Long‐term results of desensitization protocol with and without rituximab in sensitized kidney transplant recipients

Abstract

Background Desensitization protocols have been developed in order to overcome the immunological barrier of donor‐specific anti‐HLA antibodies (DSA). Methods During 2006‐2012, we implemented a program for desensitizing sensitized (positive DSA, negative NIH‐CDC crossmatch) living‐donor recipients. The long‐term outcome of 36 sensitized recipients, treated with IVIG and plasmapheresis (PP), with or without rituximab (added when > 7500 MFI), was compared to 252 non‐sensitized living‐donor recipients. Results Median peak DSA level before desensitization was 7223 (range 3567‐16 000) MFI. During a mean follow‐up of 121.9 months, graft loss occurred in 6/36 (17%) of the sensitized and 15/251 (6%) of the non‐sensitized recipients (P = 0.021). Five‐year and 10‐year death‐censored graft survival rates were 85% and 81% compared to 95% and 92%, respectively, for the non‐sensitized recipients. There was no difference in recipients’ survival. Slightly more episodes of acute rejection occurred in the sensitized group but had not influence on graft survival. At the last follow‐up, 28 recipients had functioning graft; seventeen (47%) did not have detectable DSA. Eleven recipients had excellent graft function despite having detectable DSA. Conclusion The long‐term outcomes of sensitized recipients who underwent desensitization are encouraging. Adding rituximab to PP + IVIG in candidates with very high titers may result in improved outcome.

Presence of antibodies against HLA class I and class II molecules in children before and after allo‐HSCT. Alloantibodies before and after HSCT

“…In this context, the inclusion of a desensitization protocol before allo-HSCT must be considered. 24 We should consider donor lymphoid infusion (DLI), irradiated donor T cells, or rituximab to eliminate antibodies against donor HLA molecules to facilitate correct engraftment and efficient graft function during the first 6 months after HSCT. The persistence of some of these antibodies or their appearance (de novo generation) during this time will compromise the homeostasis of leukocytes and the defense against pathogens.…”

“…We noticed that the presence of IgG antibodies against classes I and II is a constant event in patients with benign or malign hematologic diseases. In this context, the inclusion of a desensitization protocol before allo‐HSCT must be considered 24 . We should consider donor lymphoid infusion (DLI), irradiated donor T cells, or rituximab to eliminate antibodies against donor HLA molecules to facilitate correct engraftment and efficient graft function during the first 6 months after HSCT.…”

A call for transplant stewardship: The need for expanded evidence‐based evaluation of induction and biologic‐based cost‐saving strategies in kidney transplantation and beyond

“…65 Rituximab in combination with other immunomodulatory therapies has shown benefit in graft survival in the setting of desensitization. 66 Desensitization protocols vary among transplant centers, including flat dosing (500-1000mg) or body surface area (BSA) dosing (375 mg/m 2 ). 66 Rituximab is also widely utilized for AMR.…”

“…66 Desensitization protocols vary among transplant centers, including flat dosing (500-1000mg) or body surface area (BSA) dosing (375 mg/m 2 ). 66 Rituximab is also widely utilized for AMR.…”

“…Dosing is based off of BSA in oncologic indications, while rheumatoid arthritis uses a fixed-dose strategy. 66 A pharmacokinetics study comparing BSA dosing and flat dosing of 2000 mg in patients with rheumatoid arthritis found that the area under the curve was similar between both dosing schemes. 67 While there are no pharmacokinetic studies available in solid organ transplant patients comparing these dosing schemes, both strategies have been utilized in the literature.…”