Division of Hematological Malignancies and Bone Marrow Transplantation, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 1650 Orleans street, Baltimore, MD, USA 21287.
Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 550 North Broadway, Baltimore, MD, USA 21287.
Haematologica. 2023 Dec 1;108(12):3321-3332. doi: 10.3324/haematol.2023.283426.
Haploidentical donors offer a potentially readily available donor, especially for non-White patients, for hematopoietic cell transplantation (HCT). In this North American collaboration, we retrospectively analyzed outcomes of first HCT using haploidentical donor and post-transplantation cyclophosphamide (PTCy) in myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap neoplasms (MDS/MPN). We included 120 consecutive patients who underwent HCT using a haploidentical donor for MDS/MPN across 15 centers. Median age was 62.5 years and 38% were of non-White/Caucasian ethnicity. The median follow-up was 2.4 years. Graft failure was reported in seven of 120 (6%) patients. At 3 years, nonrelapse mortality (NRM) was 25% (95% confidence interval [CI]: 17-34), relapse 27% (95% CI: 18-36), grade 3-4 acute graftversus- host disease 12% (95% CI: 6-18), chronic graft-versus-host disease requiring systemic immunosuppression 14% (95% CI: 7-20), progression-free survival (PFS) 48% (95% CI: 39-59), and overall survival (OS) 56% (95% CI: 47-67). On multivariable analysis, NRM was statistically significantly associated with advancing age at HCT (per decade increment, subdistribution hazard ratio [sdHR] =3.28; 95% CI: 1.30-8.25); relapse with the presence of mutation in EZH2/RUNX1/SETBP1 (sdHR=2.61; 95% CI: 1.06-6.44); PFS with advancing age at HCT (per decade increment, HR=1.98, 95% CI: 1.13-3.45); and OS with advancing age at HCT (per decade increment, HR=2.01; 95% CI: 1.11-3.63) and splenomegaly at HCT/prior splenectomy (HR=2.20; 95% CI: 1.04-4.65). Haploidentical donors are a viable option for HCT in MDS/MPN, especially for those disproportionately represented in the unrelated donor registry. Hence, donor mismatch should not preclude HCT for patients with MDS/MPN, an otherwise incurable malignancy. In addition to patient age, disease-related factors including splenomegaly and high-risk mutations dominate outcomes following HCT.
Haploidentical 供者为血液系统恶性肿瘤患者，尤其是非白种人患者，提供了一种潜在的易得供者来源，用于造血细胞移植（HCT）。在这项北美合作研究中，我们回顾性分析了 15 个中心的 120 例连续接受 Haploidentical 供者和移植后环磷酰胺（PTCy）治疗的骨髓增生异常综合征/骨髓增殖性肿瘤（MDS/MPN）重叠肿瘤（MDS/MPN）患者的移植后结局。中位年龄为 62.5 岁，38%的患者为非白种人/高加索人。中位随访时间为 2.4 年。120 例患者中，有 7 例（6%）发生移植物失败。3 年时，非复发死亡率（NRM）为 25%（95%CI：17-34），复发率为 27%（95%CI：18-36），3-4 级急性移植物抗宿主病（GVHD）发生率为 12%（95%CI：6-18），需要系统性免疫抑制治疗的慢性 GVHD 发生率为 14%（95%CI：7-20），无进展生存期（PFS）为 48%（95%CI：39-59），总生存期（OS）为 56%（95%CI：47-67）。多变量分析显示，NRM 与 HCT 时年龄的增长显著相关（每 10 年增加一个十年，亚分布风险比[sdHR]为 3.28；95%CI：1.30-8.25）；复发与 EZH2/RUNX1/SETBP1 突变的存在相关（sdHR=2.61；95%CI：1.06-6.44）；PFS 与 HCT 时年龄的增长相关（每 10 年增加一个十年，HR=1.98，95%CI：1.13-3.45）；OS 与 HCT 时年龄的增长相关（每 10 年增加一个十年，HR=2.01；95%CI：1.11-3.63），以及 HCT 时脾肿大/脾切除术（HR=2.20；95%CI：1.04-4.65）。Haploidentical 供者是 MDS/MPN 患者进行 HCT 的可行选择，尤其是在非亲缘供者登记处比例较高的患者中。因此，对于 MDS/MPN 患者，供者不匹配不应排除 HCT 的可能，因为这种疾病目前无法治愈。除了患者年龄外，疾病相关因素，包括脾肿大和高危突变，主导着 HCT 后的结局。
