Severe persistent marrow aplasia in chronic myeloid leukemia (CML): An unusual complication of imatinib.

Abstract

Imatinib has changed the treatment of chronic myeloid leukemia (CML) drastically since 15 years. It is usually well tolerated, but severe persistent marrow aplasia is an unusual complication of imatinib while using it in CML. The aim of this study is to describe our experience confronting this rare side effect and review the available data worldwide. It was a retrospective analysis conducted at a center from February 2002 to February 2015. This study was endorsed by our Institutional Review Board (IRB) and written consent was taken from all patients. Patients diagnosed as Philadelphia (Ph) chromosome-positive CML either in chronic phase (CP), accelerated phase (AP), or blastic crisis (BC) were included. There were a total of 1,576 patients with CML treated with imatinib during this period. Karyotyping and quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) were done at the time of pancytopenia for all patients. In total, 11 (males = 5, females = 6) patients met our inclusion criteria from 1,576 patients of CML. The median age was 58 years (range 32-76). Out of 11 patients 8, 2, and 1 patients were in CP, AP, and BC phases, respectively. The median time of administration of imatinib was 3.3 months (range 1.5-6). The average time of marrow recovery was 10.4 months (range 5-15). Two patients expired (one from septicemia and the other from intracranial hemorrhage). BCR-ABL transcripts level by RT-PCR revealed the existence of the disease in all patients. Imatinib is a very well-tolerated tyrosine kinase inhibitor (TKI), but is associated with persistent myelosuppression when used in older age, advanced phase of the disease, and treated previously. After confirming persistent marrow aplasia, the treatment is mainly supportive. It is striking that the disease is still persistent, which is confirmed by RT-PCR. There is no consensus regarding recalling imatinib at lower doses or the use of second-generation TKI (nilotinib, dasatinib) in these patients.