Pre-and post-transplant quantification of measurable ('minimal') residual disease via multiparameter flow cytometry in adult acute myeloid leukemia
Leukemia, 2016•nature.com
Abstract Measurable ('minimal') residual disease (MRD) before or after hematopoietic cell
transplantation (HCT) identifies adults with AML at risk of poor outcomes. Here, we studied
whether peri-transplant MRD dynamics can refine risk assessment. We analyzed 279 adults
receiving myeloablative allogeneic HCT in first or second remission who survived at least 35
days and underwent 10-color multiparametric flow cytometry (MFC) analyses of marrow
aspirates before and 28±7 days after transplantation. MFC-detectable MRD before (n= 63) …
transplantation (HCT) identifies adults with AML at risk of poor outcomes. Here, we studied
whether peri-transplant MRD dynamics can refine risk assessment. We analyzed 279 adults
receiving myeloablative allogeneic HCT in first or second remission who survived at least 35
days and underwent 10-color multiparametric flow cytometry (MFC) analyses of marrow
aspirates before and 28±7 days after transplantation. MFC-detectable MRD before (n= 63) …
Abstract
Measurable (‘minimal’) residual disease (MRD) before or after hematopoietic cell transplantation (HCT) identifies adults with AML at risk of poor outcomes. Here, we studied whether peri-transplant MRD dynamics can refine risk assessment. We analyzed 279 adults receiving myeloablative allogeneic HCT in first or second remission who survived at least 35 days and underwent 10-color multiparametric flow cytometry (MFC) analyses of marrow aspirates before and 28±7 days after transplantation. MFC-detectable MRD before (n= 63) or after (n= 16) transplantation identified patients with high relapse risk and poor survival. Forty-nine patients cleared MRD with HCT conditioning, whereas two patients developed new evidence of disease. The 214 MRD neg/MRD neg patients had excellent outcomes, whereas both MRD neg/MRD pos patients died within 100 days following transplantation. For patients with pre-HCT MRD, outcomes were poor regardless of post-HCT MRD status, although survival beyond 3 years was only observed among the 58 patients with decreasing but not the seven patients with increasing peri-HCT MRD levels. In multivariable models, pre-HCT but not post-HCT MRD was independently associated with overall survival and risk of relapse. These data indicate that MRD pos patients before transplantation have a high relapse risk regardless of whether or not they clear MFC-detectable disease with conditioning and should be considered for pre-emptive therapeutic strategies.
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