Granulocyte-macrophage colony-stimulating factor/interleukin-3 fusion protein versus granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for non-Hodgkin's lymphoma: results of a randomized double-blind trial.

Vose, Julie M.; Pandite, Arundathy; Beveridge, Roy; Geller, Robert B.; Schuster, Michael W.; Anderson, James; LeMaistre, CF; Ahmed, Tauseef; Grañena, A; Keating, Armand; Rañada, J.M. Fernández; Stiff, P. J.; Tabbara, Imad A.; Longo, Walter L.; Copelan, Edward A.; Nichols, Craig R.; Smith, Audrey L.; Topolsky, David; Bierman, Philip J.; Lebsack, M. E.; Lange, Mary; Garrison, Leslie

doi:10.1200/jco.1997.15.4.1617

Cited by 19 publications

(11 citation statements)

References 18 publications

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“…[51][52][53][54] However, PIXY-321 (an IL-3/GM-CSF fusion protein) had little impact on platelet transfusion requirements after transplantation. 55 Sequential IL-3/ GM-CSF (IL-3 doses Յ 1 g/kg per day) also has been tested in a small group of patients with MDS (n ϭ 9 patients). 56 A clinically relevant response was seen in only one patient with thrombocytopenia.…”

Section: Discussionmentioning

confidence: 99%

Sequential interleukin 3 and granulocyte‐macrophage–colony stimulating factor therapy in patients with bone marrow failure with long‐term follow‐up of responses

Talpaz

Champlin

et al. 2003

Cancer

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BACKGROUNDInterleukin‐3 (IL‐3) and granulocyte‐macrophage–colony stimulating factor (GM‐CSF) have synergistic, hematopoietic growth‐promoting activity in preclinical studies. Because of the paucity of effective therapies for patients with chronic bone marrow failure states, the authors studied the biologic activity of sequential IL‐3/GM‐CSF in such patients.METHODSIL‐3 was given subcutaneously for 5 days (at escalating doses of 0.15 μg/kg, 0.3 μg/kg, 0.6 μg/kg, 1.2 μg/kg, 2.5 μg/kg, 5.0 μg/kg, 10.0 μg/kg, or 15.0 μg/kg per day), and GM‐CSF for was given subcutaneously for 9 days (at a dose of 5 μg/kg per day; Phase I 3 + 3 design) followed by 14 days of rest (total, 2 courses), then maintenance therapy.RESULTSThe majority of 38 evaluable patients had aplastic anemia or myelodysplastic syndrome. Most patients (79%) had neutrophil responses. Ten patients (26%), all of whom were treated with IL‐3 doses ≥ 1.2 μg/kg per day, had platelet responses, with a median increase of 132 × 109/L (range, 41–180 × 109/L) over baseline in responders. Six patients (16%) had trilineage recovery, which could be durable (the longest ongoing at 6.5 years after therapy completion). The most common toxicities were low‐grade fever, headache, and fatigue. The maximum tolerated doses were IL‐3 at 10 μg/kg per day and GM‐CSF at 5 μg/kg per day.CONCLUSIONSSequential IL‐3/GM‐CSF effectively raised blood counts in some patients with bone marrow failure at doses that were tolerated well. These results indicate that early‐acting growth factors can induce durable, multilineage responses in a subset of individuals with bone marrow failure. Cancer 2003. © 2003 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

Sequential interleukin 3 and granulocyte‐macrophage–colony stimulating factor therapy in patients with bone marrow failure with long‐term follow‐up of responses

Talpaz

Champlin

et al. 2003

Cancer

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“…[136] The fusion protein PIXY321 is significantly more potent than either GM-CSF or IL-3 alone or in combination in stimulating the in vitro growth of erythroid, monocyte, granulocyte and megakaryocyte progenitor cells. [137] However, in a phase III study comparing PIXY321 administration and GM-CSF administration in adults, [138] and in 2 studies with children, [92,139] no significant advantages were found for PIXY321. Although PIXY321 is not currently being manufactured, it is a good example of the elusiveness of demonstrating the clinical effectiveness of HGFs despite a good scientific rationale and encouraging phase I results.…”

Section: Other Colony-stimulating Factorsmentioning

confidence: 93%

Haemopoietic Growth Factors in Paediatric Oncology

Wagner

Furman

2001

Paediatric Drugs

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Recombinant haemopoietic growth factors (HGFs) are an attractive adjunct to reduce morbidity from chemotherapy regimens and their use has become widespread in paediatric oncology. Although patients receiving HGFs often have faster haematological recovery after intensive chemotherapy, this does not always translate into meaningful clinical benefits. This article reviews the clinical effectiveness of HGFs in a variety of different contexts. Most published studies have used granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) as prophylaxis to ameliorate the subsequent neutropenia following intensive chemotherapy. These 2 agents have also been used to mobilise peripheral blood stem cells for autologous transplantation. HGFs specific for anaemia and thrombocytopenia are currently in paediatric clinical trials and it is hoped that the proper context and administration strategy can be found to make their use clinically effective. This article also reviews data on toxicity, specifically focusing on differences between various formulations of growth factors. HGFs are expensive, and cost-benefit analyses reviewed in this article give an important perspective on the financial aspects of paediatric cancer care. Because HGFs do not benefit every child receiving chemotherapy and overuse increases costs and may result in unnecessary adverse effects, evidence-based guidelines for their rational use in paediatric oncology are proposed.

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“…In late clinical trials, PIXY321 improved neutrophil engraftment but not platelet mobilization compared with GM-CSF treatment in bone marrow transplantation for non-Hodgkin's lymphoma (52) (32). Reduced megakaryocytopoiesis associated with chemotherapy was often clinically insignificant because of the low platelet threshold required to prevent bleeding (52).…”

Section: Gm-csf and Il-3 Fusion Proteinmentioning

confidence: 99%

“…Reduced megakaryocytopoiesis associated with chemotherapy was often clinically insignificant because of the low platelet threshold required to prevent bleeding (52). The cost of production of PIXY321 and lack of additional clinical or economic advantage over GM-CSF halted further development of this unique molecule.…”

Section: Gm-csf and Il-3 Fusion Proteinmentioning

confidence: 99%

Development of a Recombinant Growth Factor and Fusion Protein: Lessons from GM-CSF

Schuh

Morrissey²

1999

Toxicol Pathol

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Several colony stimulating factors (CSFs) and cytokines have been successfully used to mobilize hematopoietic cells during myeloablative therapy, bone marrow failure, and transplantation and to provide supportive treatment during sepsis. The use of yeastderived recombinant human granulocyte-macrophage CSF (rhuGM-CSF) and its interleukin-3 fusion protein, PIXY321, provides an example of issues associated with development programs for recombinant hematopoietic growth factors.

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Granulocyte-macrophage colony-stimulating factor/interleukin-3 fusion protein versus granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for non-Hodgkin's lymphoma: results of a randomized double-blind trial.

Cited by 19 publications

References 18 publications

Sequential interleukin 3 and granulocyte‐macrophage–colony stimulating factor therapy in patients with bone marrow failure with long‐term follow‐up of responses

Sequential interleukin 3 and granulocyte‐macrophage–colony stimulating factor therapy in patients with bone marrow failure with long‐term follow‐up of responses

Haemopoietic Growth Factors in Paediatric Oncology

Development of a Recombinant Growth Factor and Fusion Protein: Lessons from GM-CSF

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