Sica Simona, Metafuni Elisabetta, Frioni Filippo, Limongiello Maria Assunta, Galli Eugenio, Sorà Federica, Bacigalupo Andrea, Poggi Elvira, Feccia Mariano Antonio, Manfreda Annarita, Chiusolo Patrizia, Giammarco Sabrina
Dipartimento di Scienze di Laboratorio ed Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Rome, Italy.
Front Oncol. 2024 Aug 21;14:1387181. doi: 10.3389/fonc.2024.1387181. eCollection 2024.
Donor-specific antibodies (DSAs) correspond to anti-HLA antibodies of the recipient that are specifically directed to a mismatched antigen of the donor. In the setting of solid organ transplantation DSAs are associated with rejection. Their role is still debated in allogeneic cell transplantation. International guidelines recommend testing patients for DSA before transplant, and if possible, choosing a donor with negative screening.
We collected clinical data of 236 recipients of alloSCT, performed at our institution from March 2019 to October 2023, to evaluate their impact on engraftment. Serum from all patients was tested for DSA.
186 patients (79%) achieved sustained myeloid engraftment within day 30 post alloSCT. Thirty-two out 236 (13%) patients engrafted after day 30 post alloSCT. The median times to neutrophil engraftment and platelet engraftment were respectively 21 days (range 11-121 days) and 19 days (range 10-203 days). Fourteen out 236 patients (6%) experienced PrGF. .Twenty-nine patients (12 %) were DSA-positive. Among 29 patients with DSA positivity, 17 had a haploidentical donor and 12 had a UD donor. DSA positivity directly correlates respectively with neutrophil and platelets engraftment failure at 30 days after alloSCT (p=0.01 and p= 0.0004). Univariate Cox analysis showed that factors, including DSAs positivity, disease type, disease status, donor type, conditioning regimen, patient's age, and CD34+ were correlated with neutrophil and platelet engraftment failure at 30 days after alloSCT. Younger patients with DSA negativity, with acute leukemia, in complete response at the time of transplant, who received a higher dose of CD34+ cells from a sibling donor after a myeloablative conditioning regimen, have a reduced risk of neutrophil and platelet engraftment failure at day +30 post alloSCT.Multivariate analysis confirmed the impact of the presence of DSA only for platelet engraftment, confirming the role of type and status disease, donor type, recipient age, and CD34+ cells infused on engraftment. DSA presence has no impact on TRM, DFS, and OS.
PrGF has a multifactorial pathogenesis, where DSA is not the only player, but its impact could vary depending on the transplant platform. Thus patient screening may be helpful to choose the best donor and transplant strategy.
供者特异性抗体（DSA）是指受者体内针对供者不匹配抗原的抗人类白细胞抗原（HLA）抗体。在实体器官移植中，DSA与排斥反应相关。在异基因细胞移植中，其作用仍存在争议。国际指南建议在移植前对患者进行DSA检测，如有可能，选择筛查阴性的供者。
我们收集了2019年3月至2023年10月在本机构进行异基因造血干细胞移植（alloSCT）的236例受者的临床数据，以评估其对植入的影响。检测了所有患者血清中的DSA。
186例患者（79%）在alloSCT后30天内实现了持续的髓系植入。236例患者中有32例（13%）在alloSCT后30天以后植入。中性粒细胞植入和血小板植入的中位时间分别为21天（范围11 - 121天）和19天（范围10 - 203天）。236例患者中有14例（6%）发生原发性移植物功能不良（PrGF）。29例患者（12%）DSA呈阳性。在29例DSA阳性患者中，17例有单倍体相合供者，12例有非血缘供者（UD）。DSA阳性分别与alloSCT后30天中性粒细胞和血小板植入失败直接相关（p = 0.01和p = 0.0004）。单因素Cox分析显示，包括DSA阳性、疾病类型、疾病状态、供者类型、预处理方案、患者年龄和CD34+细胞数量等因素与alloSCT后30天中性粒细胞和血小板植入失败相关。年龄较小、DSA阴性、患有急性白血病、移植时处于完全缓解状态、在清髓性预处理方案后接受来自同胞供者更高剂量CD34+细胞的患者，在alloSCT后第30天中性粒细胞和血小板植入失败的风险降低。多因素分析证实DSA的存在仅对血小板植入有影响，证实了疾病类型和状态、供者类型、受者年龄以及输入的CD34+细胞数量对植入的作用。DSA的存在对移植相关死亡率（TRM）、无病生存期（DFS）和总生存期（OS）无影响。
PrGF有多种发病机制，DSA并非唯一因素，但其影响可能因移植平台而异。因此，对患者进行筛查可能有助于选择最佳供者和移植策略。
