Onkológia 2/2020

Chronic myeloid leukemia and its treatment in patients with repeated intolerance of tyrosine kinase inhibitors

Introduction: Chronic myeloid leukemia (CML) is characterized by cytogenetic translocation between 9 and 22 chromosome t(9;22), resulting in Philadelphia chromosome with BCR/ABL fusion gene. The protein product of this gene is most commonly p210 with tyrosine kinase activity, which is responsible for disease development. By inhibiting this activity at the molecular level, complete haematological and long-term cytogenetic remissions of CML can often be achieved with a transcription decrease of 4,5 to 5 logs, with long-term survival of patients. Treatment with tyrosin kinase inhibitors (TKIs) is different with mostly well tolerated spectrum of side effects in opposite the abandoned treatment (interferon-alpha, cytarabine, allogeneic hematopoietic cell transplantation). In addition, it is an oral treatment which improves compliance, and quality of life for patients. Purpose: The aim of the case report is to monitor the effectiveness and side-specific and associated adverse effects of treatment at the time of introduction of tyrosine kinase inhibitors into medical practice, the change of the treatment strategy from interferon-alpha with cytarabine, and to monitor tolerance for sequential treatment with all three basic TKIs. Case: For our patient, we observed efficacy and tolerance during each treatment step from the initial cytoreduction of hydroxyurea, induction of haematological remission by interferon-alpha in combination with subcutaneous cytarabine, to treatment and subsequently substitution of each of the three basic tyrosine kinase inhibitors for intolerance, but with molecular cytogenetic response with cytogenetic marker capture at the detection limit. Conclusion: Treatment with new targeted TKI drugs has demonstrated its ongoing efficacy over the historical interferon-alpha with cytarabine standard. In our patient the long-term cytogenetic remission with a transcript decrease of 4,5-log persists for 17 years on TKI treatment. Specific for TKI, as well as various associated complications and side-effects occurred during the course of treatment, which finally led to escalated intolerance and exchange of individual drugs. The patient underwent treatment with imatinib, dasatinib and finally nilotinib, which was not only effective, in the form of deep cytogenetic remission, but also a well tolerable allowed the patient to continue long-term treatment.

Keywords: chronic myeloid leukemia, tyrosine-kinase activity inhibitors, side effects of treatment, treatment tolerance