Introduction. The long-term prognosis of older patients with AML is dismal. The incidence of CR with standard chemotherapy is reduced and the remissions are usually transient, with less than 10% of the patients surviving beyond 3 years. Intensive treatments are burdened with an high incidence of treatment-related mortality. Palliative treatments do not reduce the time spent in the hospital nor transfusion requirements. We have therefore initiated a study with an attenuated FLAIG induction regimen, followed by outpatient consolidation and maintenance, to improve CR rates and try to reduce hospitalization. Patients and therapy . Forty-two elderly patients (median age 66; range 60-78) with AML de novo (AML=26 pts.) or secondary to an antecedent hematological disorder (sAML=16 pts.) were treated with Fludarabine 30 mg/m2/day in 30' followed 4 hours later by Cytarabine 1 g/m2/day in 3 hours (both for 5 days in pts. 70 or for 4 days in pts.>70). Idarubicin 10 mg/m2/day was administered as a 24-hours infusion on days 1,3,5. Glycosilated G-CSF was given from day 7 to granulocytes>1000. Patients in CR after induction were given two consolidation courses on an outpatient basis: the first with the same Fludarabine and Cytarabine scheme for two days plus Idarubicin on day 2 as a bolus infusion; the second with Thioguanine 50 mg/m2/day and Cytarabine 100 mg/m2/day subcutaneously for 5 days plus oral Idarubicin 15 mg/m2 on day 1. Maintenance with Thioguanine 50 mg/m2/day for 4 days plus Cytarabine 100 mg/m2 on day 5 every week was continued for at least one year or until relapse. Results. All patients are evaluable for response. CR was obtained in 27 pts. (64.3%). The incidence of CR was 69.2% in AML and 56.2% in sAML (p=.51). Eight pts. (19%) were resistant (5 AML and 3 sAML). Seven pts. (16.7%) died: 2 during induction (1 cerebral hemorrage, 1 ARDS) and 5 during the aplastic phase. The more relevant infectious complications were: 2 pulmonary aspergillosis (one causing patient's death while in CR) and other infections grade 3/4 according to WHO in 11 more pts. Moreover, in 2 pts. a prolonged post-remissional pancytopenia was observed, with positive CMV antigenemia, which resolved after antiviral therapy. The median length of hospitalization for the induction phase was 29.5 days (1-73). The consolidation phase required readmission in 15 pts. (55%) for a median of 20 days (14-69). The median overall survival (OS) was 7.4 months, with a minimum follow-up of 3 months for censored patients and with an actuarial probability of survival at 34 months of 19.8%. OS was significantly longer in patients 65 yrs than in those >65 yrs (22.3 vs. 4.1 months; p=0.01). The median disease-free survival (DFS) was 13 months and again it was longer in pts 65 yrs (17.5 vs. 6.8 months, p=0.04).Conclusion. This attenuated FLAIG protocol provided an high incidence of CR with acceptable toxicity in this high-risk group of patients. Better maintenance procedures should be devised to control the minimal residual disease and prolong the disease-free survival, possibly without further hospitalization to improve the quality of life and to contain the costs of treatment.
Full conference title:
44th Amercian Society of Hematology Annual Meeting
- ASH 44th (2002)