关键词: Donor specific antibody Haploidentical hematopoietic stem cell transplantation IVIg Rituximab

Mesh : Humans Rituximab / therapeutic use Immunoglobulins, Intravenous / therapeutic use gamma-Globulins Retrospective Studies Hematopoietic Stem Cell Transplantation / adverse effects Antibodies Antilymphocyte Serum

来  源:   DOI:10.1016/j.jtct.2023.05.005

Abstract:
Donor-specific anti-HLA antibodies (DSAs) are a major cause of engraftment failure in patients receiving haploidentical stem cell transplantation (HaploSCT). Effective procedures are needed for those who demand urgent transplantation and have no other donor options. We here retrospectively analyzed 13 patients with DSAs successfully treated with desensitization of rituximab and intravenous γ globulin (IVIg) before HaploSCT from March 2017 to July 2022. All 13 patients had DSA mean fluorescence intensity >4000 of at least 1 loci before desensitization. Of the 13 patients, 10 patients were with the initial diagnosis of malignant hematological diseases, and 3 were diagnosed with aplastic anemia. Patients were treated with 1 (n = 3) or 2 (n = 10) doses of rituximab (375 mg/m2 for 1 dose). All patients receive the same total dose of 0.4 g/kg of IVIg within 72 hours before haploidentical stem cell administration to neutralize the remaining DSA. All patients achieved neutrophil engraftment, and 12 patients achieved primary platelet engraftment. The patient with primary platelet engraftment failure received purified CD34-positive stem cell infusion nearly 1 year after transplantation and achieved platelet engraftment thereafter. The estimated 3-year overall survival is 73.4%. Although further studies on larger numbers of patients are needed, it is clear that the combination of IVIg and rituximab is an effective way to clear DSA and has a strong effect on promoting engraftment and survival for patients with DSA. It is a practical and adaptable combination of treatment options.
摘要:
背景:供体特异性抗HLA抗体(DSA)是接受单倍体干细胞移植(HaploSCT)的患者移植失败的主要原因。对于那些需要紧急移植且没有其他供体选择的人,需要有效的程序。
目的:我们在此回顾性分析了2017年3月至2022年7月在HaploSCT之前成功接受利妥昔单抗和静脉γ球蛋白脱敏治疗的13例DSA患者。
方法:所有13例患者在脱敏前至少一个位点的DSAMFI>4000。在13名患者中,10例患者最初诊断为恶性血液病,3人被诊断为再生障碍性贫血。患者用一个(n=3)或两个(n=10)剂量的利妥昔单抗(一个剂量为375mg/m2)治疗。所有患者在给予单倍体干细胞之前的72小时内接受相同的0.4g/kg的静脉内γ球蛋白(IVIg)总剂量以中和剩余的DSA。
结果:所有患者均实现了中性粒细胞植入,12例患者实现了初次血小板植入。原发性血小板移植失败的患者在移植近1年后接受了纯化的CD34阳性干细胞输注,此后实现了血小板移植。估计3年总生存率(OS)为73.4%。
结论:尽管需要对更多患者进行进一步研究,很明显,IVIg和利妥昔单抗的联合应用是清除DSA的有效方法,对促进DSA患者的植入和生存有很强的作用.它是治疗方案的实用和适应性组合。
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