FLAG (Fludarabine, Cytarabine, G-CSF) as a second line therapy for acute lymphoblastic leukemia with myeloid antigen expression: In vitro and in vivo effects

Giuseppe Visani, Patrizia Tosi, Pier Luigi Zinzani, Silvia Manfroi, Emanuela Ottaviani, Annarita Cenacchi, Paola Carrara, Marino Clavio, Marco Gobbi, Sante Tura

Research output: Contribution to journalArticle

Abstract

Thirteen consecutive adult patients with primary refractory (n = 5) or relapsed (n = 8) acute lymphoblastic leukemia (ALL) were treated by an induction schedule (FLAG) consisting of Fludarabine (30 mg/sqm/d) plus high dose Cytarabine (HD-ara-C: 2 g/sqm/d) (d 1-5) and G-CSF (from d 0 to polymorphonuclear recovery). Patients achieving complete remission (CR) were administered a second FLAG course as consolidation and were then submitted to an individualized program of post-remission therapy, depending on the patient's age and performance status. CR was achieved in 8/12 evaluable cases (67%). The median CR duration was 22.5 w. CR attainment was significantly related to the co-expression of lymphoid and myeloid antigens. ALL/My+ patients achieved CR in 6/6 evaluable cases vs. 2/6 for ALL/My-. In vitro 3H ara-C incorporation into cellular DNA resulted significantly increased by Fludarabine (in 7/9 tested cases) and, furthermore, by the association of Fludarabine-G-CSF in 5 evaluable ALL/My+ cases; in contrast, no effect of G-CSF addition to Fludarabine was observed in 4 ALL/My-. Myelosuppression was observed in all patients: the median time to neutrophils >0.5 x 109/l was 16.3 d (range 13-22) and 16.2 d (range 9-29) to platelets > 20 x 109/l. Nonhematological toxicity was minimal. In conclusion, FLAG is an active and tolerable combination in refractory ALL, particularly in cases with myeloid antigen expression where G-CSF appears to improve efficacy, probably increasing ara-C incorporation into the DNA of leukemic cells.

Original languageEnglish
Pages (from-to)308-312
Number of pages5
JournalEuropean Journal of Haematology
Volume56
Issue number5
Publication statusPublished - 1996

Keywords

  • Acute lymphoblastic leukemia
  • Antigens
  • Fludarabine
  • G-CSF
  • Myeloid

ASJC Scopus subject areas

  • Hematology

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    Visani, G., Tosi, P., Zinzani, P. L., Manfroi, S., Ottaviani, E., Cenacchi, A., Carrara, P., Clavio, M., Gobbi, M., & Tura, S. (1996). FLAG (Fludarabine, Cytarabine, G-CSF) as a second line therapy for acute lymphoblastic leukemia with myeloid antigen expression: In vitro and in vivo effects. European Journal of Haematology, 56(5), 308-312.