Masao Ogata

Background: Venetoclax‐based regimens (VEN) have been widely adopted as frontline therapeutic options for elderly patients with acute myeloid leukemia (AML). However, comprehensive real‐world comparisons of VEN with conventional intensive or reduced‐intensity chemotherapy remain limited. Methods: In this multicenter retrospective study, we evaluated treatment patterns and outcomes in 1370 patients with newly diagnosed AML. Patients were classified into three cohorts according to their frontline treatment: intensive chemotherapy (IC), reduced‐intensity chemotherapy (rIC), or VEN. Analyses were performed in both the overall cohort and elderly patients (aged ≥ 60 years), including baseline comparisons, uni‐ and multivariable analyses, and subgroup analyses. Results: Baseline characteristics differed substantially among treatment cohorts; patients treated with VEN were older and had a higher prevalence of adverse‐risk disease than those receiving IC or rIC . In the overall cohort, VEN achieved an overall response rate ( ORR ) comparable to IC and higher than rIC (74.3% vs. 60.2%, p = 0.034). Among elderly patients, VEN was associated with a higher ORR than rIC (75.7% vs. 50.5%, p = 0.001), and the favorable ORR findings remained significant after correction for multiple testing. VEN was also associated with a lower 60‐day early‐death rate than rIC in elderly patients (1.4% vs. 20.0%, p < 0.001), suggesting better early treatment tolerability. Median event‐free survival was longer with VEN than with rIC in the primary elderly cohort analysis (9.6 vs. 6.6 months, p = 0.031), and this difference persisted in a sensitivity analysis censoring at allogeneic hematopoietic stem cell transplantation, although it was attenuated in landmark and propensity‐score‐based sensitivity analyses. Overall survival did not differ significantly between the two cohorts (15.9 vs. 11.0 months, p = 0.102). Conclusion: The higher response rate and lower early mortality with VEN were the most consistent findings, whereas comparative survival outcomes were considered supportive but exploratory.

Background: Venetoclax is a B-cell lymphoma 2 inhibitor with breakthrough therapy designations and is used in the treatment of acute myeloid leukemia, particularly in patients ineligible for conventional cytotoxic chemotherapy. However, these drugs exhibit extensive pharmacokinetic variability among patients. Therapeutic drug monitoring (TDM) is useful in determining venetoclax dosage regimens. This study aimed to develop a high-throughput method for the quantification of plasma venetoclax concentration using ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) and to apply this method to TDM. Methods: After a simple solid-phase extraction step using a 96-well µElution plate, venetoclax was analyzed using UHPLC-MS/MS in positive electrospray ionization mode. This novel method fulfilled the requirements of the US Food and Drug Administration guidelines for bioanalytical assay validation, with a 4 ng/mL lower limit of quantification. The calibration curves were linear over a concentration range of 4–50,000 ng/mL. Results: The recovery rate was 96.2 ± 18.0% (mean ± SD). The imprecision was below 7.2% coefficient of variation, and the accuracy was within 10.4% for all quality control levels. The matrix effect varied from 80.6% to 97.9%. This assay was successfully applied to the TDM of trough concentrations in 3 patients treated with venetoclax for acute myeloid leukemia. Conclusions: We successfully developed a novel high-throughput UHPLC-MS/MS method for quantifying venetoclax in human plasma. This method can be applied for TDM in patients receiving venetoclax in clinical settings.

In this registry-based study, we evaluated the efficacy of different antiviral therapies for adult patients who developed human herpesvirus-6B (HHV-6B) encephalitis after their first cord blood transplantation (CBT). Among 3,862 CBT recipients registered in Japan between January 2019 and December 2023, HHV-6B encephalitis occurred in 289 patients within 100 days post-transplant (7.5%). Antiviral treatments included foscarnet (FCN) monotherapy (n = 190), ganciclovir (GCV) monotherapy (n = 12), and FCN/GCV combination therapy (n = 74). The FCN/GCV group was associated with a potential improvement in 1-year survival compared with the FCN and GCV groups (63.2% vs. 52.5% vs. 41.7%, p = 0.38). Moreover, FCN/GCV therapy was identified as an independent predictor of improved survival compared with FCN monotherapy (HR, 0.60; 95% CI, 0.38–0.95; p = 0.031). Furthermore, the combination FCN/GCV therapy showed better survival than FCN monotherapy in the patients after neutrophil engraftment (1-year survival 68.1% vs. 51.6%), but worse survival in patients before engraftment (1-year survival 34.1% vs. 54.6%). Together, these findings provide real-world evidence linking antiviral regimen selection to post-transplant outcomes in HHV-6B encephalitis and suggest that FCN/GCV combination therapy may offer a survival advantage over FCN monotherapy in selected CBT patients, with treatment strategies potentially tailored according to hematologic recovery.

Hematopoietic stem cell transplantation (HSCT) recipients are highly susceptible to viral infections, many of which are missed by conventional diagnostic tests owing to limited coverage and slow turnaround times. This single-center, prospective observational study evaluated a rapid multiplex PCR (mPCR) assay to detect 13 DNA viruses for diagnosis and management of post-HSCT viral infections. Between December 2020 and March 2025, 63 HSCT recipients with suspected viral infections underwent mPCR testing of blood (n = 51) or cerebrospinal fluid (CSF) (n = 12) in parallel with standard diagnostics. The mPCR results were reported within 24 h and integrated into clinical decision-making. The etiology was identified in 44 of 51 (86%) blood samples (30 infections) and 9 of 12 (75%) CSF samples (5 infections). mPCR provided the sole etiological diagnosis in 19 of 63 (30%) episodes: 15 of 51 (29%) blood and 4 of 12 (33%) CSF samples. mPCR enabled targeted treatment in 15 of 63 (24%) episodes: 11 of 51 (22%) blood and 4 of 12 (33%) CSF samples. Unexpected infections, such as varicella-zoster virus meningitis and human herpesvirus 7 encephalitis, were identified only by mPCR. Rapid mPCR provided timely, actionable diagnosis and directly influenced the clinical management of post-HSCT patients.

Background: Cytomegalovirus reactivation (CMV‐react) is an indicator for the worse non‐relapse mortality (NRM) and overall survival (OS) after allogeneic hematopoietic stem cell transplantation using HLA‐matched related donor (MRD) and unrelated donor (URD) for adult T‐cell leukemia/lymphoma (ATL). However, it remains unclear whether CMV‐react correlates with outcomes after unrelated cord blood (U‐CB) transplantation. Methods: We conducted a retrospective nationwide study to evaluate the impact of CMV‐react on the outcomes after posttransplant 100 days. Data were collected from 205, 461, and 268 patients who used MRD, URD, and U‐CB, respectively, between 2001 and 2022 and survived without relapse for over 100 days after transplantation. Results: In multivariate analyses, CMV‐react correlated with worse OS in the MRD (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.02–2.39; p = 0.04) and URD groups (HR, 1.45; 95% CI, 1.00–2.09; p = 0.05), but not in the U‐CB group (HR, 1.34; 95% CI, 0.88–2.03; p = 0.2). CMV‐react correlated with higher NRM in the MRD (HR, 1.79; 95% CI, 1.01–3.16; p = 0.05) and URD groups (HR, 1.68; 95% CI, 1.01–2.82; p = 0.05), but not in the U‐CB group (HR, 1.16; 95% CI, 0.62–2.19; p = 0.6). CMV‐react did not correlate with the incidence of relapse in any group. Conclusion: CMV‐react was not associated with the outcomes in the U‐CB group, while CMV‐react correlates with worse OS and NRM in the MRD and URD groups, indicating the need for a more intensive strategy for late‐phase complications in U‐CB transplantation for ATL with and without CMV‐react.