Paroxysmal cold hemoglobinuria (PCH) is a form of cold autoimmune hemolytic anemia characterized by the presence of the Donath-Landsteiner antibody, which triggers complement-mediated intravascular hemolysis when the body temperature changes from cold to warm. PCH occurs primarily in children as a rare, self-limiting disease following viral infections. In contrast, adult-onset PCH is very rare and associated with a diverse range of underlying conditions, which complicates its management and treatment. We describe a case of adult-onset PCH following COVID-19, effectively managed with a single dose of sutimlimab, a selective classical complement pathway inhibitor. This intervention was performed during a life-threatening hemolytic crisis, at a time requiring swift decision-making when specific tests to differentiate from other hemolytic anemias were not readily available. This case illustrates the potential of using a single dose of sutimlimab to manage life-threatening hemolytic crises in PCH, highlighting the significance of inhibiting the classical complement pathway.