First Line Therapy with Fludarabine Combinations in 42 Patients with Either Post Myelodysplastic Syndrome or Therapy Related Acute Myeloid Leukaemia

Abstract

Acute myeloid leukaemias (AML) evolving from a myelodysplastic syndrome (MDS) or secondary to chemoradiotherapy frequently display unfavorable biologic characteristics. This may explain the lower remission rate obtained with conventional chemotherapy. Recently, the association of Fludarabine with intermediate dose Ara-C has produced interesting results particularly in high risk AML patients. Here, we report on 42 secondary AML patients treated with a combination of Fludarabine, intermediate dose Ara-C, G-CSF with or without an antracycline (FLANG, FLAG-IDA or FLAG). Overall, complete remissions (CR) were documented in 14 patients (33%) and partial responses (PR) in 12 (29%), while 10 patients proved resistant (24%). Six patients (14%) died early. The presence of a prognostically unfavorable karyotype had a negative impact on the CR rate (20% compared to 50% for patients with an intermediate 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 follow-up of 12 months, the mean duration of CR is 16 months (range 3–66) and the mean survival is 11 months (range 1–67). The median time to granulocyte recovery (neutrophils > 0.5 × 10⁹/1) was 20 days (range 12–39) and 50 × 10⁹/1 platelets were reached at a median of 26 days (range 9–56).

Taken together, these Fludarabine containing regimens proved to be an effective and tolerable treatment for patients with secondary AML. Patients above 70 years of age may also benefit from this therapy, however the problem of treating patients with adverse chromosomal abnormalities still remains unresolved.

Key Words:

• Fludarabine combinations
• AML induction therapy
• karyotype
• MDS-AML
• therapy-related AML