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Vol 13, No 1 (2022)
Case report
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Efficacy of midostaurin combined with intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation in a patient with NPM1 and FLT3-TKD mutated acute myeloid leukaemia with clinical high-risk features

Elżbieta Patkowska1, Monika Prochorec-Sobieszek2, Ewa Lech-Marańda1, Barbara Nasiłowska-Adamska3
DOI: 10.5603/HCP.2022.0004
·
Hematology in Clinical Practice 2022;13(1):23-30.
Affiliations
  1. Department of Haematology, Institute of Haematology and Transfusion Medicine, Warsaw, Poland
  2. Department of Haematological Diagnostics, Institute of Haematology a nd Transfusion Medicine, Warsaw, Poland
  3. Department of Haematopoietic Cell Transplantation, Institute of Haematology and Transfusion Medicine, Warsaw, Poland

open access

Vol 13, No 1 (2022)
CASE REPORTS

Abstract

Many genetic disorders occur in patients suffering from acute myeloid leukaemia (AML). The most common mutations found in such patients are in the nucleophosmin (NPM) gene and the FLT3 tyrosine kinase receptor gene. NPM1 mutation is observed in 30–35% of adult AML patients (50–60% of AML with normal karyotype), showing a favourable prognosis. The presence of point FLT3 comutations occur in the tyrosine kinase domain (TKD) are associated with even more favourable prognosis. However FLT3 comutations i.e. internal tandem duplication (ITD) in particular with high allelic ratio (ITDhigh) worsen the course of leukemia and treatment outcomes. Deploying FLT3 tyrosine kinase inhibitors thus offers a prospect for improving treatment and prolonging the survival of patients with AML, burdened with the FLT3 gene mutation. Midostaurin and gilteritinib are type I FLT3 inhibitors which are used to treat patients with AML FLT3-TKD due to their mechanism of action.

This paper presents the case of a 30-year-old AML patient diagnosed with NPM1 and FLT3-TKD mutations, bone marrow reticuline fibrosis and extramedullary sites of AML. Treatment was individualized and induction chemotherapy was combined with midostaurin. After first-line treatment with midostaurin, complete remission was achieved, as confirmed by histopathological examination of the bone marrow. Subsequently, two cycles of consolidation chemotherapy were given, and allogeneic haematopoietic stem cells were transplanted from an unrelated donor after myeloablative conditioning. The patient has remained in complete leukaemia remission, 3 years after diagnosis.



Abstract

Many genetic disorders occur in patients suffering from acute myeloid leukaemia (AML). The most common mutations found in such patients are in the nucleophosmin (NPM) gene and the FLT3 tyrosine kinase receptor gene. NPM1 mutation is observed in 30–35% of adult AML patients (50–60% of AML with normal karyotype), showing a favourable prognosis. The presence of point FLT3 comutations occur in the tyrosine kinase domain (TKD) are associated with even more favourable prognosis. However FLT3 comutations i.e. internal tandem duplication (ITD) in particular with high allelic ratio (ITDhigh) worsen the course of leukemia and treatment outcomes. Deploying FLT3 tyrosine kinase inhibitors thus offers a prospect for improving treatment and prolonging the survival of patients with AML, burdened with the FLT3 gene mutation. Midostaurin and gilteritinib are type I FLT3 inhibitors which are used to treat patients with AML FLT3-TKD due to their mechanism of action.

This paper presents the case of a 30-year-old AML patient diagnosed with NPM1 and FLT3-TKD mutations, bone marrow reticuline fibrosis and extramedullary sites of AML. Treatment was individualized and induction chemotherapy was combined with midostaurin. After first-line treatment with midostaurin, complete remission was achieved, as confirmed by histopathological examination of the bone marrow. Subsequently, two cycles of consolidation chemotherapy were given, and allogeneic haematopoietic stem cells were transplanted from an unrelated donor after myeloablative conditioning. The patient has remained in complete leukaemia remission, 3 years after diagnosis.



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Keywords

acute myeloid leukaemia, FLT3-TKD, NPM1, midostaurin

About this article
Title

Efficacy of midostaurin combined with intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation in a patient with NPM1 and FLT3-TKD mutated acute myeloid leukaemia with clinical high-risk features

Journal

Hematology in Clinical Practice

Issue

Vol 13, No 1 (2022)

Article type

Case report

Pages

23-30

Page views

1778

Article views/downloads

133

DOI

10.5603/HCP.2022.0004

Bibliographic record

Hematology in Clinical Practice 2022;13(1):23-30.

Keywords

acute myeloid leukaemia
FLT3-TKD
NPM1
midostaurin

Authors

Elżbieta Patkowska
Monika Prochorec-Sobieszek
Ewa Lech-Marańda
Barbara Nasiłowska-Adamska

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