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

35 Citations (Scopus)

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

Fingerprint

Cytarabine
Granulocyte Colony-Stimulating Factor
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Antigens
Therapeutics
DNA
In Vitro Techniques
fludarabine
Appointments and Schedules
Neutrophils
Blood Platelets

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

FLAG (Fludarabine, Cytarabine, G-CSF) as a second line therapy for acute lymphoblastic leukemia with myeloid antigen expression : In vitro and in vivo effects. / Visani, Giuseppe; Tosi, Patrizia; Zinzani, Pier Luigi; Manfroi, Silvia; Ottaviani, Emanuela; Cenacchi, Annarita; Carrara, Paola; Clavio, Marino; Gobbi, Marco; Tura, Sante.

In: European Journal of Haematology, Vol. 56, No. 5, 1996, p. 308-312.

Research output: Contribution to journalArticle

Visani, Giuseppe ; Tosi, Patrizia ; Zinzani, Pier Luigi ; Manfroi, Silvia ; Ottaviani, Emanuela ; Cenacchi, Annarita ; Carrara, Paola ; Clavio, Marino ; Gobbi, Marco ; Tura, Sante. / FLAG (Fludarabine, Cytarabine, G-CSF) as a second line therapy for acute lymphoblastic leukemia with myeloid antigen expression : In vitro and in vivo effects. In: European Journal of Haematology. 1996 ; Vol. 56, No. 5. pp. 308-312.
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T1 - FLAG (Fludarabine, Cytarabine, G-CSF) as a second line therapy for acute lymphoblastic leukemia with myeloid antigen expression

T2 - In vitro and in vivo effects

AU - Visani, Giuseppe

AU - Tosi, Patrizia

AU - Zinzani, Pier Luigi

AU - Manfroi, Silvia

AU - Ottaviani, Emanuela

AU - Cenacchi, Annarita

AU - Carrara, Paola

AU - Clavio, Marino

AU - Gobbi, Marco

AU - Tura, Sante

PY - 1996

Y1 - 1996

N2 - 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.

AB - 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.

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