Granulocyte colony-Stimulating factor (G-CSF, filgrastim) after or during an intensive remission induction therapy for adult acute lymphoblastic leukaemia: Effects, role of patient pretreatment characteristics, and costs

Abstract

An early intensive anthracycline therapy can improve therapeutic outcome in adult acute lymphoblastic leukaemia (ALL) but is usually associated with marked myelosuppressive effects and significant morbidity by infections. To reduce this risk, we employed granulocyte colony-stimulating factor (G-CSF, filgrastim 5 microg/kg/d) as an adjunct to a myelotoxic, 14-day long induction regimen with idarubicin-vincristine-L-asparaginase-prednisone (IVAP). Owing to changes in study design, patients received 'late' (n = 28) or 'early' (n = 37) G-CSF from days 15 or 4 of IVAP, respectively, until resolution of severe neutropenia. Study endpoints included time to recovery from neutropenic nadir, duration of neutropenia <0.5 x 10(9)/l, incidence of infectious complications, assessment of variables affecting G-CSF response, clinical outcome and costs. Sixty-five consecutive cases were evaluable. Patients in early G-CSF group recovered significantly faster from the neutropenic nadir (p < 0.002), contracted less infectious complications (p = 0.007), and required less intravenous antibiotic (p = 0.008) and antifungal (p = 0.002) medications. Although these reductions did not compensate for the increased G-CSF treatment cost, the overall supportive care cost was not significantly increased by early G-CSF. Interestingly, T-ALL phenotype (p = 0.02) and higher neutrophil presentation count (p = 0.03) were associated with a shorter neutropenic course even with late G-CSF. Early G-CSF may be a valid approach to mitigate chemotherapy-induced neutropenia of IVAP and other similarly myelosuppressive adult ALL regimens.

Cytosine arabinoside in addition to VCAA‐based protocols for the treatment of canine lymphoma with bone marrow involvement: does it make the difference?

“…In fact, the use of ara‐C in a myeloablative regimen needs to be accompanied by an administration of colony‐stimulating factors, which are expensive. Indeed, to minimize the risk of infection in the induction period, which is the unavoidable complication of aggressive, marrow‐ablative chemotherapy, supportive care including prophylactic parenteral antibiotics and colony‐stimulating factors were administered 27,28 . In particular, growth‐factor support allowed the use of this dose‐intensive regimen at scheduled intervals with acceptable toxicity.…”

Adult acute lymphoblastic leukaemia

“…Three randomised studies demonstrated some advantages for G-CSF-treated patients in terms of CR rate, time to recovery of >1 × 10 9 l −1 neutrophils, incidence of febrile neutropenia and infectious complications, and reduced chemotherapy delays. Since the safety of this regimen and the lack of untoward effects were confirmed, the use of G-CSF at 5 mg/kg as an adjunct to induction therapy is recommended on a type 1 level of evidence [297][298][299], particularly with the more myelotoxic schedules employing anthracyclines on three consecutive days and in the elderly [300]. Delay of G-CSF administration until day 10 did not increase risk of neutropenic complications using the hyper-CVAD regimen [301].…”

Treatment of acute myelogenous leukemia in older adults

“…Studies of cost-effectiveness, using yeast-derived GM-CSF or G-CSF have also shown the benefit of growth factors. [59][60][61][62][63] An exception has been a cost-effectiveness study using the more toxic E. coli-derived GM-CSF in AML. 64 Thus, cytokines should be routinely used, following induction therapy for acute leukemia, at least in those patients with anticipated high risk for therapy-related morbidity.…”