Prolonged survival in chronic myelogenous leukemia after cytogenetic response to interferon-alpha therapy. The Leukemia Service.
OBJECTIVE
To determine whether a cytogenetic response after interferon-alpha therapy in patients with chronic myelogenous leukemia is independently associated with improved survival.


METHODS
Retrospective analysis.


METHODS
274 patients with a diagnosis of Philadelphia chromosome-positive chronic myelogenous leukemia in early chronic phase who were treated with interferon-alpha-based programs between 1982 and 1990.


METHODS
Therapy with daily subcutaneous interferon-alpha given at 5 x 10(6) U/m2 body surface area (highest dose schedule allowed on studies) or the maximally tolerated lower-dose schedule.


RESULTS
Overall, 219 (80%) patients achieved a complete hematologic response and 104 (38%) achieved a major cytogenetic response (< 35% Philadelphia chromosome-positive cells). Estimated median survival was 89 months. Several pretreatment factors were associated with failure to achieve a major cytogenetic response and with worse survival. The existing prognostic models were generally predictive of which patients were likely to achieve a major cytogenetic response (P < or = 0.01) and of survival outcomes (P < or = 0.01). Multivariate analysis identified bone marrow basophilia (P < 0.01) and splenomegaly (P < 0.01) as independent poor prognostic factors for survival. Achievement of a major cytogenetic response, entered as a time-dependent variable while accounting for the other independent factors, was associated with improved survival (P < 0.001). Comparison of survival (dated from 12 months into therapy) with cytogenetic response at 12 months showed that a cytogenetic response was associated with longer survival (P < 0.001).


CONCLUSIONS
Achieving a cytogenetic response with interferon-alpha therapy in patients with chronic myelogenous leukemia was independently associated with improved survival when tested as a time-dependent variable in a multivariate analysis, and this association was confirmed by landmark analysis at 12 months.
Kantarjian
H M
HM
Department of Hematology, M.D. Anderson Cancer Center, Houston, TX 77030.
Smith
T L
TL
O'Brien
S
S
Beran
M
M
Pierce
S
S
Talpaz
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D002452:Cell Count / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D007370:Interferon Type I / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D011994:Recombinant Proteins; D013163:Splenomegaly; D015996:Survival Rate
D007370:Interferon Type I; D016898:Interferon-alpha; D011994:Recombinant Proteins; D006918:Hydroxyurea