Safety and Tolerability of Donor Type Red Blood Cell Transfusion before Allogeneic Stem Cell Transplantation in Children with Major ABO Mismatch

Abstract

Background Major ABO mismatch in allogeneic bone marrow transplant (BMT) can cause clinical problems like severe transfusion reactions, acute haemolysis, and delay of red blood cell (RBC) engraftment or manifestation of pure red cell aplasia, related to circulating isoagglutinin titers. Even there is no increased incidence of graft failure or slower engraftment of neutrophils and platelets ABO mismatch leads to an increase of transplant related mortality. To reduce circulating isoagglutinin titers pre transplant plasma exchange during conditioning period can be performed. This procedure can be wearing for the patient and rebound effects are observed. RBC depletion can cause a loss of CD34+stem cells in bone marrow. A further strategy to reduce circulating isoagglutinin titers is in vivo immunoadsorption due to donor type RBC transfusion pre transplant. Aim of the study The Aim of the retrospective single center study was to investigate the safety and tolerability of donor-type red blood cell transfusion prior to allogeneic stem cell transplantation in children with major ABO mismatch. Methods From 2007-2015 37 children (median age 7 years, range 0.6-18.4) received an ABO mismatched RBC transfusion (2-3 ml KG BW) pre transplant under antihistaminic and steroid cover. Reaction to donor type RBC and graft transfusion, number of donor type RBC transfusions, haemolysis parameters, and trend of isoagglutinin titers, and engraftment data were observed. Wilcoxon signed-rank test was used to examine the difference between the paired values of titers (Conventional test tube, CTT; titration method using nonspecific anti-IgG antibody; Anti-IgG gel titer) before and after donor type RBC transfusion. Age and time until engraftment were reported using median and ranges. The quantitative values were reported using frequency and percentage. All statistical tests were two-sided with a significance level of 5%. Data analysis was performed using commercial software R.Statistical methods. Results Safety of mismatched RBC transfusions Compared with accidentally transfused RBC no severe complications are observed in our cohort. 34 (92%) children presented no reactions (Grade 0), 1 child had a minimal oxygen demand,1 child showed a mild hypertension (Grade 1) and 1 child a moderate hypertension, requiring treatment. Neither severe reactions nor anaphylactic shock were observed. Efficiency of mismatched RBC transfusion A significant reduction of isoagglutinin titers was defined as a final titer of 1:4 or at least a reduction of 3 titer steps was achieved. 23 of 37 (64%) required 1 donor type RBC transfusion to reduce significant the isoagglutinin titers, 8 patients (22%) needed a second and 5 patients (14%) a third transfusion. Figure 1 showed the significant reduction of isoagglutinin titers in the different patients groups after donor type RBC transfusion. The pairwise analysis of isoagglutinin titers indicates that the initial titer of patients required one donor type transfusion of RBC was significant lower than in the patient group required 2 or 3 transfusions. Engraftment data The median time to WBC and platelet engraftment was 21.5 (range 19-24) and 28 (range 26-60) days respectively. Haemolysis parameter post mismatched RBC transfusion Haemolysis parameter lactat dehydrogenase (LDH) and bilirubin was determined on a daily base. In all patients no significant increase of bilirubin levels was observed. Conclusion Donor type RBC transfusion is a safe, tolerable and effective procedure to reduce the isoagglutinin titers prior to allogeneic ABO mismatched bone marrow transplantation in children. In our cohort no severe transfusion reactions, acute haemolysis, delay of engraftment or manifestation of pure red cell aplasia was observed. Figure Figure. Disclosures Jarisch: Novartis: Consultancy. Bader:Novartis: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Medac: Research Funding; Riemser: Research Funding; Neovii: Research Funding.

Major incompatible red blood cell transfusions prior to bone marrow transplantation: Not worth the risk

“…The authors' very small study of only 52 patients does not prove that giving major ABO-incompatible transfusions is 'safe and efficient'. 1 In weighing the risk-benefit ratio, we hope other centres will be circumspect in considering starting, and centres already performing might consider stopping, this intervention in the light of established product red cell reduction procedures.…”

“…To the editor, As Medical Directors of cellular therapy processing laboratories and transfusion medicine physicians, we have concerns regarding the article by Jarisch et al entitled 'Donor-type red blood cell transfusion to deplete isoagglutinins prior to allogeneic stem cell transplantation from ABO major incompatible bone marrow donors'. 1 Given ABO incompatible transfusions can be fatal, any claimed benefit requires especially critical review. 2 How clear are the risks from major incompatible transfusions?…”

“…In the authors' words 'relevant intravascular haemolysis can cause shock, acute renal failure occasionally necessitating dialysis, disseminated intravascular coagulation, and, if large volumes of ABO-incompatible RBCs are transfused, is frequently lethal'. 1,3 Even an infusion of 1.5-2 cc/kg as in the Jarisch et al protocol would be the equivalent of up to 120 cc in a 60-kg adult. The study that 'inspired' the current report infused 35 adult patients with 50-150 cc of incompatible red cells and 4 had severe reactions requiring stopping the transfusion.…”

“…4 Of note, 50% of patients in the Jarisch et al study had Grade 2 events with 6% having Grade 3 events that included oxygen desaturation and arterial hypertension. 1 While, according to the authors, 'none of the side effects necessitated discontinuation of the transfusion', standard practice is to stop transfusions for reactions such as those described, let alone in the setting of incompatible products, and the patients were fortunate to not have had worse outcomes. 3 There are already well-established processes for removing red blood cells from marrow products to prevent acute haemolysis.…”

“…In regard to non-acute effects of major incompatible grafts, as the authors correctly note, while inferior outcomes related to these transplants have been reported, they are 'not universally confirmed'. 1,[8][9][10] In addition, this lack of clarity is despite thousands of such transplants being performed over decades with most centres not resorting to pre-graft infusion patient treatment to manage. 5 While pure red cell aplasia and associated morbidity is a risk for individuals receiving ABO major mismatched transplants, it occurs in approximately 10% or less of patients, can be treated with compatible red cell transfusions and typically resolves.…”