First line therapy with fludarabine combinations in 42 patients with either post myelodysplastic syndrome or therapy related acute myeloid leukaemia

Acute myeloid leukaemias (AML) evolving from a myelodysplastic syndrome (MD S) or secondary to chemoradiotherapy frequently display unfavorable biologi c characteristics. This may explain the lower remission rate obtained with conventional chemotherapy. Recently, the association of Fludarabine with in termediate dose Ara-C has produced interesting results particularly in high risk AML patients. Here, we report on 42 secondary AML patients treated wi th a combination of fludarabine, intermediate dose Ara-C, G-CSF with or wit hout an antracycline (FLANG, FLAG-IDA or FLAG). Overall. complete remission s (CR) were documented in 14 patients (33%) and partial responses (PR) in 1 2(29%), while 10 patients proved resistant (24%). Six patients (14%) died e arly. The presence of a prognostically unfavorable karyotype had a negative impact on the CR rate (20% compared to 50% for patients with an intermedia te prognosis karyotype, p 0.05). Patients treated with FLAG, FLANG and FLAG -IDA had similar CR rates. At the time of this analysis, after a mean follo w-up of 12 months, the mean duration of CR is 16 months (range 3-66) and th e mean survival is 11 months(range 1-67). The median time to granulocyte re covery (neutrophils > 0.5 x 10(9) / 1) was 20 days (range 12-39) and 50 x 1 0(9) /1 platelets were reached at a median of 16 days (range 9-56). Taken together. these Fludarabine containing regimens proved to be an effec tive and tolerable treatment for patients with secondary AML. Patients abov e 70 years of age may also benefit from this therapy, however the problem o f treating patients with adverse chromosomal abnormalities still remains un resolved.