Complete cytogenetic remission after decitabine treatment in a patient with secondary AML harbouring high p15 INK4b gene methylation and high global DNA methylation

Abstract

Dear Editor, Myeloid neoplasias are characterized by extensive epigenetic aberrations, namely aberrant promoter hypermethylation [1]. Therefore, several different treatment regiments have been developed which aim at the reversion of aberrant DNA methylation in patients with MDS or acute myeloid leukaemia [2]. Raj et al. [3] recently reported that MDS patients with a high methylation level of the p15 gene did not respond to demethylation therapy using azacitidine. Accordingly, they suggested a threshold of >24% methylation of the p15 gene and absence of p15 mRNA expression for consideration of alternative dosing or combination therapy. Here, we present a patient with secondary AML with high p15 gene methylation and also high global DNA methylation level who responded very well to four courses of decitabine, an azacitidine analogue that also irreversibly inhibits DNA methyltransferase activity. A 60-year-old Caucasian male was transferred to our department for further evaluation and therapy of transfusion-dependent pancytopenia and infectious complications. Two months earlier, the patient was diagnosed with MDS in another hospital. On admission, the patient had dyspnoea and was febrile (39.5°C). Lung auscultation revealed crackles bilaterally and chest X-ray was consistent with a bilateral pneumonia. He also had epistaxis, mucosal and gastrointestinal bleeding. Blood counts showed marked pancytopenia: WBC 2.8×10/l (ANC 1.6×10/l, 3% blasts), haemoglobin 5.3 g/dl, platelets 3×10/l. Bone marrow evaluation revealed a secondary acute myeloid leukaemia with 50% blasts. Cytogenetic analysis showed a complex karyotype including monosomy 7: 41–45, XY, del (3)(p14), del(4)(q2?6), −5, −7, add(15)(q2?6), +mar, +1 [cp9]/46, XY [7]. The pneumonia was treated empirically with antibiotics and antifungals and the patient received transfusions for severe anaemia and thrombocytopenia. The patient was not considered eligible for intensive chemotherapy and therefore treatment with decitabine was started after clinical improvement of the pneumonia. Treatment consisted of the standard decitabine regimen (15 mg/qm TID i.v. for 3 days) and was well tolerated. After the first course of decitabine the patient achieved a complete remission with less than 5% blasts in the bone marrow and normalized peripheral cell counts (WBC 6,6×10/l with ANC 3,8×10/l and no blasts, haemoglobin 10,2 g/dl, platelets 175×10/l). The cytogenetic examination after two decitabine courses revealed a normal karyotype without evidence of the former monosomy 7. Ann Hematol (2009) 88:275–277 DOI 10.1007/s00277-008-0584-7