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Complete hematologic remissions induced by 2-chlorodeoxyadenosine in
children with newly diagnosed acute myeloid leukemia
VM Santana, CA Hurwitz, RL Blakley, WR Crom, X Luo, WM Roberts, R Ribeiro, H Mahmoud and RA Krance
Department of Hematology-Oncology, St Jude Children's Research Hospital,
Memphis, TN.
The majority of children with acute myeloid leukemia (AML) who are treated
exclusively with chemotherapy die of progressive disease. Improvement in
outcome will likely require new active drugs capable of eradicating
resistant blast cells early in the clinical course. We therefore assessed
the cytoreductive potential of 2- chlorodeoxyadenosine (2-CdA), a
halogenated purine analogue, in 22 consecutive children with newly
diagnosed AML. The drug was administered as a single 120-hour continuous
infusion (8.9 mg/m2 of body surface area per day) before the introduction
of standard remission induction therapy. Six patients (27%) had complete
hematologic remissions by a median of 21 days after treatment with the
nucleoside (range, 14 to 33 days). Seven others had partial responses,
yielding a total response rate of 59%. The drug also eliminated leukemic
cells from cerebrospinal fluid in 4 of the 6 patients tested.
Concentrations of 2-CdA in cerebrospinal fluid on day 5 after the
initiation of treatment ranged from 12.4% to 38.0% (mean, 22.7%) of the
steady-state plasma concentrations. Severe but reversible myelosuppression
and thrombocytopenia developed in all patients. Analysis of factors that
may have influenced the complete remission rate suggested a better outcome
in patients with myeloblastic leukemia (M0-M2 subtypes in the revised
French-American-British classification system). These results demonstrate
clinically significant activity by 2- CdA against previously untreated AML
in children, including leukemic blast cells in the central nervous system.
Its use in combination chemotherapy may improve the outlook for patients
with this often fatal hematologic cancer.
Volume 84,
Issue 4,
pp. 1237-1242,
08/15/1994
Copyright © 1994 by The American Society of Hematology
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