Prognostic significance of hepatotoxicity during maintenance chemotherapy for childhood acute lymphoblastic leukaemia

Abstract

In a population-based study of 115 children with non-B-cell acute lymphoblastic leukaemia, we analysed the relation of the degree of leukopenia and risk of relapse to the degree of hepatotoxicity (as measured by serum aminotransferase (AT] during oral methotrexate (MTX) and 6-mercaptopurine (6MP) maintenance chemotherapy (MT). Hepatotoxicity was calculated as a mean of all AT-measurements (mATMT). Lack of hepatotoxicity was defined as a mATMT less than or equal to 40 IUl-1. A highly significant correlation was demonstrated between the mean AT during the first, second, and third year of MT (r greater than 0.70, P less than 0.00001). mATMT was not related to the mean WBC during MT (r = -0.03, P = 0.36), but was related to the rise in WBC following cessation of therapy (r = 0.24, P = 0.06). Patients with recurrent disease had significantly lower mATMT than patients staying in remission (P = 0.03 for both over-all and haematological relapse risk). Patients with a mATMT greater than 40IUl-1 had a lower risk of relapse than patients with a mATMT less than or equal to 40IUl-1 (4.5 year CCR: 0.70 and 0.50, P = 0.06; and 4.5 year haematological remission: 0.83 and 0.63, P = 0.03). The favourable outcome for patients with hepatoxicity could be demonstrated for all risk groups.