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Results of intensive therapy in childhood acute myeloid leukemia,
incorporating high-dose melphalan and autologous bone marrow
transplantation in first complete remission
K Tiedemann, KD Waters, GP Tauro, D Tucker and H Ekert
Department of Clinical Haematology, Royal Children's Hospital, Parkville
Vic, Australia.
Childhood acute myeloid leukemia (AML) has a poor prognosis with standard
chemotherapy. Allogeneic bone marrow transplantation (BMT) in remission
improves the outlook only for the one third of patients with sibling
donors. Autologous BMT with a lower morbidity and mortality is available to
all. In this study, maximum cytoreduction was achieved by intensive early
chemotherapy. Final intensification, with autologous BMT was offered to all
those remaining in first complete remission (CR). Patients received two
induction and two consolidation courses of intensively scheduled
chemotherapy. Cytoreduction was assessed on day 14 and remission was
assessed after courses 2 and 4. Bone marrow was harvested after recovery
from the second consolidation course or after the first maintenance course
and separated on a discontinuous percoll gradient before cryopreservation.
Twenty-eight of 31 consecutively enrolled patients achieved CR. Three
relapsed early and, of the 25 eligible, 24 underwent autologous BMT.
Twenty-three patients received high-dose melphalan and 1 received busulphan
and cyclophosphamide before autologous BMT at a median of 113 days (range,
86 to 301) after initial CR. Trilineage engraftment occurred in all.
Neutrophil recovery to greater than 0.5 x 10(9)/L occurred at a median of
46 days (range, 13 to 92) after autologous BMT. Platelet recovery was
delayed, with a median time to achieve greater than 20 x 10(9)/L of 42 days
(range, 18 to 215). With a minimum follow up of 25 months following
autologous BMT only 3 children have relapsed. The 5-year event-free
survival rate (EFS) from diagnosis is 68% (95% confidence interval, 46% to
90%). Five- year EFS following autologous BMT is 87% (95% confidence
interval, 67% to 100%). Autologous BMT with high-dose melphalan
administration after intensive chemotherapy has produced EFS equivalent to
allogeneic BMT and is associated with a strikingly low relapse rate.
High-dose melphalan appears to be a valuable agent for conditioning therapy
in AML.
Volume 82,
Issue 12,
pp. 3730-3738,
12/15/1993
Copyright © 1993 by The American Society of Hematology
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