Sundberg Rabbit - immunoglobulin G levels in patients receiving

The outcomes of unrelated donor hematopoietic stem cell transplantation (HSCT) have substantially improved during the past decade. The reason for this is more sophisticated tissue typing and perhaps also better supportive care. However, graft-versus-host disease (GVHD) is a major cause of morbidity and mortality using unrelated donors. The risk of graft failure is also higher in unrelated donor HSCT. By adding antithymocyte globulin (ATG) to the pre-transplant conditioning protocol, acute GVHD and early mortality of unrelated donor HSCT have been reduced to levels similar to those of matched related HSCT. Many different doses and types of ATG are used in transplant centers. The optimal dose of the various ATG preparations, as regards the prevention of graft failure and GVHD, is not yet fully understood. However, the dose of ATG may not be the sole cause of the level of in vivo depletion of donor Tcells. The distribution in the patient’s tissues and elimination also affect the level and rate of T-cell depletion. Thymoglobulin is produced by immunizing pathogen-free rabbits with fresh human thymocytes. The g immunoglobulin (Ig) fraction contains polyclonal antibodies against multiple cell surface antigens. Thymoglobulin binds to T cells and, to a lesser extent, to B cells, monocytes, macrophages and neutrophils. It also binds to platelets and red blood cells, albeit at low levels. It produces its effect via antibody-dependent cell-mediated cytotoxicity (ADCC), induction of apoptosis and down-regulation of cell surface antigens. The elimination half-life after 1 day of treatment has been shown to be 23 days. Since 1990, we have mainly used four doses of thymoglobulin as part of the pre-transplant conditioning therapy in unrelated donor HSCT and have found a dose-dependent effect of ATG on acute GVHD grades II-IV and III-IV. Here we have analyzed rabbit IgG levels in 61 patients and compared these with the dose of ATG given and GVHD. From the Department of Clinical Immunology (MR, BS) and Center for Allogeneic Stem Cell Transplantation (MR), Karolinska Institutet, Karolinska University Hospital, SE-141 86 Stockholm, Sweden.