Proinflammatory Cytokines and Their Role in the Development of Major Transplant-Related Complications in the Early Phase After Allogeneic Bone Marrow Transplantation

Leukemia. 2003 Jun;17(6):1150-6. doi: 10.1038/sj.leu.2402946.


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.

MeSH terms

  • Adult
  • Bacteremia / blood
  • Bacteremia / etiology
  • Bacteremia / pathology
  • Bone Marrow Transplantation / adverse effects*
  • C-Reactive Protein / analysis
  • Capillary Leak Syndrome / blood
  • Capillary Leak Syndrome / etiology
  • Capillary Leak Syndrome / pathology
  • Female
  • Graft vs Host Disease / blood
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / pathology
  • Hepatic Veno-Occlusive Disease / blood
  • Hepatic Veno-Occlusive Disease / etiology
  • Hepatic Veno-Occlusive Disease / pathology
  • Humans
  • Interleukin-6 / blood*
  • Interleukin-8 / blood*
  • Leukemia / blood
  • Leukemia / therapy*
  • Male
  • Neural Tube Defects / therapy
  • Pneumonia / blood
  • Pneumonia / etiology
  • Pneumonia / pathology
  • Risk Factors
  • Transplantation Conditioning / adverse effects
  • Transplantation, Homologous
  • Tumor Necrosis Factor-alpha / metabolism*


  • Interleukin-6
  • Interleukin-8
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein