TY - JOUR
T1 - Fludarabine and cytosine arabinoside in the treatment of refractory or relapsed acute lymphocytic leukemia
AU - Suki, Samer
AU - Kantarjian, Hagop
AU - Gandhi, Varsha
AU - Estey, Elihu
AU - O'Brien, Susan
AU - Beran, Miloslav
AU - Rios, Mary Beth
AU - Plunkett, William
AU - Keating, Michael
PY - 1993/10/1
Y1 - 1993/10/1
N2 - 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.
AB - 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.
KW - acute lymphocytic leukemia
KW - cytosine arabinoside
KW - fludarabine
KW - salvage
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U2 - 10.1002/1097-0142(19931001)72:7<2155::AID-CNCR2820720715>3.0.CO;2-V
DO - 10.1002/1097-0142(19931001)72:7<2155::AID-CNCR2820720715>3.0.CO;2-V
M3 - Article
C2 - 8374873
AN - SCOPUS:0027183997
SN - 0008-543X
VL - 72
SP - 2155
EP - 2160
JO - Cancer
JF - Cancer
IS - 7
ER -