Department of Hematology and Hemotherapy, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Translational Oncology Section, Gregorio Marañón Health Research Institute, Madrid, Spain.
Front Immunol. 2023 May 26;14:1165759. doi: 10.3389/fimmu.2023.1165759. eCollection 2023.
Donor-specific antibodies (DSAs) are IgG allo-antibodies against mismatched donor HLA molecules and can cause graft failure (GF) in the setting of haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Our aim was to report the experience of the Spanish Group of Hematopoietic Transplant (GETH-TC) in DSA-positive patients who had undergone haplo-HSCT.
We conducted a survey of patients who underwent haplo-HSCT in GETH-TC centers between 2012 and 2021. Data were collected on the DSA assay used, monitoring strategy, complement fixation, criteria for desensitization, desensitization strategies and transplant outcomes.
Fifteen centers from the GETH-TC responded to the survey. During the study period, 1,454 patients underwent haplo-HSCT. Seventy of the transplants were performed in 69 DSA-positive patients, all of whom lacked a suitable alternative donor; 61 (88%) patients were female (90% with prior pregnancies). All patients received post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis. Regarding baseline DSA intensity, 46 (67%) patients presented mean fluorescence intensity (MFI) >5,000, including 21 (30%) with MFI >10,000 and three (4%) with MFI >20,000. Six patients did not receive desensitization treatment, four of them with MFI <5,000. Of 63 patients receiving desensitization treatment, 48 (76%) were tested after desensitization therapy, and a reduction in intensity was confirmed in 45 (71%). Three patients (5%) experienced an increase in MFI after desensitization, two of whom experienced primary GF. Cumulative incidence of neutrophil engraftment at day 28 was 74% in a median of 18 days (IQR, 15─20); six patients died before engraftment due to toxicity or infection and eight patients had primary GF despite desensitization in seven of them. After a median follow-up of 30 months, two-year overall and event-free survival were 46.5% and 39%, respectively. The two-year cumulative incidence of relapse was 16% and non-relapse mortality (NRM) was 43%. Infection was the most frequent cause of NRM, followed by endothelial toxicity. Multivariate analysis identified baseline MFI >20,000 as an independent risk factor for survival and an increase in titers after infusion as an independent risk factor for GF.
Haplo-HSCT is feasible in DSA-positive patients, with high rates of engraftment after desensitization guided by DSA intensity. Baseline MFI >20,000 and increased intensity after infusion are risk factors for survival and GF.
供体特异性抗体（DSA）是针对 mismatched 供体 HLA 分子的 IgG 同种抗体，可导致半相合造血干细胞移植（haplo-HSCT）中移植物失功（GF）。我们的目的是报告西班牙造血移植组（GETH-TC）在接受 haplo-HSCT 的 DSA 阳性患者中的经验。
我们对 2012 年至 2021 年期间在 GETH-TC 中心接受 haplo-HSCT 的患者进行了调查。收集了用于 DSA 检测的方法、监测策略、补体固定、脱敏标准、脱敏策略和移植结果。
GETH-TC 的 15 个中心对调查做出了回应。研究期间，1454 例患者接受了 haplo-HSCT。70 例移植发生在 69 例 DSA 阳性患者中，所有患者均缺乏合适的替代供体；61 例（88%）患者为女性（90%有过妊娠）。所有患者均接受了基于环磷酰胺的移植后移植物抗宿主病预防。关于基线 DSA 强度，46 例（67%）患者的平均荧光强度（MFI）>5000，包括 21 例（30%）MFI>10000 和 3 例（4%）MFI>20000。6 例患者未接受脱敏治疗，其中 4 例 MFI<5000。在接受脱敏治疗的 63 例患者中，48 例（76%）在脱敏治疗后进行了检测，并确认 45 例（71%）的强度降低。3 例（5%）患者在脱敏后 MFI 增加，其中 2 例发生原发性 GF。中位 18 天（IQR，15-20）时，28 天中性粒细胞植入的累积发生率为 74%；由于毒性或感染，有 6 例患者在植入前死亡，有 8 例患者尽管在 7 例患者中进行了脱敏治疗，但仍发生原发性 GF。中位随访 30 个月后，2 年总生存率和无事件生存率分别为 46.5%和 39%。2 年累积复发率为 16%，非复发死亡率（NRM）为 43%。感染是 NRM 最常见的原因，其次是内皮毒性。多变量分析发现，基线 MFI>20000 是生存的独立危险因素，输注后滴度增加是 GF 的独立危险因素。
DSA 阳性患者可进行 haplo-HSCT，通过 DSA 强度指导脱敏后植入率较高。基线 MFI>20000 和输注后强度增加是生存和 GF 的危险因素。
