Kindwall-Keller T, Isola L M
University Hospitals of Cleveland, Case Medical Center, Cleveland, OH, USA.
Bone Marrow Transplant. 2009 Apr;43(8):597-609. doi: 10.1038/bmt.2009.28. Epub 2009 Mar 2.
Allogeneic hematopoietic SCT (allo-HCT) is the only curative therapy for myelodysplastic syndrome (MDS). Numerous myeloablative (MA), nonmyeloablative SCT (NST) and reduced conditioning transplant (RIC) studies have included MDS patients. Twenty-four MA HCT studies published from 2000 and 2008 reported OS and disease-free survival (DFS) ranging from 25 and 16% at 2 years to 52 and 50% at 4 years. In these publications, the incidence of grades II-IV acute GVHD was 18-100%, chronic GVHD 13-88%, relapse risk 24% at 1 year to 54.5% at 4 years and TRM 19% at day 100 to 61% at 5 years. From 2003 to 2008, 30 publications combining RIC and NST reported OS and DFS from 22 and 20% at 2 years to 79 and 79% at 4 years. Incidence of grades II-IV acute GVHD ranged from 9 to 63%, chronic GVHD 18 to 80%, relapse risk 6 to 61% and TRM 0% at day 100 to 34% at 5 years. The wide range in the published results leaves many unanswered questions. Although no ideal transplant conditioning has emerged, many of the MA and RIC studies used BU-based regimens and used a recipient age cutoff of 50-55 years for MA HCT. Similarly, there is no agreement on the use of induction or hypomethylating therapy before HCT, but azacitidine and decitabine are gaining increasing attention as a bridge to HCT. Until recently, the International Prognostic Scoring System (IPSS) dictated the use and timing of HCT. The WHO classification and WHO Prognostic Scoring System (WPSS) may be better suited in predicting the outcomes and should probably be incorporated in transplant algorithms. Most published MDS transplant series combine matched related donors (MRD) and matched unrelated donors (MUD). Umbilical cord blood (UCB) grafts will likely broaden the population of MDS patients eligible for allografting, but outcome data for MDS are scant. At this time, it is reasonable to consider the availability of an MRD or MUD as separate from an UCB graft in the decision of transplantation for MDS. The development of RIC, improvements in supportive therapy and alternative donor selection will provide better OS for MDS patients undergoing transplantation. Simultaneously, better understanding and medical therapy of MDS are leading us to re-examine patient selection and the timing of HCT. The results of HCT for MDS continue to improve together with the outlook of patients afflicted with myelodysplasia.
异基因造血干细胞移植(allo-HCT)是骨髓增生异常综合征(MDS)唯一的治愈性疗法。众多清髓性(MA)、非清髓性干细胞移植(NST)及减低预处理移植(RIC)研究纳入了MDS患者。2000年至2008年发表的24项MA HCT研究报告显示,2年总生存期(OS)和无病生存期(DFS)分别为25%和16%,4年时为52%和50%。在这些出版物中,II-IV级急性移植物抗宿主病(GVHD)的发生率为18%-100%,慢性GVHD为13%-88%,复发风险1年时为24%,4年时为54.5%,移植相关死亡率(TRM)100天时为19%,5年时为61%。2003年至2008年,30项结合RIC和NST的出版物报告显示,2年OS和DFS分别为22%和20%,4年时为79%和79%。II-IV级急性GVHD的发生率为9%-63%,慢性GVHD为18%-80%,复发风险为6%-61%,TRM 100天时为0%,5年时为34%。已发表结果的广泛差异留下了许多未解答的问题。尽管尚未出现理想的移植预处理方案,但许多MA和RIC研究使用了以白消安(BU)为基础的方案,且MA HCT的受者年龄截止值为50-55岁。同样,对于HCT前诱导或低甲基化疗法的使用也没有达成共识,但阿扎胞苷和地西他滨作为HCT的桥梁越来越受到关注。直到最近,国际预后评分系统(IPSS)决定了HCT的使用和时机。世界卫生组织(WHO)分类和WHO预后评分系统(WPSS)可能更适合预测结果,并且可能应纳入移植算法中。大多数已发表的MDS移植系列纳入了匹配的相关供者(MRD)和匹配的无关供者(MUD)。脐带血(UCB)移植可能会扩大适合接受同种异体移植的MDS患者群体,但MDS的结果数据很少。此时,在MDS移植决策中,将MRD或MUD的可用性与UCB移植分开考虑是合理的。RIC的发展、支持治疗的改善和替代供者选择将为接受移植的MDS患者提供更好的OS。同时,对MDS更好地理解和医学治疗正促使我们重新审视患者选择和HCT的时机。MDS的HCT结果与骨髓增生异常患者的前景一起持续改善。