Department of Haematological Medicine,Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom.
Department of Medical Statistics & Bioinformatics, EBMT Statistical Unit, Leiden, The Netherlands.
Biol Blood Marrow Transplant. 2019 Mar;25(3):522-528. doi: 10.1016/j.bbmt.2018.10.017. Epub 2018 Nov 5.
This analysis included 56 myelofibrosis (MF) patients transplanted from family mismatched donor between 2009 and 2015 enrolled in the European Society for Blood and Marrow Transplantation database. The median age was 57years (range, 38 to 72); 75% had primary MF and 25% had secondary MF. JAK2 V617F was mutated in 61%. Donors were HLA mismatched at 2 or more loci. Stem cells were sourced from bone marrow in 66% and peripheral blood in 34%. The median CD34 cell dose was 4.8 × 10/kg (range, 1.7 to 22.9; n = 43). Conditioning was predominantly myeloablative in 70% and reduced intensity in the remainder. Regimens were heterogeneous with thiotepa, busulfan, fludarabine, and post-transplant cyclophosphamide used in 59%. The incidence of neutrophil engraftment by 28days was 82% (range, 70% to 93%), at a median of 21days (range, 19 to 23). At 2years the cumulative incidence of primary graft failure was 9% (95% CI 1% to 16%) and secondary graft failure was 13% (95% CI 4% to 22%). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV and III to IV was 28% (95% CI 16% to 40%) and 9% (95% CI 2% to 17%) at 100days. The cumulative incidence of chronic GVHD at 1 year was 45% (95% CI 32% to 58%), but the cumulative incidence of death without chronic GVHD by 1 year was 20% (95% CI 10% to 31%). With a median follow-up of 32 months, the 1- and 2-year overall survival was 61% (95% CI 48% to 74%) and 56% (95% CI 41% to 70%), respectively. The 1- and 2- year progression-free survival was 58% (95% CI 45% to 71%) and 43% (95% CI 28% to 58%), respectively, with a 2-year cumulative incidence of relapse of 19% (95% CI 7% to 31%). The 2-year nonrelapse mortality was 38% (95% CI 24% to 51%). This retrospective study of MF allo-SCT using family mismatched donors demonstrated feasibility of the approach, timely neutrophil engraftment in over 80% of cases, and acceptable overall and progression-free survival rates with relapse rates not dissimilar to the unrelated donor setting. However, strategies to minimize the risk of graft failure and the relatively high nonrelapse mortality need to be used, ideally in a multicenter prospective fashion.
本分析纳入了 2009 年至 2015 年间在欧洲血液和骨髓移植学会数据库中登记的 56 例接受亲缘全相合供者异基因骨髓纤维化（MF）移植的患者。中位年龄为 57 岁（范围，38 至 72 岁）；75%为原发性 MF，25%为继发性 MF。61%存在 JAK2 V617F 突变。供者 HLA 存在 2 个或以上位点错配。干细胞来源于骨髓的占 66%，来源于外周血的占 34%。中位 CD34 细胞剂量为 4.8×10/kg（范围，1.7 至 22.9；n=43）。预处理方案主要为清髓性（70%）和减低强度（其余 30%）。方案具有异质性，59%使用噻替哌、白消安、氟达拉滨和移植后环磷酰胺。28 天中性粒细胞植入的发生率为 82%（范围，70%至 93%），中位时间为 21 天（范围，19 至 23 天）。2 年时原发性移植物失败的累积发生率为 9%（95%CI，1%至 16%），继发性移植物失败的累积发生率为 13%（95%CI，4%至 22%）。100 天时急性移植物抗宿主病（GVHD）Ⅱ至Ⅳ级和Ⅲ至Ⅳ级的累积发生率分别为 28%（95%CI，16%至 40%）和 9%（95%CI，2%至 17%）。1 年时慢性 GVHD 的累积发生率为 45%（95%CI，32%至 58%），但 1 年时无慢性 GVHD 的死亡累积发生率为 20%（95%CI，10%至 31%）。中位随访 32 个月时，1 年和 2 年的总生存率分别为 61%（95%CI，48%至 74%）和 56%（95%CI，41%至 70%）。1 年和 2 年时无进展生存率分别为 58%（95%CI，45%至 71%）和 43%（95%CI，28%至 58%），2 年时复发的累积发生率为 19%（95%CI，7%至 31%）。2 年时非复发死亡率为 38%（95%CI，24%至 51%）。本研究回顾性分析了 MF 患者接受亲缘全相合供者异基因骨髓移植的情况，结果显示这种方法具有可行性，超过 80%的患者中性粒细胞植入及时，总生存率和无进展生存率可接受，复发率与无关供者移植的结果相似。但是，需要使用策略来降低移植物失败和相对较高的非复发死亡率的风险，理想情况下是采用多中心前瞻性方法。
