High-vs low-dose cytarabine combined with interferon alfa in patients with first chronic phase chronic myeloid leukemia. A prospective randomized phase III study.
A prospective randomized phase III study was performed to evaluate whether intensified cytarabine would induce a higher response rate and longer event-free interval as compared to low-dose cytarabine in chronic myeloid leukemia (CML). One hundred and eighteen patients with CML in early chronic phase entered the study. Twenty-eight out of 32 patients assigned to group A received two cycles of a combination of intensified cytarabine and idarubicin followed by interferon alfa (IFN-alpha) maintenance, 28 patients in group B received standard treatment by a combination of low-dose cytarabine and IFN-alpha. Forty-nine patients with a human leukocyte antigen-identical sibling donor proceeded to allogeneic stem cell transplantation (allo-SCT) and nine patients were excluded from the analysis. Hematological response was observed in 97% of the patients in group A vs 86% of the patients in group B during the first year of treatment. In group A, 16 patients (50%) achieved a major cytogenetic response, which compared to seven patients (25%) with a major cytogenetic response in group B. With a median follow-up of 58 months (range 34-76), event-free survival was not significantly different between arms A and B. The estimated 5-year survival rate was 56% in the intensified arm and 77% in the low-dose arm (P = 0.05). Recipients of allo-SCT showed a 5-year estimated survival rate of 55%. Although intensified cytarabine induced a higher initial percentage of major and complete cytogenetic responses, responses were not sustained by IFN-alpha maintenance therapy.
Deenik
W
W
Department of Hematology, Erasmus University Medical Center/Daniel den Hoed, Groene Hillendijk, Rotterdam, The Netherlands.
van der Holt
B
B
Verhoef
G E G
GE
Schattenberg
A V M B
AV
Verdonck
L F
LF
Daenen
S M G J
SM
Zachée
P
P
Westveer
P H M
PH
Smit
W M
WM
Wittebol
S
S
Schouten
H C
HC
Löwenberg
B
B
Ossenkoppele
G J
GJ
Cornelissen
J J
JJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D003561:Cytarabine / Q000008:administration & dosage / Q000627:therapeutic use*; D003582:Cytogenetics; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D033581:Stem Cell Transplantation; D015996:Survival Rate; D014184:Transplantation, Homologous
D016898:Interferon-alpha; D003561:Cytarabine