Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Pediatrics, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania.
Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania.
Biol Blood Marrow Transplant. 2020 Mar;26(3):493-501. doi: 10.1016/j.bbmt.2019.11.022. Epub 2019 Nov 22.
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.
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，使用无关供体（URD）或部分匹配的相关供体（PMRD）进行替代性供体移植会增加移植物抗宿主病（GVHD）和死亡率的风险。我们假设，对 URD 或 PMRD 外周造血干细胞移植（PSCT）进行部分 CD3/CD19 耗竭的策略将减轻 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%）发生原发性移植物失败。23 名患者（27.4%；累积发生率 26.3%）发生复发，17 名患者（20.2%）发生非复发死亡率（NRM）。18 名患者（21.4%）出现 3 级或 4 级急性 GVHD，24 名患者（35.3%）和 8 名患者（11.7%）出现慢性 GVHD，其严重程度为局限性和广泛性。3 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 降低（P=.05）和 EFS 降低（P=.05）相关。第二次完全缓解的儿童复发更为常见（P =.03）。部分 CD3 耗竭的替代性供体 PSCT 的 NRM、OS 和 EFS 与之前发表的 T 细胞富含 PSCT 研究结果相比具有优势。历史上，与局限性慢性 GVHD 相比，T 细胞富含 PSCT 与更广泛的慢性 GVHD 相关，这可能解释了尽管我们的研究队列中慢性 GVHD 的总体发生率相似，但复发和 NRM 率较低。部分 T 细胞耗竭通过减轻但不能消除慢性 GVHD，可能会扩大对恶性移植适应证且缺乏匹配相关供体的儿童的供体选择。
