Secondary acute myeloid leukemia with monosomy 7 in Ph-negative cells in a patient with chronic myeloid leukemia in chronic phase

Abstract

Clonal cytogenetic abnormalities in Philadelphia chromosome-negative (CCA/Ph–) bone marrow cells are very rarely seen when chronic myeloid leukemia (CML) is diagnosed and have only been observed in 4–8% of patients undergoing treatment with BCR-ALB1 tyrosine kinase inhibitors (TKI). Moreover, the aetiology, clinical significance and potential risk factors of CCA/Ph– occurring remain unresolved. Some of these constitute significant risk factors, especially monosomy of chromosome 7, for the development of myelodysplastic syndrome or acute myeloid leukaemia (AML) associated with a poor prognosis. In this study the case of a 56-year old man in whom CML was diagnosed in 2001 is reported. Therapy was started with hydroxyurea followed by treatment with interferon alpha and TKI, including imatinib, nilotinib, and dasatinib. Monosomy of chromosome 7 in Ph– cells was detected during the imatinib therapy. The development of secondary AML, in the presence of a complex karyotype, occurred 32 months after CCA/Ph– was detected when a complete cytogenic response had been achieved during treatment with dasatinib. Despite receiving daunorubicine and arabinoside in a 3 + 7 induction regimen and one cycle of azacititdine, the patient responded poorly. Indeed, after 4 months from when AML had been diagnosed the patient died due to infectious complications. This case demonstrates the problems in making a diagnosis and of applying appropriate therapy during prolonged exposure to TKI in a patient with CML and a secondary AML.
Hematologia 2011; 2, 3: 294–301