A comparative pathological study of liver injury after different combination chemotherapies for leukemia

A form of liver injury characterized by bile ductule-like transformation of hepatocytes, prominent hemosiderin deposition and fibrosis, was occasionally encountered in autopsy cases we examined during the period from 1973 to 1981. It was found that this liver injury was irreversible and intimately related to combination chemotherapy with the DCMP regimen (daunorubicin, cytosine arabinoside, 6MP and prednisolone) for acute non-lymphocytic leukemia (ANLL). Its correlation was reconfirmed by the fact that this liver injury disappeared after withdrawal of the DCMP regimen in 1981. After 1978, the regimen of combination chemotherapy for adult ANLL was partly changed, 6-thioguanine being utilized (DCTP) instead of the 6MP in the DCMP regimen. The hepatic injury occurring after the change in the regimen was different from that produced with DCMP, showing reversible intrahepatic cholestasis. These facts indicated that substitution for one drug in a combination chemotherapy regimen could cause a different type of hepatic change.