Gomez E, Duléry R, Langlois C, Coiteux V, Terriou L, Magro L, Gauthier J, de Berranger E, Duhamel A, Yakoub-Agha I
Unité de Greffe de Cellules Souches Hématopoïétiques, Service des Maladies du Sang, CHRU Lille, Lille, France.
Centre d'Etude et de Recherche en Informatique Médicale, Faculté de Médecine Lille 2, Lille, France.
Bone Marrow Transplant. 2014 Dec;49(12):1492-7. doi: 10.1038/bmt.2014.193. Epub 2014 Sep 15.
In an attempt to reduce the incidence of chronic GVHD (cGVHD) after reduced-intensity conditioning (RIC), we used BM instead of PBSC and added melphalan 100 mg/m(2) to the classical association of fludarabine, 30 mg/m(2)/day for 3 days and TBI, 200 cGy (FLUIM regimen). Between 2000 and 2012, 51 patients received BM with the FLUIM regimen (group A), and 124 received BM (n=22) or PBSC (n=102) with another RIC regimen (group B). Donors were siblings (n=123) or HLA-matched 10/10 unrelated (n=52). Full donor-type chimerism at day 100 was more often recorded in group A (86%) than in group B (62%); P<0.001. There was no difference between the two groups in terms of OS and EFS, acute GVHD, relapse and non-relapse mortality incidence. cGVHD occurred more often in group B (41%) than in group A (23%); P=0.021. In multivariate analysis, the two risk factors associated with the development of cGVHD were conditioning in group B (hazard ratio (HR)=2.871, 95% confidence interval (CI) (1.372-6.006); P=0.005) and CD34(+) count (HR=1.009, 95% CI (1.006-1.011); P<0.001). In conclusion, the FLUIM regimen followed by BM leads to more frequent full-donor chimerism and a reduced incidence of cGVHD without compromising relapse and survival.
为降低减低预处理强度（RIC）后慢性移植物抗宿主病（cGVHD）的发生率，我们使用骨髓（BM）而非外周血干细胞（PBSC），并在经典的氟达拉滨（30mg/m²/天，共3天）和全身照射（TBI，200cGy）方案（FLUIM方案）中加入100mg/m²的美法仑。2000年至2012年期间，51例患者接受了FLUIM方案的骨髓移植（A组），124例患者接受了骨髓移植（n = 22）或外周血干细胞移植（n = 102）以及另一种RIC方案（B组）。供者为同胞（n = 123）或10/10 HLA配型相合的无关供者（n = 52）。A组在第100天时完全供者型嵌合的发生率（86%）高于B组（62%）；P<0.001。两组在总生存期（OS）、无事件生存期（EFS）、急性移植物抗宿主病、复发及非复发死亡率方面无差异。cGVHD在B组的发生率（41%）高于A组（23%）；P = 0.021。多因素分析显示，与cGVHD发生相关的两个危险因素为B组的预处理方案（风险比（HR）= 2.871，95%置信区间（CI）（1.372 - 6.006）；P = 0.005）和CD34⁺细胞计数（HR = 1.009，95%CI（1.006 - 1.011）；P<0.001）。总之，采用FLUIM方案后进行骨髓移植可导致更频繁的完全供者嵌合，并降低cGVHD的发生率，且不影响复发率和生存率。
