Physiology and clinical applications of platelet growth factors

Current Opinion in Hematology

Volumn 6, Issue 3, 1999, Pages 127-134

  Harker, Laurence A ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PLATELET DERIVED GROWTH FACTOR;

ANIMAL CELL; ANTIBODY PRODUCTION; ARTICLE; CELL GROWTH; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MEGAKARYOPOIESIS; NONHUMAN; PHYSIOLOGY; PRIORITY JOURNAL; RISK BENEFIT ANALYSIS; SIGNAL TRANSDUCTION; STEM CELL; THROMBOCYTE COUNT; THROMBOCYTE FUNCTION;

CONTROLLED CLINICAL TRIALS; HUMANS; PLATELET-DERIVED GROWTH FACTOR; POLYETHYLENE GLYCOLS; RECOMBINANT PROTEINS; THROMBOPOIETIN;

EID: 0032868726     PISSN: 10656251     EISSN: None     Source Type: Journal    
DOI: 10.1097/00062752-199905000-00002     Document Type: Article

References (66)

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57. 57 Basser RL, Rasko JEJ, Clarke K, Cebon J, Green MD, Hussein S, et al.: Thrombopoietic effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) in patients with advanced cancer. Lancet 1996, 348:1279-1281.
58. 58 Basser RL, Rasko JEJ, Clarke K, Cebon J, Green MD, Grigg AP, et al.; Randomized, blinded, placebo-controlled phase I trial of pegylated recombinant human megakaryocyte growth and development factor with filgrastim after dose-intensive chemotherapy in patients with advanced cancer. Blood 1997, 89:3118-3128. This is a comprehensive, carefully performed, controlled clinical trial evaluating PEG-rHuMGDF in combination with G-CSF in cancer patients receiving dose-intensive myelosuppressive chemotherapy. Because this protocol is similar in design to the positive study reported by Fanucchi et al. (N Engl J Med 1997, 336:404-409), it seems that even minor changes in the protocol would yield positive outcomes. The study design used by Tepler et al. (Blood 1996, 87:3607-3614) in evaluating interleukin-11 appears to be more efficient.
59. 59 Beveridge R, Schuster M, Waller E, Stuart R, Abboud C, Cruickshank S, et al.: Randomized, double-blind, placebo-controlled trial of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) in breast cancer patients (Pts) following autologous bone marrow transplanlation (ABMT) [abstract]. Blood 1997, 90:580a. The effects of PEG-rHuMGDF on persistent thrombocytopenia were evaluated in a controlled clinical trial involving breast cancer patients receiving dose-intensive chemotherapy and conventional autologous bone marrow transplantation. Treatment with PEG-rHuMGDF was clearly beneficial. The relevance of this study is challenged by change in practice away from using bone marrow as the source of hematopoietic stem cells to achieving stem cell rescue using autologous peripheral blood progenitor cells.
60. 60 Bolwell B, Vredenburgh J, Overmoyer B, Gilbert C, Chap L, Menchaca D, et al.: Safety and biologic effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) in breast cancer patients following autologous peripheral blood progenitor cell transplantation (PEPC) [abstract]. Blood 1997, 90:171a. These data clearly demonstrate the benefits of peripheral blood progenitor stem cell rescue over conventional bone marrow transplantation. Indeed, Glaspy et al. (Blood 1997, 90[suppl1]:580a) state that recovery after transplantion of the spectrum of blood-derived progenitor cells is so brisk that there are no clinically relevant benefits produced by administering substantial doses of PEG-rHuMGDF either before or after chemotherapy.
61. 61 Glaspy J, Vredenburgh J, Demetri GD, Chap L, Gilbert C, Overmoyer B, et al.: Effects of PEGylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) before high dose chemotherapy (HDC) with peripheral blood progenitor cell (PBPC) support [abstract]. Blood 1997, 90(suppl 1):580a.
62. 62 Cole JL, Marzec UM, Gunthel CJ, Karpatkin S, Waller EK, Sundell IB, et al.: Ineffective platelet production in thrombocytopenic HIV-infected patients. Blood 1998, 91:3239-3246.
63. 63 Harker LA, Marzec UM, Novembre F, Sundell IB, Waller EK, Karpatkin S, et al.: Treatment of thrombocytopenia in chimpanzees infected with human immunodeficiency virus by pegylated recombinant human megakaryocyte growth and development factor. Blood 1998, 91:4427-4433.
64. 64 Harker LA, Carter RA, Marzec UM, Cherry JK, Gunthel CJ, Lennox JL, et al.: Correction of thrombocytopenia and ineffective platelet production in patients infected with human immunodeficiency virus (HIV) by PEG-rHuMGDF therapy [abstract]. Blood 1998, 92(suppl I):707a. These remarkable results show that treating HIV-infected thrombocytopenic patients with PEG-rHuMGDF is highly efficacious and safe. The surprising outcome is the antiapoptotic mechanism underlying the benefit. However, it will be necessary to complete these studies using a different platelet growth factor because PEG-rHuMGDF will not be available. Presumably, the lack of antibody formation against PEG-rHuMGDF is related to the immunosuppressed state of HIV-infected patients.
65. 65 Kuter D, McCullough J, Romo J, DiPersio J, Peterson R, Armstrong S, et al.: Treatment of platelet (PLT) donors with pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) increases circulating PLT counts (CTS) and PLT apheresis yields and increases platelet increments in recipients of PLT transfusions [abstract]. Blood 1997, 90:579a.
66. 66 Tepler I, Elias L, Smith W: A randomized placebo-controlled trial of recombinant IL-11 in cancer patients with severe thrombocytopenia due to cancer. Blood 1996, 87:3607-3614.