Consequences of ABO incompatibility in allogeneic hematopoietic stem cell transplantation

Abstract

Summary:Aside from causing hemolytic reactions the ABO blood group system does not have an impact on outcome after allogeneic bone marrow or peripheral blood stem cell transplantation (SCT). However, only a few studies have addressed the effect of ABO incompatibility on the incidence of GVHD, time to engraftment, relapse and survival. Therefore, we performed a retrospective twocenter analysis of 562 consecutive patients receiving allogeneic SCT, including 361 ABO-identical, 98 minor, 86 major and 17 bidirectional ABO-incompatible SCT. In multivariate analysis adjusted for potential confounders survival was significantly associated with ABO incompatibility (P = 0.006). Compared to ABO-identical SCT, bidirectional ABO incompatibility increased the risk significantly (RR, 2.8; 95% CI, 1.5-5.1; P = 0.0009), whereas survival of patients with minor (RR, 1.2; 95% CI, 0.9-1.7; P = 0.27), or major ABO-incompatible SCT (RR, 1.3; 95% CI, 0.9-1.8; P = 0.18) was not significantly different. RBC engraftment was delayed in major ABO-incompatible SCT (RR, 0.66; 95% CI, 0.51-0.85; P = 0.001). The incidence of acute GVHD (grade I-IV) was higher in minor ABO-incompatible SCT as compared to ABO identity (RR, 2.8; 95% CI, 1.3-5.9, P = 0.009). This difference was limited to mild GVHD; in moderate-to-severe GVHD (grade II-IV) no significant difference was found among the groups (P = 0.53). The relapse rate was not influenced by ABO incompatibility (P = 0.78). In conclusion, these results suggest that ABO incompatibility represents a risk factor not only for post-transplant hemolysis, but also for survival and the rate of mild GVHD after allogeneic SCT. In contrast to RBC transfusion and solid organ transplantation, approximately one-third of all allogeneic bone marrow or peripheral blood stem cell transplantations (SCT) are performed across the ABO blood group barrier. 1,2 There are three groups of ABO incompatibility: minor ABO incompatibility (eg from an O-type donor to an A-type recipient) is characterized by the ability of donor B lymphocytes to produce anti-recipient isoagglutinins. In clinical practice, preformed anti-host isoagglutinins are removed from the stem cell inoculum by centrifugation prior to transplantation. In contrast, major ABO-incompatible SCT (eg from an A-type donor to an O-type recipient) is characterized by the presence of preformed anti-donor isoagglutinins. In bidirectional ABO incompatibility (eg A-type donor to a B-type recipient), a combination of both the major and minor barrier has to be overcome.It is well known that ABO-incompatible SCT increases the risk of hemolytic reactions in all groups, 3 but it is believed that ABO incompatibility between donor and recipient is of no importance for the overall clinical outcome. [4][5][6][7] Nevertheless, over the past two decades, improvements in GVHD prophylaxis and transplantation technologies have led to a generally lower overall mortality, theoretically unraveling an effect of the ABO system on the outcome of SCT. In particular, there are several lines of ...

The impact of graft composition on clinical outcomes in unmanipulated HLA-mismatched/haploidentical hematopoietic SCT

“…Conflicting data still exist as to the influence of ABO mismatch on GVHD and survival. Bacigalupo et al 29 and Stussi et al 30 suggested that ABO incompatibility represents a risk factor for aGVHD after allogeneic SCT. A possible reason may be that broadly distributed ABO Ags may damage the host endothelium, potentially triggering GVHD in incompatible SCT.…”

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

“…2,8,[12][13][14] Immunological effects of ABO BD and MJ mismatch include acute haemolysis, pure red cell aplasia and delayed engraftment, leading to increased transfusion requirements. [15][16][17] In HSCT patients with ABO MN mismatch, acute or delayed haemolysis occur in up to 15-30% due to the development of passenger lymphocyte syndrome.…”

“…21 The impact of ABO mismatch on transplant outcomes is variable, with a number of small and heterogeneous studies in the literature. 4,8,[22][23][24][25][26][27][28][29] Of the larger studies, a French registry study of 1108 RIC HSCT patients reported that MN ABO incompatibility was associated with reduced OS. 30 In the RIC subgroup of the largest registry study to date, Kimura et al 2 reported increased transplantrelated mortality (TRM) for MN, MJ and BD ABO-mismatched patients.…”

Prolonged red cell aplasia after major ABO-incompatible allogeneic hematopoietic stem cell transplantation: removal of persisting isohemagglutinins with Ig-Therasorb® immunoadsorption

“…There is an intense debate about the impact on outcome, severity of hemolysis, association with graft-versus-host disease and survival after blood group-incompatible stem cell transplantation. [1][2][3] Since blood group antigens are inherited independently of the human leukocyte antigen (HLA) complex, 4 ABO incompatibility between donor and recipient is observed in about 30% of HSCT. 5 Red cell incompatibility is classified according to whether donor's isohemagglutinins, isoantigens or both are incompatible with those of the recipient.…”