The Role of Measurable Residual Disease (MRD) in Hematopoietic Stem Cell Transplantation for Hematological Malignancies Focusing on Acute Leukemia

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.

Measurable residual disease (MRD) testing for acute leukemia in EBMT transplant centers: a survey on behalf of the ALWP of the EBMT

“…Thus, incorporating pretransplant MRD as an additional parameter in large transplant registry databases, though challenging, is of special importance. Accordingly, several reports from the ALWP of the EBMT have evidenced higher risk of relapse and worse transplantation outcomes in patients with detectable MRD at transplantation in various transplantation setting [18][19][20][21][22][23].…”

Allogeneic hematopoietic stem cell transplant in pediatric acute myeloid leukemia: Lessons learnt from a tertiary care center in India

“… 42‐44 . Given its strong independent predictive value, MRD assessment is recommended at various time points in treatment of AML patients, including that before proceeding to transplant 45,46 . In the absence of MRD assessment, our study has identified two useful clinical parameters—short duration of CR1 and presence of active disease—that may be useful to better select transplant candidates in a resource‐limited setting.…”

“…Presence of MRD using multiparameter flow cytometry or real-time quantitative polymerase chain reaction or fluorescence in situ hybridization before transplant is associated with a high risk of relapse and inferior outcomes.. [42][43][44] Given its strong independent predictive value, MRD assessment is recommended at various time points in treatment of AML patients, including that before proceeding to transplant. 45,46 In the absence of MRD assessment, our study has identified two useful clinical parameters-short duration of CR1 and presence of active disease-that may be useful to better select transplant candidates in a resource-limited setting.…”

Immunophenotypic Profile of Blast Cells as a Marker for Diagnosis of Relapsed Children Acute Lymphoblastic Leukemia

“…1). Оскільки бластні клітини -це незрілі клітини, які під час дозрівання перетворюються в функціональні клітини крові, то підвищений їхній рівень в КМ, після проведення курсу хіміотерапії, вказує на порушення процесів кровотворення -бластні клітини не дозрівають у функціонально-активні клітини крові [14,15].…”