Published online 22 October 2008
Haematologica, Vol 93, Issue 12, 1852-1858 doi:10.3324/haematol.13033
Copyright © 2008 by Ferrata Storti Foundation
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Web of Science (1)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dunbar, E. M.
Right arrow Articles by Reddy, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dunbar, E. M.
Right arrow Articles by Reddy, V.

Stem Cell Transplantation

The relationship between circulating natural killer cells after reduced intensity conditioning hematopoietic stem cell transplantation and relapse-free survival and graft-versus-host disease

Erin M. Dunbar1, Mathew P. Buzzeo3, Jeff B. Levine1, Jesse D. Schold2, Herwig-Ulf Meier-Kriesche2, Vijay Reddy1

1 Division of Hematology/Oncology, Department of Medicine, University of Florida, Gainesville, Florida
2 Division of Nephrology, Hypertension and Renal Transplantation; Department of Medicine, University of Florida, Gainesville, Florida
3 University of South Florida College of Medicine, Tampa, FL, USA

Correspondence: Vijay Reddy, M.D., Ph.D., 2501 North Orange Ave., Suite 581, Orlando, FL 32804 USA., E-mail:vijay.reddy.md{at}flhosp.org

Background: Natural killer cells are known to have anti-tumor activity in haploidentical hematopoietic stem cell transplantation. We hypothesized that reconstituted circulating natural killer cells may be associated with improved relapse-free survival after HLA-matched hematopoietic stem cell transplantation.

Design and Methods: Serial peripheral blood absolute natural killer cell counts were prospectively measured by flow cytometry of lymphocytes expressing CD56 and CD16 in 167 patients. Cluster analysis was used at engraftment and 60 days post-transplant to distinguish patients with high and low absolute natural killer cell counts. At engraftment 80 patients had high counts (> 22.2/mm3) and 43 had low counts. At 60 days post-transplant 84 patients had high counts (> 18.2/mm3) and 38 had low counts. The primary study end-points were death, relapse and acute graft-versus-host disease. The median follow-up was 373 days (range, 67–1767).

Results: Among patients given reduced intensity conditioning, a low absolute natural killer cell count at 60 days post-transplant was independently associated with relapse [adjusted hazard ratio (AHR) = 28.4, 95% confidence interval (CI) 4.3–186.4] and death (AHR = 17.5, 95% CI 4.3–71.3). Furthermore, patients given reduced intensity conditioning who had a high absolute natural killer cell count at 60 days had a significantly better 1-year survival than those with a low count by Kaplan-Meier analysis (83% vs. 11%, p<0.001). Multivariate analysis confirmed that low 60-day absolute natural killer count in patients given reduced intensity conditioning was independently associated with an increase in relapse or death (AHR = 20.22, 95% CI 4.76–85.40). In contrast, there was no significant association between 60-day absolute natural killer cell counts and clinical outcomes in patients receiving myeloablative conditioning. There was no significant association between absolute natural killer cell count and graft-versus-host disease.

Conclusions: High natural killer cell reconstitution is associated with reduced relapse and death without an increased incidence of graft-versus-host-disease after reduced intensity conditioning allogeneic hematopoietic stem cell transplantation. Measuring reconstituted natural killer cells expressing CD56+/CD16+ post-transplant may have novel prognostic and therapeutic implications.

Key words: natural killer cells, hematopoietic stem cell transplantation, relapse-free survival, graft-versus-host-disease.