Combination of liposomal daunorubicin (DaunoXome), fludarabine, and cytarabine (FLAD) in patients with poor-risk acute leukemia

Abstract

Sixty-two patients with high-risk acute leukemia were treated with the FLAD regimen [3 days of treatment with fludarabine 30 mg/m(2), cytarabine (AraC) 2 g/m(2), and liposomal daunorubicin 80 mg/m(2)]. The acute myeloid leukemia (AML) patients were either refractory to standard induction regimens (8), were in first or second relapse (13), or received therapy as first-line treatment [21 patients, 16 were above 60 years of age and 5 had post-myelodysplastic syndrome (MDS) AML]. The acute lymphoblastic leukemia (ALL) patients were treated for relapsed (7) or refractory disease (10). Three patients had chronic myeloid leukemia (CML) in the blastic phase. FLAD was well tolerated by most patients. Ten major infectious complications were recorded while no signs of cardiac toxicity were observed. Five patients (8%) died before day 28 with hypocellular marrow, mainly of infection or hemorrhage, and response could not be evaluated. Complete response rate was 62% and 69% among AML patients treated at diagnosis or for relapsed disease, respectively, and 59% among the ALL patients. Furthermore, FLAD managed to overcome the negative impact of poor prognosis karyotype in ALL patients, since five of the seven patients with t(9;22) or complex karyotype achieved complete remission (CR). Nine patients underwent bone marrow transplantation (BMT). Among the AML patients who were treated at diagnosis or for relapse, the median duration of CR was 7 months (range: 2-18) and 8 months (range: 2-26), respectively. Median survival among these patients was 8 (range: 1-40) and 12 (range: 1-30) months, respectively. Similar values were found in ALL patients. In conclusion, FLAD may be an effective alternative treatment for patients with relapsed AML and for patients with ALL who failed first-line therapy.

Sequential continuous infusion of fludarabine and cytarabine associated with liposomal daunorubicin (DaunoXome®) (FLAD) in primary refractory or relapsed adult acute myeloid leukemia patients

“…Similar results have been recently published by Clavio et al [29] using a salvage treatment with the same drugs as in this study but without continuous infusion in a variety of patients with poor-risk acute leukemias (ALL, AML resistant or relapsed, de novo AML in elderly people).…”

FLAG-liposomal Doxorubicin (Myocet) Regimen for Refractory or Relapsed Acute Leukemia Pediatric Patients

“…15,16 Recent studies have utilized a combination of liposomal daunorubicin (DNX), fludarabine, and cytarabine in patients with poor risk acute leukemia and proved to be effective in inducing high complete response (CR) rates without the occurrence of significant toxicity. [16][17][18] Similarly, Melillo et al 19 reported the experience of the combination of nonpegylated liposomal doxorubicin (Myocet) with FLAG regimen in a cohort of adult poor prognosis AML patients. Myocet has a longer half life than standard doxorubicin, significantly less cardiotoxicity, and comparable antitumor efficacy.…”

Combination of Fludarabine and Imatinib Induces Apoptosis Synergistically Through Loss of Mitochondrial Membrane Potential and Increases in Caspase-3 Enzyme Activity in Human K562 Chronic Myleloid Leukemia Cells

“…This form of fludarabine has the ability to prevent the activity of enzymes involved in DNA synthesis and DNA repair. Inhibition of DNA polymerase alpha, DNA primase, ligase, and reductase induces DNA damage and arrest the cell cycle (10)(11)(12)(13).…”