Inhibition of CFU-C growth by VP-16 containing plasma samples obtained from patients after conditioning therapy for bone marrow transplantation

Bone Marrow Transplant. 1995 Jan;15(1):9-15.

Abstract

The introduction of VP-16 into high-dose therapy regimens used for conditioning before BMT or PBSCT has resulted in higher remission rates and prolonged disease-free survival, even in high risk patients. VP-16 levels have been measured in plasma at the time of transplantation. The question is, is there a biological activity that corresponds with the risk of delayed engraftment or graft failure? We investigated the inhibitory effects of plasma samples obtained from patients under high-dose VP-16 therapy on the growth of human bone marrow progenitor cells. Bone marrow cells from healthy donors were exposed to the plasma samples and seeded into methylcellulose-culture (CFU-C-assay). We found a dose dependent CFU-C inhibition related to VP-16 plasma levels at the time of transplantation (k = 0.769, P < 0.01). There were signs of a correlation between CFU-C growth inhibition at the time of BMT and haematological recovery (k = 0.656, P < 0.05) between CFU-C inhibition and the time until leucocytes reached 0.2 x 10(9)/l. Patients with CFU-C growth inhibition at the time of BMT may show delayed engraftment of leucocytes and that there might be a correlation with VP-16 levels, but further investigation is necessary to determine the significance of the latter thesis and if VP-16 plasma levels could lead to failure of engraftment. We recommend a minimum time interval between VP-16 infusion and graft transplantation of 72 h.

MeSH terms

  • Adolescent
  • Adult
  • Bone Marrow Transplantation*
  • Child
  • Etoposide / blood
  • Etoposide / pharmacology*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects*
  • Humans
  • Infusions, Intravenous
  • Middle Aged
  • Neoplasms / blood*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Tumor Cells, Cultured
  • Tumor Stem Cell Assay

Substances

  • Etoposide