Kumamoto Medical Center

This study aimed to identify patient groups in which myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) regimens induced superior progression-free survival (PFS) in patients with acute myeloid leukemia (AML) in complete remission (CR) using a machine-learning approach. Our study included 3273 patients aged 40–69 with AML in CR. The patients were divided into training (N = 2020) and validation cohorts (N = 1253). We employed a machine learning-based group identification model in the training cohort. Subsequently, in the validation cohort, we estimated the impact of the optimal conditioning group compared with the non-optimal conditioning group on PFS using an inverse probability weight analysis. The developed model was consistent with the eight factors and combinations, and the high score suggested that RIC was more appropriate than MAC. In the validation cohort, 127 patients with high scores and who received RIC and 769 patients with low scores and who received MAC were categorized into the optimal conditioning group (896, 71.5%). The weighted hazard ratio for PFS was 0.73 (95% confidence interval: 0.57–0.94) in the optimal conditioning group compared with the non-optimal conditioning group (P = 0.016). In conclusion, we developed an easy-to-use model that helps the physician choose a patient-specific conditioning regimen for patients with AML in CR.

Chemotherapy-induced nausea and vomiting (CINV) is a distressing adverse effect of chemotherapy that requires aggressive prevention. This study aimed to evaluate the antiemetic efficacy of a 4-day dexamethasone (DEX) regimen compared with the guideline-recommended 1-day DEX regimen against delayed CINV in patients receiving low-emetic-risk chemotherapy (LEC). Pooled patient-level data from a multicenter, prospective, observational study, including 132 patients receiving LEC, divided into 1-day and 4-day DEX groups, were analyzed. An inverse probability of treatment weighting (IPTW) model was applied to balance patient characteristics. The primary endpoint was the incidence of delayed CINV, with secondary endpoints including symptom severity, food intake, and daily incidence patterns. After IPTW adjustment, the incidence of delayed nausea was significantly lower in the 4-day DEX group (3.19%) than in the 1-day group (22.78%, p = 0.001), with no significant difference in acute nausea between the groups (14.49% vs. 5.83%, p = 0.167). In a multivariate model, both female sex and the 1-day DEX regimen were independently associated with a higher risk of delayed CINV. The 4-day DEX group showed favorable trends in nausea incidence, severity, and food intake regardless of the presence of acute CINV. Although 1-day DEX remains the standard approach recommended by antiemetic guidelines, a 4-day DEX regimen shows promise as an alternative strategy for managing delayed nausea, especially in patients who experience acute CINV or have inadequate symptom control.

SummaryThe prognosis for patients with relapsed/refractory (R/R) adult T‐cell leukaemia‐lymphoma (ATL) remains dismal. Recently, valemetostat, a dual inhibitor for enhancer of zeste homologue (EZH) 1 and 2, was approved in Japan for R/R aggressive ATL. However, there is no real‐world data on the efficacy and prognosis of valemetostat. We therefore analysed clinical outcomes in 28 patients with R/R aggressive ATL who received valemetostat at three hospitals in Kumamoto Prefecture between February 2023 and January 2025. The overall response rate (ORR) and complete response (CR) rate were 54.2% and 33.3% respectively. With a median follow‐up of 19.2 months (7.3–21.7) for surviving patients, the median survival time was 15.8 months and median progression‐free survival (PFS) was 8.3 months. The probabilities of 1‐year overall survival (OS) and PFS were 55.8% and 44.1% respectively. Furthermore, the probabilities of 1‐year duration of response and duration of CR were 56.2% and 71.4% respectively. Notably, the probability of 1‐year OS was 90.9% in patients who achieved CR/partial response (PR) (‘responders’) compared to 17.0% in patients who did not achieve CR/PR (p < 0.001). Thus, valemetostat has the potential to be a reliable therapy for patients with R/R aggressive ATL, especially for responders.

Chemotherapy-induced neutropenia has been identified as a potential prognostic marker for multiple cancers. However, only one retrospective study, NN-2301, has investigated the relationship between neutropenia and treatment effects of nanoliposomal irinotecan/5-fluorouracil/folinic acid (NFF) in pancreatic cancer. In this prospective study, we aimed to clarify whether NFF-induced neutropenia could serve as a prognostic marker in pancreatic cancer. Data were analyzed from the prospective cohort of the NAPOLEON-2 trial, an observational study involving patients with unresectable pancreatic cancer treated with NFF. Neutropenia severity was categorized into three cutoffs: Cutoff A (Grade [Gr] 0 vs. Gr 1-4), cutoff B (Gr 0-1 vs. Gr 2-4), and Cutoff C (Gr 0-2 vs. Gr 3-4), using the Common Terminology Criteria for Adverse Events version 5.0, owing to conformity with previous studies and simplicity. The primary endpoint was overall survival (OS); progression-free survival (PFS) was the secondary endpoint. The neutropenic groups included Gr 1, 2, 3, and 4, with 79, 23, 34, and 7 patients, respectively. At each cutoff, OS and PFS were significantly better in the severe neutropenia groups. Higher neutropenia grades correlated with improved OS (log-rank trend test: χ2 = 8.62, p < .01). Multivariate Cox regression analysis revealed significant differences for all cutoffs: adjusted hazard ratios were 0.57 (95% confidence interval [CI] 0.40-0.83) (Cutoff A), 0.53 (95% CI 0.36-0.78) (Cutoff B), and 0.52 (95% CI 0.34-0.80) (Cutoff C). NFF-induced neutropenia is a valuable prognostic marker in pancreatic cancer and may guide treatment selection.

The optimal alternative donor type for patients lacking human leucocyte antigen (HLA)-matched related or unrelated donors remains unclear. In comparative studies evaluating donor types, graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) represents a well-established end-point but has limitations. The win ratio approach addresses these limitations by analysing multiple end-points with varying severities to account for the relative component priorities. We compared HLA-mismatched unrelated donors, haploidentical donors and cord blood using both the hazard ratio (HR) of GRFS and the win ratio related to GRFS. The haploidentical donor group had a similar HR of GRFS (HR: 1.01, 95% confidence interval [CI]: 0.85-1.19, p = 0.916) and win ratio (win ratio: 0.86, 95% CI: 0.72-1.02, p = 0.081) to HLA-mismatched unrelated donors. Cord blood transplantation showed similar GRFS compared to HLA-mismatched unrelated donors in the Cox proportional model (HR: 1.14, 95% CI: 0.98-1.32, p = 0.085), significantly lower win ratio (win ratio: 0.80, 95% CI: 0.68-0.93, p = 0.004) and similar outcomes to haploidentical donors. HLA-mismatched unrelated donor transplantation showed comparable to superior outcomes among alternative donor types. Our results indicate the need to present the win ratio alongside conventional methods to assess the end-point robustly.

Midline establishment is a fundamental process during early embryogenesis for Bilaterians. Midline morphogenesis in non-amniotes can occur without mitosis, through Planar Cell Polarity (PCP) signaling. By contrast, amniotes utilize both cellular processes for developing the early midline landmark, the primitive streak (PS). This study focused on the role of cell proliferation for midline development at pre- and post-PS-extension stages and analyzed PCP signaling components at post-PS-extension stages. In contrast to pre-PS-extension stages, embryos under mitotic arrest during the post-PS-extension preserved notochord (NC) extension and Hensen's node (HN)/PS regression judged by both morphology and marker genes; although they became shorter, their lengths remained proportional to the embryo length. Laterality and segmentation of paraxial mesoderm were lost upon mitotic arrest. Accompanied by mitotic arrest-induced embryonic size reduction, cells including midline tissue displayed hypertrophy. This study has identified at least two distinct mitosis sensitivity phases during early midline development: One is PS extension that requires both mitosis and PCP, and the other is mitotic arrest-resistant midline development at post-PS-extension stages, with a still undefined influence by PCP signaling components.