Bazarbachi Ali, Labopin Myriam, Battipaglia Giorgia, Djabali Azedine, Forcade Edouard, Arcese William, Socié Gerard, Blaise Didier, Halter Joerg, Gerull Sabine, Cornelissen Jan J, Chevallier Patrice, Maertens Johan, Schaap Nicolaas, El-Cheikh Jean, Esteve Jordi, Nagler Arnon, Mohty Mohamad
Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
Department of Anatomy, Cell Biology, and Physiological Sciences, American University of Beirut, Beirut, Lebanon.
Clin Hematol Int. 2019 Mar 18;1(1):58-74. doi: 10.2991/chi.d.190310.001. eCollection 2019 Mar.
Acute myeloid leukemia (AML) with -mutation carries a poor prognosis, and allogeneic stem cell transplantation (allo-SCT) is recommended at first complete remission (CR1). We assessed 462 adults (median age 50 years) with -mutated AML allografted between 2010 and 2015 from a matched related (40%), unrelated (49%), or haploidentical donor (11%). The median follow-up of alive patients was 39 months. Day-100 acute graft host disease (GVHD) grades II-IV and III-IV were encountered in 26% and 9%, whereas the 2-year incidence of chronic and extensive chronic GVHD were 34% and 16%, respectively. The 2-year incidences of relapse and nonrelapse mortality were 34% and 15%, respectively. The 2-year leukemia-free survival, overall survival (OS), and GVHD relapse-free survival (GRFS) were 51%, 59%, and 38%, respectively. In multivariate analysis, -mutation, transplantation in CR1, T-cell depletion, and posttransplant sorafenib improved OS, whereas more than one induction (late CR1) negatively affected OS. Similarly, NPM1-mutation, a haploidentical donor, T-cell depletion, and sorafenib maintenance improved GRFS, whereas late CR1 or persistent disease negatively affected it. In conclusion, FLT3-mutated AML remains a challenge even following allo-SCT. T-cell depletion and posttransplant sorafenib significantly improve OS and GRFS, and may be considered as standard of care.
伴有FLT3突变的急性髓系白血病（AML）预后较差，建议在首次完全缓解（CR1）时进行异基因干细胞移植（allo-SCT）。我们评估了2010年至2015年间接受移植的462例伴有FLT3突变的成年AML患者（中位年龄50岁），供者为匹配的亲属（40%）、非亲属（49%）或单倍体相合供者（11%）。存活患者的中位随访时间为39个月。100天时，II-IV级和III-IV级急性移植物抗宿主病（GVHD）的发生率分别为26%和9%，而慢性广泛性慢性GVHD的2年发生率分别为34%和16%。复发和非复发死亡率的2年发生率分别为34%和15%。2年无白血病生存率、总生存率（OS）和无GVHD复发生存率（GRFS）分别为51%、59%和38%。多因素分析显示，FLT3突变、CR1期移植、T细胞去除和移植后使用索拉非尼可改善OS，而不止一次诱导缓解（晚期CR1）对OS有负面影响。同样，NPM1突变、单倍体相合供者、T细胞去除和索拉非尼维持治疗可改善GRFS，而晚期CR1或疾病持续存在则对其有负面影响。总之，即使在allo-SCT后，FLT3突变的AML仍然是一个挑战。T细胞去除和移植后使用索拉非尼可显著改善OS和GRFS，可考虑作为标准治疗方案。
