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Blood, 15 November 2002, Vol. 100, No. 10, pp. 3457-3469
REVIEW ARTICLE
Recombinant human thrombopoietin: basic biology and
evaluation of clinical studies
David J. Kuter and
C. Glenn Begley
From the Hematology/Oncology Unit, Massachusetts
General Hospital, Harvard Medical School, Boston, MA; and the Centre
for Child Health Research, The University of Western Australia and
Western Australian Institute for Medical Research, Perth, Western
Australia.
Thrombocytopenia is a common medical problem for which the
main treatment is platelet transfusion. Given the increasing use of
platelets and the declining donor population, identification of a safe
and effective platelet growth factor could improve the management of
thrombocytopenia. Thrombopoietin (TPO), the c-Mpl ligand, is the
primary physiologic regulator of megakaryocyte and platelet
development. Since the purification of TPO in 1994, 2 recombinant forms
of the c-Mpl ligand recombinant human thrombopoietin (rhTPO) and
pegylated recombinant human megakaryocyte growth and development factor
(PEG-rHuMGDF)have undergone extensive clinical investigation. Both
have been shown to be potent stimulators of megakaryocyte growth and
platelet production and are biologically active in reducing the
thrombocytopenia of nonmyeloablative chemotherapy. However, neither TPO
has demonstrated benefit in stem cell transplantation or leukemia
chemotherapy. Other clinical studies have investigated the use of TPO
in treating chronic nonchemotherapy-induced thrombocytopenia associated
with myelodysplastic syndromes, idiopathic thrombocytopenic purpura,
thrombocytopenia due to human immunodeficiency virus, and liver
disease. Based solely on animal studies, TPO may be effective in
reducing surgical thrombocytopenia and bleeding, ex vivo expansion of
pluripotent stem cells, and as a radioprotectant. Ongoing and
future studies will help define the clinical role of recombinant TPO
and TPO mimetics in the treatment of chemotherapy- and
nonchemotherapy-induced thrombocytopenia.
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