Use of Human Granulocyte Colony-Stimulating Factor (G-CSF) in Consolidation Chemotherapy in Adult Acute Myeloid Leukaemia (AML) (original) (raw)
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Annals of Hematology, 1993
Our purpose was to evaluate the ability of recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) as an adjunct to induction chemotherapy of acute lymphoblastic leukemia (ALL) to ameliorate chemotherapy-induced neutropenia and thus allow patients to receive full doses of chemotherapy on time. Sixteen consecutive patients with adult ALL (13 de novo, three relapsed) were treated with induction chemotherapy according to the BMFT protocol and received in addition r-metHuG-CSF (200 pg/m2/day). Patients who were treated with the same induction chemotherapy but without G-CSF between 1982 and 1990 served as controis. Fifteen of the 16 patients achieved complete hematological remission. One patient died because of fungal septicemia. Compared with historical controls, G-CSFtreated patients had a significantly faster neutrophil recovery in phase I, resulting in neutrophil counts > 1000/pl at day 17 vs day 26 (in median) in controls. In phase II, the onset of severe leukocytopenia (< 1500//A) was significantly (p = 0.01) delayed and the degree of leukocytopenia less pronounced (mean nadir 3300//A) in G-CSF-treated patients compared with controls (1880/pl). The number of days of febrile neutropenia was not different in phase I. In phase II it was lower in study patients (0 vs 1.1 days), but the difference did not reach statistical significance (19 = 0.09). Full doses of chemotherapy could be given on time to 11/13 (85o7o) G-CSF patients but to only 7/30 (23~ controls. These data indicate that (a) G-CSF can be given along with chemotherapy in induction treatment of ALL without compromising efficacy; (b) the duration of neutropenia in phase I is markedly shortened and the degree of leukocytopenia in phase II ameliorated; (c) these beneficial effects allow patients to receive full doses of chemotherapy on time.
Blood
The treatment of adult patients greater than 55 t o 70 years of age with acute myelogenous leukemia (AMLI is associated with a treatment-related mortality of approximately 25%. This prospective, double-blind randomized study was designed t o see if the use of granulocyte-macrophage colony stimulating factor (GM-CSF; yeast-derived) could shorten the period of neutropenia and t o determine any effect this would have on therapy-related morbidity and mortality. A total of 124 patients entered this study. Induction consisted of standard daunorubicin and cytarabine. A day-l0 bone marrow was examined; if this was aplastic without leukemia, patients received blinded placebo or GM-CSF from day 11 until neutrophil recovery. Patients who entered complete remission received the identical study medication (blinded GM-CSF or placebo) in consolidation that they had received E ARLY DEATH DURING induction therapy for acute myelogenous leukemia (AML) still remains an important clinical problem. The mortality rate increases with age. For patients greater than 55 to 60 years of age, the treatment-related early death rate is on the order of 20% to
New England Journal of Medicine, 2003
Sensitization of leukemic cells with hematopoietic growth factors may enhance the cytotoxicity of chemotherapy in acute myeloid leukemia (AML). methods In a multicenter randomized trial, we assigned patients (age range, 18 to 60 years) with newly diagnosed AML to receive cytarabine plus idarubicin (cycle 1) and cytarabine plus amsacrin (cycle 2) with granulocyte colony-stimulating factor (G-CSF) (321 patients) or without G-CSF (319). G-CSF was given concurrently with chemotherapy only. Idarubicin and amsacrin were given at the end of a cycle to allow the cell-cycle-dependent cytotoxicity of cytarabine in the context of G-CSF to have a greater effect. The effect of G-CSF on disease-free survival was assessed in all patients and in cytogenetically distinct prognostic subgroups.
Leukemia, 2001
The Australian Leukaemia Study Group (ALSG) investigated whether G-CSF would accelerate haemopoietic recovery after induction treatment for acute myeloid leukaemia (AML) intensified with high-dose cytarabine, and therefore improve response rates and survival. Patients were randomised to receive lenograstim (glycosylated recombinant human G-CSF) 5 g per kg body weight subcutaneously daily from day 8 after starting chemotherapy, or no cytokine, following chemotherapy with cytarabine 3 g/m 2 every 12 h on days 1, 3, 5, and 7, together with idarubicin 9 or 12 mg/m 2 on days 1, 2, and 3, plus etoposide 75 mg/m 2 on days 1 to 7 inclusive. Patients had untreated AML, and were aged 16 to 60 years. Overall, 54 evaluable patients were randomised to receive lenograstim and 58 to no cytokine. Patients in the lenograstim arm had a significantly shorter duration of neutropenia Ͻ0.5 × 10 9 /l compared to patients in the no cytokine arm (median 18 vs 22 days; P = 0.0005), and also shorter duration of total leucopenia Ͻ1.0 × 10 9 /l (17 vs 19 days; P = 0.0002), as well as a reduction in duration of treatment with therapeutic intravenous antibiotics (20 vs 24 days; P = 0.015) and a trend to reduced number of days with fever Ͼ38.0°C (9 vs 12 days; P = 0.18). There were no differences between the two groups in platelet recovery, red cell or platelet transfusions, or non-haematological toxicities. For patients achieving CR after their first induction course, a reduction in the time to the start of the next course of therapy was observed in the lenograstim arm, from a median of 40.5 days to a median of 36 days (P = 0.082). The overall complete response rates to chemotherapy were similar, 81% in the lenograstim arm vs 75% for the no cytokine arm (P = 0.5), and there was no significant difference in the survival durations. We conclude that the granulopoietic stimulating effect of G-CSF is observed after induction therapy for AML intensified by highdose cytarabine, resulting in an improvement in a number of clinically important parameters with no major adverse effects.
Blood, 1995
This prospective multicenter study examined whether simultaneous administration of granulocyte colony-stimulating factor (G-CSF; Filgrastim) and induction chemotherapy for adult acute lymphoblastic leukemia (ALL) could prevent treatment-related neutropenia, infections, and resulting treatment delays. Seventy-six patients were randomly assigned to receive either G-CSF (n = 37) or no growth factor (n = 39) in conjunction with a uniform chemotherapy consisting of cyclophosphamide, cytarabine, mercaptopurine, intrathecal methotrexate, and cranial irradiation. The median duration of neutropenia (absolute neutrophil count < 1 x 10(9)/L) during chemotherapy was 8 days in patients receiving C-CSF, compared with 12.5 days in the control group (P < .002). A similar reduction from 11.5 to 7 days was observed in patients with T-ALL receiving additional mediastinal irradiation (P = .13). Infections occurred in 43% and 56% of patients in the G-CSF and control arm, respectively (P = .25); th...
Blood, 1996
Hematopoietic growth factors are being administered to patients with acute myeloid leukemia (AML) both to shorten the duration of chemotherapy-induced neutropenia and in an attempt to increase cytotoxicity of cell cycle-specific agents. However, limited information is available concerning the effects of growth factors in AML patients. To examine the in vivo effects of recombinant human granulocyte colony-stimulating factor (G-CSF) on AML cells, laboratory studies were performed before and after a 72-hour intravenous infusion of G-CSF (10 micrograms/kg/d) administered to 28 untreated AML patients. Twenty-seven patients (96%) showed increases in at least one of the following parameters after G-CSF: blood blasts, bone marrow (BM) blasts, leukemia cells in S phase or interphase cells with leukemia- specific markers shown by fluorescence in situ hybridization. The median paired change in absolute blast count was +2.7 x 10(9)/L (P = .0001) after G-CSF, as compared with 0.0 during the 72 h...
British Journal of Haematology, 2004
The incidence of acute myeloid leukaemia (AML) increases with age and, in Sweden, more than 70% of the patients are older than 60 years. To cure AML with chemotherapy it is necessary to use intensive therapy, leading to severe myelosuppression with infectious complications. Elderly patients tolerate intensive cytotoxic treatment less well than younger ones and the proportion of elderly patients that die during induction treatment is high (Rees et al, 1986). The remission duration can be comparable with that of younger patients not receiving stem cell transplantation, but overall survival (OS) is shorter (Tucker et al, 1990; Stone et al, 1995). Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) is a glycoprotein that stimulates the proliferation and differentiation of granulocyte and macrophage progenitor cells. GM-CSF also induces the growth of leukaemic stem cells in vitro in a majority of patients with AML (Griffin et al, 1986; Asano et al, 1987; Sundman-Engberg et al, 1996) and it has been shown that the number of dividing leukaemic blasts increases when GM-CSF is given 24 h prior to cytostatic treatment (Bettelheim et al, 1991). In 90% of the patients whose leukaemic cells were stimulated to divide in vitro, in vivo proliferation was also induced within 3 d after the start of GM-CSF treatment (Estrov et al, 1992). In addition, GM-CSF has been shown to reduce the neutropenic period after cytostatic treatment of AML (
International Journal of Hematology-Oncology and Stem Cell Research, 2021
Background: Acute myeloid leukemia (AML) patients are often neutropenic as a result of their disease alone or following their chemotherapy. In this randomized clinical trial the efficacy of Iranian short-acting (PD-Grastim) and long-acting G-CSF (PD-Lasta) were compared in term of time to recovery from neutropenia in de novo AML patients following the consolidation chemotherapy. Materials andMethods: Patients (n = 51) received one or two courses of Cytarabine and Daunorubicin as an induction. If complete remission was achieved, the treatment was followed by high-dose Cytarabine as consolidation chemotherapy. Twenty- four hours after the consolidation chemotherapy, patient were randomized to receive either daily short-acting G-CSF (PD-Grastim) (300 µg/kg) or single-dose long-acting G-CSF (PD-Lasta) (6 mg). Results: The median time to recovery of neutrophils was 11.00 and 13.00 days for short-acting G-CSF (PD-Grastim) (n=22) and long-acting G-CSF (PD-Lasta) (n=29) groups, respectively...