稲本 賢弘

Antiemetic therapy is an essential component of supportive care following hematopoietic stem cell transplantation (HSCT). Chemotherapy and irradiation used in conditioning regimens frequently induce severe nausea and vomiting, which can significantly impair patients' quality of life. Although recent guidelines recommend a triple combination of a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist, dexamethasone, and an neurokinin 1 (NK1) receptor antagonist, antiemetic practices vary widely across countries and regions. This study aimed to investigate current antiemetic policies among the Asia-Pacific Blood and Marrow Transplantation (APBMT) centers. A web-based questionnaire survey using SurveyMonkey was distributed via email from the APBMT office between December 7, 2021, and January 21, 2022. The survey addressed antiemetic strategies used in HSCT conditioning regimens. Responses were received from 28 centers across 14 countries. Among the participating centers, 93% reported that physicians were primarily responsible for antiemetic decision-making, with limited involvement from pharmacists or multidisciplinary teams. The most commonly used conditioning regimens for allogeneic HSCT were busulfan and cyclophosphamide (Bu-CY) (72%) and fludarabine and busulfan (Flu-Bu) (62%), whereas high-dose melphalan (83%) and carmustine (BCNU), etoposide, cytarabine arabinoside, and melphalan (BEAM) (69%) were predominant for autologous HSCT. Despite guidelines recommending olanzapine as an additional antiemetic in highly emetogenic chemotherapy, its routine implementation remains limited, even in high-risk settings. Notably, dexamethasone is frequently avoided in allogeneic HSCT, likely due to concerns about its immunosuppressive effects. The incidence of vomiting varied, with 36% of centers reporting rates of 10% or higher, even among those with institutional antiemetic policies. In conclusion, this survey highlighted substantial variation in antiemetic strategies across the APBMT centers. The limited use of olanzapine reflects ongoing concerns regarding its side effects, while the frequent avoidance of dexamethasone in allogeneic HSCT represents a deviation from current guideline recommendations. Given the complexity of HSCT and the varying side effect profiles of antiemetic agents, a multidisciplinary approach to treatment planning, including that of pharmacists and dietitians, could optimize supportive care. Future prospective studies are warranted to evaluate the safety, efficacy, and feasibility of olanzapine- and steroid-sparing antiemetic strategies to improve patient outcomes.

Chronic graft-versus-host disease (cGVHD) is a leading cause of late morbidity and mortality after allogeneic hematopoietic cell transplantation. Corticosteroids remain the standard first-line therapy; however, many patients develop steroid-refractory or steroid-dependent disease, underscoring the need for more effective and better-tolerated treatments. Ruxolitinib has emerged as the most evidence-supported option for steroid-refractory cGVHD, with the phase 3 REACH3 trial demonstrating higher response rates, durable disease control, and clinically meaningful improvements in symptom burden compared with best available therapy. Belumosudil and axatilimab have also shown encouraging efficacy and safety in heavily pretreated populations. The addition of novel agents to standard corticosteroid-based therapy has been explored in clinical trials. Interest in combination strategies, such as ruxolitinib with extracorporeal photopheresis or belumosudil, is increasing, though prospective studies are required to define their role. Key challenges include optimizing long-term safety, mitigating infectious complications, and preserving the graft-versus-leukemia effect. This review summarizes current therapeutic strategies and discusses evolving treatment algorithms, emphasizing practical considerations in therapy selection. Approaches targeting specific pathogenic mechanisms, combining agents with distinct mechanisms of action, and incorporating biomarker-driven strategies are expected to further improve outcomes and quality of life for patients with cGVHD.

BACKGROUND/AIM:  Bruton's tyrosine kinase inhibitors (BTKi) are important targeted agents for hematological malignancies. Second-generation BTKi are considered to have fewer off-target enzyme effects than first-generation agents; however, real-world comparative data on adverse events (AEs) remain limited. AEs of special interest with BTKi include bone marrow suppression, infection, hemorrhage, and cardiac-related events. This study aimed to investigate the frequency and severity of AEs of special interest associated with the three BTKi, namely, ibrutinib (IBR), tirabrutinib (TIR), and acalabrutinib (ACB), in real-world clinical practice. METHODS: We retrospectively investigated cytopenia and non-hematologic toxicities, including infections, bleeding, and cardiovascular AEs, for up to one year in patients who received BTKi at Fujita Health University Hospital and an affiliated hospital between March 2016 and March 2025 (IBR, n = 24; TIR, n = 24; ACB, n = 5). Data were collected from electronic medical records and graded according to the Common Terminology Criteria for Adverse Events, version 5.0. RESULTS: In the IBR group, the median age was 76 years (range, 76-81 years). Cytopenia, infections, bleeding, and cardiovascular AEs occurred in 21 (87.5%), nine (37.5%), eight (33.3%), and four (16.6%) patients, respectively. In the TIR group, the median age was 70 years (range, 64-76 years). Cytopenia, infections, and bleeding occurred in 17 (70.8%), seven (29.1%), and six (25.0%) patients, respectively. In the ACB group, the median age was 68 years (range, 52-75 years), and cytopenia was observed in four (80.0%) patients. CONCLUSION: All BTKi agents were associated with bone marrow suppression, infection, and bleeding, whereas cardiac-related AEs occurred only with IBR. Several Grade 3 or higher events were identified, underscoring the need for careful monitoring of patients receiving BTKi in clinical practice.

Adult T-cell leukemia-lymphoma (ATL) is one of the most intractable peripheral T-cell neoplasms caused by human T-cell leukemia virus type I (HTLV-1) infection. Recently, the incidence of HTLV-1 infection and ATL has increased in non-endemic metropolitan areas in Japan. This retrospective study evaluated the clinical features and outcomes of patients with aggressive ATL aged 70 years or younger treated at a core hospital in Tokyo between 2004 and 2016. The median follow-up was 124.4 months for survivors. Among the 71 patients, 46 (64.8%) underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). The 3 year overall survival rate was 45.7% in allo-HSCT group versus 0% in non-allo-HSCT group. Patients who achieved complete/partial remission before allo-HSCT had a significantly better survival rate than those with stable/progressive disease (51.4% vs 27.3%). The 2 year cumulative incidence of relapse/progression and non-relapse mortality after allo-HSCT was 41.3% and 21.7%, respectively. In this study, a large percentage of patients underwent allo-HSCT and achieved favorable outcomes. As cases continue to rise in metropolitan areas, core hospitals will play a critical role in ATL treatment.