Department of Haematology and Bone Marrow Transplantation, St Vincent's Hospital, Sydney, Australia.
Department of Haematology and Bone Marrow Transplantation, Royal Brisbane and Women's Hospital, Brisbane, Australia; University of Queensland, St Lucia, Australia.
Biol Blood Marrow Transplant. 2020 Dec;26(12):2252-2261. doi: 10.1016/j.bbmt.2020.08.024. Epub 2020 Aug 27.
To review the updated trends of national practice and outcomes in transplantation to treat myelofibrosis (MF), we retrospectively evaluated 142 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) for primary (n = 94) or secondary (n = 48) MF at an Australian/New Zealand transplantation center between 2006 and 2017. The median duration of follow-up was 51.8 months (range, 3.1 to 148 months). The median age at allo-HSCT was 56 years (range, 26 to 69 years). Fifty-two percent of the patients had HLA-identical sibling donors, and 45% had matched unrelated donors (UD). Conditioning regimens were predominantly reduced intensity (83%). Before transplantation, 16% of the patients had undergone splenectomy or splenic irradiation, and 38% (n = 54) received JAK inhibitor therapy. JAK2 mutation testing was performed in 66.9% of the patients, whereas other mutations (CALR, MPL, ASXL1, SRSF2, U2AF1Q57, EZH2, and IDH1/2) were rarely tested (1.4% to 8.4%). Only 4.2% of patients had next-generation sequencing mutation analysis. The median time to neutrophil engraftment was 19 days (range, 10 to 43 days), and the median time to platelet engraftment was 27 days (range, 13 to 230 days). The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 21.4% at 100 days, and that of extensive chronic GVHD (cGVHD) at 5 years was 18.1%. Overall survival (OS) was 67% at 1 year and 57% at 5 years. GVHD-free, relapse-free survival was 54% at 1 year and 42% at 5 years. The cumulative incidence of nonrelapse mortality (NRM) was 16% at 100 days and 25% at 1 year. In multivariate analysis, age ≥65 years and use of an UD were identified as significant unfavorable risk factors for OS and NRM. Use of an UD increased the incidence of aGVHD, whereas administration of antithymocyte globulin/alemtuzumab lowered the risk of both aGVHD and cGVHD. Pretransplantation splenectomy/splenic irradiation had a positive influence on time to engraftment. There have been no improvements in the outcomes of allo-HSCT for MF in Australasia over the last decade, with a low uptake of molecular genomic technology due to limited access to funding.
为了回顾国家实践和同种异体造血干细胞移植（allo-HSCT）治疗骨髓纤维化（MF）治疗结果的最新趋势，我们回顾性评估了 2006 年至 2017 年期间在澳大利亚/新西兰移植中心接受 allo-HSCT 治疗原发性（n=94）或继发性（n=48）MF 的 142 例患者。中位随访时间为 51.8 个月（范围，3.1 至 148 个月）。allo-HSCT 时的中位年龄为 56 岁（范围，26 至 69 岁）。52%的患者有 HLA 完全匹配的同胞供者，45%有匹配的无关供者（UD）。预处理方案主要为强度降低（83%）。移植前，16%的患者接受了脾切除术或脾照射，38%（n=54）接受了 JAK 抑制剂治疗。在 66.9%的患者中进行了 JAK2 突变检测，而其他突变（CALR、MPL、ASXL1、SRSF2、U2AF1Q57、EZH2 和 IDH1/2）很少进行检测（1.4%至 8.4%）。只有 4.2%的患者进行了下一代测序突变分析。中性粒细胞植入的中位时间为 19 天（范围，10 至 43 天），血小板植入的中位时间为 27 天（范围，13 至 230 天）。100 天时，Ⅱ-Ⅳ级急性移植物抗宿主病（aGVHD）的累积发生率为 21.4%，5 年时广泛慢性移植物抗宿主病（cGVHD）的发生率为 18.1%。1 年时总生存率（OS）为 67%，5 年时为 57%。1 年时无复发、无进展生存率为 54%，5 年时为 42%。100 天时非复发死亡率（NRM）的累积发生率为 16%，1 年时为 25%。多变量分析显示，年龄≥65 岁和使用 UD 是 OS 和 NRM 的显著不利危险因素。使用 UD 增加了 aGVHD 的发生率，而使用抗胸腺细胞球蛋白/阿仑单抗则降低了 aGVHD 和 cGVHD 的风险。移植前脾切除术/脾照射对植入时间有积极影响。在过去的十年中，澳大利亚和新西兰同种异体 HSCT 治疗 MF 的结果没有改善，由于获得资金有限，分子基因组技术的应用率很低。
