Concurrent RhGM‐CSF does not offset myelosuppression from intensive chemotherapy: Randomized placebo‐controlled study in childhood acute lymphoblastic leukemia

Abstract

To determine whether recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) can offset the myelosuppressive effects of intensive chemotherapy, we carried out a double-blind placebo-controlled trial in which 40 patients with acute lymphoblastic leukemia (ALL) were randomized into two groups of 20 each. One group received rhGM-CSF (5.5 micrograms/kg SC) coadministered with chemotherapy and the other, placebo coadministered with chemotherapy from day 5 to day 11 and from day 19 to day 25 of the 28-day intensification phase of our institutional high-risk protocol for childhood ALL. The results indicate that, at the dose and schedule used, rhGM-CSF did not prevent neutropenia or shorten the number of days required to complete this phase of therapy. In addition, the treated and placebo groups showed no significant difference in absolute neutrophil counts, number of days with neutropenia, number of days with fever, number of days spent in hospital, or number of days on antibiotics during the 28-day study period. There was also no difference between the two groups in the number, type, or severity of infectious episodes. Two of 20 patients in the treatment group have relapsed, whereas none of the patients in the placebo group has yet relapsed (follow-up: 3-37 months), but these events were not statistically significant. We conclude that treatment with rhGM-CSF at the dose and schedule employed is not clinically beneficial.

A randomised study of prophylactic G‐CSF following MRC UKALL XI intensification regimen in childhood ALL and T‐NHL

“…This was in keeping with the study by Calderwood et al [17] which also failed to show any advantage in the use of Rh-GM-CSF given concomitantly with chemotherapy in 40 patients with poor-prognosis ALL undergoing intensi®cation therapy. Prophylactic use of G-CSF in the treatment of solid tumours in childhood has shown little bene®t.…”

Cytoprotection in the treatment of pediatric cancer: Review of current strategies in adults and their application to children

“…Rescue therapy with a CSF accelerates neutrophil recovery by stimulating the growth of hematopoietic stem cells. However, it has been shown both in adults [36] and in children with ALL receiving intensive chemotherapy [37] that simultaneous administration of CSF with cytotoxic treatment is ineffective or may even result in an exacerbation of neutropenia and thrombocytopenia.…”

Recommendations on the use of colony-stimulating factors in children: conclusions of a European panel

“…Two randomised placebo-controlled studies have examined the eects of CSFs in a total of 72 children with ALL: neither G-CSF (10 lg/kg per day) nor GM-CSF (5 lg/kg per day) reduced the incidence of chemotherapy-associated infections [14,20]. However, a recent interim report of a randomised trial involving 34 children (aged 2±16 years) with high-risk ALL showed that G-CSF (5 lg/kg per day) administration between chemotherapy courses (total of 258 courses) was eective in reducing the incidence (17% vs. 40% with placebo, P 0.007) and duration (6.2 vs. 20.3 days, P 0.02) of febrile neutropenia, the number of culture-proven infections (8% vs. 15%, P 0.04), and duration of antibiotic administration (12.5 days vs. 20.9 days, P 0.02).…”