Children's Haematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne Hospital National Health System Foundation Trust, Newcastle upon Tyne, United Kingdom; Department of Paediatrics, Leiden University Medical Centre, Leiden, The Netherlands.
Children's Haematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne Hospital National Health System Foundation Trust, Newcastle upon Tyne, United Kingdom.
J Allergy Clin Immunol. 2020 Aug;146(2):406-416. doi: 10.1016/j.jaci.2020.04.053. Epub 2020 May 19.
Post hematopoietic cell transplantation (HCT) autoimmune cytopenia (AIC) is a potentially life-threatening complication, but studies focusing on large cohorts of patients transplanted for primary immunodeficiency are lacking.
This study sought to determine the incidence, risk factors, and outcomes of post-HCT AIC and B-lymphocyte function following rituximab.
We retrospectively studied 502 children with primary immunodeficiency who were transplanted at our center between 1987 and 2018.
Thirty-six patients (9%) developed post-HCT AIC, with a median onset of 6.5 months post-HCT. On univariate analysis, pre-HCT AIC, mismatched donor, alemtuzumab, anti-thymocyte antiglobulin, and acute and chronic graft versus host disease were significantly associated with post-HCT AIC. After multivariate analysis, alemtuzumab (subdistribution hazard ratio, 9.0; 95% CI, 1.50-54.0; P = .02) was independently associated with post-HCT AIC. Corticosteroid and high-dose intravenous immunoglobulin achieved remission in 50% (n = 18), additional rituximab led to remission in 25% (n = 9), and the remaining 25% were treated with a combination of various modalities including sirolimus (n = 5), bortezomib (n = 3), mycophenolate mofetil (n = 2), splenectomy (n = 2), and second HCT (n = 3). The mortality of post-HCT AIC reduced from 25% (4 of 16) prior to 2011 to 5% (1 of 20) after 2011. The median follow-up of 5.8 years (range, 0.4 to 29.1 years) showed that 26 of 30 survivors (87%) were in complete remission, and 4 were in remission with ongoing sirolimus and low-dose steroids. Of the 17 who received rituximab, 7 had B-lymphocyte recovery, 5 had persistent low B-lymphocyte count and remained on intravenous immunoglobulin replacement, 2 had second HCT, and 3 died.
The frequency of post HCT AIC in our cohort was 9%, and the most significant risk factors for its occurrence were the presence of graft versus host disease and the use of alemtuzumab.
造血细胞移植(HCT)后自身免疫性血细胞减少症(AIC)是一种潜在的危及生命的并发症,但缺乏针对原发性免疫缺陷患者进行大样本队列研究的报道。
本研究旨在确定原发性免疫缺陷患儿接受 HCT 后发生 AIC 的发生率、风险因素和结局,以及利妥昔单抗治疗后 B 淋巴细胞功能的变化。
我们回顾性分析了 1987 年至 2018 年在我们中心接受 HCT 的 502 例原发性免疫缺陷患儿的临床资料。
36 例患儿(9%)发生了 HCT 后 AIC,中位发病时间为 HCT 后 6.5 个月。单因素分析显示,HCT 前存在 AIC、供者不合、阿伦单抗、抗胸腺细胞球蛋白、急性和慢性移植物抗宿主病与 HCT 后 AIC 显著相关。多因素分析显示,阿伦单抗(亚分布风险比,9.0;95%CI,1.50-54.0;P =.02)是 HCT 后 AIC 的独立危险因素。皮质激素和大剂量静脉注射免疫球蛋白治疗后,50%(18 例)患儿缓解,25%(9 例)加用利妥昔单抗后缓解,其余 25%患儿接受了包括西罗莫司(5 例)、硼替佐米(3 例)、霉酚酸酯(2 例)、脾切除术(2 例)和再次 HCT(3 例)等多种方法联合治疗。HCT 后 AIC 的死亡率从 2011 年前的 25%(16 例中的 4 例)降至 2011 年后的 5%(20 例中的 1 例)。中位随访 5.8 年(0.4-29.1 年)显示,30 例存活者中 26 例(87%)完全缓解,4 例持续存在西罗莫司和低剂量皮质激素治疗。17 例接受利妥昔单抗治疗的患儿中,7 例 B 淋巴细胞恢复,5 例持续存在低 B 淋巴细胞计数,仍需静脉注射免疫球蛋白替代治疗,2 例行再次 HCT,3 例死亡。
本研究中患儿 HCT 后 AIC 的发生率为 9%,其发生的最重要危险因素是存在移植物抗宿主病和使用阿伦单抗。