Leukemia & Lymphoma, April 2015; 56(4): 1143-1144 © 2014 Informa UK, Ltd. ISSN: 1042-8194 print /1029-2403 online DOI: 10.3109/10428194.2014.941831 informa healthcare LETTER TO THE EDITOR Development of myelodysplastic syndrome in a patient with chronic myelogenous leukemia treated with imatinib Nabhajit Mallik1, Anita Chopra1, Akash Jha2, Ajay Gogia2 & Rajive Kumar1 1 Department of Laboratory Oncology and 2Department of Medical Oncology, Dr. B. R. A., Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India Chronic myelogenous leukemia (CML) is a myeloprolifera tive neoplasm that is constantly associated with the BCR- ABL1 fusion gene [1], This fusion gene encodes a chimeric protein with increased tyrosine kinase activity that plays a central role in the pathogenesis of CML [2], Imatinib mesy late is a potent and selective competitive inhibitor of the BCR-ABL protein tyrosine kinase. It is used as a front-line therapy for CML, and induces complete hematological and cytogenetic response in most patients with chronic phase CML [3], During treatment for CML, a subset of patients develop chromosomal abnormalities in the Philadelphia chromosome (Ph) negative cells that emerge as they respond to therapy [4], However, the incidence and signifi cance of these abnormalities are poorly understood. Some of these abnormalities are associated with myelodysplastic syndrome (MDS). However, only a few cases that harbor these cytogenetic abnormalities along with MDS are reported [5], We report a case of MDS arising in a patient who was being treated for CML with imatinib. A 60-year-old male presented with a history of weak ness, fever and splenomegaly in August 2005 at our center, and was diagnosed as having Ph positive chronic phase CML. He was started on imatinib at a dose of 400 mg/day. The treatment was interrupted many times initially due to low platelet counts. The dosage of imatinib was reduced to 300 mg/day, and he achieved complete hematological response in June 2007. The patient continued on the drug and was asymptomatic until September 2012, when he presented with bleeding, and was found to have low hemo globin and platelets. He developed pancytopenia, with progressively decreasing counts, and required multiple blood transfusions. Imatinib was stopped in April 2013. Bone marrow examination showed dysmegakaryopoiesis and dyserythropoiesis, along with 4% blasts. Cytogenetics study by fluorescence in situ hybridization (FISH) showed that 100% cells were Ph negative. However, new clonal cytogenetic abnormalities were noted, with del 7q being observed in 86% of cells, monosomy 7 in 6% of cells and del 20q in 32% of cells. The patient was diagnosed as hav ing MDS, high risk (according to the revised International Prognostic Scoring System [IPSS-R]). He was started on decitabine injection, 20 mg/m2 (day 1 to day 5), every 28 days. The patient has to date received four cycles of decit abine. Bone marrow examination after four cycles showed progression to refractory anemia with excess blasts-2 (RAEB-2), with 12% blasts. There have been no episodes of febrile neutropenia or bleeding. The patient is now on close hematological follow-up. The development of cytogenetic abnormalities in Ph neg ative metaphases in patients with CML treated with imatinib has been reported, but its clinical implications are poorly understood. Most cytogenetic abnormalities encountered in Ph negative cells of patients treated with imatinib are not related to myelodysplasia, and some seem to be transient [6,7], In a study of 272 patients treated with imatinib, this phenomenon was seen in 21 (8%) cases [6], Trisomy 8 has been found to be the most frequent cytogenetic abnormality in such cases [5]. Development of MDS in patients with Ph negative meta phases after treatment with imatinib, however, is rare [8-11]. Interestingly, in such patients, chromosome 7 abnormalities have been found to be particularly common [12], especially monosomy 7, which was also seen in our patient. This abnor mality is common in secondary MDS or acute myelogenous leukemia (AML), evolving after exposure to alkylating agents, and patients with MDS or AML with this abnormality have poor outcomes. The etiology of imatinib induced MDS is yet to be com pletely understood. Two mechanisms have been proposed. First, imatinib may provide an advantage to abnormal clones that were already present in the patient at low levels. Second, these changes could be directly due to imatinib toxicity [5]. To conclude, MDS developing in patients with CML treated with imatinib is a rare entity. Further studies with long-term follow-up are required to understand the etiology Correspondence: Dr. Anita Chopra, Room No 423, 4th Floor, Dr. BRAIRCH, AIIMS, Ansari Nagar, New Delhi-110029, India. Tel: 91-11-29575415. Fax: 91-11- 26588663. E-mail: chopraanita2005@gmail.com Received 11 February 2014; revised 17 June 2014; accepted 29 June 2014 1143