International Journal of Hematology最新文献

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.

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.

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.

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.

Ruxolitinib, a Janus kinase (JAK1-JAK2) inhibitor, has demonstrated safety and efficacy in patients with graft-versus-host disease (GvHD). This phase 3 randomized trial (REACH3) evaluated the efficacy and the safety of ruxolitinib 10 mg twice daily compared with investigator-selected best available therapy (BAT) in a subgroup of Japanese patients (n = 37) with steroid-refractory or dependent (SR/D) chronic GvHD. At data cut-off, treatment was ongoing in 17 patients and discontinued in 20. The overall response rate (complete or partial) at week 24 was greater with ruxolitinib than BAT (50% vs. 20%; odds ratio, 4.13 [95% CI, 0.90-18.9]). The best overall response rate (complete or partial response at any time point up to week 24) was higher with ruxolitinib than BAT (68.2% vs. 46.7%; odds ratio, 2.69 [95% CI, 0.66-10.9]). Ruxolitinib led to longer median failure-free survival than BAT (18.6 months vs. 3.7 months; hazard ratio, 0.34; [95% CI, 0.14-0.85]). The most common grade ≥ 3 adverse events up to week 24 were anemia (ruxolitinib: 22.7%; BAT: 6.7%) and pneumonia (22.7% and 20.0%, respectively). Ruxolitinib showed a higher response rate and improvement in failure-free survival in Japanese patients with SR/D chronic GvHD, with a safety profile consistent with the overall study population.

Ropeginterferon alfa-2b (ropegIFN), a new-generation interferon-based agent, has been approved in Japan for patients with polycythemia vera (PV) who are ineligible for or respond inadequately to conventional treatment. However, long-term outcomes with ropegIFN in Japanese patients have not been reported. This extension of a phase 2 study of ropegIFN in Japanese patients with PV aimed to determine its long-term safety/efficacy, and changes over time in JAK2 V617F allele burden. Here, we report data from the phase 2 study and subsequent extension over a period of 36 months. The primary endpoint was the complete hematologic response (CHR) maintenance rate without phlebotomy (hematocrit value < 45% without phlebotomy during the previous 12 weeks, platelet count ≤ 400 × 10⁹/L, and white blood cell count ≤ 10 × 10⁹/L). The CHR maintenance rates were 8/27 (29.6%), 18/27 (66.7%), and 22/27 (81.5%) at 12, 24, and 36 months, respectively. No thrombotic or hemorrhagic events occurred. The median allele burden change from baseline was - 74.8% at 36 months. All patients experienced adverse events; 25/27 (92.6%) experienced adverse drug reactions (ADRs), but no serious ADRs or deaths occurred. This interim analysis demonstrated the safety and efficacy of ropegIFN over 36 months in Japanese patients with PV.

Idiopathic thrombocytopenic purpura (ITP), an autoimmune hematologic disorder characterized by severe platelet count reduction, can be treated with romiplostim. However, post-marketing safety and effectiveness data for romiplostim in Japan are scarce. This prospective, observational, post-marketing Specified Use-Results Survey evaluated the real-world safety and effectiveness of romiplostim for 2 years. All patients treated with romiplostim during the survey period were eligible. Of the 1622 patients in the safety analysis set, 94.08% (1526/1622) had chronic ITP. The mean single dose of romiplostim was stable after 12 weeks and remained < 6 μg/kg in approximately 70% of patients until 104 weeks. Within 2 years, 14.92% of patients discontinued romiplostim because of adverse events, while 6.47% discontinued because of suspected adverse drug reactions. In contrast, 14.00% of patients discontinued romiplostim because of symptom improvement. Before romiplostim initiation, platelet count was < 2.0 × 10⁴/µL in 60.54% of patients, and the mean platelet count was 2.84 ± 5.76 × 10⁴/µL. Platelet count was 9.19 ± 13.01 × 10⁴/µL after 4 weeks, and remained between 10.34 ± 10.72 and 12.38 ± 12.63 × 10⁴/µL from 8 to 104 weeks of treatment. No specific concerns were revealed regarding the safety and effectiveness of romiplostim in chronic ITP; the findings demonstrated a favorable risk-benefit balance for romiplostim in this population. Trial registration: UMIN000047864 ( www.umin.ac.jp/ctr ).