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Haemopoietic progenitor and myeloid cell kinetics in humans treated with interleukin‐3 and granulocyte/macrophage colony‐stimulating factor in combination
Author(s) -
Lord Brian I.,
Testa Nydia G.,
Bretti Sergio,
Chang James,
Demuynck Hilda,
Coutinho Lucia,
De Campos Edson,
Fitzsimmons Lesley,
Howard Scarffe J.
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910590409
Subject(s) - bone marrow , progenitor cell , granulopoiesis , myeloid , immunology , myelopoiesis , interleukin 3 , medicine , endocrinology , biology , andrology , stem cell , t cell , immune system , antigen presenting cell , microbiology and biotechnology
Patients with advanced adenocarcinoma of the colon, rectum or pancreas were entered into trials for evaluation of treatment with sequential doses of IL‐3 and GM‐CSF. They received 0.25 to 5μgIL‐3/kg/d for up to 7days, followed by I μgGM‐CSF/kg/day for a maximum of 10 further days. We assessed the kinetics of bone‐marrow cell proliferation and of blood production using tritiated thymidine labelling in vitro and in vivo . Megakaryocytic‐CFC were unaffected but proliferation rates of GM‐CFC and BFU‐E were increased. Progenitor cells were mobilized (12‐fold over baseline) into the peripheral blood. The proliferative activity of maturing cells in the marrow was increased (cell‐cycle times were reduced by at least 30%). This translated into amplified blood cell production (WCC ∼30 × 10 9 /1), a 2.2‐fold increase in platelet counts and significant eosinophilia. Newly generated neutrophils appeared in the circulation at the normal time and their peripheral half‐life was also normal. The calculated 3.2‐fold amplification in neutrophil production required nearly 2 extra divisions in the marrow, shared between the progenitors and the proliferating granulocytic cells. The results were compared with those of a previous trial using GM‐CSF only, although at a 10‐fold higher dose level. Comparable levels of peripheral neutrophils were obtained in both trials but significant ineffective granulopoiesis developed in the earlier study. This was overcome in the present study, the priming dose of IL‐3 apparently giving the latitude to utilize lower doses of GM‐CSF with less risk of complications. © 1994 Wiley‐Liss, Inc.