Department of Hematology and Bone Marrow Transplantation, Wroclaw Medical University, Ludwik Pasteur 4, 50-367 Wroclaw, Poland.
Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Derech Sheba 2, 52-621 Ramat Gan, Israel.
Int J Mol Sci. 2019 Oct 28;20(21):5362. doi: 10.3390/ijms20215362.
The significance of measurable residual disease (MRD) in hematopoietic stem cell transplantation (HSCT) is well recognized in different hematological malignancies, but the evidence indicate that pre-transplant MRD status is of particular importance in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). In ALL, inadequate response at the level of MRD is a commonly accepted risk factor for relapse and thus an indication for allogeneic HSCT. Similarly, growing evidence from the literature strongly suggest that MRD detected by multiparameter flow cytometry or molecular techniques should be also used for risk stratification in AML at the time of HSCT. Despite the well-defined association of MRD and outcomes of HSCT in acute leukemias, there are still many open issues such as the role of additional pre-transplant consolidation for MRD eradication, the ability of HSCT to overcome negative influence of MRD positivity on survival, the impact of conditioning regimen intensity on MRD clearance post HSCT, and transplantation outcomes or the selection of optimal donor with regards to MRD status. In addition, the role of MRD assessment in guiding post-transplant maintenance treatment should also be addressed in prospective trials. These open issues mostly awaiting further clinical studies will be discussed in our current review.
在不同的血液恶性肿瘤中，造血干细胞移植（HSCT）中可测量残留疾病（MRD）的意义已得到广泛认可，但有证据表明，移植前 MRD 状态在急性淋巴细胞白血病（ALL）和急性髓细胞白血病（AML）中尤为重要。在 ALL 中，MRD 水平的不充分反应是复发的常见危险因素，因此也是进行异基因 HSCT 的指征。同样，来自文献的越来越多的证据强烈表明，在 HSCT 时，通过多参数流式细胞术或分子技术检测到的 MRD 也应该用于 AML 的风险分层。尽管 MRD 与 HSCT 在急性白血病中的结果之间存在明确的关联，但仍存在许多悬而未决的问题，例如在消灭 MRD 方面额外的移植前巩固治疗的作用、HSCT 克服 MRD 阳性对生存的负面影响的能力、预处理方案强度对 HSCT 后 MRD 清除的影响、移植结果或根据 MRD 状态选择最佳供体等。此外，MRD 评估在指导移植后维持治疗中的作用也应在前瞻性试验中得到解决。这些悬而未决的问题主要有待进一步的临床研究，我们将在本次综述中进行讨论。
