Treatment stratification based on initial in vivo response in acute myeloid leukaemia in children without Down's syndrome: results of NOPHO‐AML trials

Summary. Three consecutive protocols for childhood acute myeloid leukaemia (AML) have been used in the Nordic countries since 1984: the Nordic Society for Paediatric Haematology and Oncology (NOPHO)‐AML84 was of moderate intensity, NOPHO‐AML88 of high intensity with upfront loading and aggressive consolidation. NOPHO‐AML93 utilized the same treatment blocks as NOPHO‐AML88, but after the first block those children with a hypoplastic non‐leukaemic bone marrow were allowed to recover from aplasia. Poor responders received intensified induction therapy. Between January 1993 and December 2000, 219 children without Down's syndrome were entered on NOPHO‐AML93. Compared with NOPHO‐AML88, the event‐free survival (EFS) at 7 years increased from 41% to 49% ( P = 0·06) and 7‐year overall survival increased from 47% to 64% ( P < 0·01). Toxic death during induction was reduced from 10% to 3%. Survival was similar in patients receiving stem cell transplantation or chemotherapy only in first remission. The major prognostic factors in NOPHO‐AML93 were response to therapy and cytogenetics. A total of 67% of patients achieved remission after the first induction course and showed an EFS of 56% compared with 35% in those not in remission ( P < 0·01). Cytogenetic results were obtained in 95% of patients. Patients with t(9;11) (p22;q23) ( n = 16) experienced a significantly better EFS (86%) than other cytogenetic groups. The overall outcome was improved by employing the previous toxic protocol with different timings, and through individualizing therapy according to the initial response of the patient.