Fludarabine and cytosine arabinoside in the treatment of refractory or relapsed acute lymphocytic leukemia.
BACKGROUND
The objectives of the study were to evaluate the antileukemic efficacy and toxicity profiles of the combination of fludarabine and intermediate-dose cytosine arabinoside (ara-C) in refractory or relapsed adult acute lymphocytic leukemia (ALL). PATIENTS AND METHODS. Thirty adults with refractory or relapsed ALL were treated. Their median age was 45 years, 60% were in second or subsequent relapse, and 37% had Philadelphia chromosome-positive disease. Treatment consisted of ara-C 1 g/m2 during a period of 2 hours daily for 6 days, and fludarabine 30 mg/m2 during a period of 30 minutes daily for 5 days on days 2-6. Fludarabine was given 4 hours before ara-C to increase the rate of ara-C 5'-triphosphate (ara-CTP) accumulation in leukemic cells. Courses were repeated every 3 weeks or longer, depending on patient response and side effects.


RESULTS
Nine (30%) patients achieved a complete remission (CR), 8 (27%) died during remission induction, and 13 (43%) had resistant disease. The median CR duration was 22 weeks, and the median survival was 12 weeks for all patients, and 34 weeks for those who had a response to treatment. Except for low platelet counts, which predicted shorter survival time, no other prognostic factors were demonstrated, considering the small number of patients treated. Myelosuppression-associated febrile episodes were the most common side effects, occurring in 28 (93%) patients. Neurotoxicity was noted in two (7%) patients.


CONCLUSIONS
Fludarabine and ara-C are an active and relatively safe antileukemic combination in refractory or relapsed ALL. Future studies will incorporate other anti-ALL agents, such as topoisomerase II-reactive drugs, to improve the overall efficacy, and growth factors, to reduce myelosuppression-related complications.
Department of Hematology, M. D. Anderson Cancer Center, Houston, Texas 77030.
S
S
Suki
H
H
Kantarjian
V
V
Gandhi
E
E
Estey
S
S
O'Brien
M
M
Beran
M B
MB
Rios
W
W
Plunkett
M
M
Keating
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000633:toxicity; D003561:Cytarabine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
D000970:Antineoplastic Agents; D003561:Cytarabine; D014740:Vidarabine; C024352:fludarabine