Grunwald Michael R, Sha Wei, He Jiaxian, Sanikommu Srinivasa, Gerber Jonathan M, Ai Jing, Knight Thomas G, Fasan Omotayo, Boseman Victoria, Kaizen Whitney, Chojecki Aleksander, Ragon Brittany K, Symanowski James, Avalos Belinda, Copelan Edward, Ghosh Nilanjan
Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, North Carolina; Section On Hematology and Medical Oncology, Wake Forest University School of Medicine, Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, North Carolina.
Department of Biostatistics and Data Sciences, Levine Cancer Institute, Atrium Health, Wake Forest University School of Medicine, Charlotte, NC, 28204.
Transplant Cell Ther. 2024 Dec;30(12):1211.e1-1211.e11. doi: 10.1016/j.jtct.2024.09.021. Epub 2024 Sep 26.
Using haploidentical donors for allogeneic hematopoietic cell transplantation (HCT) broadens transplant accessibility to a growing number of patients with hematologic disorders. Moreover, haploidentical HCT with post-transplant cyclophosphamide (PTCy) has become widespread practice due to accumulating evidence demonstrating favorable rates of survival and graft-versus-host disease (GvHD). Most studies comparing outcomes by donor sources have been confounded by variability in conditioning regimens, graft type (peripheral blood [PB] or bone marrow), and post-transplant GvHD prophylaxis (PTCy or non-PTCy), making it difficult to define the effect of donor source on outcomes. Levine Cancer Institute started a transplant and cellular therapy program in 2014, with both haploidentical and matched related donor (MRD) transplants initially performed using a uniform reduced-intensity conditioning (RIC) regimen, PB grafts, and PTCy-based GvHD prophylaxis. This retrospective observational study was conducted to compare the clinical outcomes associated with RIC haploidentical HCT and MRD HCT in patients receiving identical conditioning regimens, graft types, and supportive care. Our transplant database was queried to evaluate demographic characteristics, clinical features, and outcomes of RIC HCT for consecutive patients with hematologic malignancies who received haploidentical or MRD grafts between March 2014 and December 2017. An MRD was the preferred donor source; when unavailable, a haploidentical donor was used. Sixty-seven patients underwent haploidentical HCT and 25 MRD HCT. Overall, characteristics of transplant recipients were similar for the haploidentical and MRD groups; however, haploidentical donors were younger than MRDs (median 36 yr versus 57 yr, P < .0001). Results of univariable analysis showed similar overall survival (OS) for haploidentical and MRD HCT (hazard ratio [HR], 1.15; 95% CI, 0.61 to 2.15; P = .669). One-year, 1-yr, and 5-yr OS were 80.2%, 54.7%, and 41.2% for haploidentical HCT and 76.0%, 55.7%, and 51.1% for MRD HCT, respectively. With a median follow-up of 81.90 months, results of multivariable analysis revealed that donor source (haploidentical versus MRD) was not significantly associated with OS (HR, 0.97; 95% CI, 0.51 to 1.87; P = .933), relapse-free survival (HR, 0.75; 95% CI, 0.42 to 1.35; P = .337), cumulative incidence of relapse (HR, 0.81; 95% CI, 0.39 to 1.70; P = .579), or non-relapse mortality (HR, 1.12; 95% CI, 0.40 to 3.14; P = .827). Cumulative incidences of acute GvHD (aGvHD) and chronic GvHD (cGvHD) were not significantly different for haploidentical and MRD HCT (grades II to IV aGvHD: HR, 1.78; 95% CI, 0.72 to 4.37; P = .210; grades III to IV aGvHD: HR, 2.84; 95% CI, 0.34 to 23.63; P = .335; cGvHD: HR, 1.00; 95% CI 0.36 to 2.76; P = .995). With care that was homogenous in terms of conditioning regimens, graft type, GvHD prophylaxis, and supportive care, 92 patients who were biologically randomized to either haploidentical HCT or MRD HCT after RIC with PTCy had comparable outcomes.
使用单倍体相合供者进行异基因造血细胞移植（HCT）可扩大移植的可及性，使越来越多的血液系统疾病患者能够接受移植。此外，由于越来越多的证据表明移植后环磷酰胺（PTCy）用于单倍体相合HCT的生存率和移植物抗宿主病（GvHD）发生率良好，这种方法已得到广泛应用。大多数比较不同供者来源移植结果的研究因预处理方案、移植物类型（外周血[PB]或骨髓）以及移植后GvHD预防措施（PTCy或非PTCy）的差异而受到干扰，难以确定供者来源对移植结果的影响。莱文癌症研究所在2014年启动了一项移植和细胞治疗项目，最初单倍体相合和匹配的相关供者（MRD）移植均采用统一的减低强度预处理（RIC）方案、PB移植物以及基于PTCy的GvHD预防措施。本回顾性观察性研究旨在比较接受相同预处理方案、移植物类型和支持治疗的患者中，RIC单倍体相合HCT与MRD HCT的临床结果。我们查询了移植数据库，以评估2014年3月至2017年12月期间接受单倍体相合或MRD移植物的连续血液系统恶性肿瘤患者的人口统计学特征、临床特征及RIC HCT的结果。MRD是首选的供者来源；若无法获得MRD，则使用单倍体相合供者。67例患者接受了单倍体相合HCT，25例接受了MRD HCT。总体而言，单倍体相合组和MRD组移植受者的特征相似；然而，单倍体相合供者比MRD供者年轻（中位年龄36岁对57岁，P <.0001）。单因素分析结果显示，单倍体相合HCT和MRD HCT的总生存期（OS）相似（风险比[HR]，1.15；95%可信区间[CI]，0.61至2.15；P =.669）。单倍体相合HCT的1年、3年和5年OS分别为80.2%、54.7%和41.2%，MRD HCT分别为76.0%、55.7%和51.1%。中位随访81.90个月，多因素分析结果显示，供者来源（单倍体相合与MRD）与OS（HR，0.97；95%CI，0.51至1.87；P =.933）、无复发生存期（HR，0.75；95%CI，0.42至1.35；P =.337）、累积复发率（HR，0.81；95%CI，0.39至1.70；P =.579）或非复发死亡率（HR，1.12；95%CI，0.40至3.14；P =.827）均无显著相关性。单倍体相合HCT和MRD HCT的急性GvHD（aGvHD）和慢性GvHD（cGvHD）累积发生率无显著差异（II至IV级aGvHD：HR，1.78；95%CI，0.72至4.37；P =.210；III至IV级aGvHD：HR，2.84；95%CI，0.34至23.63；P =.335；cGvHD：HR，1.00；95%CI 0.36至2.76；P =.995）。在预处理方案、移植物类型、GvHD预防措施和支持治疗均相同的情况下，92例在RIC联合PTCy后接受单倍体相合HCT或MRD HCT的患者，其结果具有可比性。
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