Galvin Robert T, Cao Qing, Miller Weston P, Knight-Perry Jessica, Smith Angela R, Ebens Christen L
University of Minnesota, Department of Pediatrics; Minneapolis, MN, USA.
University of Minnesota, Biostatistics Core at Masonic Cancer Center; Minneapolis, MN, USA.
Transplant Cell Ther. 2021 Apr;27(4):316.e1-316.e8. doi: 10.1016/j.jtct.2021.01.015. Epub 2021 Jan 20.
Immune-mediated cytopenias (IMC)-isolated or combined hemolytic anemia, thrombocytopenia, or neutropenia-are increasingly recognized as serious complications after allogeneic hematopoietic cell transplantation (HCT) for nonmalignant disorders (NMD). However, IMC incidence, duration, response to therapy, and risk factors are not well defined. This retrospective chart review identified cases of IMC with serologic confirmation among patients who underwent HCT for NMD at a single institution between 2010 and 2017. IMC after HCT for NMD in a large pediatric cohort (n = 271) was common with a cumulative incidence of 18%, identified at a median of 136 days after HCT. Treatment included prolonged immune suppression (>3 months) in 58% of all IMC cases, 91% when multiple cell lines were affected. Multiple therapeutic agents were used for the majority affected, and median time to resolution of IMC was 118 days from diagnosis. Fine-Gray competing risk multivariate regression analysis identified a combined risk factor of younger age (<3 years) and inherited metabolic disorder, as well as hemoglobinopathy (at any age) associated with 1-year incidence of IMC (P < .01). We expand these findings with the observation of declining donor T-lymphoid chimerism from day 60 to 100 and lower absolute CD4+ counts at day 100 (P < .01), before median onset of IMC, for patients with IMC compared to those without. In this cohort, 4 deaths (8%) were associated with IMC, including 2 requiring second transplantation for secondary graft failure. Although the pathogenesis of IMC post-HCT for NMD remains elusive, further research may identify approaches to prevent and better treat this HCT complication.
免疫介导的血细胞减少症（IMC）——孤立性或合并性溶血性贫血、血小板减少症或中性粒细胞减少症——越来越被认为是异基因造血细胞移植（HCT）治疗非恶性疾病（NMD）后的严重并发症。然而，IMC的发病率、持续时间、对治疗的反应以及危险因素尚未明确界定。这项回顾性图表审查确定了2010年至2017年间在单一机构接受NMD-HCT治疗的患者中经血清学确认的IMC病例。在一个大型儿科队列（n = 271）中，NMD-HCT后的IMC很常见，累积发病率为18%，在HCT后中位数136天被发现。治疗包括在所有IMC病例中有58%采用延长免疫抑制（>3个月），当多个细胞系受影响时这一比例为91%。大多数受影响患者使用了多种治疗药物，IMC从诊断到缓解的中位时间为118天。精细灰色竞争风险多变量回归分析确定年龄较小（<3岁）和遗传性代谢紊乱以及血红蛋白病（任何年龄）的合并危险因素与IMC的1年发病率相关（P <.０1）。我们通过观察发现，与无IMC的患者相比，有IMC的患者在IMC中位发病前，从第60天到第100天供体T淋巴细胞嵌合体下降，且在第100天绝对CD4 +计数较低（P <.０1），从而扩展了这些发现。在这个队列中，4例死亡（8%）与IMC相关，其中2例因继发性移植物失败需要二次移植。尽管NMD-HCT后IMC的发病机制仍然难以捉摸，但进一步的研究可能会确定预防和更好治疗这种HCT并发症的方法。
