Granulocyte-macrophage colony-stimulating factor in combination with pentavalent antimony for the treatment of visceral leishmaniasis

Abstract

The efficacy of GM-CSF was investigated in 20 neutropenic patients (< 1500 neutrophils/microliters) with acute visceral leishmaniasis due to Leishmania chagasi. Patients were randomized to receive either GM-CSF, 5 micrograms/kg daily (intravenously or subcutaneously), or placebo for ten days, in combination with pentavalent antimony, 10-20 mg/kg daily for 20 days. Neutrophil counts were significantly greater on days 5 and 10 of treatment in the GM-CSF group compared with the placebo group (p < 0.02). Eosinophil and monocyte counts were also significantly increased in the GM-CSF group at day 10 (p < or = 0.03). Interestingly, at day 30, platelet counts were significantly increased in the GM-CSF group on days 5 and 10 (p = 0.04 and 0.02, respectively). Patients in the GM-CSF group experienced fewer secondary bacterial or viral infections than placebo patients. Infections occurred in only three patients given GM-CSF compared with eight patients given placebo (p < 0.04). All patients had complete resolution of disease symptoms at three months. Few adverse events were recorded. GM-CSF given subcutaneously at a dose of 5 micrograms/kg daily for ten days was well tolerated, reversed neutropenia rapidly and reduced the number of secondary infections in patients with leishmaniasis.

Evaluation of adjuvant activity of fractions derived from Agaricus blazei, when in association with the recombinant LiHyp1 protein, to protect against visceral leishmaniasis

“…Some studies have evaluated products containing this immune activity, such as interleukin-12 (Coelho et al, 2003), granulocyte macrophage-colony stimulating factor (Badaró et al, 1994), bacille Calmette-Guérin (Misra et al, 2001), montanide ISA 720 (Tonui et al, 2004), aluminum salts (Misra et al, 2001), monophosphoryl lipid A (Coler et al, 2007), CpG oligodeoxynucleotides (Stacey and Blackwell, 1999), liposomes (Kahl et al, 1989), glucans (Holbrook et al, 1981), Corynebacterium parvum (Carvalho et al, 2007), saponins (Giunchetti et al, 2007), and Freund's adjuvant (Panaro et al, 2001).…”

Immunotherapy for Drug‐Refractory Mucosal Leishmaniasis

“…We selected GM-CSF for reasons of convenience and because of reported adjuvant and antileishmanial activity [38][39][40][41]. Although there is evidence for complementary therapeutic effects of GM-CSF and Sb in leishmaniasis [42][43][44], it is unlikely that GM-CSF alone was responsible for the clinical resolutions seen. Our previous experience using GM-CSF, with or without Sb, to treat patients with refractory ML was not successful (R. Badaro, unpublished observation).…”

Cytological clues of bone marrow findings in Kala‐Azar

“…6 In terms of another mechanism for the myeloid hypoplasia seen in our study, we could mention the work of Raziuadin et al, 8 as highly deficient G.M-CSF production may be implicated in abnormalities in the synthesis of hematopoietic lineages of cells in this disease. Badaro et al 9 used GM.CSF in combination with pentavalent antimony for the treatment of VL.…”