The haemopoietic effects of thrombopoietin administered post-myelosuppressive carboplatin therapy compared to either pre- and post- or pre-chemotherapy.
Balb/c mice (n = 10) were treated with 50 microg/kg recombinant human thrombopoietin (rhTPO) or placebo control by subcutaneous injection daily for 5 d before (pre), or 8d after (post), or 5 d before and 8d after (pre/post) carboplatin (125 mg/kg). RhTPO given post significantly abrogated the platelet (PLT) nadir (413.0 +/- 52.0 v 42.0 +/- 6.0 (x10(9)/l), P<0.01), reduced days to mean PLT recovery (2 v 8d), and increased progenitor (CFU-Meg) colony formation (74.7 +/- 6.7 v 40.7 +/- 3.3 (colonies/10(5) cells), P<0.001) compared to controls. Further, rhTPO given pre/post also significantly abrogated the PLT nadir (132 +/- 29 v 42.0 +/- 6.0 (x10(9)/l), P<0.05), increased megakaryocytes per high-powered field (MHPF) (5.67 +/- 0.9 v 0.33 +/- 0.3, P<0.001) and CFU-Meg (137.7 +/- 13.9 v 40.7 +/- 3.3, P<0.001) compared with controls. However, when comparing the three treatment groups, animals receiving rhTPO post exhibited significantly higher PLT nadirs (413.0 +/- 52.0 v 190 +/- 29 and 132 +/- 29 (x 10(9)/l), P<0.01) and increased CFU-GM (93.7 +/- 10.7 v 20.33 +/- 0.9 and 14.7 +/- 1.45, P< 0.001). All rhTPO groups experienced an abrogation of the haematocrit (HCT) nadir (P< 0.01), although, only the post cohort had a reduction in the days to mean HCT recovery (2 v 12d, P<0.01). These results suggested that post therapeutic rhTPO (post) appears to be more effective in abrogating the platelet nadir and enhancing platelet and HCT recovery following myelosuppressive chemotherapy, than either prophylactic or pre- and post-rhTPO therapy.
Division of Hematology/Oncology and Blood and Marrow Transplantation, Children's Hospital of Orange County, Orange, California, USA.
C
C
van de Ven
G W
GW
Fernandez
T
T
Herbst
A
A
Knoppel
S T
ST
Kulczyk
M S
MS
Cairo
D000818:Animals; D001855:Bone Marrow Diseases / Q000139:chemically induced*; D016190:Carboplatin / Q000009:adverse effects*; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006400:Hematocrit; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009503:Neutropenia / Q000188:drug therapy; D011994:Recombinant Proteins; D013921:Thrombocytopenia / Q000188:drug therapy*; D013926:Thrombopoietin / Q000627:therapeutic use*; D013997:Time Factors
D011994:Recombinant Proteins; D013926:Thrombopoietin; D016190:Carboplatin