Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands; Laboratory of Diagnostics, Princess Máxima Center for Pediatric Oncology, Utrecht University, Utrecht, The Netherlands.
Biol Blood Marrow Transplant. 2020 Jan;26(1):114-122. doi: 10.1016/j.bbmt.2019.07.022. Epub 2019 Jul 22.
Development of autoimmune cytopenia (AIC) after allogeneic hematopoietic cell transplantation (HCT) is a serious complication requiring urgent intensification of immunosuppressive therapy. The pathophysiology and predictors of AIC are not completely understood. In this retrospective cohort analysis of 380 pediatric patients, we evaluated the incidence, outcomes, and related various variables, including immune reconstitution markers to AIC. Three hundred eighty patients (median age, 7.4 years; range, .1 to 22.7) were included, of which 30 patients (7.8%) developed AIC in 1 (n = 6), 2 (n = 6), or 3 (n = 16) cell lineages at a median of 133 days (range, 46 to 445) after HCT. Using multivariate analysis we found that chemo-naivety before HCT, acute graft-versus-host disease (aGVHD) grades II to IV, and serotherapy were associated with the development of AIC. Development of AIC was preceded by increased levels of IgM, IgA, and IgG. Immune profiles of total absolute lymphocytes were very similar between AIC patients and control subjects. However, CD3CD16CD56 natural killer cells, CD3 T cells, CD3CD4 T cell subset, and CD3CD8 T cell subset were lower in AIC patients. Overall survival was good, at 83% (similar between AIC patients and control subjects). In conclusion, we identified chemo-naivety before HCT, preceding aGVHD grades II to IV, and serotherapy as predictors for development of AIC. Increasing levels of IgM, IgA, and IgG preceded AIC development. These data provide clues to further study the biology of AIC.
自身免疫性血细胞减少症（AIC）是异基因造血细胞移植（HCT）后的严重并发症，需要立即强化免疫抑制治疗。AIC 的病理生理学和预测因素尚未完全阐明。在这项对 380 例儿科患者的回顾性队列分析中，我们评估了发病率、结局和相关的各种变量，包括与 AIC 相关的免疫重建标志物。380 例患者（中位年龄，7.4 岁；范围，0.1 至 22.7）中，30 例（7.8%）在 HCT 后 1（n=6）、2（n=6）或 3（n=16）个细胞谱系中出现 AIC，中位数为 133 天（范围，46 至 445）。多变量分析发现，HCT 前化疗初治、急性移植物抗宿主病（aGVHD）Ⅱ至Ⅳ级和血清治疗与 AIC 的发生相关。AIC 的发生先于 IgM、IgA 和 IgG 水平升高。AIC 患者和对照组的总绝对淋巴细胞免疫谱非常相似。然而，AIC 患者的 CD3CD16CD56 自然杀伤细胞、CD3 T 细胞、CD3CD4 T 细胞亚群和 CD3CD8 T 细胞亚群较低。总生存率良好，为 83%（AIC 患者与对照组相似）。总之，我们发现 HCT 前化疗初治、aGVHD Ⅱ至Ⅳ级和血清治疗是发生 AIC 的预测因素。IgM、IgA 和 IgG 水平升高先于 AIC 发生。这些数据为进一步研究 AIC 的生物学提供了线索。
