60-year-old woman diagnosed in January 2010 with BCR-ABL positive CML. From diagnosis until April 2011 she received treatment with imatinib 400mg/day with acceptable tolerance (moderate symptoms of tiredness, pain, burning and swelling in the legs, oedema of the eyelids and appearance of whitish lesions in the nail bed) and a very rapid haematological response, with normalisation of the haemogram within a week. In April 2011, due to the progression of the molecular signal and the acquisition of the Y253F mutation in peripheral blood (PB) and bone marrow (BM), imatinib was replaced by dasatinib 100mg/day. The Y253F mutation confers resistance to imatinib, intermediate sensitivity to nilotinib and sensitivity to dasatinib. The patient presented good clinical tolerance during treatment with dasatinib, except for the appearance of a persistent cough and asthenia, achieving a major molecular response.
During treatment with dasatinib, the patient developed pancytopenia with blast infiltration of the BM, a diagnosis of lymphoid blast crisis was made and the T315I mutation in the ABL kinase domain was detected.
Once morphological remission of the blast crisis was achieved after the administration of induction chemotherapy with vincristine, daunorubicin, steroids and intrathecal prophylaxis and given the previous exposure to imatinib and dasatinib, the haematology department decided to start treatment with ponatinib in September 2012. Initially, the dose administered was 45mg per day, which had to be reduced to 30mg per day due to clinical intolerance, mainly osteomuscular pain, asthenia and elevated blood pressure, which required adjustment of the antihypertensive treatment.
Currently, the patient maintains a complete haematological and molecular response with acceptable tolerance. She has recently been assessed in the pre-transplant consultation of the Haematology Department for the possibility of consolidation with allogeneic HSCT from an unrelated donor, as she does not have an HLA-matched sibling.