Allogeneic hematopoietic stem cell transplantation from a 2-HLA-haplotype-mismatched family donor for posttransplant relapse: a prospective phase I/II study
Allogeneic hematopoietic stem cell transplantation from a 2-HLA-haplotype-mismatched family donor for posttransplant relapse: a prospective phase I/II study
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DOI：
10.1038/s41409-020-0980-8
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发表时间：
2020-06-20
影响因子：
4.8
通讯作者：
Fujimori, Yosihiro
中科院分区：
文献类型：
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作者：
Kazuhiro, Ikegame;Katsuji, Kaida;Fujimori, Yosihiro
HLA单倍型造血干细胞移植（HSCT），即来自1-HLA单倍型不匹配的家族供体的HSCT，甚至作为移植后复发的第二次移植也已成功进行。 HSCT中HLA错配的极限是单倍体吗？为了探讨单倍相合亲属以外的家庭捐献者发生HLA不匹配HSCT的可能性，我们进行了2-HLA单倍型不匹配HSCT（2-haplo-mismatch HSCT）的前瞻性I/II期研究。我们招募了 30 名移植后复发的患者（急性髓细胞白血病：18 例，急性淋巴细胞白血病：11 例，非霍奇金淋巴瘤：1 例）。第二至第六次移植进行了2-单倍体不匹配HSCT。捐赠者包括兄弟姐妹 (n = 12)、表兄弟姐妹 (n = 16) 和远房表兄弟姐妹 (n = 2)。预处理方案包括氟达拉滨、阿糖胞苷、美法仑、低剂量抗胸腺细胞球蛋白和3 Gy全身照射。移植物抗宿主病（GVHD）预防措施包括他克莫司、甲泼尼龙和吗替麦考酚酯。除一例早亡病例外，所有患者均实现中性粒细胞移植。 II-IV级和III-IV级急性GVHD的累积发生率分别为36.7%和16.7%。 1 年总生存率、复发死亡率和非复发死亡率分别为 30.1%、38.9% 和 44.3%。考虑到移植后复发的不良预后，2-单倍体不匹配HSCT可以作为第二次或第三次移植的替代选择。
HLA haploidentical hematopoietic stem cell transplantation (HSCT), i.e., HSCT from a 1-HLA-haplotype-mismatched family donor, has been successfully performed even as a second transplantation for posttransplant relapse. Is the haploidentical the limit of HLA mismatches in HSCT? In order to explore the possibility of HLA-mismatched HSCT from family donors beyond haploidentical relatives, we conducted a prospective phase I/II study of 2-HLA-haplotype-mismatched HSCT (2-haplo-mismatch HSCT). We enrolled 30 patients with posttransplant relapse (acute myeloid leukemia: 18, acute lymphoblastic leukemia: 11, non-Hodgkin lymphoma: 1). 2-haplo-mismatch HSCT was performed as the second to sixth transplantations. The donors were siblings (n = 12), cousins (n = 16), and second cousins (n = 2). The conditioning regimen consisted of fludarabine, cytarabine, melphalan, low-dose anti-thymocyte globulin, and 3 Gy of total body irradiation. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus, methylprednisolone, and mycophenolate mofetil. All patients achieved neutrophil engraftment, except for a case of early death. The cumulative incidences of grades II-IV and III-IV acute GVHD were 36.7% and 16.7%, respectively. The overall survival at 1 year, relapse, and non-relapse mortality rates was 30.1%, 38.9%, and 44.3%, respectively. Considering the poor prognosis of posttransplant relapse, 2-haplo-mismatch HSCT can be an alternative option in a second or third transplantation.