Abstract
The objective was to evaluate the prognostic impact of pre-transplant minimal residual disease (MRD) as determined by real-time quantitative polymerase chain reaction in 67 adult NPM1-mutated acute myeloid leukemia patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Twenty-eight of the 67 patients had a FLT3-ITD (42%). Median age at transplantation was 54.7 years, median follow-up for survival from time of allografting was 4.9 years. At transplantation, 31 patients were in first, 20 in second complete remission (CR) and 16 had refractory disease (RD). Pre-transplant NPM1 MRD levels were measured in 39 CR patients. Overall survival (OS) for patients transplanted in CR was significantly longer as compared to patients with RD (P=0.004), irrespective of whether the patients were transplanted in first or second CR (P=0.74). There was a highly significant difference in OS after allogeneic HSCT between pre-transplant MRD-positive and MRD-negative patients (estimated 5-year OS rates of 40 vs 89% P=0.007). Multivariable analyses on time to relapse and OS revealed pre-transplant NPM1 MRD levels >1% as an independent prognostic factor for poor survival after allogeneic HSCT, whereas FLT3-ITD had no impact. Notably, outcome of patients with pre-transplant NPM1 MRD positivity >1% was as poor as that of patients transplanted with RD.
Highlights
Allogeneic hematopoietic stem cell transplantation (HSCT) is considered to be the treatment strategy with the highest antileukemic efficacy for acute myeloid leukemia (AML) patients.[1]
Relapse remains the major cause of treatment failure even after allogeneic HSCT in complete remission (CR),[1,2,3] suggesting that the sensitivity of morphological remission assessment is too low to allow for the detection of clinically relevant residual leukemia left behind after conventional chemotherapy
The aim of this study was to evaluate the prognostic impact of pre-transplant NPM1 minimal residual disease (MRD) levels determined by RT-qPCR in correlation to clinical characteristics and genetic abnormalities assessed at initial diagnosis in a cohort of adult AML patients receiving allogeneic HSCT
Summary
Allogeneic hematopoietic stem cell transplantation (HSCT) is considered to be the treatment strategy with the highest antileukemic efficacy for acute myeloid leukemia (AML) patients.[1]. Schnittger and colleagues reported on 252 NPM1-mutated AML patients, of whom 53 underwent allogeneic HSCT.[12] their analyses were primarily focused on the correlation of outcome with MRD levels after chemotherapy. Pre-transplant MFC-MRD has been shown to be predictive for post-transplant outcome with high relapse rates of 60 to 70% after two or three years in MRD-positive patients as compared to only 8 to 21% in MRD-negative patients, respectively.[16,17,18] The aim of this study was to evaluate the prognostic impact of pre-transplant NPM1 MRD levels determined by RT-qPCR in correlation to clinical characteristics and genetic abnormalities assessed at initial diagnosis in a cohort of adult AML patients receiving allogeneic HSCT. In patients with a concurrent FLT3-ITD the allelic ratio was quantified by GeneScan-based fragment-length analysis; in cases with
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