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Abstract：
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.
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.
摘要：
目的：探讨造血细胞移植（HCT）治疗严重联合免疫缺陷（SCID）的疗效，初级免疫缺陷治疗联盟（PIDTC）在美国和加拿大的儿童中进行了回顾性研究，多中心自然史研究。
方法：我们评估了1982-2012年在32个PIDTC中心移植的399名患者的SCIDHCT后的慢性和晚期效应（CLE）。合格标准包括在HCT后存活至少2年而不需要随后的细胞治疗。CLE被定义为在HCT2年之前的任何时间存在的未解决（慢性），或在HCT（晚期）后超过2年发展的新条件。
结果：在2年存活的人群中，CLE的累积发生率为25%，HCT后15年增加到41%。CLE在神经系统中最普遍(9%)，神经发育(8%)和牙科(8%)类别。基于化疗的条件与HCT后2-5年身高z评分降低相关（p<0.001），内分泌（p<0.001）和牙科（p=0.05）CLE。CD4计数≤500/μl和/或移植后持续需要免疫球蛋白替代>2年与较低的身高z评分相关。HCT后2至15年的持续生存率为90％。任何CLE的存在与晚期死亡风险增加相关(HR7.21;2.71-19.18,p<0.001)。
结论：SCID在HCT后的晚期发病率很高，对总体生存率有不利影响。这项研究为基于SCID的HCT后患者的疾病特征和治疗暴露提供了制定生存指南的证据。
方法：我们评估了1982-2012年在32个PIDTC中心移植的399名患者的SCIDHCT后的慢性和晚期效应（CLE）。合格标准包括在HCT后存活至少2年而不需要随后的细胞治疗。CLE被定义为在HCT2年之前的任何时间存在的未解决（慢性），或在HCT（晚期）后超过2年发展的新条件。
结果：在2年存活的人群中，CLE的累积发生率为25%，HCT后15年增加到41%。CLE在神经系统中最普遍(9%)，神经发育(8%)和牙科(8%)类别。基于化疗的条件与HCT后2-5年身高z评分降低相关（p<0.001），内分泌（p<0.001）和牙科（p=0.05）CLE。CD4计数≤500/μl和/或移植后持续需要免疫球蛋白替代>2年与较低的身高z评分相关。HCT后2至15年的持续生存率为90％。任何CLE的存在与晚期死亡风险增加相关(HR7.21;2.71-19.18,p<0.001)。
结论：SCID在HCT后的晚期发病率很高，对总体生存率有不利影响。这项研究为基于SCID的HCT后患者的疾病特征和治疗暴露提供了制定生存指南的证据。
