Fludarabine, arabinosyl cytosine and idarubicin (FLAI) for remission induction in poor-risk acute myeloid leukemia.
Progress in treatment of acute myeloid leukemia (AML) is slow and treatment intensification alone has limited effects, particularly in poor-risk cases. Poor-risk cases, that are identified mainly by prior history, leukemic cell mass and cytogenetic abnormalities, share multiple mechanisms of drug resistance that are responsible for treatment failure. Since Pgp-mediated resistance to anthracycline can be reduced with Idarubicin (IDA) and resistance to arabinosyl cytosine (AC) can be reduced with Fludarabine (FLUDA), we tested a combination of high dose AC (2000 mg/sqm, 5 doses), FLUDA (30 mg/sqm, 5 doses) and IDA (12 mg/sqm, 3 doses) for remission induction and consolidation in 45 consecutive cases of poor-risk AML. The complete remission (CR) rate was 71% after the first course and 82% overall, with a projected 2-year survival and relapse-free survival of 44% and 50% respectively. Non-hematologic toxicity was very mild, that is very important in elderly patients, but hemopoietic toxicity was substantial, with a time to hematologic recovery of 3 to 4 weeks and two cases of death in CR. Peripheral blood stem cells (PBSC) could be mobilized and collected successfully only in 11 cases. This three-drug combination is effective and has a limited non-hematologic toxicity, but FLUDA may increase the difficulty of obtaining PBSC early after remission induction.
Russo
D
D
Department of Bone Marrow Transplantation, University of Udine, Italy. Domenico@Russo@drmm.uniud.it
Pricolo
G
G
Michieli
M
M
Michelutti
A
A
Raspadori
D
D
Bertone
A
A
Marin
L
L
Pierri
I
I
Bucalossi
A
A
Zuffa
E
E
De Vivo
A
A
Mazza
P
P
Gobbi
M
M
Lauria
F
F
Zaccaria
A
A
Baccarani
M
M
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000633:toxicity; D015331:Cohort Studies; D003561:Cytarabine / Q000008:administration & dosage / Q000633:toxicity; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000633:toxicity; D007951:Leukemia, Myeloid / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010198:Pancytopenia / Q000139:chemically induced; D010865:Pilot Projects; D012074:Remission Induction; D016879:Salvage Therapy; D016019:Survival Analysis; D015996:Survival Rate; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity
D003561:Cytarabine; D014740:Vidarabine; C024352:fludarabine; D015255:Idarubicin