Proinflammatory cytokines and their role in the development of major transplant-related complications in the early phase after allogeneic bone marrow transplantation.
Serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor (TNF)-alpha were frequently measured during the first 30 days after allogeneic bone marrow transplantation (BMT) in 84 consecutive adult patients. Major transplant-related complications (MTCs) occurred in 33% of cases and included veno-occlusive liver disease, idiopathic pneumonia syndrome, severe endothelial leakage syndrome and >grade II acute graft-versus-host disease. Compared with patients having minor complications, those with MTCs developed higher levels at times of maximal clinical signs (all cytokines, P<0.001), between days 0-5 post-BMT (IL-6 and IL-8, P<0.05) and days 6-10 (L-6, P<0.001; IL-8 and TNF, P<0.01) post-BMT. We could not discriminate patterns of cytokine release that were specific for any subtype of MTC. Higher levels of IL-8 during days 0-5 were associated (P=0.044) with early (<40 days) death. Multivariate analysis including patient and transplant characteristics as well as post-BMT levels of C-reactive protein showed that high average levels of one or more of the cytokines within the first 10 days post-BMT were independently associated with MTC (Odd's ratio: 2.3 [1.2-4.5], P=0.011). This study shows that systemic release of proinflammatory cytokines contributes to the development of MTC and provides a rationale for pre-emptive anti-inflammatory treatment in selected patients.
Schots
R
R
BMT-Unit, Academisch Ziekenhuis-Vrije Universiteit Brussel (VUB), Laarbeeklaan 101, Brussels 1090, Belgium.
Kaufman
L
L
Van Riet
I
I
Ben Othman
T
T
De Waele
M
M
Van Camp
B
B
Demanet
C
C
D000328:Adult; D016470:Bacteremia / Q000097:blood / Q000209:etiology / Q000473:pathology; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002097:C-Reactive Protein / Q000032:analysis; D019559:Capillary Leak Syndrome / Q000097:blood / Q000209:etiology / Q000473:pathology; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000209:etiology / Q000473:pathology; D006504:Hepatic Veno-Occlusive Disease / Q000097:blood / Q000209:etiology / Q000473:pathology; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D016209:Interleukin-8 / Q000097:blood*; D007938:Leukemia / Q000097:blood / Q000628:therapy*; D008297:Male; D009436:Neural Tube Defects / Q000628:therapy; D011014:Pneumonia / Q000097:blood / Q000209:etiology / Q000473:pathology; D012307:Risk Factors; D019172:Transplantation Conditioning / Q000009:adverse effects; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein