Host lymphocyte depletion as a strategy to facilitate early full donor chimerism after reduced-intensity allogeneic stem cell transplantation

Rachel B. Salit, Daniel H. Fowler, Robert M. Dean, Steven Z. Pavletic, Frances T. Hakim, Seth M. Steinberg, Nancy T. Hardy, Claude Sportes, Ronald E. Gress, Michael R. Bishop

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (RIC-alloHSCT) is associated with lower toxicity but higher rates of prolonged mixed chimerism than myeloablative conditioning. Decreased pretransplantation host T cell numbers are associated with less graft rejection and early full donor chimerism. To compensate for variability in pretransplantation host lymphocyte numbers and facilitate the achievement of rapid full donor chimerism, we tested a strategy of targeted lymphocyte depletion (TLD) using chemotherapy at conventional doses to provide cytoreduction and lymphocyte depletion before RIC-alloHSCT. In our study, 111 patients with advanced hematologic malignancies received 1 to 3 cycles of conventional-dose chemotherapy to reduce circulating lymphocytes to a predetermined level. Patients then underwent RIC-alloHSCT from HLA-matched siblings. Patients received a median of 2 cycles of TLD chemotherapy, resulting in a median 71% decline in CD4+ count. All patients engrafted; there were no late graft failures. By day+14, median CD3+ chimerism was 99% donor and was significantly associated with lower post-TLD CD4+ counts (P=012). One- and 5-year treatment-related mortality were 15% and 21%, respectively. At 1-year follow-up, 66% of patients had achieved complete remission (CR) of which 92% were not in CR at the time of transplantation. Overall survival at 1 and 5years post transplantation were 66% and 47%, respectively.

Original languageEnglish (US)
Pages (from-to)1509-1513
Number of pages5
JournalBiology of Blood and Marrow Transplantation
Volume19
Issue number10
DOIs
StatePublished - Oct 1 2013

Keywords

  • Engraftment
  • Lymphocyte depletion
  • Reduced-intensity transplantation

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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    Salit, R. B., Fowler, D. H., Dean, R. M., Pavletic, S. Z., Hakim, F. T., Steinberg, S. M., Hardy, N. T., Sportes, C., Gress, R. E., & Bishop, M. R. (2013). Host lymphocyte depletion as a strategy to facilitate early full donor chimerism after reduced-intensity allogeneic stem cell transplantation. Biology of Blood and Marrow Transplantation, 19(10), 1509-1513. https://doi.org/10.1016/j.bbmt.2013.08.001