Molecular Response of CML Patients to INFα Based Treatment or to STI Based Therapy.

Introduction:

Continous improving results have been obtained during last two decades in the control of Ph’positive chronic myeloid leukemia(CML). However the final goal of molecular remission remains difficult to obtain even in the STI age.

Aims :

Evaluation of the rate of molecular response to IFNα,IFNα based treatment,to STI or to STI-INFα combination was analized in 100 consecutive Ph+ CML patients observed in a single Institution over a period of 20 years.

Patients, Methods and Results

All patients were treated at the time of diagnosis (87) or late (13) during the course of their disease. Distribution according to treatment was: INFα,63pts (late or early:13,50);INFα-ARA-C combination,20pts;STI,14 pts;STI-INFα association, 3 pts. Two pts, both initially assigned to INFα-ARA-C combination, were crossed-over to STI, one because relapsing off-therapy after a long lasting continous (25 mths) molecular remission and the other in cytogenetic response because intolerant to the initial treatment. In addition, other 3 pts patients, with persistent complete cytogenetic, but not molecular remission to INFα or INFα-ARA-C combination were subsequentially trated with the STI-IFNα association. At present,99/100 pts are evaluable. The median times of follow-up for the entire group and form the different treatment subgroups are: late IFNα 154 months(42–263); early IFNα, 71 months(1–197); IFNα-ARA-C, 61 months(5–203); STI- IFNα,78 mths(11–47), STI,31 mths(3–41). A complete kariotypic remission(CKR) was observed in 15/63 IFNα treated pts, in 10/20 IFNα-ARA-C pts group, in 10/13 cases of STI group and in 3 /3 pts who received STI-IFNα. A molecular response(RT-nested PCR, JQ Guo, Leukemia: 2002,15,2447–53) was observed in 4/15,2/10,5/10 and in 2/3 CKR pts initially trated with the different modalities listed above. Response was confirmed from 2 to 7 consecutive or not consecutive times in the 2/4 cases responsive to INFα, in the 2 cases responsive to INFα-ARA-C combination,4/5cases responsive to STI and in 2/3 cases responsive to STI-IFNα association. The 2nd and the 3rd molecular remission to STI were obtained in the patient molecularly and cytogenetically relapsed off-therapy and, for the first time from the diagnosis, in the other patient in CKR to IFNα-ARA-C combination and crossed to STI treatment. Furthermore, all 3 cases, in CKR, but not molecular response to other treatments at the time of cross-over to STI-IFNα combination, achieved a persistent (in 2 to 3 tests over a period ranging from 6+ to 12+ mths) molecular remission. The first interval between the start of the treatment and the first molecular response varied from 12 to 52, from 3 to 22, from 11 to 24, from 5 to 11 mths in the groups initially treated with IFNα, IFNα-ARA-C, STI or STI-IFNα respectively. The 2 pts, crossed-over to STI alone, both, obtained a response after 29 mths of therapy. In addition in the 3 pts crossed-over to STI-IFNα therapy, the molecular response was obtained after 14,23 and 25 mths from the start of last treatment.

Conclusion

It is not possible to achieve any conclusion regarding the treatment effect on molecular response duration because of the different length of follow-up of various groups of patients. However in responsive patients to IFN alone or combined to ARA-C or STI, consecutive negative RT-PCR tests were observed more frequently than in patients receving STI alone.