Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: final results of AML-13, a randomized phase-3 study

Abstract

The role of glycosylated recombinant human granulocyte colony-stimulating factor (G-CSF) in the induction treatment of older adults with acute myeloid leukemia (AML) is still uncertain. In this trial, a total of 722 patients with newly diagnosed AML, median age 68 years, were randomized into 4 treatment arms: (A) no G-CSF; (B) G-CSF during chemotherapy; (C) G-CSF after chemotherapy until day 28 or recovery of polymorphonuclear leukocytes; and (D) G-CSF during and after chemotherapy. The complete remission (CR) rate was 48.9% in group A, 52.2% in group B, 48.3% in group C, and 64.4% in group D. Analysis according to the 2 ؋ 2 factorial design indicated that the CR rate was significantly higher in patients who received G-CSF during chemotherapy (58.3% for groups B ؉ D vs 48.6% for groups A ؉ C; P ‫؍‬ .009), whereas no significant difference was observed between groups A ؉ B and C ؉ D (50.6% vs 56.4%, P ‫؍‬ .12). In terms of overall survival, no significant differences were observed between the various groups. Patients who received G-CSF after chemotherapy had a shorter time to neutrophil recovery (median, 20 vs 25 days; P < .001) and a shorter hospitalization (mean, 27.2 vs 29.7 days; P < .001). We conclude that although priming with G-CSF can improve the CR rate, the use of G-CSF during and/or after chemotherapy has no effect on the long-term outcome of AML in older patients. (Blood. 2005;106:27-34)

Which AML subsets benefit from leukemic cell priming during chemotherapy? Long‐term analysis of the ALFA‐9802 GM‐CSF study

“…The schedule of administration seems important with a better benefit when repeating priming during all consolidation chemotherapy courses, instead of a unique sequence of administration during induction chemotherapy. 16 It appeared in our study that there was a potentiation of GM-CSF priming with the theoretical effect of TSC on cell cycle more than only on the cytotoxic efficacy of cytarabine. Indeed, a significant difference in terms of CR was initially observed after the first course of induction chemotherapy, 5 and a significant difference between GM-CSF and no GM-CSF was also noted in terms of EFS among patients receiving the ALFA-9000 TSC consolidation course, while there were no differences for those randomized in the CALGB-like, high-dose cytarabine consolidation study arm.…”

“…16 The reasons for these Figure 3. Event-free survival (EFS) according to the assigned treatment (GM-CSF vs no GM-CSF) and the risk groups are depicted.…”

Continuous drip infusion of low dose cytarabine and etoposide with granulocyte colony‐stimulating factor for elderly patients with acute myeloid leukaemia ineligible for intensive chemotherapy

“…Non-haematological adverse effects in the first induction course with AVG therapy AVG regimen regarding the degree of mylosuppression (data was not shown). Several studies about the role of G-CSF during and/or after induction therapy were initiated, but no conclusion could be made in this regard [12,21,22]. It is possible that the priming effect with G-CSF is different between intensive regimens and low dose regimens.…”

Filgrastim support in allogeneic HSCT for myeloid malignancies: a review of the role of G-CSF and the implications for current practice

“…With extensive clinical use, G-CSF and GM-CSF have been found to be safe and without an increase in mortality in patients undergoing induction therapy for AML. [7][8][9] The administration of G-CSF to patients with early myelodysplastic syndrome has not been shown to increase the risk of leukemic transformation. 12 Lessons from aplastic anemia and severe chronic neutropenia Karyotypic abnormalities involving chromosome 7 produce the most adverse outcomes in patients with AML and MDS.…”

“…[4][5][6] The majority of controlled studies have shown that overall survivals for patients with leukemia or BMT treated with G-CSF have not significantly differed from control and that regulatory approval has resulted in the widespread use of G-CSF. [7][8][9] Filgrastim in myeloid malignancies The risk of leukemogenesis has been a concern with the use of filgrastim because it can induce the release of immature myeloid precursors into the circulation. Myeloid leukemic cells may express G-CSF and/or GM-CSF receptors.…”