Complete hematologic remissions in chronic-phase, Philadelphia-chromosome-positive, chronic myelogenous leukemia after 2-chlorodeoxyadenosine.
BACKGROUND
2-Chlorodeoxyadenosine (Cladribine, Leustatin, Ortho Biotech, Raritan, NJ) (2-CdA) is a purine analog with activity in the treatment of lymphoid neoplasms. Interferon induces cytogenetic remissions in chronic myeloid leukemia (CML) and partial remissions in hairy cell leukemia, a disorder in which single courses of 2-CdA induce complete remissions. In vitro clonal growth of immature myeloid progenitors from normal marrow is markedly inhibited by 2-CdA.


METHODS
2-CdA was administered to 12 patients with Philadelphia-chromosome-positive CML, 11 chronic phase, and 1 accelerated phase, at 0.1 mg/kg/day by continuous intravenous infusion for 7 days every 28-35 days, until maximum peripheral hematologic response.


RESULTS
Of 12 patients, 10 (83%) achieved complete hematologic responses and 2 (17%) partial hematologic responses after a median of two courses of 2-CdA. The median first hematologic response duration was 3 months. Of the seven patients who relapsed and were retreated with a median of two further courses of 2-CdA, five obtained responses (four complete and one partial) and two did not respond. The median second hematologic response duration was 4 months. No patient had significant Philadelphia-chromosome suppression. Reversible myelosuppression and severe cumulative T-cell immunosuppression associated with opportunistic infections in four patients were the principal toxicities.


CONCLUSIONS
2-CdA is active in CML, inducing complete hematologic responses, but the absence of cytogenetic responses and severe immunosuppression may limit its clinical use.
Saven
A
A
Division of Hematology/Oncology, Cecil H. and Ida M. Green Cancer Center, Scripps Clinic and Research Foundation, La Jolla, CA 92037.
Piro
L D
LD
Lemon
R H
RH
Figueroa
M L
ML
Kosty
M
M
Ellison
D J
DJ
Beutler
E
E
D000328:Adult; D000368:Aged; D001772:Blood Cell Count; D001853:Bone Marrow / Q000187:drug effects; D017338:Cladribine / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction
D017338:Cladribine