Cytopenia and leukocyte recovery shape cytokine fluctuations after myeloablative allogeneic hematopoietic stem cell transplantation

Jan Joseph Melenhorst, Xin Tian, Dihua Xu, Netanya G. Sandler, Philip Scheinberg, Angelique Biancotto, Priscila Scheinberg, John Phil McCoy, Nancy F. Hensel, Zach McIver, Daniel C. Douek, Austin John Barrett

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Background Allogeneic hematopoietic stem cell transplantation is associated with profound changes in levels of various cytokines. Emphasis has been placed on conditioning-associated mucosal damage and neutropenia and associated bacterial translocation as the initiating conditions predisposing to acute graft-versus-host disease. The post-transplant period is, however, also associated with increases in certain homeostatic cytokines. It is unclear how much the homeostatic drive to lymphocyte recovery and the production of cytokines from the engrafting donor immune system determine cytokine fluctuations in the peri- and immediate post-transplant period. The aim of this study was to examine the contributions of the conditioning regimen, donor engraftment, infections, and graft-versus-host disease to fluctuations in cytokines involved in homeostasis and inflammation. Design and Methods We examined the levels of 33 cytokines in relation to peri- and post-transplant events such as conditioning regimen, chimerism, and acute graft-versus-host disease in myeloablative, non-T cell-replete HLA-identical sibling donor stem cell transplantation for hematologic malignancies. Results We identified two cytokine storms. The first occurred following conditioning and reached peak levels when all the leukocytes were at their lowest concentrations. The second cytokine storm occurred concurrently with hematopoietic reconstitution and subsided with the achievement of full donor lymphocyte chimerism. Conclusions Our results indicate that both recipient-related and donor-related factors contribute to the changes in cytokine levels in the recipient following allogeneic hematopoietic stem cell transplantation. The study reported here was performed using plasma samples drawn from patients enrolled in the ClinicalTrials.gov-registered trials NCT00467961 and NCT00378534

Original languageEnglish (US)
Pages (from-to)867-873
Number of pages7
JournalHaematologica
Volume97
Issue number6
DOIs
StatePublished - Jun 1 2012

Keywords

  • Allogeneic stem cell transplantation
  • Conditioning
  • Cytokines
  • Post-transplantation

ASJC Scopus subject areas

  • Hematology

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    Melenhorst, J. J., Tian, X., Xu, D., Sandler, N. G., Scheinberg, P., Biancotto, A., Scheinberg, P., McCoy, J. P., Hensel, N. F., McIver, Z., Douek, D. C., & Barrett, A. J. (2012). Cytopenia and leukocyte recovery shape cytokine fluctuations after myeloablative allogeneic hematopoietic stem cell transplantation. Haematologica, 97(6), 867-873. https://doi.org/10.3324/haematol.2011.053363