Fujioka Machiko, Itonaga Hidehiro, Nakazawa Hideyuki, Nishida Tetsuya, Kataoka Keisuke, Ikeda Takashi, Kako Shinichi, Matsuoka Ken-Ichi, Adachi Koji, Fujiwara Shin-Ichiro, Aotsuka Nobuyuki, Kawakita Toshiro, Sakaida Emiko, Kanda Yoshinobu, Ichinohe Tatsuo, Atsuta Yoshiko, Miyazaki Yasushi, Ishiyama Ken
Department of Hematology, Sasebo City General Hospital, Sasebo, Japan; Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan.
Transfusion and Cell Therapy Unit, Nagasaki University Hospital, Nagasaki, Japan.
Transplant Cell Ther. 2025 Jan;31(1):18.e1-18.e12. doi: 10.1016/j.jtct.2024.09.026. Epub 2024 Oct 6.
The fludarabine/intravenous busulfan 12.8 mg/kg (FB4) regimen is an effective conditioning regimen in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome (MDS); however, limited data is available on the prognostic impact of FB4 with low-dose anti-thymoglobulin (ATG ≤ 5 mg/kg) or low-dose total body irradiation (TBI ≤ 4 Gy). Therefore, we retrospectively evaluated the outcomes in 280 adults with de novo MDS who underwent their first transplantation from an unrelated donor between 2009 and 2018. Median age was 61 years (range, 16 to 70 years). In the FB4 alone (FB4), FB4 plus ATG (FB4-ATG), and FB4 plus TBI (FB4-TBI) groups, 3-years overall survival (OS) rates were 39.9%, 64.8%, and 43.7%; 3-years nonrelapse mortality (NRM) were 32.1%, 22.1%, and 27.1%; and 3-years relapse incidences were 34.7%, 21.2%, and 28.9%, respectively. The multivariate analyses showed that FB4-ATG group significantly correlated with better OS (hazard Ratio [HR], 0.51; 95% confidence interval [CI], 0.27 to 0.95; P = .032) than FB4 group. FB4-ATG group tended to correlate with lower NRM (HR, 0.36; 95% CI, 0.13 to 1.06; P = .063) than FB4 group. In comparison with FB4-TBI group, FB4-ATG group showed better OS (HR 0.52, 95% CI 0.27 to 0.99, P = .049) and NRM (HR 0.034, 95% CI 0.11 to 0.92, P = .034). No significant differences were observed in OS and NRM between the FB4-TBI and FB4 groups. The present study demonstrated that the FB4 plus low-dose ATG regimen improved OS and NRM, but FB4 plus low-dose TBI regimen had no clear benefit over FB4 alone, in MDS patients who used unrelated donors.
氟达拉滨/静脉注射白消安12.8mg/kg（FB4）方案是骨髓增生异常综合征（MDS）异基因造血干细胞移植中一种有效的预处理方案；然而，关于低剂量抗胸腺细胞球蛋白（ATG≤5mg/kg）或低剂量全身照射（TBI≤4Gy）的FB4方案的预后影响，现有数据有限。因此，我们回顾性评估了2009年至2018年间280例首次接受无关供体移植的初发MDS成年患者的结局。中位年龄为61岁（范围16至70岁）。在单纯FB4（FB4）组、FB4加ATG（FB4-ATG）组和FB4加TBI（FB4-TBI）组中，3年总生存率（OS）分别为39.9%、64.8%和43.7%；3年非复发死亡率（NRM）分别为32.1%、22.1%和27.1%；3年复发率分别为34.7%、21.2%和28.9%。多因素分析显示，与FB4组相比，FB4-ATG组与更好的OS显著相关（风险比[HR]，0.51；95%置信区间[CI]，0.27至0.95；P = 0.032）。FB4-ATG组与较低的NRM相关（HR，0.36；95%CI，0.13至1.06；P = 0.063），但与FB4组相比无统计学差异。与FB4-TBI组相比，FB4-ATG组显示出更好的OS（HR 0.52，95%CI 0.27至0.99，P = 0.049）和NRM（HR 0.034，95%CI 0.11至0.92，P = 0.034）。FB4-TBI组和FB4组之间在OS和NRM方面未观察到显著差异。本研究表明，在使用无关供体的MDS患者中，FB4加低剂量ATG方案改善了OS和NRM，但FB4加低剂量TBI方案与单纯FB4相比无明显益处。
