Background:
Gemtuzumab is used to treat patients with previously untreated or recurrent acute myelogenous leukemia (aml). the fludarabine and cytarabine (ara-c) regimen is active in these patients. resistance to gemtuzumab is associated with blast multidrug resistance (mdr). the objectives of this study were to evaluate the efficacy and toxicity of a combination regimen of gemtuzumab, fludarabine, ara-c, and the mdr modifier (cyclosporine [cya]) in patients with previously untreated aml, refractory anemia with excess blasts (raeb), or raeb in transformation (raebt).
Methods:
The mfac regimen was comprised of gemtuzumab (mylotarg trade mark ) (6 mg/m(2) intravenously [i.v.] on day 1); fludarabine and ara-c (15 mg/m(2) and 0.5 g/m(2), respectively, twice daily on days 2-6); and csa (6 mg/kg loading dose before gemtuzumab, followed by 16 mg/kg continuous i.v. infusion on days 1 and 2).
Results:
Fifty-nine evaluable patients were treated: 39 patients (66%) had aml and 20 patients (34%) had raeb/raebt. their median age was 57 years (range, 27-76 years). the mfac regimen induced complete remission (cr) in 27 patients (46%) and cr with incomplete platelet recovery (crp) in 1 patient (2%). the median survival period is 8 months. at 12 months, the survival rate is 38% and the event-free survival rate in patients with cr/crp is 27%. infections complicated 38% of the courses of chemotherapy. grade 3/4 toxicity included hyperbilirubinemia in 31% and transaminitis in 7% of the patients. four patients (7%) developed hepatic venoocclusive disease (vod).
Conclusions:
The mfac regimen may merit further study in patients with aml if measures to avoid and/or treat vod can be incorporated into the regimen.