A modified AIDA protocol with anthracycline-based consolidation results in high antileukemic efficacy and reduced toxicity in newly diagnosed PML/RARalpha-positive acute promyelocytic leukemia. PETHEMA group.
The Spanish PETHEMA group designed a protocol for newly diagnosed PML/RARalpha-positive acute promyelocytic leukemia (APL) in which induction and consolidation followed the original AIDA regimen, except for the omission of cytarabine and etoposide from consolidation. Induction consisted of 45 mg/m(2) all-trans retinoic acid (ATRA) daily until complete remission (CR) and 12 mg/m(2) idarubicin on days 2, 4, 6, and 8. Patients in CR received 3 monthly chemotherapy courses: idarubicin 5 mg/m(2)/d x 4 (course no. 1), mitoxantrone 10 mg/m(2)/d x 5 (course no. 2), and idarubicin 12 mg/m(2)/d x 1 (course no. 3). Maintenance therapy consisted of 90 mg/m(2)/d mercaptopurine orally, 15 mg/m(2)/wk methotrexate intramuscularly, and, intermittently, 45 mg/m(2)/d ATRA for 15 days every 3 months. Between November 1996 and December 1998, 123 patients with newly diagnosed PML/RARalpha-positive APL from 39 centers were enrolled. A total of 109 patients achieved CR (89%; 95% confidence interval [CI], 83 to 95), 12 died of early complications, and the remaining 2 were resistant. Consolidation treatment was associated with very low toxicity and no deaths in remission were recorded. Molecular assessment of response by reverse transcriptase-polymerase chain reaction (RT-PCR) showed conversion to PCR-negative in 48 of 99 (51%) and 82 of 88 patients (93%) after induction and consolidation, respectively. The 2-year Kaplan-Meier estimates of overall survival and event-free survival were 82% +/- 4% and 79% +/- 4%, respectively. For patients who achieved CR, the 2-year disease-free survival (DFS) was 92% +/- 3%. These data indicate that a significant reduction in toxicity might be obtained in APL using a less intensive consolidation without apparently compromising the antileukemic effect. These results also suggest a minor role for cytarabine and etoposide in the treatment of newly diagnosed PML/RARalpha-positive APL patients.
Sanz
M A
MA
Servicio de Hematología, Hospital Universitario La Fe, Valencia, Spain. msanz@uv.es
Martín
G
G
Rayón
C
C
Esteve
J
J
González
M
M
Díaz-Mediavilla
J
J
Bolufer
P
P
Barragán
E
E
Terol
M J
MJ
González
J D
JD
Colomer
D
D
Chillón
C
C
Rivas
C
C
Gómez
T
T
Ribera
J M
JM
Bornstein
R
R
Román
J
J
Calasanz
M J
MJ
Arias
J
J
Alvarez
C
C
Ramos
F
F
Debén
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000009:adverse effects; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects
D018943:Anthracyclines; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin; D015255:Idarubicin