acute myeloid leukemia | Acta Medica Marisiensis

FLT3 Internal Tandem Duplication and D835 Mutations in Acute Myeloid Leukemia

Bănescu Claudia¹, Dobreanu Minodora², Duicu Carmen³, Benedek I⁴, Macarie I⁵, Köpeczi Judit⁴

1 Department of Genetics, University of Medicine and Pharmacy, Tîrgu Mureş, Romania
2 Department of Clinical Biochemistry, University of Medicine and Pharmacy, Tîrgu Mureş, Romania
3 Pediatric Clinic, University of Medicine and Pharmacy, Tîrgu Mureş, Romania
4 Hematology Clinic 2, University of Medicine and Pharmacy, Tîrgu Mureş, Romania
5 Hematology Clinic 1, University of Medicine and Pharmacy, Tîrgu Mureş, Romania

Introduction: FLT3 is a member of receptor tyrosine kinases expressed in leukemic cells. Internal tandem duplications (ITDs) and D835 mutations in FLT3 tyrosine kinase receptor have been shown to confer a bad prognosis in acute myeloid leukemia (AML). The aim of the present study was to determine the incidence of both ITD and D835 mutations in the FLT3 gene, in patients with AML from Tg-Mures, Romania.
Materials and methods: DNA was obtained from peripheral blood samples. ITDs were investigated by polymerase chain reaction (PCR). D835 mutations were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), with the digestion of restriction endonuclease EcoR V. The amplified and restricted products were finally electrophoresed on agarose gel stained with ethidium bromide.
Results: Alterations in the FLT3 gene were detected in 8 patients out of the 23 cases analyzed. These aberrations included ITD in 4 cases, D835 mutations in 2 cases and both types of alteration (ITD + D835) in 2 patients.
Conclusion: In this study we demonstrated that FLT3 mutations are frequent molecular abnormalities in AML patients with an incidence of 34.8%. Although our data do not support its value as a prognostic factor in AML patients because of the small cohort, further investigation is required.

Autologous Stem Cell Transplantation in Patients with Acute Myeloid Leukemia: a Single-Centre Experience

Kakucs Enikő1, Benedek I^1,2, Benedek Erzsébet¹, Köpeczi Judit Beáta¹, Tunyogi Aliz¹, Istrati Monica¹

1 Clinical Hematology and Bone Marrow Transplantation Clinic, Tîrgu Mureş, Romania
2 University of Medicine and Pharmacy, Tîrgu Mureş, Romania

DOI: 10.2478/amma-2013-0021

Introduction: Autologous haemopoietic stem cell transplantation (SCT) is an important treatment modality for patients with acute myeloid leukemia with low and intermediate risk disease. It has served advantages over allogenic transplantation, because it does not need a matched donor, there is no graft versus host disease, there are less complications and a faster immune reconstitution than in the allo-setting. The disadvantage is the lack of the graft versus leukaemia effect.
Materials and methods: In the Bone Marrow Transplantation Unit Tîrgu Mureș 14 patients with acute myeloid leukemia received an autologous SCT. Mobilization of the stem cells was performed using chemotherapy and granulocytic colony stimulating factor. The conditioning regimen for SCT consists in monotherapy with busulfan (Bu) 16 mg/kg, BuCy: busulfan in combination with Cyclophosphamide (CY) 120 mg/kg or BuMel: Busulfan in association with Melphalan (Mel) 140 mg/m2.
Results: The median patient age was 36 years (range 20–55), 9 (64%) were males and 5 (36) were females and the median time interval from diagnosis to autologous SCT was 9 months (range 3–25). All the patients were transplanted successfully, all of them achieved a sustained neutrophil count (> 0.5 G/L), median time 11 days (9–15) and platelet count (> 20 G/L) median time 14 days (10–19) after transplantation.
Conclusions: We conclude that autologous stem cell transplantation is an effective treatment in acute myeloid leukemia with the possibility of long survival, particularly in patients with standard risk disease.