Diagnosis and treatment of adult acute myeloid leukemia with NPM-MLF1 fusion gene and literatures review

Abstract

Objective To evaluate the clinical features, treatment and prognosis of acute myeloid leukemia (AML) with nucleophosmin (NPM)-myelodysplasia/myeloid leukemia factor (MLF)1 fusion gene. Methods On 16 February 2016, a case of AML patient with NPM-MLF1 fusion gene who was admitted to Changhai Hospital Affiliated to Second Military Medical University was included in this study. When the patient was admitted, bone marrow morphology, cytochemical staining and immunophenotype analysis of leukemia blasts, cytogenetics and molecular genetic analysis were conducted and diagnosis was made base on those test results. On 17 February 2016, the patient recieved two courses of daunorubicin+ arabinosylcytosin (DA) 3+ 7 induction therapy. Subsequently, the patient recieved one course of fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG) regimen and 5 courses of high-dose of cytarabine. In the meantime, bone marrow morphology and minimal residual disease (MRD) were conducted during the chemotherapy. On 6 April 2017, the patient received bone marrow morphology, immunophenotype analysis of leukemia blasts and molecular genetic analysis on her visit. The clinical features, diagnosis and treatment of this patient were analyzed retrospectively, and the related literatures were reviewed. Results ①When the patient was admitted, bone marrow morphology revealed hyper-cellular marrow with 48.0% leukemia blasts. Cytochemical staining showed that peroxidase (POX) staining in some leukemia blasts were positive, and naphthol AS-D chloroacetate esterase (CE) staining in a few leukemia blasts were positive, and non-specific estertase (NSE) staining in some leukemia blasts were positive. The results of immunophenotype analysis revealed the ratio of the blasts cell was about 39.9%, and the ratio of immature cell was about 13.6%. R banding karyotype analysis marked with 46, XX, t(3; 5)(q25; q34)[3]/46, XX[7]. Molecular genetic analysis showed NPM/MLF1 fusion gene was positive. According to above, the diagnosis of patient was AML-subtype M4 with NPM-MLF1 fusion gene. ②After the patient was treated with the first course of induction therapy, and the reexamined bone marrow morphology post therapy showed partial remission (PR). The patient received complete remission (CR) after the second course of induction therapy. After the patient received consolidation therapy, and bone marrow morphology showed the patient obtained sustained CR status. On the patient′s last visit, bone marrow morphology revealed a total of 25.0% leukemia blasts, consisting of 21.0% blasts and 4.0% immature cell, suggesting AML recurrenced. Immunophenotyping of leukemia blasts showed approximately 28.5% of the early myeloid cells in bone marrow which was consistent with AML recurrence. Molecular genetic analysis showed that the MPM-MLF1 fusion gene was positive (66.1%). During the treatment, bone marrow MRD decreased, then increased. The patient went back to local hospital for treatment after AML relapsed. Conclusions AML-subtype M4 patient with NPM-MLF1 fusion gene can achieve CR after chemotherapy, but prone to early recurrence, and NPM-MLF1 fusion gene may be a poor prognostic factor for AML. Key words: Leukemia, myeloid, acute; Drug therapy; NPM-MLF1; t (3;5)