Treatment of chronic myeloid leukemia with tyrosine kinase inhibitors: the UMCG experience

Chronic myeloid leukemia (CML) is a myeloproliverative neoplasia that is characterized by overproduction of cells of the myeloid lineage. Disease course consists of three phases: chronic phase (CP), acceleration phase (AP), and blast crisis (BC). Hallmark of the disease is the fusion of BCR-gene on chromosome 22 and ABL-gene on chromosome 9, which is almost always caused by a reciprocal translocation of chromosome 9 and chromosome 22, the Philadelphia chromosome. Since 2001, tyrosine kinase inhibitors (TKIs) have become standard treatment of CML. TKIs inhibit BCR-ABL fusion gene product. TKIs have improved CML survival tremendously. To optimize TKI treatment, several efforts have been made, including co-medication with interferon alfa or chemotherapy. To discriminate at diagnosis between low-risk and high-risk patients, Sokal, Euro/Hasford, and EUTOS risk assessment scores have been proposed. We aimed to evaluate the treatment and response of CML patients in the University Medical Center Groningen (UMCG). Secondly, we assessed whether Sokal, Euro, and Hasford risk scores at diagnosis influence outcome to TKI treatment. Finally, we assessed the influence of pretreatment with the chemotherapeutic agent hydroxyurea on response to TKI, and we assessed whether concurrent treatment with proton pump inhibitors has an effect on response to TKI treatment. In order to do so, we set up a database, which consisted of 62 CP CML patients, who were treated with a TKI in the UMCG. Twenty-nine of them were pretreated with hydroxyurea, and 15 received concurrent PPI treatment.