Intensive chemotherapy with idarubicin, cytarabine, etoposide, and G-CSF priming in patients with advanced myelodysplastic syndrome and high-risk acute myeloid leukemia.
In an attempt to improve the complete remission (CR) rates and to prolong the remission duration especially in elderly patients > 50 years of age, we have used a combination chemotherapy of idarubicin (10 mg/m2 IV x 3 days), cytarabine (AraC, 100 mg/m2 CIVI x 7d), and etoposide (100 mg/m2 x 5 days) in combination with granulocyte colony-stimulating factor (G-CSF) priming [5 mg/kg SQ day 1 until absolute neutrophil count (ANC) recovery] for remission induction. Responding patients received two consolidation courses of idarubicin, AraC, and etoposide, followed by a late consolidation course of intermediate-dose AraC (600 mg/m2 IV every 12 h x 5 days) and amsacrine (60 mg/m2 IV x 5 days). A total of 112 patients (57 male/55 female) with a median age of 58 years (range: 22-75) have been entered and are evaluable for response: 19 refractory anemia with excess of blast cells in transformation (RAEB-T), 84 acute myeloid leukemia (AML) evolving from myelodysplastic syndrome (MDS), and 9 secondary AML after chemotherapy/radiotherapy. The overall CR rate was 62%, partial remission (PR) rate 10%, treatment failure 16%, and early death rate 12%. The CR rate was higher in patients < or = 60 years (68 vs 55%), mainly due to a lower early death rate (5 vs 21%, p<0.001). After a median follow-up of 58 months, the median overall survival is 14.5% and median duration of relapse-free survival 8 months. After 60 months, the probability of CR patients to still be in CR and alive is 16% (20% in patients < or = 60 years and 13% in patients >60 years), while the probability of overall survival is 12% (15% in patients < or = 60 years and 9% in patients > 60 years). Compared to our previous trial (AML-MDS Study 01-92) which was done with identical chemotherapy but no G-CSF priming in 110 patients with RAEB-T, AML after MDS, or secondary AML (identical median age, age range, and distribution of subtypes), the CR rate in all patients, as well as CR rate, overall survival, and relapse-free survival in patients > 60 years have significantly been improved. Thus, intensive chemotherapy with G-CSF priming is both well tolerated and highly effective for remission induction in these high-risk patients.
Hofmann
W K
WK
Department of Hematology/Oncology, Johann Wolfgang Goethe University Hospital, University of Frankfurt/Main, Theodor-Stern-Kai 7, Frankfurt/Main, Germany. w.k.hofmann@em.uni-frankfurt.de
Heil
G
G
Zander
C
C
Wiebe
S
S
Ottmann
O G
OG
Bergmann
L
L
Hoeffken
K
K
Fischer
J T
JT
Knuth
A
A
Kolbe
K
K
Schmoll
H J
HJ
Langer
W
W
Westerhausen
M
M
Koelbel
C B
CB
Hoelzer
D
D
Ganser
A
A
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000677:Amsacrine / Q000008:administration & dosage; D000754:Anemia, Refractory, with Excess of Blasts / Q000188:drug therapy / Q000401:mortality; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D003561:Cytarabine / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000401:mortality*; D012074:Remission Induction / Q000379:methods; D012306:Risk; D015996:Survival Rate; D016896:Treatment Outcome
D000677:Amsacrine; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D015255:Idarubicin