Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2020 Aug;99(8):1845-1853.
doi: 10.1007/s00277-020-04026-1. Epub 2020 Apr 24.

Pre-transplant FLT3/ITD status predicts outcome in FLT3-mutated acute myeloid leukemia following allogeneic stem cell transplantation

Grzegorz Helbig  1 , Anna Koclęga  2 , Agata Wieczorkiewicz-Kabut  2 , Krzysztof Woźniczka  2 , Anna Kopińska  2 , Kinga Boral  2 , Iwona Grygoruk-Wiśniowska  2 , Małgorzata Stachowicz  2 , Agnieszka Karolczyk  2
Affiliations
Clinical Trial

Pre-transplant FLT3/ITD status predicts outcome in FLT3-mutated acute myeloid leukemia following allogeneic stem cell transplantation

Grzegorz Helbig et al. Ann Hematol. 2020 Aug.

Abstract

Acute myeloid leukemia (AML) with fetal liver tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) is associated with poor prognosis, and allogeneic stem cell transplantation (Allo-SCT) seems to be the preferred therapeutic approach. However, the predictors of post-transplant outcomes were not well-defined. The aim of the study was to evaluate the significance of FLT3/ITD mutation by polymerase chain reaction as minimal residual disease (MRD) marker of outcomes after transplantation. We identified 43 patients (28 females and 15 males) with FLT3-mutated AML at the median age of 45 years who were allografted between 2009 and 2019. Hematological status at transplant was as follows: the first complete remission (CR1) in 29 patients, CR2 in 5, and 9 patients were transplanted in marrow aplasia (MA). Twenty-seven patients were FLT3 MRD negative at transplant. Median time from diagnosis to transplant was 16.7 months. Post-allograft CR rate was 88%. The relapse incidence (RI) was lower for patients who were FLT3 MRD negative at transplant when compared with those with FLT3 MRD positivity (41% vs 59%; p = 0.01). The patients who eradicated FLT3/ITD at day + 30 after transplant had lower RI than those with detectable FLT3/ITD (23% vs 76%; p = <0.001). The 2-year LFS and OS were 53% and 54%, with the median OS and LFS of 28 months and 27 months, respectively. Patients with CR1/2 and FLT3 MRD(-) had a 2-year OS of 80%. The FLT3 MRD negativity at transplant prolonged LFS in multivariate analysis (HR 5.3 95%CI 1.97-14.2); p < 0.001), whereas FLT3 MRD negativity and unrelated donor predicted favorable OS.

Keywords: Acute myeloid leukemia; Allogeneic stem cell transplantation; FLT3/ITD mutation; Leukemia-free survival; Minimal residual disease; Overall survival.

PubMed Disclaimer

Conflict of interest statement

GH has received a speaker honorarium from Novartis. All other authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Overall survival for FLT3-mutated AML patients
Fig. 2
Fig. 2
Leukemia-free survival for FLT3-mutated AML patients
Fig. 3
Fig. 3
Overall survival depending on FLT3 MRD status at transplant
Fig. 4
Fig. 4
Overall survival depending on donor source
See this image and copyright information in PMC

References

    1. Stirewalt DL, Radich JP. The role of FLT3 in hematopoietic malignancies. Nat Rev Cancer. 2003;3:650–665. doi: 10.1038/nrc1169. - DOI - PubMed
    1. Frӧhling S, Schlenk RF, Breitruck J, et al. Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML study group Ulm. Blood. 2002;100:4372–4380. doi: 10.1182/blood-2002-05-1440. - DOI - PubMed
    1. Rombouts WJ, Blokland I, Lowenberg B, et al. Biological characteristics and prognosis of adult acute myeloid leukemia with internal tandem duplications in the Flt3 gene. Leukemia. 2000;14:675–683. doi: 10.1038/sj.leu.2401731. - DOI - PubMed
    1. Dӧhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129:424–447. doi: 10.1182/blood-2016-08-733196. - DOI - PMC - PubMed
    1. Bornhauser M, Illmer T, Schaich M, et al. Improved outcome after stem-cell transplantation in FLT3-ITD positive AML. Blood. 2007;109:2264–2265. doi: 10.1182/blood-2006-09-047225. - DOI - PubMed

Publication types

Substances