Use of a T cell-specific monoclonal antibody, T10B9, in a novel allogeneic stem cell transplantation protocol for hematologic malignancy high-risk patients

John S. Thompson, Claire Pomeroy, Richard J. Kryscio, Stephen A. Brown, Donna Reece, Rita Kramer, Dianna S. Howard, Gary vanZant, Suzanne Humphries, Gordon Phillips

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

To reduce the toxicity of traditional conditioning regimens for allogeneic stem cell transplantation (allo-SCT), we used single-agent chemotherapy conditioning with either busulfan (total cumulative dose, 16 mg/kg) or melphalan (200 to 240 mg/m2), followed by the anti-T cell-specific monoclonal antibody T10B9 (MEDI-500) daily for 3 days. T cell-replete SCT was performed from HLA-identical sibling donors. Acute graft-versus-host disease (aGVHD) prophylaxis consisted of 7 additional days of T10B9 and delayed onset of cyclosporine (ie, on day +4 or +5). Twenty-six high-risk hematologic malignancy patients were entered onto this study. All 24 patients who survived longer than 8 days engrafted, although 1 patient experienced late graft failure. Deaths occurred in 21 of 26 patients because of infection (n = 7), progression/recurrence of primary disease (n = 6), aGVHD (n = 4), regimen-related toxicity (n = 1), and other causes (n = 3). Five of these patients are enjoying disease-free survival with a median survival of 1193 days after allo-SCT. The conditioning regimen induced modulation of surface expression of CD3 (but not CD4 or CD8) and was associated with decreasing tumor necrosis factor-α (but not interleukin-6) serum levels. In conclusion, single-agent chemotherapy conditioning with T10B9 produced durable engraftment and long-term survival in some patients who would not have qualified for a traditional allo-SCT.

Original languageEnglish (US)
Pages (from-to)858-866
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume10
Issue number12
DOIs
StatePublished - Dec 2004
Externally publishedYes

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Keywords

  • Acute graft-versus-host disease
  • Anti-T cell monoclonal antibody MEDI-500 (T10B9)
  • IL-6
  • Regimen-related toxicity
  • Stem cell transplantation
  • TNF-α

ASJC Scopus subject areas

  • Transplantation

Cite this

Thompson, J. S., Pomeroy, C., Kryscio, R. J., Brown, S. A., Reece, D., Kramer, R., Howard, D. S., vanZant, G., Humphries, S., & Phillips, G. (2004). Use of a T cell-specific monoclonal antibody, T10B9, in a novel allogeneic stem cell transplantation protocol for hematologic malignancy high-risk patients. Biology of Blood and Marrow Transplantation, 10(12), 858-866. https://doi.org/10.1016/j.bbmt.2004.09.006