Most children who may benefit from stem cell transplantation lack a matched related donor. Alternative donor transplantations with an unrelated donor (URD) or a partially matched related donor (PMRD) carry an increased risk of graft-versus-host-disease (GVHD) and mortality compared with matched related donor transplantations. We hypothesized that a strategy of partial CD3+/CD19+ depletion for URD or PMRD peripheral stem cell transplantation (PSCT) would attenuate the risks of GVHD and mortality. We enrolled 84 pediatric patients with hematologic malignancies at the Children's Hospital of Philadelphia and the Children's Hospital of Wisconsin between April 2005 and February 2015. Two patients (2.4%) experienced primary graft failure. Relapse occurred in 23 patients (27.4%; cumulative incidence 26.3%), and 17 patients (20.2%) experienced nonrelapse mortality (NRM). Grade III-IV acute GVHD was observed in 18 patients (21.4%), and chronic GVHD was observed and graded as limited in 24 patients (35.3%) and extensive in 8 (11.7%). Three-year overall survival (OS) was 61.8% (95% confidence interval [CI], 50.2% to 71.4%) and event-free survival (EFS) was 52.0% (95% CI, 40.3% to 62.4%). Age ≥15 years was associated with decreased OS (P= .05) and EFS (P= .05). Relapse was more common in children in second complete remission (P = .03). Partially CD3+-depleted alternative donor PSCT NRM, OS, and EFS compare favorably with previously published studies of T cell-replete PSCT. Historically, T cell-replete PSCT has been associated with a higher incidence of extensive chronic GVHD compared with limited chronic GVHD, which may explain the comparatively low relapse and NRM rates in our study cohort despite similar overall rates of chronic GVHD. Partial T cell depletion may expand donor options for children with malignant transplantation indications lacking a matched related donor by mitigating, but not eliminating, chronic GVHD.

中文翻译：

---

部分 CD3+ 耗尽的无关和半相合供体外周干细胞移植在小儿血液系统恶性肿瘤中具有良好的移植物抗宿主病和存活率。

大多数可能受益于干细胞移植的儿童缺乏匹配的相关供体。与匹配的相关供体移植相比，非亲缘供体 (URD)​​ 或部分匹配的相关供体 (PMRD) 的替代供体移植具有更高的移植物抗宿主病 (GVHD) 和死亡率风险。我们假设 URD 或 PMRD 外周干细胞移植 (PSCT) 的部分 CD3+/CD19+ 耗竭策略将降低 GVHD 和死亡率的风险。我们在 2005 年 4 月至 2015 年 2 月期间在费城儿童医院和威斯康星州儿童医院招募了 84 名患有血液系统恶性肿瘤的儿科患者。两名患者 (2.4%) 经历了原发性移植失败。23 名患者（27.4%；累积发生率 26.3%）和 17 名患者（20.5%）发生复发。2%) 经历了非复发死亡率 (NRM)。18 名患者 (21.4%) 观察到 III-IV 级急性 GVHD，24 名患者 (35.3%) 观察到慢性 GVHD，并将其分级为有限，8 名 (11.7%) 为广泛。三年总生存率 (OS) 为 61.8%（95% 置信区间 [CI]，50.2% 至 71.4%），无事件生存率 (EFS) 为 52.0%（95% CI，40.3% 至 62.4%）。年龄≥15 岁与 OS (P= .05) 和 EFS (P= .05) 降低相关。复发在第二次完全缓解的儿童中更常见（P = .03）。部分 CD3+ 耗尽的替代供体 PSCT NRM、OS 和 EFS 与先前发表的 T 细胞充足 PSCT 研究相比具有优势。从历史上看，与有限的慢性 GVHD 相比，充满 T 细胞的 PSCT 与广泛的慢性 GVHD 的发生率更高有关，这可能解释了尽管慢性 GVHD 的总体发生率相似，但我们研究队列中的复发率和 NRM 率相对较低。部分 T 细胞耗竭可能会通过减轻但不能消除慢性 GVHD，为缺乏匹配相关供体的恶性移植适应症儿童提供更多供体选择。