title: Complete hematologic remissions induced by 2-chlorodeoxyadenosine in children with newly diagnosed acute myeloid leukemia.
abstract: 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.
authors.affiliation: Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN.
authors.forename: V M
authors.initials: VM
authors.lastname: Santana
authors.forename: C A
authors.initials: CA
authors.lastname: Hurwitz
authors.forename: R L
authors.initials: RL
authors.lastname: Blakley
authors.forename: W R
authors.initials: WR
authors.lastname: Crom
authors.forename: X
authors.initials: X
authors.lastname: Luo
authors.forename: W M
authors.initials: WM
authors.lastname: Roberts
authors.forename: R
authors.initials: R
authors.lastname: Ribeiro
authors.forename: H
authors.initials: H
authors.lastname: Mahmoud
authors.forename: R A
authors.initials: RA
authors.lastname: Krance
mesh_terms: D000293:Adolescent; D001752:Blast Crisis / Q000188:drug therapy / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D017338:Cladribine / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D005260:Female; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male
chemical_list: D017338:Cladribine