Abstract

An intensive 6-month schedule of drugs was devised with both systemic and central nervous system activity, known by the acronym 'MACHO', to treat 24 newly and consecutively diagnosed children, 13 with stage IV B-cell non-Hodgkin's lymphoma (B-NHL) and 11 with B-cell acute lymphoblastic leukaemia (B-ALL). There were three deaths from complications of chemotherapy (two infective, one biochemical). Five children with central nervous system disease at diagnosis (CNS+) received planned additional megatherapy/bone marrow transplants. Event-free survival (EFS) at 1 year for the 11 cases of B-ALL is 64% (95% confidence intervals [CI] 31-89%) and of 13 stage IV B-NHL cases is 50% (95% CI 19-75%). Patients with bulky abdominal disease had a 32% EFS at 1 year (CI 13-68%) compared with 76% (CI 39-94%) for those without bulky abdominal disease. Overall EFS for eight CNS+ patients is 73% at 1 year (95% CI 34-97%) compared with 48% (95% 24-74%) for those without CNS disease (CNS-). However, only two of the CNS+ cases had bulky abdominal disease (patients 10 and 12) and the difference is not significant (P less than 0.5). A score of 1 was given for each of the following potential prognostic features: bulky abdominal disease, pleural effusion and severe renal dysfunction within 48 h of presentation. Patients who scored 0 or 1 fared significantly better than those who scored 2 or 3 (EFS at 1 year 78% [CI 49-95%] versus 24% [6-65%], P less than 0.04). Two patients with a score of 2 survived past 6 months and another is currently well, but has not regenerated his marrow following autologous transplantation. This protocol is relatively effective for patients who have B-ALL, but those patients who have bulky abdominal disease, often associated with severe renal dysfunction, and those with CNS disease, do not fare so well and require new approaches to therapy.