Imatinib-induced Severe Hepatitis in a 9-Year-old Girl With Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia

Abstract

Imatinib mesylate has dramatically improved the outcome of children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph* ALL) and is now included as first-line therapy. Uncommon adverse effects of this drug for pediatric use, however, are largely unknown. We report the first case of a 9-year-old child who developed severe acute hepatitis with grade 4 transaminases and bilirubin elevation during imatinib treatment for Ph* ALL. Liver biopsy showed extensive lobular and pericentral necrosis of hepatocytes. Liver function recovered after discontinuing imatinib with a 4-week prednisolone. Extensive hepatic necrosis should be considered not only in adults but also in children under imatinib administration.

Clinical characteristics and analysis of treatment result in children with Ph‐positive acute lymphoblastic leukaemia in Poland between 2005 and 2017

“…Children with Ph+ ALL were included in the high‐risk group (HRG) due to a poor outcome despite intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). The disease‐free survival (DFS) using chemotherapy was reported at 25%, and allogeneic HSCT from a matched related donor during the first remission increased DFS to 40% . The 5‐year event‐free survival (EFS) and overall survival (OS) were 55% and 62% for the HRG in the randomised intercontinental trial ALL IC‐BFM 2002 (Acute Lymphoblastic Leukaemia Intercontinental Berlin‐Frankfurt‐Münster Study Group) …”

“…Literature data show that incorporation of imatinib into intensive chemotherapeutic regimens and frequent use of hematopoietic stem cell transplantation (HSCT) in the first remission improved the prognosis of children with Ph+ ALL. Chemotherapy with imatinib and HSCT resulted in 3‐year EFS of 70%‐80% …”

“…The disease-free survival (DFS) using chemotherapy was reported at 25%, and allogeneic HSCT from a matched related donor during the first remission increased DFS to 40%. 4 The 5-year event-free survival (EFS) and overall survival (OS) were 55% and 62% for the HRG in the randomised intercontinental trial ALL IC-BFM 2002 (Acute Lymphoblastic Leukaemia Intercontinental Berlin-Frankfurt-Münster Study Group). 5 Imatinib was the first tyrosine kinase (TK) inhibitor that has revolutionised the treatment of chronic myeloid leukaemia in the paediatric population by replacing the previous method of treatment with HSCT and allowing a high percentage of OS and EFS.…”

“…Chemotherapy with imatinib and HSCT resulted in 3-year EFS of 70%-80%. 4,11 The aim of this study was to explore the clinical characteristics and outcome of children diagnosed with Ph+ ALL and treated in Poland between the years 2005 and 2017 (Polish Paediatric Leukaemia and Lymphoma Study Group Report). The patients treated according to EsPhALL protocol received imatinib, which was incorporated into combination chemotherapy and 0.61 for chemotherapy alone, P = 0.22, while EFS was 0.66 (imatinib therapy) and 0.…”

The histopathological evaluation of drug‐induced liver injury

“…Imatinib DILI is probably the best‐characterized histologically. It causes a severe acute hepatitis, sometimes with areas of confluent or multi‐acinar necrosis . Bortezomib and pazopanib have also been reported to cause an acute hepatitis with cholestasis .…”