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

Abstract

The online version of this article has a Supplementary Appendix. BackgroundAllogeneic 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 MethodsWe 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. ResultsWe 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. ConclusionsOur 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

Neutrophils differentially attenuate immune response toAspergillusinfection through complement receptor 3 and induction of myeloperoxidase

“…Cytokinemia along the spectrum surmounting to a cytokine storm have been reported in myeloablative HSCT (Melenhorst et al, ). The actual mechanisms behind this phenomenon remain to be fully understood, given the competing complexity of the primary disease and patient host factors, as well as the chemotherapeutic/conditioning regimens used (Dickinson & Holler, ).…”

“…Cytokinemia along the spectrum surmounting to a cytokine storm have been reported in myeloablative HSCT (Melenhorst et al, 2012).…”

Infusion of CD3/CD28 costimulated umbilical cord blood T cells at the time of single umbilical cord blood transplantation may enhance engraftment

“…2B). These elevated cytokines preceded the infusion of T cells and may be attributable to myeloablation and lymphodepletion [20]. However, of the two patients with evaluable samples prior to initiation of the conditioning regimen, both had high levels of BAFF and FLT3L, suggesting this milieu may be intrinsic to hematologic malignancies and/or their treatment [21].…”

National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Subsequent Neoplasms Working Group Report

“…The surge of interleukin (IL)-15 after HCT promotes rapid T-cell clonal expansion leading to a restricted T-cell repertoire. 85,86 Expanding donor T-cells often have the phenotype of large granular lymphocytes, but occasionally a true clonal expansion of large granular lymphocyte disease can develop. 87–92 Defective T-cell immunity permits reactivation of Epstein-Barr virus (EBV) and other oncogenic viruses, but post-HCT immune deficiency may increase the risk of other SN, as demonstrated in solid organ transplant recipients.…”