Abstract:
With the use of post-transplantation cyclophosphamide (PTCy), the outcomes of mismatched related donor hematopoietic cell transplantation (HCT) are now approaching those of matched donor HCT. Here we compared haploidentical donor HCT versus HLA-matched unrelated donor (MUD) HCT and HLA-identical sibling donor (MSD) HCT in a cohort in which all patients received PTCy for graft-versus-host disease (GVHD) prophylaxis. We included 661 patients (275 haploidentical, 246 MUD, and 140 MSD HCT). The most common diagnoses were acute myelogenous leukemia and myelodysplastic syndrome. In multivariate analysis, the haploidentical group was found to have significantly higher nonrelapse mortality (NRM) (hazard ratio [HR], 3.2; 95% confidence interval [CI], 2 to 4.9; P < .001) and inferior progression-free survival (HR, 1.8; 95% CI, 1.4 to 2.4; P < .001) and overall survival (OS; HR, 2.2; 95% CI, 1.6 to 3; P < .001) compared with the MUD group. Relapse was the most common cause of death in all groups. Among causes of NRM, the haploidentical group had more infection-related deaths and fewer GVHD-related deaths than the other groups. The haploidentical group also had a higher risk of viral and fungal infections, grade ≥3 hemorrhagic cystitis, and cardiovascular toxicities and slower reconstitution of CD4, CD8, and regulatory T cells but faster reconstitution of natural killer cells. In an exploratory analysis, older patients with older donors (>50 years for both) appeared to have particularly high NRM and lower OS in the haploidentical group compared with the other groups. Our data suggest that even with the use of PTCy, the outcomes of haploidentical HCT are inferior to those of HLA-matched donor HCT.
摘要:
随着移植后环磷酰胺(PTCy)的使用,不匹配相关供者造血细胞移植(HCT)的结局现在接近匹配供者HCT的结局.在这里,我们比较了单倍体相同的供体HCT与HLA匹配的无关供体(MUD)HCT和HLA相同的同胞供体(MSD)HCT,其中所有患者均接受PTCy预防移植物抗宿主病(GVHD)。我们纳入661例患者(275例单倍体,246泥浆,和140MSDHCT)。最常见的诊断是急性骨髓性白血病和骨髓增生异常综合征。在多变量分析中,发现单倍体组的非复发死亡率(NRM)明显更高(风险比[HR],3.2;95%置信区间[CI],2至4.9;P<.001)和较差的无进展生存期(HR,1.8;95%CI,1.4~2.4;P<.001)和总生存期(OS;HR,2.2;95%CI,1.6~3;P<.001)与MUD组比较。复发是所有人群中最常见的死亡原因。在NRM的原因中,与其他组相比,单倍体组感染相关死亡较多,GVHD相关死亡较少.单倍体组病毒和真菌感染的风险也较高,≥3级出血性膀胱炎,和心血管毒性和CD4,CD8和调节性T细胞重建较慢,但自然杀伤细胞重建较快。在探索性分析中,与其他组相比,单倍体相合组的有年龄较大供者(均>50岁)的老年患者的NRM特别高,OS也特别低.我们的数据表明,即使使用PTCy,单倍体相合HCT的结局劣于HLA匹配供者HCT.