2-Chlorodeoxyadenosine produces a high rate of complete hematologic remission in relapsed acute myeloid leukemia.
OBJECTIVE
The purine analog 2-chlorodeoxyadenosine (2-CDA) was well tolerated and showed promising anti-leukemic activity in a phase I trial conducted at St Jude Children's Research Hospital. To substantiate and extend this result, we performed a phase II trial in a representative group of children and young adults with relapsed acute leukemia.


METHODS
Twenty-four patients (median age, 11 years) with acute myeloid or lymphoid leukemia in first or later relapse (acute myeloid leukemia [AML], 17; acute lymphoid leukemia [ALL], seven) were given continuous infusion 2-CDA for 5 days at 8.9 mg/m2/d. Patients with residual blast cells 10 days after treatment received a second course of 2-CDA that was identical to the first. Detailed pharmacokinetic studies were performed on plasma collected from five patients.


RESULTS
Eight (47%) of the 17 patients with AML had complete hematologic remissions (four after the initial course of 2-CDA), and two (12%) had partial remissions, for a total response rate of 59%. Only one child with ALL achieved remission. Seven of the responding patients underwent allogeneic or autologous bone marrow transplantation, with six remaining free of leukemia for a median of 7 months (range, 1 to 11 months). The major form of drug-induced toxicity was hematologic, with severe neutropenia and thrombocytopenia (National Cancer Institute [NCI] grade 3 or 4) developing in 34 of the 36 courses of 2-CDA. In responding patients, the median times to recovery of neutrophil counts greater than 0.5 x 10(9)/L and platelet counts greater than 50 x 10(9)/L were 18 and 21 days, respectively. There were no deaths due to toxicity. The mean steady-state plasma concentration of 2-CDA was 34.6 nmol/L (range, 20 to 54 nmol/L).


CONCLUSIONS
2-CDA given by prolonged continuous infusion has clinically significant activity against AML and merits further testing in multidrug regimens for this disease.
Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN 38101.
V M
VM
Santana
J
J
Mirro
C
C
Kearns
M J
MJ
Schell
W
W
Crom
R L
RL
Blakley
D015762:2-Chloroadenosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D017338:Cladribine; D003131:Combined Modality Therapy; D003839:Deoxyadenosines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007951:Leukemia, Myeloid / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D012008:Recurrence; D012044:Regression Analysis; D012074:Remission Induction
D000970:Antineoplastic Agents; D003839:Deoxyadenosines; D015762:2-Chloroadenosine; D017338:Cladribine