Impact of AB0-blood group incompatibility on the outcome of recipients of bone marrow transplants from unrelated donors in the Japan Marrow Donor Program

The impact of ABO incompatibility on clinical outcomes following haematopoietic SCT (HSCT) remains controversial. This retrospective study assessed the effect of ABO mismatch on transplant outcomes and transfusion requirements in 594 patients undergoing reduced-intensity conditioned (RIC) HSCT with alemtuzumab in three UK transplant centres. We found no significant effects of minor, major or bidirectional ABO mismatch on overall survival, relapse-free survival, nonrelapse mortality or relapse incidence. Although the rate of acute GVHD was unaffected by ABO mismatch, the incidence of extensive chronic GVHD was higher in patients with minor and major mismatch compared with those who were ABO matched (hazard ratio (HR) 1.74, P = 0.032 for minor, HR 1.69 P = 0.0036 for major mismatch). Red cell and platelet transfusion requirements in the first 100 days post transplant did not differ by ABO mismatch. In this large UK series, ABO mismatch in RIC HSCT has no clinically significant effect on survival outcomes but appears to modify susceptibility to extensive chronic GVHD.Bone Marrow Transplantation (2015) 50, 931-938;

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of ABO blood group mismatch in alemtuzumab-based reduced-intensity conditioned haematopoietic SCT

Brierley

Littlewood

Peniket

et al. 2015

“…More severe cases can result in renal failure, cardiovascular collapse and ensuing death due to multi-organ failure. Delayed neutrophil engraftment has been reported, 3 most likely due to a combination of haematopoietic progenitor cell loss during graft manipulation and recipient derived isoagglutinins binding to donor A or B Ags absorbed onto the surface of neutrophils or their precursors. 4 Delayed red cell recovery and increased transfusion requirements are common and pure red cell aplasia occurs in 15-20% 4,5 due to persisting, host-derived isoagglutinins suppressing donor red cell production.…”

Section: Discussionmentioning

confidence: 99%

Major ABO incompatible BMT in children: determining what residual volume of donor red cells can safely be infused following red cell depletion

Patrick

Lau

Gassas

et al. 2015

Major ABO incompatible BM transplantation carries a risk of acute haemolysis. Red cell depletion reduces this risk but not all incompatible RBC (iRBCs) are removed and in children the residual volume can be significant relative to body weight. We sought to determine the volume of iRBCs that can be safely given to children. All patients receiving fresh BM from a donor with a major ABO blood group mismatch between January 2000 and July 2013 at the Hospital for Sick Children, Toronto, were included. Seventy-eight patients were identified. The median volume of iRBCs transfused was 1.6 mL/kg (range 0.1-10.6 mL/kg). Thirty-five patients had minor haemolytic events and five patients had clinically significant adverse events. Two patients, who received 3.66 and 3.9 mL iRBCs/kg, developed renal impairment and in one case hypoxia and hyperbilirubinaemia. One patient had mild hypotension that resolved with i.v. fluid. Two patients developed hypotension secondary to sepsis and unrelated to BM infusion. Although signs of haemolysis occur, with appropriate hydration and monitoring of renal function, clinically significant adverse events related to the infusion of ABO incompatible BM are rare, and, in this study, were only seen in patients receiving 43 mL/kg of iRBCs per kg.Bone Marrow Transplantation (2015) 50, 536-539; doi:10.1038/bmt.2014.309; published online 26 January 2015 INTRODUCTION ABO incompatibility between donor and recipient is not a contraindication to allogeneic haematopoietic SCT (HSCT). However, a number of immunohaematological issues must be carefully considered and appropriately managed. 1 Major ABO mismatch is characterised by preformed recipient isoagglutinins to donor red cell antigens, and minor ABO mismatch occurs when the graft contains isoagglutinins directed against recipient red cells. Bidirectional mismatch occurs when both situations are present. 1 The risks of major ABO incompatibility include acute haemolysis at the time of graft infusion, delayed engraftment and pure red cell aplasia. 2 The literature suggests that 20-30 mL of incompatible RBCs (iRBCs) can be safely infused into an adult 2 and this has been extrapolated to 0.2-0.4 mL/kg, but there is no evidence about safe volumes in children. In the case of major ABO incompatibility, most centres will red cell deplete donor BM using centrifugation or sedimentation techniques. 2 Even with the best available technology it is not possible to remove all iRBCs and in small children this can result in a volume of red cells per kilogram of wt that is significantly higher than would routinely be transfused into an adult. In our experience we are rarely able to red cell deplete BM such that 40.4 mL/kg of iRBCs remain, without significantly reducing the total nucleated cell dose and thus jeopardising engraftment. Therefore, we sought to determine what volume of iRBCs can safely be given to children in the context of allogeneic HSCT using fresh BM.

“…7 Others have reported long-term consequences of increased incidence of graft failure, 8 increased GVHD and treatment-related mortality (TRM) 9 and poorer OS. 5,10 Conversely, some have found that ABO incompatibility has no significant impact on these outcomes. [11][12][13] The variability in reported outcomes may reflect differences in patient populations, progenitor cell source, conditioning and GVHD-prophylaxis.…”

Section: Introductionmentioning

confidence: 99%

“…3,4 The literature provides inconsistent conclusions about the effect of donor-recipient ABO incompatibility on haematopoietic progenitor cell transplant outcomes. Some authors have reported adverse short-term effects, including increased time to engraftment 5,6 and increased transfusion requirements. 7 Others have reported long-term consequences of increased incidence of graft failure, 8 increased GVHD and treatment-related mortality (TRM) 9 and poorer OS.…”

Section: Introductionmentioning

confidence: 99%

Major ABO-incompatible BMT: isohemagglutinin reduction with plasma exchange is safe and avoids graft manipulation

Sheppard

Tay

Bryant

et al. 2013

The impact of donor-recipient ABO incompatibility on long-term BMT outcomes remains controversial. A common strategy is to deplete the donor marrow of red cells, although this variably reduces the number of CD34 þ cells. This 10-year retrospective study assessed the impact of recipient plasma exchange in major ABO-incompatible allogeneic BMT on outcomes and survival. Target Ab titres werep1:4 for anti-A andp1:8 for anti-B. Patients with higher titres underwent plasma exchange before marrow infusion. Of 133 patients who underwent allogeneic BMT, 34 had a major ABO-incompatible donor. The median number of exchanges was 2 (range 1-4). There were no acute haemolytic transfusion reactions. Engraftment times, transfusion requirements and acute and chronic GVHD were no different from those of patients with an ABO-identical donor. Treatment-related mortality at 100 days was 21% in the group with a major ABO-incompatible donor and 17% in the group with an identical donor (P ¼ 0.8). Plasma exchange of the recipient is a safe method of managing donor-recipient major ABO incompatibility before BMT without the risk of haematopoietic progenitor cell loss associated with red cell depletion of the graft.Bone Marrow Transplantation (2013) 48, 953-957;