Department of Hematology, Catholic Hematology Hospital, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Am J Hematol. 2021 Jan;96(1):98-109. doi: 10.1002/ajh.25993. Epub 2020 Nov 24.
Despite comparable outcomes of haploidentical transplants (Haplo-HSCT) with HLA-matched unrelated transplants (MUD-HSCT) in retrospective comparisons, few studies have prospectively compared Haplo-HSCT with MUD-HSCT in AML. Here, we prospectively compared the outcomes of Haplo-HSCT with MUD-HSCT for AML in remission (n = 110) to prove non-inferiority of overall survival in Haplo-HSCT. Both groups were well balanced in factors related to biological features of AML and measurable residual disease (MRD) status by Wilms' tumor gene 1 (WT1) assay. A unique, reduced-toxicity preparative regimen was used for Haplo-HSCT, whereas mostly-myeloablative regimen was for MUD-HSCT. Both groups showed similar patterns of neutrophil and platelet recovery, whereas delayed T-cell reconstitution in Haplo-HSCT was found compared with MUD-HSCT. No significant differences were found in acute or chronic graft-vs-host-disease (GVHD) and post-transplant infectious events with an exception of EBV or CMV infection, which occurred more frequently in Haplo-HSCT. After a median follow-up of 47 months, no significant differences in overall survival (65% vs 54%, P = .146), disease-free survival (67% vs 53%, P = .142), relapse (20% vs 21%, P = .858), non-relapse mortality (14% vs 26%, P = .103), or GVHD-free/relapse-free survival (54% vs 41%, P = .138) were observed for Haplo-HSCT vs MUD-HSCT. In multivariate analysis, WT1 expression before transplantation independently predicted relapse, resulting in inferior survival. Separate analysis of unenrolled patients (n = 110) who were excluded or refused to participate in this study showed consistent results with enrolled patients. This prospective study demonstrated the non-inferiority of Haplo-HSCT to MUD-HSCT for AML in remission, and validated the role of WT1 quantification as an MRD marker (ClinicalTrial.gov identifier: NCT01751997).
尽管在回顾性比较中，半相合移植（Haplo-HSCT）与 HLA 匹配的无关供体移植（MUD-HSCT）的结果相当，但很少有前瞻性研究比较 AML 患者的 Haplo-HSCT 与 MUD-HSCT。在这里，我们前瞻性地比较了缓解期 AML 患者的 Haplo-HSCT 与 MUD-HSCT 的结果，以证明 Haplo-HSCT 在总体生存方面不劣于 MUD-HSCT。两组在与 AML 生物学特征和 Wilms 瘤基因 1（WT1）检测可测量残留疾病（MRD）状态相关的因素方面均平衡良好。Haplo-HSCT 采用了独特的、降低毒性的预处理方案，而 MUD-HSCT 则采用了主要是清髓性的方案。两组的中性粒细胞和血小板恢复模式相似，而与 MUD-HSCT 相比，Haplo-HSCT 中发现 T 细胞恢复延迟。除 EBV 或 CMV 感染外，两组在急性或慢性移植物抗宿主病（GVHD）和移植后感染事件方面无显著差异，而 EBV 或 CMV 感染在 Haplo-HSCT 中更为常见。中位随访 47 个月后，Haplo-HSCT 与 MUD-HSCT 之间在总生存率（65% vs 54%，P = 0.146）、无病生存率（67% vs 53%，P = 0.142）、复发率（20% vs 21%，P = 0.858）、非复发死亡率（14% vs 26%，P = 0.103）或 GVHD 无复发/复发无生存率（54% vs 41%，P = 0.138）方面均无显著差异。多变量分析显示，移植前 WT1 表达独立预测复发，导致生存状况较差。对未入组的患者（n = 110）进行单独分析，这些患者被排除或拒绝参加这项研究，结果与入组患者一致。这项前瞻性研究表明，在缓解期 AML 患者中，Haplo-HSCT 不劣于 MUD-HSCT，并且验证了 WT1 定量作为 MRD 标志物的作用（ClinicalTrials.gov 标识符：NCT01751997）。
