Eurocord, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Institut de Recherche Saint Louis (IRSL) EA3518, Université de Paris, Paris, France.
Laboratorio de Investicacao Medica (LIM) 31, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Blood Adv. 2020 Dec 22;4(24):6327-6335. doi: 10.1182/bloodadvances.2020002258.
Double-unit unrelated cord blood transplantation (DUCBT) is an option in patients for whom a single unit is not sufficient to provide an adequate number of cells. As current guidelines on UCB unit selection are mainly based on single-unit UCB data, we performed a retrospective analysis of 1375 adult recipients of DUCBT for hematologic malignancies to determine optimal criteria for graft selection. Cryopreserved total nucleated cells (TNCs; ≤3.5 vs >3.5 × 107/kg: hazard ratio [HR], 1.53; 30% vs 45%; P = .01), number of HLA mismatches (≥2 vs 0-1: HR, 1.28; 42% vs 48%; P = .01), and ABO compatibility (minor/major ABO incompatibility vs compatibility: HR, 1.28; P = .04) were independent risk factors for OS. Cryopreserved CD34+ cell dose ≥0.7 × 105/kg in the winning UCB was associated with improved OS (HR, 1.34; P = .03). Low TNC (≤3.5 × 107/kg) and CD34+ (≤1.4 × 105/kg) cell doses were related to decreased neutrophil recovery (HR, 0.65 [P = .01] and HR, 0.81 [P = .01], respectively). DUCBT recipients with ≥2 HLA mismatches had a higher incidence of grade II-IV and III-IV acute graft-versus-host disease (HR, 1.26 [P = .03] and 1.59 [P = .02], respectively). Low TNC dose (HR, 1.57; P = .02) and receiving UCB with ≥2 HLA mismatches (HR, 1.35; P = .03) were associated with increased transplant-related mortality. Our data support selecting adequately HLA-matched UCB units with a double-unit cryopreserved TNC dose >3.5 × 107/kg and CD34+ cell dose of ≥0.7 × 105/kg per unit in DUCBT candidates.
双份无关脐带血移植（DUCBT）是一种选择，适用于单个单位不足以提供足够数量细胞的患者。由于目前关于 UCB 单位选择的指南主要基于单份 UCB 数据，我们对 1375 名接受 DUCBT 的血液系统恶性肿瘤成人患者进行了回顾性分析，以确定移植物选择的最佳标准。冷冻保存的总核细胞（TNC；≤3.5 与>3.5×107/kg：风险比[HR]，1.53；30%与 45%；P=.01）、HLA 错配数（≥2 与 0-1：HR，1.28；42%与 48%；P=.01）和 ABO 相容性（次要/主要 ABO 不相容与相容：HR，1.28；P=.04）是 OS 的独立危险因素。在获胜的 UCB 中，冷冻保存的 CD34+细胞剂量≥0.7×105/kg 与 OS 改善相关（HR，1.34；P=.03）。TNC（≤3.5×107/kg）和 CD34+（≤1.4×105/kg）细胞剂量低与中性粒细胞恢复减少相关（HR，0.65[P=.01]和 HR，0.81[P=.01]）。具有≥2 个 HLA 错配的 DUCBT 受者发生 2 级至 4 级和 3 级至 4 级急性移植物抗宿主病的发生率较高（HR，1.26[P=.03]和 1.59[P=.02]）。TNC 剂量低（HR，1.57；P=.02）和接受具有≥2 个 HLA 错配的 UCB（HR，1.35；P=.03）与移植相关死亡率增加相关。我们的数据支持在 DUCBT 候选者中选择充分 HLA 匹配的 UCB 单位，每个单位的双份冷冻保存 TNC 剂量>3.5×107/kg 和 CD34+细胞剂量≥0.7×105/kg。
