Shinohara A., Shindo M., Yamasaki S., Kato K., Yoshihara S., Yamamoto G., Kataoka K., Ikeda T., Kobayashi H., Serizawa K., Mori Y., Takayama N., Nakazawa H., Ito A., Katayama Y., Kanda Y., Yoshimitsu2025 · 記述言語： 日本語 掲載種別： 研究論文（学術雑誌） 出版者・発行元： Transplantation and Cellular Therapy In recent years, there have been notable advancements in the treatment of malignant lymphoma. However, a certain percentage of patients are unlikely to achieve a cure through chemotherapy alone. Therefore, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a crucial curative treatment for malignant lymphoma. FluBu4, comprising fludarabine (Flu) combined with a myeloablative dose of intravenous busulfan (Bu; 12.8 mg/kg in total), is a widely used conditioning regimen for allo-HSCT, but its usefulness in malignant lymphoma (ML) has not been fully investigated. The objective of this study was to evaluate the efficacy and safety of FluBu4 in allo-HSCT for lymphoma by comparing the outcomes of two conditioning regimens: FluBu4 and FluMel140. We used a Japanese national database from the Transplant Registry Unified Management Program to retrospectively analyze the first allo-HSCT for ML in patients aged ≥16 years. Allo-HSCT cases treated with posttransplant cyclophosphamide were excluded. Two groups, namely FluBu4 and FluMel140 were selected by propensity score matching (PSM) with a case ratio of 1:2. From 921 cases, 113 were selected by PSM for the FluBu4 group and 226 for the FluMel140 group. The median age was 54 (19 to 68) years, the median observation period of survivors was 33.8 months, and 145 (42.7%) had a history of autologous HSCT. There were no significant differences in patients’ backgrounds between the two groups after PSM. Three-year overall survival (OS) was significantly worse for FluBu4 than for FluMel140 (28.0% versus 48.6%; P < .01). The 3-year cumulative relapse rate was comparable for FluBu4 and FluMel140 (40.1% versus 38.5%; P = .65). However, 3-year nonrelapse mortality was significantly higher for FluBu4 than for FluMel140 (35.3% versus 22.5%; P = .02). There was no significant difference between the two treatment groups in the cumulative incidence of acute graft-versus-host disease (aGVHD) at day 100 after allo-HSCT and the 3-year cumulative incidence of chronic GVHD. While the common and major cause of death was the relapse of lymphoma, aGVHD, and noninfectious lung complications were observed more frequently with FluBu4 than with FluMel140. One-year cumulative incidence of interstitial pneumonia was significantly higher for FluBu4 than for FluMel140 (5.3% versus 0.4%; P = .03). FluBu4 use was associated with worse nonrelapse mortality (NRM) and OS in allo-HSCT for ML compared with FluBu4 and FluMel140 adjusted by PSM. Patients treated with FluBu4 had a higher incidence of noninfectious pulmonary complications and an increased number of associated deaths. A higher rate of NRM in the patients treated with FluBu4 was particularly evident in patients aged ≥60, and its use should be avoided in this patient population. DOI： 10.1016/j.jtct.2025.03.008 Scopus PubMed
Okada Y, Sakatoku K, Shirane S, Murata M, Takenaka K, Hamano Y, Doki N, Kanda Y, Uchida N, Tanaka M, Nishida T, Ishikawa J, Asada N, Hasegawa Y, Machida S, Mori Y, Eto T, Yoshimitsu M, Fukuda T, Atsut2025 · 記述言語： 英語 掲載種別： 研究論文（学術雑誌） 出版者・発行元： Transplantation and Cellular Therapy The Dynamic International Prognostic Scoring System (DIPSS) for primary myelofibrosis (MF) has been reported to predict transplant outcomes in MF patients. Recently, the pretransplant use of JAK inhibitors has become common in clinical practice, but it is unclear whether DIPSS is also useful for predicting transplant outcomes for these patients. In this study, we compared the prognostic impact of DIPSS between MF patients with and without pretransplant ruxolitinib therapy. DIPSS stratified overall survival (OS) in patients without pretransplant ruxolitinib therapy (P = .002), but not in those with it (P = .23). In an exploratory analysis, palpable splenomegaly appeared to be a potential prognostic factor among patients who received pretransplant ruxolitinib therapy (hazard ratio [HR] 1.53, 95% confidence interval [CI]: 0.86 to 2.72, P = .15). Here we propose a modified scoring system, DIPSS with Splenomegaly (DIP3S), and demonstrate that DIP3S high-risk status (defined as DIPSS low-, intermediate-1-, and intermediate-2-risk with splenomegaly, or DIPSS high-risk) is independently associated with inferior OS (HR 2.20, 95% CI: 1.09 to 4.45, P = .027), delayed neutrophil engraftment (HR 0.54, 95% CI: 0.37 to 0.77, P < .001), and delayed platelet engraftment (HR 0.32, 95% CI: 0.20 to 0.52, P < .001). On the other hand, neither DIPSS (HR 0.62, 95% CI: 0.34 to 1.12, P = .11 for low/intermediate-1-risk; HR 0.96, 95% CI: 0.50 to 1.84, P = .90 for high-risk) nor splenomegaly (HR 1.51, 95% CI: 0.83 to 2.75, P = .17) was significantly associated with inferior OS when each factor was independently included in the multivariable analysis. Therefore, the DIP3S risk may be able to identify high-risk patients among those who receive pretransplant JAK inhibitors. Further validation studies are needed to clarify the prognostic impact of DIP3S. DOI： 10.1016/j.jtct.2025.09.002 Scopus PubMed
