Abstract
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.
Highlights
In acute leukemias, measurable residual disease (MRD) is defined as the presence of residual leukemic cells in bone marrow (BM) or peripheral blood (PB) in patients who achieved morphologic complete remission
The significance of MRD in hematopoietic stem cell transplantation 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) as it correlates with the risk of relapse after hematopoietic stem cell transplantation (HSCT)
In a pooled analysis of the GMALL 06/99 and 07/03 trials focused on prospective MRD monitoring by real-time quantitative polymerase chain reaction (RQ-PCR) directed to T-cell receptor (TCR) and Ig gene rearrangements, it was demonstrated that the probability of disease-free survival (DFS) after 5 years was significantly higher for patients with persistent MRD > 104 who underwent HSCT in first CR than for those patients that did not undergo HSCT in first CR (50% versus 16%, p = 0.004) [7]
Summary
Measurable residual disease (MRD) is defined as the presence of residual leukemic cells in bone marrow (BM) or peripheral blood (PB) in patients who achieved morphologic complete remission (mCR). In ALL, inadequate response at the level of MRD is a commonly accepted risk factor for relapse and an indication for allo-hematopoietic stem cell transplantation (allo-HSCT) as was recently emphasized in the consensus paper by panel of international experts on behalf of the European Working Group for Adult Acute Lymphoblastic Leukemia (EWALL) and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation [2]. The role of MRD assessment in guiding post-transplant prophylactic and pre-emptive treatment should be addressed in prospective trials. These open issues mostly awaiting further clinical studies will be discussed in our current review
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