Increased Serum Levels of Tumor Necrosis Factor α Precede Major Complications of Bone Marrow Transplantation

Acute graft-versus-host disease, interstitial pneumonitis, endothelial leakage syndrome, and veno-occlusive disease are major complications of bone marrow transplantation. Though several new regimens for prophylaxis and treatment of these syndromes have been introduced, the overall incidence has been only slightly reduced over the last few years. We retrospectively analyzed tumor necrosis factor alpha (TNFα) serum levels between day -8 and day 100 after bone marrow transplantation in 56 patients transplanted in our unit for a variety of hematological diseases. In 34 patients with uneventful courses, mean TNFα levels rose to a maximum of 76 ± 29 pg/mL. In contrast, 22 patients with major transplant related complications showed mean increases of TNFα of 492 ± 235 pg/mL (P < .0001). Increases of TNFα occurred before interstitial pneumonitis and severe acute graft-versus-host disease with a latency of 25 to 54 days. Early complications such as endothelial leakage syndrome and veno-occlusive disease were closely associated with increases of TNFα serum levels. Our study suggests two pathways of TNFα release: activation of host macrophages and stimulation of donor cells in the course of acute graft-versus-host disease. Cytokine monitoring should be helpful for prediction and earlier treatment of major transplant related complications.