Cytokine production during myeloablative and reduced intensity therapy before allogeneic stem cell transplantation

Department of Clinical Immunology, Centre of Allogeneic Stem Cell Transplantation, Karolinska Institutet, Huddinge University Hospital (MR), SE-141 86 Stockholm, Sweden. mats.remberger@labmed.ki.se

BACKGROUND AND OBJECTIVES: The aim of this study was to elucidate the effect of the type of chemo-radio therapy given before allogeneic hematopoietic stem-cell transplantation (HSCT) on cytokine release. DESIGN AND METHODS: We analyzed serum cytokine levels during pre-transplant therapy in 178 HSCT recipients. Samples were drawn daily during the treatment and serum levels of tumor necrosis factor-alpha (TNF-alpha) were analyzed by automated chemo-luminescence immunoassay. Conventional high-dose myeloablative therapy was given to 119 patients, while 59 patients received reduced intensity therapy (RIC). Most patients had a hematologic malignancy: their median age was 37 years (range 1-67). Anti-thymocyte globulin (ATG) was given to 126 patients as part of the pre-transplant treatment. RESULTS:The use of ATG significantly increased the TNF-alpha levels in the last four days before transplantation. We found significantly higher TNF-alpha levels, days -4 to -2 before transplant, in patients given RIC compared to myeloablative therapy independently of ATG treatment. No effect of age or disease stage was found. In patients not given ATG, we found a correlation between high TNF-alpha levels on day -2 and moderate-to-severe acute graft-versus-host disease (GVHD). INTERPRETATION AND CONCLUSIONS: To conclude, during the pre-transplant treatment for HSCT, patients receiving RIC and those treated with ATG had increased levels of TNF-alpha.