Open AccessRecombinant human thrombopoietin clinical development
Author(s) -
Jones Dennie V.,
Ashby Mark,
Hellmann Sue,
Fyfe Gwen,
VadhanRaj Saroj,
Champlin Richard,
Gajewski James,
Somlo George
Publication year - 1998
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.5530160723
Subject(s) - thrombopoietin , carboplatin , immunology , platelet transfusion , progenitor cell , medicine , platelet , leukapheresis , thrombopoiesis , chemotherapy , hematology , stem cell , biology , oncology , megakaryocyte , haematopoiesis , cd34 , genetics , cisplatin
Patients undergoing anticancer therapy are often at risk for developing severe and/or prolonged posttreatment thrombocytopenia. This can be associated with significant bleeding; currently, it is treated with supportive platelet transfusions. Frequent platelet transfusions can cause alloimmunization which requires HLA‐matched donors and more frequent blood transfusions, and transmission of both viral and bacterial infections via platelet transfusions remains a concern. Furthermore, thrombocytopenia can mandate a decrease in the dose intensity of cytotoxic therapy by causing either delays or dose reductions in therapy administration. An intervention that reduces the risk or shortens the duration of severe thrombocytopenia would represent an important medical advance. Thrombopoietin (TPO), a naturally occurring, glycosylated polypeptide that was cloned by Genentech in 1994, is capable of inducing differentiation of stem cells into megakaryocytes and accelerating the maturation of megakaryocytes, thereby increasing the platelet count. Recombinant human TPO (rHuTPO) is currently undergoing testing in phase 1 and 2 studies in patients receiving myelosuppressive or myeloablative therapy. For the purposes of illustration, preliminary safety and activity data from one ongoing phase 1 myelosuppression trial (rHuTPO in women with advanced gynecologic malignancies receiving carboplatin) and one ongoing phase 1 myeloablation trial (rHuTPO for peripheral blood progenitor cell mobilization prior to myeloablative chemotherapy for high risk breast cancer) will be presented.