Department of Hematology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan.
Department of Hematology, Osaka International Cancer Institute, Osaka, Japan.
Transplant Cell Ther. 2024 May;30(5):514.e1-514.e13. doi: 10.1016/j.jtct.2024.02.017. Epub 2024 Feb 18.
The purine analog fludarabine (Flu) plays a central role in reduced-intensity conditioning and myeloablative reduced-toxicity conditioning regimens because of limited nonhematologic toxicities. Few reports assess the impact of different dose of Flu on the clinical outcomes and the Flu doses vary across reports. To compare the effect of Flu dose, the clinical outcomes of patients who received Flu and busulfan (FB; n = 1647) or melphalan (Flu with melphalan (FM); n = 1162) conditioning for unrelated bone marrow transplantation were retrospectively analyzed using Japanese nationwide registry data. In the FB group, high-dose Flu (180 mg/m; HFB) and low-dose Flu (150/125 mg/m; LFB) were given to 1334 and 313 patients, respectively. The 3-year overall survival (OS) rates were significantly higher in the HFB group than in the LFB group (49.5% versus 39.2%, P < .001). In the HFB and LFB groups, the cumulative incidences were 30.4% and 36.6% (P = .058) for 3-year relapse and 25.1% and 28.1% (P = .24) for 3-year nonrelapse mortality (NRM), respectively. In the multivariate analysis for OS and relapse, Flu dose was identified as an independent prognostic factor (hazard ratio: 0.83, P = .03; hazard ratio: 0.80, P = .043). In the FM group, high-dose Flu (180 mg/m; HFM) and low-dose Flu (150/125 mg/m; LFM) were given to 118 and 1044 patients, respectively. The OS, relapse, and NRM after 3 years did not differ significantly between the HFM and LFM groups (48.3% versus 48.8%, P = .92; 23.7% versus 27.2%, P = .55; 31.9% versus 30.8%, P = .67). These findings suggest that high-dose Flu was associated with favorable outcomes in the FB group but not in the FM group.
嘌呤类似物氟达拉滨（Flu）由于其非血液学毒性有限，在减强度预处理和骨髓清除性低毒性预处理方案中起着核心作用。很少有报道评估氟达拉滨剂量对临床结果的影响，而且不同的报道氟达拉滨剂量也不同。为了比较氟达拉滨剂量的影响，我们使用日本全国登记数据回顾性分析了接受氟达拉滨和白消安（FB；n=1647）或氟达拉滨和马法兰（Flu 联合马法兰（FM）；n=1162）预处理的无关骨髓移植患者的临床结果。在 FB 组中，1334 例和 313 例患者分别接受高剂量氟达拉滨（180mg/m；HFB）和低剂量氟达拉滨（150/125mg/m；LFB）。HFB 组的 3 年总生存率（OS）明显高于 LFB 组（49.5%对 39.2%，P<.001）。在 HFB 和 LFB 组中，3 年复发的累积发生率分别为 30.4%和 36.6%（P=0.058），3 年非复发死亡率（NRM）分别为 25.1%和 28.1%（P=0.24）。在 OS 和复发的多变量分析中，氟达拉滨剂量被确定为独立的预后因素（危险比：0.83，P=0.03；危险比：0.80，P=0.043）。在 FM 组中，118 例和 1044 例患者分别接受高剂量氟达拉滨（180mg/m；HFM）和低剂量氟达拉滨（150/125mg/m；LFM）。3 年后 HFM 和 LFM 组的 OS、复发和 NRM 无显著差异（48.3%对 48.8%，P=0.92；23.7%对 27.2%，P=0.55；31.9%对 30.8%，P=0.67）。这些发现表明，高剂量氟达拉滨与 FB 组的良好结果相关，但与 FM 组无关。
