title: Response at three months is a good predictive factor for newly diagnosed chronic myeloid leukemia patients treated by recombinant interferon-alpha.
abstract: 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.
authors.affiliation: Service des Maladies du Sang, Centre Hospitalier Universitaire de Bordeaux, Hôpital Haut-Levêque, Pessac, France.
authors.forename: F X
authors.initials: FX
authors.lastname: Mahon
authors.forename: C
authors.initials: C
authors.lastname: Fabères
authors.forename: S
authors.initials: S
authors.lastname: Pueyo
authors.forename: P
authors.initials: P
authors.lastname: Cony-Makhoul
authors.forename: R
authors.initials: R
authors.lastname: Salmi
authors.forename: J M
authors.initials: JM
authors.lastname: Boiron
authors.forename: G
authors.initials: G
authors.lastname: Marit
authors.forename: C
authors.initials: C
authors.lastname: Bilhou-Nabera
authors.forename: A
authors.initials: A
authors.lastname: Carrère
authors.forename: M
authors.initials: M
authors.lastname: Montastruc
authors.forename: A
authors.initials: A
authors.lastname: Pigneux
authors.forename: P
authors.initials: P
authors.lastname: Bernard
authors.forename: J
authors.initials: J
authors.lastname: Reiffers
mesh_terms: 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
chemical_list: D007370:Interferon Type I; D011994:Recombinant Proteins