Profound but Transient Changes in the Inflammatory Milieu of the Blood During Autologous Hematopoietic Stem Cell Transplantation

Abstract

A B S T R A C TLittle is known about the inflammatory milieu in the blood during autologous hematopoietic stem cell transplantation (AHSCT) and how it is affected by the stem cell mobilization, collection, and reinfusion and conditioning regimen. In this study, we analyzed 92 proteins connected to inflammation at 10 time points during and after AHSCT in 16 patients with multiple sclerosis (MS). Serum from 29 patients with newly diagnosed MS and 15 healthy controls were included for comparative analysis. There were no significant differences in inflammatory serum protein levels between patients with newly diagnosed MS and healthy controls, but 29 out of 73 detectable proteins were significantly altered between at least 2 adjacent sampling time points during AHSCT. The predominant changes occurred after the conditioning regimen had been administered, whereas stem cell mobilization, collection, and reinfusion appeared to have less impact. Two distinct response patterns could be discerned, likely representing loss of basal cytokine production and homeostasis. The analyzed serum proteins gradually returned to baseline levels after treatment, with no remaining differences at 3 months after AHSCT. We conclude that treatment with AHSCT has a major but transient impact on the inflammatory milieu of peripheral blood.

Long-Term Suppression of Circulating Proinflammatory Cytokines in Multiple Sclerosis Patients Following Autologous Haematopoietic Stem Cell Transplantation

“…Next, we investigated early cytokine changes in our MS cohort up to 3 months post-AHSCT, where substantial cytokine shifts have previously been reported ( 40 ). Additionally, because AHSCT is known to alter the cytokine profile of NHL patients ( 47 ), we also investigated cytokine changes in NHL patients undergoing AHSCT to compare the effect of our transplant regimen to previously reported regimens and determine any possible diseases specific cytokine changes following AHSCT.…”

“…It is also the first to report these cytokine changes in comparison to a non-autoimmune disease cohort undergoing similar therapy. Few studies have examined the evolution of the cytokine milieu in patients with autoimmune diseases post-AHSCT ( 40 , 41 , 61 , 62 ). These studies described significant reductions in the cytokine levels in the blood of both systemic sclerosis ( 62 ) and MS ( 40 , 41 ) patients early post-AHSCT.…”

“…Few studies have examined the evolution of the cytokine milieu in patients with autoimmune diseases post-AHSCT ( 40 , 41 , 61 , 62 ). These studies described significant reductions in the cytokine levels in the blood of both systemic sclerosis ( 62 ) and MS ( 40 , 41 ) patients early post-AHSCT. However, these changes were transient and the overall cytokine concentrations were reported to return to baseline levels by 3-12 months post-AHSCT.…”

“…Thus far, only two studies have investigated the evolution of the cytokine milieu in the blood of MS patients following AHSCT ( 40 , 41 ), with both employing a lymphoablative cyclophosphamide chemotherapy regimen. Wiberg and colleagues ( 40 ) demonstrated significant but transient changes to cytokines predominantly associated with innate immunity following AHSCT that returned to baseline levels by the 3 month timepoint.…”

“…Thus far, only two studies have investigated the evolution of the cytokine milieu in the blood of MS patients following AHSCT ( 40 , 41 ), with both employing a lymphoablative cyclophosphamide chemotherapy regimen. Wiberg and colleagues ( 40 ) demonstrated significant but transient changes to cytokines predominantly associated with innate immunity following AHSCT that returned to baseline levels by the 3 month timepoint. Jaime-Perez and colleagues ( 41 ) reported significant reductions in proinflammatory cytokines IL-21 and IL-22, and increased levels of anti-inflammatory cytokines CCL2 and CCL4 at 14 days following transplantation without longer term follow-up.…”