Allogeneic hematopoietic cell transplant (HCT) is often the only curative therapy for patients with nonmalignant diseases; however, many patients do not have an HLA-matched donor. Historically, poor survival has been seen after HLA-haploidentical HCT because of poor immune reconstitution, increased infections, graft-versus-host disease (GVHD), and graft failure. Encouraging results have been reported using a nonmyeloablative T cell–replete HLA-haploidentical transplant approach in patients with hematologic malignancies. Here we report the outcomes of 23 patients with various nonmalignant diseases using a similar approach. Patients received HLA-haploidentical bone marrow (n = 17) or granulocyte colony-stimulating factor–mobilized peripheral blood stem cell (n = 6) grafts after conditioning with cyclophosphamide 50 mg/kg, fludarabine 150 mg/m², and 2 or 4 Gy total body irradiation. Postgrafting immunosuppression consisted of cyclophosphamide, mycophenolate mofetil, tacrolimus, ± sirolimus. Median patient age at HCT was 10.8 years. Day 100 transplant-related mortality (TRM) was 0%. Two patients died at later time points, 1 from intracranial hemorrhage/disseminated fungal infection in the setting of graft failure and 1 from infection/GVHD. The estimated probabilities of grades II to IV and III to IV acute GVHD at day 100 and 2-year National Institutes of Health consensus chronic GVHD were 78%, 26%, and 42%, respectively. With a median follow-up of 2.5 years, the 2-year overall and event-free rates of survival were 91% and 78%, respectively. These results are encouraging and demonstrate favorable disease-specific lineage engraftment with low TRM in patients with nonmalignant diseases using nonmyeloablative conditioning followed by T cell–replete HLA-haploidentical grafts. However, additional strategies are needed for GVHD prevention to make this a viable treatment approach for patients with nonmalignant diseases.

异基因造血细胞移植（HCT）通常是非恶性疾病患者的唯一治愈疗法；然而，许多患者没有 HLA 匹配的供体。从历史上看，由于免疫重建不良、感染增加、移植物抗宿主病 (GVHD) 和移植物失败，HLA 半相合 HCT 后的存活率较差。在血液系统恶性肿瘤患者中使用非清髓性 T 细胞充足的 HLA 半相合移植方法已报告了令人鼓舞的结果。在这里，我们使用类似的方法报告了 23 名患有各种非恶性疾病的患者的结果。患者在环磷酰胺 50 mg/kg、氟达拉滨 150 mg/m2 预处理后接受 HLA 半相合骨髓（n = 17）或粒细胞集落刺激因子动员的外周血干细胞（n = 6）移植物²，以及 2 或 4 Gy 全身照射。移植后免疫抑制包括环磷酰胺、霉酚酸酯、他克莫司、±西罗莫司。HCT 的中位患者年龄为 10.8 岁。第 100 天移植相关死亡率 (TRM) 为 0%。两名患者在稍后的时间点死亡，一名死于移植失败时的颅内出血/播散性真菌感染，一名死于感染/GVHD。在第 100 天和第 2 年美国国立卫生研究院共识慢性 GVHD 的 II 至 IV 级和 III 至 IV 级急性 GVHD 的估计概率分别为 78%、26% 和 42%。中位随访 2.5 年，2 年总生存率和无事件生存率分别为 91% 和 78%。这些结果令人鼓舞，并证明了在非恶性疾病患者中使用非清髓性预处理和 T 细胞充足的 HLA 半相合移植物可实现低 TRM 的疾病特异性谱系移植。然而，需要额外的策略来预防 GVHD，以使其成为非恶性疾病患者的可行治疗方法。