Successful Administration of Rituximab To Prevent Recurrence of Delayed Haemolytic Transfusion Reaction Developed in a Sickle Cell Disease Patient.

Abstract

Background: Delayed hemolytic transfusion reaction (DHTR) is a life-threatening complication frequently reported in sickle cell disease patients (SCD) patients. The hallmarks of DHTR in SCD are a dramatic drop in post-transfusion hemoglobin (Hb) caused by destruction of both donor and recipient red blood cells (RBCs) and hemolysis exacerbation by further transfusion. Destruction of autologous and transfused RBCs can be triggered by auto-antibodies produced as a result of transfusion. As rituximab specifically targets circulating B cells and is successfully used to treat several auto-immune diseases, we thought that it could be beneficial in preventing this immune-mediated transfusion complication. We report the case of a SCD patient who already experienced many DHTR due to auto-antibodies and who needed again transfusion for surgery. Rituximab was administered prior transfusion.Patient and method: The SCD patient was a poly-immunized 33-year-old man who had experienced 2 life-threatening DHTR with auto and allo-antibodies following transfusion for orthopedic surgery. He was scheduled again in 2005 and 2007 for hip replacement. In 2007, he received 1000 mg of rituximab 3 days before surgery and transfusion and 7 days after the procedure. For both episodes, routine serological evaluation, hematologic parameters and lymphocyte subsets were determined. IL-10 transcripts were quantified. IL6 and TNFα were evaluated in sera after rituximab infusion.Results: In 2005, the patient received 7 crossmatched-compatible units at day 0 of surgery and developed a severe auto-immune haemolytic anemia at day 13 as demonstrated by serological evaluation revealing RBC auto-antibodies without new allo-antibodies, a positive direct antiglobulin test (DAT) with anti-C3d/anti-IgG. Hb dropped to 2 g/dL and patient consciousness was impaired. Renal failure ensued. Then, he received 6 more units compatible with the known allo-antibodies, and was given steroids, cyclophosphamide and erythropoietin. The patient clinical status gradually improved. Lymphocyte subsets increased on day 14. Natural killer cells increased ten times. IL10 transcripts were over 900 copies at day 15 and around 50 copies at day 32. In 2007, as transfusion was absolutely necessary for hip replacement, we thought that rituximab could prevent recurrence of DHTR for this patient by inhibiting development of auto-antibodies. Seven crossmatched-compatible units were transfused. Sera remained compatible with transfused RBCs, DAT and eluate remained negative. Hb A rose up to 40% after transfusion and decreased slowly to reach 17% on day 21. Rituximab treatment resulted in marked depletion of B cells. Existing allo-antibodies (anti-C, anti-Fya, anti-S) and levels of total IgG, IgM and IgA remained stable. Dosage of IL6 and TNFα after rituximab infusions did not reveal any cytokine-release syndrome attesting the immediate safety of the procedure. Three months after treatment, the patient was in good condition.Conclusion: This observation shows for the first time that DHTR can be prevented. We believe that the use of rituximab should be considered when a new transfusion seems inevitable in patients with SCD and a prior history of life-threatening DHTR with production of auto-antibodies. In this setting, rituximab prevented DHTR without causing significant side-effects.