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The effect of the GM‐CSF/IL‐3 fusion protein PIXY321 on bone marrow and circulating haemopoietic cells of previously untreated patients with cancer
Author(s) -
Ghielmini Michele,
Pettengell Ruth,
Coutinho Lucia H.,
Testa Nydia,
Crowther Derek
Publication year - 1996
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1996.4731015.x
Subject(s) - bone marrow , haematopoiesis , platelet , granulocyte macrophage colony stimulating factor , progenitor cell , immunology , granulocyte , medicine , andrology , cfu gm , biology , stem cell , cytokine , genetics
This is a phase I/II study of the GM‐CSF/IL‐3 fusion protein PIXY321. Patients were treated with PIXY321 at a daily subcutaneous dose of 500, 750 and 1000 μg/m 2 for 14 d. Side‐effects were mild and consisted mainly of injection‐site reactions and constitutional symptoms. A biphasic modest increase of white blood count (2.5‐fold) and platelets (1–1.5‐fold) was seen, accompanied by an increased bone marrow cellularity and an increase in circulating progenitors. Colony‐forming cells in the blood rose to a median of 184 granulocyte/macrophage‐colony forming cells (GM‐CFC)/ml, eight Mix‐CFC/ml, 250 burst forming units‐erythroid (BFU‐E)/ml and 140 CFU‐megakaryocytes/ml, corresponding to a 10‐, 2.5‐, 8‐ and 30‐fold increase respectively. When seeded for long‐term culture on irradiated bone marrow stroma, the mobilized cells were not able to sustain haemopoiesis in vitro to the same degree as bone marrow. Taken together, these results indicate that PIXY321 has a biological effect in humans more similar to that of IL‐3 than to that of GM‐CSF.