Mats Remberger1, Marie Jaksch, Mehmet Uzunel, Jonas Mattsson. 1. Department of Clinical Immunology and Centre for Allogeneic Stem Cell Transplantation, Huddinge University Hospital, Stockholm, Sweden. mats.remberger@labmed.ki.se
Abstract
BACKGROUND: Some patients become full donor chimeras (DC) early after stem-cell transplantation (SCT), while others remain mixed chimeras for a longer time. Little is known about the mechanism behind these phenomena. METHODS: Serum cytokine levels during conditioning and during the first month after SCT were analysed in 30 patients. Of the 21 patients who became full T-cell DC from the first analysed sample, 12 developed grade II-IV acute graft-vs.-host disease (GVHD) and the other nine, mild or no acute GVHD. Another nine patients were T-cell mixed chimeras (MC). All MC patients had no or mild acute GVHD. RESULTS: During the pretransplant conditioning, DC patients had higher levels of tumour necrosis factor (TNF)-alpha and lower levels of transforming growth factor (TGF)-beta and interleukin (IL)-10, compared with MC patients. During the first week after SCT, lower levels of TGF-beta and IL-10 and higher levels of soluble Fas (sFas) were found in DC patients compared with MC patients. During the second and third weeks after SCT, increased levels of TNF-alpha, interferon (IFN)-gamma and sFas were found among DC patients compared with MC patients. Patients who developed moderate-to-severe acute GVHD had higher levels of TNF-alpha, IFN-gamma, IL-10 and sFas at 2 weeks post-SCT than in those with less GVHD. Patients homozygous for the TNFd microsatellite alleles 3 or 4 had significantly higher TNF-alpha levels during conditioning and more often developed acute GVHD grades II-IV. CONCLUSION: These results indicate that an imbalance between pro-inflammatory and immune- modulating cytokines are involved in the development of chimerism and acute GVHD after allo-SCT. The Fas/FasL pathway is probably involved in the elimination of recipient cells leading to full donor chimerism.
BACKGROUND: Some patients become full donor chimeras (DC) early after stem-cell transplantation (SCT), while others remain mixed chimeras for a longer time. Little is known about the mechanism behind these phenomena. METHODS: Serum cytokine levels during conditioning and during the first month after SCT were analysed in 30 patients. Of the 21 patients who became full T-cell DC from the first analysed sample, 12 developed grade II-IV acute graft-vs.-host disease (GVHD) and the other nine, mild or no acute GVHD. Another nine patients were T-cell mixed chimeras (MC). All MC patients had no or mild acute GVHD. RESULTS: During the pretransplant conditioning, DC patients had higher levels of tumour necrosis factor (TNF)-alpha and lower levels of transforming growth factor (TGF)-beta and interleukin (IL)-10, compared with MC patients. During the first week after SCT, lower levels of TGF-beta and IL-10 and higher levels of soluble Fas (sFas) were found in DC patients compared with MC patients. During the second and third weeks after SCT, increased levels of TNF-alpha, interferon (IFN)-gamma and sFas were found among DC patients compared with MC patients. Patients who developed moderate-to-severe acute GVHD had higher levels of TNF-alpha, IFN-gamma, IL-10 and sFas at 2 weeks post-SCT than in those with less GVHD. Patients homozygous for the TNFd microsatellite alleles 3 or 4 had significantly higher TNF-alpha levels during conditioning and more often developed acute GVHD grades II-IV. CONCLUSION: These results indicate that an imbalance between pro-inflammatory and immune- modulating cytokines are involved in the development of chimerism and acute GVHD after allo-SCT. The Fas/FasL pathway is probably involved in the elimination of recipient cells leading to full donor chimerism.