Hematology, Department of Translational and Precision Medicine, Sapienza University, Rome, Italy.
Immunohematology and Transfusion Medicine, Sapienza University, Rome, Italy.
Blood Transfus. 2024 Mar;22(2):157-165. doi: 10.2450/BloodTransfus.464. Epub 2023 Sep 21.
In the setting of mismatched-hematopoietic stem cells transplantation, the detection of antibodies directed against donor-specific HLA allele(s) or antigen(s) (DSA) represents a barrier for engraftment. It is thus necessary to plan an immunosuppressive strategy, or to select an alternative donor. This prospective study aimed at evaluating the efficacy of our strategy for testing DSAs and the efficacy of the desensitization strategy (DS) employed between November 2017 and November 2020.
The anti-HLA antibody search was performed using the Luminex bead assays (Lifecode ID and LSA I/II-Immucor) and expressed as mean fluorescence intensity (MFI >1,000 positive). If the patient had DSAs and no alternative donors, a DS was employed with rituximab (day -15), 2 single volume plasmaphereses (PP; days -9 and -8), intravenous immunoglobulins (day -7) and infusion of HLA selected platelets, if persistent DSAs were directed against class I HLA. DS was scheduled with or without PP, according to the DSA MFI (>1,000 or <5,000) and FCXM (flow cytometry crossmatch).
Twenty-two out of 126 patients (17.46%) showed anti-HLA antibodies, 5 of them DSAs (3.97% of total); 3 patients underwent DS obtaining engraftment. Female gender (p=0.033) and a history of previous pregnancies or miscarriages (p=0.009) showed a statistically significant impact on alloimmunization. Factors associated with a delayed neutrophil engraftment were patient's female gender (p=0.039), stem cell source (p=0.025), and a high HSCT-specific comorbidity index (p=0.028). None of the analyzed variables, including the DSA detection, influenced engraftment.
Our study confirms the importance to test DSAs in mismatched-hematopoietic stem cells transplantation The DS used proved successful in removing DSAs. Prospective multicenter studies are needed to better define and validate consensus strategies on DSA management in HSCT.
在造血干细胞移植不匹配的情况下，针对供体特异性 HLA 等位基因（s）或抗原（s）的抗体（DSA）的检测是植入的障碍。因此，有必要计划免疫抑制策略，或选择替代供体。本前瞻性研究旨在评估我们检测 DSA 的策略的疗效，以及我们在 2017 年 11 月至 2020 年 11 月期间采用的脱敏策略（DS）的疗效。
使用 Luminex 珠分析（Lifecode ID 和 LSA I/II-Immucor）检测抗 HLA 抗体，并以平均荧光强度（MFI > 1000 为阳性）表示。如果患者有 DSA 且没有其他供体，则采用 DS，用利妥昔单抗（第 -15 天）、2 次单体积血浆置换（PP；第 -9 天和第 -8 天）、静脉注射免疫球蛋白（第 -7 天）和输注 HLA 选择的血小板，如果持续存在的 DSA 针对 HLA Ⅰ类。根据 DSA MFI（> 1000 或 < 5000）和 FCXM（流式细胞交叉配型），DS 可与或不与 PP 一起安排。
126 例患者中有 22 例（17.46%）出现抗 HLA 抗体，其中 5 例为 DSA（占总数的 3.97%）；3 例患者接受 DS 获得植入。女性（p=0.033）和既往妊娠或流产史（p=0.009）对同种免疫有统计学显著影响。与中性粒细胞植入延迟相关的因素包括患者的女性性别（p=0.039）、干细胞来源（p=0.025）和高 HSCT 特异性合并症指数（p=0.028）。包括 DSA 检测在内的分析变量均未影响植入。
本研究证实了在造血干细胞移植不匹配的情况下检测 DSA 的重要性。使用的 DS 成功地去除了 DSA。需要前瞻性多中心研究来更好地定义和验证 HSCT 中 DSA 管理的共识策略。
