Thrombopoietin: an update on therapeutic potential.
Thrombopoietin (TPO), the central regulator of megakaryocytopoiesis, was first identified in 1994 and since then much has been learnt about megakaryocyte and platelet physiology. Two forms of TPO have entered clinical trials, the full length recombinant version (rhTPO) and a truncated form (megakaryocyte growth and development factor, MGDF). Both have equivalent biological activity in preclinical studies and both have been demonstrated to have potent biological activity in humans. TPO and MGDF administration cause a dose-dependent increase in platelet count with no effect on white cell count or haematocrit. These platelets are morphologically and functionally normal. When administered following myelosuppressive chemotherapy, MGDF and TPO significantly enhance platelet recovery, although scheduling in relation to chemotherapy may be important in optimising the full effects. TPO and MGDF mobilise progenitor cells of multiple haematopoietic lineages and may enhance the effects of filgrastim on peripheral blood progenitor cell levels after chemotherapy. Both forms of TPO are well tolerated and cause few acute toxicities. Numerous studies are underway to help determine the precise role of TPO in clinical practice.
Underhill
C R
CR
Centre for Developmental Cancer Therapeutics, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Basser
R L
RL