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We report 12 years' experience with histocompatible, related donor marrow transplantation for 123 patients with acute lymphoblastic leukaemia; 104 > or = second remission. Four regimens were studied: cyclophosphamide (Cy)-+total body irradiation (TBI) (n = 35); Cy+fractionated TBI (n = 45); TBI+high-dose cytarabine (n = 15); and hyperfractionated TBI+Cy (n = 28). 45 patients survive (34 +/- 9%; 95% confidence interval) between 1 and 12.7 years (median 7.8 years) following BMT and 29 +/- 8% survive leukaemia-free. Significantly improved disease-free survival was observed in patients with an initial WBC < 50 x 10(9)/l (P = 0.02). Conditioning regimens tested yielded similar outcomes, though TBI/cytarabine led to greater treatment-associated mortality. Leukaemia relapse was the most frequent cause of failure in 56 +/- 11%; median time of relapse 8 months following BMT, none beyond 2.2 years. Relapse was more frequent with higher WBC, shorter initial remission and previous CNS leukaemia. Acute and/or chronic GVHD was associated with a strong trend (P = 0.06) towards less relapse. Allogeneic BMT may be curative for a substantial fraction of patients with ALL, but additional anti-leukaemic measures beyond these conditioning modifications tested will be required to prevent post-transplant leukaemia recurrence.

We report four children with acute megakaryoblastic leukaemia (AMKL) and compare their clinical course with 16 previously reported cases of AMKL in children. In adults, AMKL has been reported as a rapidly progressive disease characterized by pancytopenia associated with bone marrow fibrosis, absence of organomegaly, and unresponsiveness to therapy. Although some of the childhood cases present with these features, the clinical course can be quite variable, particularly in young children, with both organomegaly and leucocytosis occurring. Down syndrome, or other constitutional abnormalities of chromosome 21 were present in four of 20 reported cases. Two of the four cases reported herein were initially diagnosed cytologically as childhood acute lymphoblastic leukaemia (ALL). All four patients achieved a complete remission, and three remain in remission from 34 to 56 months from diagnosis. Greater recognition of AMKL in the future will help to clarify the disease characteristics, prognosis and optimal treatment of this unusual form of leukaemia.

Advances in both allogeneic marrow transplantation and conventional therapy for acute leukaemia have complicated the choice between bone marrow transplantation (BMT) and other remission treatment options. Because older patients may be more susceptible to BMT-related complications, this study analysed the effect of age on clinical outcome for 149 patients with acute leukaemia in remission receiving allogeneic BMT. Overall projected relapse-free survival at 3 years post-transplant is equivalent for 48 adults (18 years or older) and 101 children (less than 18) at 45.4% (31.1-59.6; 95% confidence interval) and 39.9% (30.1-49.7; 95% C.I.), respectively. Among 73 patients with acute lymphocytic leukaemia (ALL) 35.3% of adults and 30.1% of children survive relapse-free at 3 years. Cox multiple regression analysis demonstrated that higher diagnostic white count, but not pre-transplant extramedullary leukaemia, remission number, or age, was important as an independent adverse clinical prognostic factor for patients with ALL. Overall outcome was better for 76 patients with acute myeloid leukaemia (AML) with 51.6% of adults and 52.9% of children surviving relapse-free at 3 years post-transplant. Cox multivariate regression analysis identified first remission status and lower white cell count, but not patient age, as independent predictors of improved relapse-free survival for AML patients. Adults had greater transplant morbidity, predominantly related to a higher incidence of acute graft-versus-host disease (GVHD), resulting in longer hospital stay. Survival at 100 d, long-term survival and clinical performance status were similar in both age groups. These data suggest that results of allogeneic BMT for adults with acute leukaemia compare favourably with those found in children and are superior to most reports of conventional chemotherapy. Allogeneic BMT remains a reasonable option for remission acute leukaemia patients up to the age of 45.