Novel Score-based Decision Approach in Chronic Myeloid Leukemia Patients After Acute Toxic Imatinib-induced Liver Injury

摘要

The tyrosine kinase inhibitor (TKI) imatinib in rare cases can cause acute toxic hepatitis, hepatic failure, and death. Currently, the choice of further chronic myeloid leukemia (CML) therapy in patients after acute hepatotoxicity is still a difficult question, which requires a complex individual approach based on the clinical guidelines of adverse event?management. Data about the further follow-up strategy approach in patients with CML after acute toxic imatinib-induced liver injury are of concern, and at times controversial. In addition, one of the questions is about the necessity and safety of the imatinib therapy resumption after acute hepatotoxicity. In some publications, imatinib resumption without the recurrence of hepatotoxicity has been discussed; in others, imatinib resumption with the recurrence of imatinib hepatotoxicity has been mentioned. There are a few publications about the experience of administration of the second-line TKIs after acute imatinib hepatotoxicity. There are no clear data on which factors the physician’s decision should be based on in patients with CML after acute toxic imatinib-induced liver injury. Imatinib should be restarted or withdrawn, when and for whom second-line therapy should be started. The physician’s decision is usually based on the published data of similar cases, personal experience, and the severity of hepatotoxicity. We have discussed the clinical guidelines devoted to the peculiarities of the patient’s management after acute toxic imatinib-induced hepatitis and main strategy approaches. A complex score-based decision algorithm for choosing the further strategy approach after acute toxic imatinib-induced hepatitis in patients with CML has been presented. The following parameters should be assessed: the grade of hepatotoxicity reaction, the presence of liver?transplantation or imatinib-induced liver cirrhosis and its possible pathogenetic mechanism, the presence of early molecular response (EMR) to imatinib therapy defined as three-month BCR-ABL1 ≤10% according to the international scale (BCR-ABL1supIS/sup) or/and six-month BCR-ABL1supIS?/sup1%; and the presence of the offender concomitant drug that probably caused the drug interaction with imatinib and the presence of viral hepatitis reactivation identified by polymerase chain reaction (PCR).