Division of Pediatric Hematology-Oncology-BMT, University of Colorado, Aurora, Wash.
Fred Hutchinson Cancer Center, Seattle, Wash; Department of Pediatrics, University of Washington, Seattle, Wash.
J Allergy Clin Immunol. 2024 Jan;153(1):287-296. doi: 10.1016/j.jaci.2023.09.027. Epub 2023 Oct 2.
The Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children in the United States and Canada onto a retrospective multicenter natural history study of hematopoietic cell transplantation (HCT).
We investigated outcomes of HCT for severe combined immunodeficiency (SCID).
We evaluated the chronic and late effects (CLE) after HCT for SCID in 399 patients transplanted from 1982 to 2012 at 32 PIDTC centers. Eligibility criteria included survival to at least 2 years after HCT without need for subsequent cellular therapy. CLE were defined as either conditions present at any time before 2 years from HCT that remained unresolved (chronic), or new conditions that developed beyond 2 years after HCT (late).
The cumulative incidence of CLE was 25% in those alive at 2 years, increasing to 41% at 15 years after HCT. CLE were most prevalent in the neurologic (9%), neurodevelopmental (8%), and dental (8%) categories. Chemotherapy-based conditioning was associated with decreased-height z score at 2 to 5 years after HCT (P < .001), and with endocrine (P < .001) and dental (P = .05) CLE. CD4 count of ≤500 cells/μL and/or continued need for immunoglobulin replacement therapy >2 years after transplantation were associated with lower-height z scores. Continued survival from 2 to 15 years after HCT was 90%. The presence of any CLE was associated with increased risk of late death (hazard ratio, 7.21; 95% confidence interval, 2.71-19.18; P < .001).
Late morbidity after HCT for SCID was substantial, with an adverse impact on overall survival. This study provides evidence for development of survivorship guidelines based on disease characteristics and treatment exposure for patients after HCT for SCID.
原发性免疫缺陷治疗联合会（PIDTC）招募了美国和加拿大的儿童参与一项回顾性多中心造血细胞移植（HCT）自然史研究。
我们研究了严重联合免疫缺陷（SCID）患者接受 HCT 的结果。
我们评估了 32 个 PIDTC 中心于 1982 年至 2012 年间接受 HCT 的 399 例 SCID 患者的慢性和迟发性效应（CLE）。入选标准包括 HCT 后至少 2 年无后续细胞治疗仍存活。CLE 定义为 HCT 后 2 年内任何时间仍存在未解决的情况（慢性），或 HCT 后 2 年以上出现的新情况（迟发性）。
2 年时存活患者的 CLE 累积发生率为 25%，HCT 后 15 年时增至 41%。CLE 最常见于神经系统（9%）、神经发育（8%）和牙科（8%）类别。基于化疗的预处理与 HCT 后 2 至 5 年时身高 z 评分降低有关（P<0.001），与内分泌（P<0.001）和牙科（P=0.05）CLE 有关。HCT 后 2 年时 CD4 计数≤500 个/μL 和/或持续需要免疫球蛋白替代治疗>2 年与身高 z 评分较低有关。HCT 后 2 至 15 年持续存活的患者为 90%。任何 CLE 的存在与迟发性死亡风险增加相关（危险比，7.21；95%置信区间，2.71-19.18；P<0.001）。
SCID 患者接受 HCT 后的迟发性发病率很高，对总体生存有不利影响。本研究为制定基于疾病特征和治疗暴露的 SCID 患者 HCT 后生存指南提供了证据。
