Response at three months is a good predictive factor for newly diagnosed chronic myeloid leukemia patients treated by recombinant interferon-alpha.
In a single institution, we have used recombinant interferon- (IFN-) to treat 116 newly diagnosed Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) patients and analyzed the predictive factors for response and survival. The patients whose median age was 50.3 years (range, 9 to 70) were administered IFN- (5 million units/m2/d) subcutaneously. The IFN- dose was subsequently adjusted to maintain the white blood cell and platelet counts between 1.5 and 5 x 10(9)/L, 50 and 100 x 10(9)/L, respectively. At diagnosis, the Sokal score was used to classify the patients into three groups: low (n = 57), intermediate (n = 42), and high risk (n = 16). A complete hematological response (CHR) was achieved in 93 cases (80.2%). Of the 116 patients, 113 were available for cytogenetic evaluation. Fifty patients (43%) achieved a major cytogenetic response (MCR) (=65% marrow Ph- cells), 37 of them having a complete cytogenetic response (CCR). The estimated 5-year survival of the 116 patients was 68% +/- 11% (95% confidence interval [CI]) with a median follow-up of 42 months (range, 3 to 114) and 85% +/- 11% (95% CI) with a median follow-up of 30.9 (range, 3 to 111) when patients were censored at the time of transplantation. Event-free survival at 5 years (adding death and transplant as event) was 46% +/- 11% (95% CI). Using proportional hazards regression to study time-dependent variables, we confirmed that the most significant factor associated with survival was the cytogenetic response (MCR or CCR) (P <.0001). This factor was independent compared with the Sokal score and baseline variables used to calculate the Sokal score. Moreover, using either univariate or multivariate analysis, the achievement of CHR within 3 months was strongly correlated with MCR (P <.0001). Minimum cytogenetic response (mCR, ie, at least 5% of Ph- metaphases) at 3 months was also a significant predictive factor for MCR (P <.0001). These results show that IFN- can induce a high rate of hematological and cytogenetic response when administered in doses leading to myelosuppression. Factors such as the achievement of CHR and mCR within 3 months could be useful to identify early those patients who will not respond to IFN- and who need alternative treatments such as stem cell transplantation.
Mahon
F X
FX
Service des Maladies du Sang, Centre Hospitalier Universitaire de Bordeaux, Hôpital Haut-Levêque, Pessac, France.
Fabères
C
C
Pueyo
S
S
Cony-Makhoul
P
P
Salmi
R
R
Boiron
J M
JM
Marit
G
G
Bilhou-Nabera
C
C
Carrère
A
A
Montastruc
M
M
Pigneux
A
A
Bernard
P
P
Reiffers
J
J
D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011994:Recombinant Proteins; D016019:Survival Analysis; D013997:Time Factors
D007370:Interferon Type I; D011994:Recombinant Proteins