Metafuni Elisabetta, Busnego Barreto Maria Teresa, Valentini Caterina Giovanna, Giammarco Sabrina, Limongiello Maria Assunta, Sorà Federica, Bianchi Maria, Massini Giuseppina, Piccirillo Nicola, Putzulu Rossana, Frioni Filippo, Bacigalupo Andrea, Teofili Luciana, Chiusolo Patrizia, Sica Simona
Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica e Ematologia; Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Hematology and Hemotherapy Service, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
Front Oncol. 2024 Jul 2;14:1386670. doi: 10.3389/fonc.2024.1386670. eCollection 2024.
Pure red cell aplasia (PRCA) is a possible complication after allogeneic hematopoietic stem cell transplantation (HSCT) with major ABO incompatibility. Patients experience delayed engraftment of the erythroid series, with prolonged transfusion-dependent anemia and iron overload.
We performed a revision of the most recent literature about post-HSCT PRCA treatment procedures. Moreover, we conducted a retrospective study, over the last 13-years, which included all consecutive major ABO mismatched HSCT performed in our unit, with the aim to assess PRCA incidence, risk factors, and response to different treatments. Overall, 194 patients received a major ABO mismatched transplant from 2010 to 2022. For each patient, data about demographic and transplant characteristics, engraftment, blood transfusion, and possible treatment received were collected.
The literature review returned 23 eligible papers on PRCA treatment, with high success rate using plasma-exchange (PEX) and immunoadsorption procedures, daratumumab, and eltrombopag. Our study identified a total of 24 cases of PRCA. Among risk factors for PRCA development, we have found older recipient age (p=0.01), high pre-HSCT IgG and IgM IHA titer (p<0.0001), major rather than bidirectional ABO incompatibility (p=0.02), low T CD8 lymphocyte count in the graft (p=0.006), relative donor (p=0.02) and bone marrow as stem cell source (p=0.002). However, multivariate analysis confirmed only pre-HSCT IgG IHA titer as the unique risk factor for PRCA occurrence. The optimal cut-off value of pre-HSCT IgG IHA for PRCA development, resulted to be 1/64, with a 100% sensitivity and 68.8% specificity (p<0.0001). All patients with PRCA had received rhEPO and transfusion support and 20 patients received additional treatments like PEX, rituximab, and more recently daratumumab. Comprehensively, PEX and rituximab obtained a response in half of the cases, at a variable time, while the few cases of patients we treated with daratumumab suggest promising results. The overall response rate in our cohort was 75%, with significantly better survival (94.4% vs. 16.7%) and lower transplant-related mortality (6.3% vs. 80%) for PRCA responders.
Standardized guidelines on when and how to treat PRCA are necessary because the current treatment is controversial among centers.
纯红细胞再生障碍性贫血（PRCA）是主要ABO血型不合的异基因造血干细胞移植（HSCT）后的一种可能并发症。患者会出现红系延迟植入，伴有输血依赖型贫血持续时间延长和铁过载。
我们对有关HSCT后PRCA治疗程序的最新文献进行了综述。此外，我们进行了一项回顾性研究，涵盖过去13年在我们单位进行的所有连续的主要ABO血型不匹配的HSCT，旨在评估PRCA的发生率、危险因素以及对不同治疗的反应。总体而言，2010年至2022年期间有194例患者接受了主要ABO血型不匹配的移植。对于每位患者，收集了有关人口统计学和移植特征、植入、输血以及可能接受的治疗的数据。
文献综述检索到23篇关于PRCA治疗的合格论文，血浆置换（PEX）和免疫吸附程序、达雷妥尤单抗和艾曲泊帕的成功率较高。我们的研究共确定了24例PRCA病例。在PRCA发生的危险因素中，我们发现受者年龄较大（p = 0.01）、HSCT前IgG和IgM血型抗体效价较高（p < 0.0001）、主要而非双向ABO血型不合（p = 0.02）、移植物中T CD8淋巴细胞计数低（p = 0.006）、相对供者（p = 0.02）以及骨髓作为干细胞来源（p = 0.002）。然而，多因素分析仅证实HSCT前IgG血型抗体效价是PRCA发生的唯一危险因素。HSCT前IgG血型抗体效价对于PRCA发生的最佳临界值为1/64，敏感性为100%，特异性为68.8%（p < 0.0001）。所有PRCA患者均接受了重组人促红细胞生成素（rhEPO）和输血支持，20例患者接受了额外治疗，如PEX、利妥昔单抗，以及最近的达雷妥尤单抗。总体而言，PEX和利妥昔单抗在一半的病例中在不同时间获得了反应，而我们用达雷妥尤单抗治疗的少数病例显示出有希望结果。我们队列中的总体反应率为75%，PRCA反应者的生存率显著更高（94.4%对16.7%），移植相关死亡率更低（6.3%对80%）。
由于目前各中心对PRCA的治疗存在争议，因此需要制定关于何时以及如何治疗PRCA的标准化指南。
