PRE-TRANSPLANT QUANTITATIVE MONITORING OF NPM1 MUTATION SIGNIFICANTLY PREDICTS OUTCOME OF ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN NORMAL KARYOTYPE AML IN COMPLETE REMISSION.
Author(s): ,
Michal Karas
Affiliations:
Hematology and Oncology dpt.,CHARLES UNIVERSITY HOSPITAL PILSEN,Pilsen,Czech Republic
,
Katerina Steinerova
Affiliations:
Hematology and Oncology dpt.,CHARLES UNIVERSITY HOSPITAL PILSEN,Pilsen,Czech Republic
,
Samuel Vokurka
Affiliations:
Hematology and Oncology dpt.,CHARLES UNIVERSITY HOSPITAL PILSEN,Pilsen,Czech Republic
,
Alexandra Jungova
Affiliations:
Hematology and Oncology dpt.,CHARLES UNIVERSITY HOSPITAL PILSEN,Pilsen,Czech Republic
,
Marcela Hrabetova
Affiliations:
Hematology and Oncology dpt.,CHARLES UNIVERSITY HOSPITAL PILSEN,Pilsen,Czech Republic
,
Daniel Lysak
Affiliations:
Hematology and Oncology dpt.,CHARLES UNIVERSITY HOSPITAL PILSEN,Pilsen,Czech Republic
Pavel Jindra
Affiliations:
Hematology and Oncology dpt.,CHARLES UNIVERSITY HOSPITAL PILSEN,Pilsen,Czech Republic
EHA Library. Karas M. Jun 12, 2015; 100584; P341 Disclosure(s): CHARLES UNIVERSITY HOSPITAL PILSEN
Hematology and Oncology dpt. Bone Marrow Transplant Foundation Czech Republic
Dr. Michal Karas
Dr. Michal Karas
Contributions
Abstract
Abstract: P341

Type: Poster Presentation

Presentation during EHA20: From 12.06.2015 17:15 to 12.06.2015 18:45

Location: Poster area (Hall C)

Background

detection and the level of minimal residual disease (MRD) affects prognosis of AML patients (pts) treated with intensive chemotherapy alone. But impact of MRD in the setting of allogeneic hematopoietic stem cell transplantation (alloHSCT) especially in pts with normal karyotype AML in complete remission (CR) is less clear.



Aims

with the aim to evaluate the potential role of pre-transplant MRD we studied impact of pre-transplant MRD level on outcome of alloHSCT in 60 consecutive pts with normal karyotype AML harboring NPM1 mutations in complete remission. MRD level was determined using quantitative real-time polymerase chain reaction (qPCR) for detection of NPM1 mutations.



Methods

from 2/2005 to 9/2014 60 consecutive pts with median of age 54 years (range, 30-66 years) with normal normal karyotype AML harboring NPM1 mutations (53% FLT3/ITD positivity) in 1st CR (45 pts) and 2nd CR (15pts) underwent myeloablative (16 pts) or reduced-intensity (44 pts) alloHSCT (27% HLA identical related, 50% HLA matched unrelated, 23% HLA mismatched unrelated). Source of stem cells was in 80% peripheral blood and in 20% bone marrow. MRD level was determined using real-time qPCR for detection of NPM1 mutations before start of conditioning regimen from bone marrow. Pre-transplant prognostic factors (age, type of donor, donor recipient sex combination, CMV status, type of conditioning regimen, source of stem cells, number of CR, FLT3/ITD status, MRD level) were included in the univariate and multivariate statistical analysis.



Results

all pts fully engrafted with ongoing CR after alloHSCT. 36 pts (60%) developed aGVHD and 24 pts (40%) developed chGVHD. With median follow-up 52 months (range, 4-101 months) 35 pts (58%) are alive. 16 pts (27%) relapsed and 13 of them died. 12 pts (20%) died due to NRM. The estimated probabilities of 3-years EFS and OS are 54% and 59%. Statistical analysis showed that only age over 63 years and MRD level affected alloHSCT outcome in multivariate analysis. Pre-transplant MRD level 10 NPM1mut/10000 ABL copies had the strongest statistical significance. The estimated probabilities of 3-years relapse incidence, EFS and OS were for pts with low MRD level (≤ 10 NPM1mut copies) 6%, 72% and 75% and for pts with high MRD level (> 10 NPM1mut copies) 31%, 35% and 40%.



Summary

our data show that pre-transplant quantitative assessment of NPM1 mutation in pts with normal karyotype AML harboring NPM1 mutation in CR provides important prognostic information, which as an independent prognostic factor predicts transplant results.



Keyword(s): Acute myeloid leukemia, Allogeneic hematopoietic stem cell transplant, Minimal residual disease (MRD), Quantitative molecular analysis

Session topic: Stem cell transplantation - Clinical 1

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