Effect of c-mpl ligands after total body irradiation, (TBI) with and without allogeneic hematopoietic stem cell transplantation: Low-dose TBI does not prevent sensitization

Richard A. Nash*, Alessandra Takatu, Ziding Feng, Sherrill Slichter, Kraig Abrams, German Espino, M. John Gass, George E. Georges, Peter A. McSweeney, Howard M. Shulman, Rainer Storb

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

This study investigates the potential role of the recombinant c-mpl ligands (recombinant human thrombopoietin [rhTPO] and pegylated recombinant human megakaryocyte growth and development factor [PEG-rhMGDF]) on the recovery of platelet counts after TBI with and without allogeneic hematopoietic stem cell transplantation (HSCT) in an established canine model. Initially, 3 cohorts, each with 2 nonirradiated dogs, received increasing doses of rhTPO (5 μg/kg per day; 10 μg/kg per day; 20 μg/kg per day) for 7 days to determine the optimal dose. The dose of 10 μg/kg per day of rhATPO was selected for subsequent studies. Ten dogs then received either rhTPO or placebo for 28 days after 200 cGy TBI without HSCT. The rhTPO group had fewer days with platelet counts <20,000/μL (9.8 days versus 17.8 days, P < .05) and significantly increased granulocyte counts (n = 5) compared to the controls (n = 5). RhTPO-specific antibodies developed in 2 dogs, which caused a significant but transient decrease of the platelet counts. Retreatment of these sensitized dogs with rhTPO resulted in profound transient decreases in platelet counts. In the next study, 20 dogs received either PEG-rhMGDF or placebo for 21 days after 920 cGy TBI and allogeneic HSCT. The median time to platelet recovery (>20,000/μL) for the PEG-rhMGDF group (n = 10) was 14.0 days compared to 15.5 days for the control group (n = 10; log rank, P = .35). There were no significant differences in the total time to platelet counts <20,000/μL or in the time to recover neutrophil counts >500/μL. The effects of rhTPO on recovery of platelet and granulocyte counts after sublethal TBI were modest, and no effects of PEG-rhMGDF were observed on hematopoietic recovery after high-dose TBI and allogeneic HSCT. The significant effect that rhTPO-specific antibodies had on the platelet counts may limit the clinical role of recombinant c-mpl ligands unless sensitization can be prevented.

Original languageEnglish (US)
Pages (from-to)360-367
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume8
Issue number7
DOIs
StatePublished - 2002

Keywords

  • Antibodies
  • Dogs
  • PEG-rhMGDF
  • Platelet recovery
  • Sensitization
  • Thrombopoietin
  • Total body irradiation
  • c-mpl ligand
  • rhTPO

ASJC Scopus subject areas

  • Transplantation
  • Hematology

Fingerprint

Dive into the research topics of 'Effect of c-mpl ligands after total body irradiation, (TBI) with and without allogeneic hematopoietic stem cell transplantation: Low-dose TBI does not prevent sensitization'. Together they form a unique fingerprint.

Cite this