The effect of ABO incompatibility on the outcomes of AML patients undergoing haplo-HCT

Haploidentical Hematopoietic Stem Cell Transplantation (haplo-HCT) is an alternative donor source for Acute Myeloid Leukemia (AML) patients lacking a matched related donor or a matched unrelated donor. However, a significant amount of haplo-HCTs are performed with ABO-mismatched donors. The effect of ABO incompatibility on the clinical outcome of AML patients receiving haplo-HCT is still debatable and there is currently no data on the impact of ABO incompatibility on the outcomes of AML patients. 

Jonathan Canaani from Chaim Sheba Medical Center, Tel Aviv, Israel, and colleagues, on behalf of the European Society for Blood and Transplantation (EMBT), retrospectively studied the role of ABO compatibility on the outcomes of AML patients undergoing haplo-HCT. The results of the study were published ahead of print in Haematologica on 2^nd March 2017.

Using the EMBT registry, the authors identified 837 patients that received haplo-HCT between 2005–2014. Patients were either ABO-matched (n = 522) or ABO-mismatched (n = 315). ABO-mismatched patients were further divided into patients that were either minor mismatch ABO (n = 150), major mismatch ABO (n = 127), or bidirectional mismatch ABO (n = 38).

The key results of the study were:

• Day 100 engraftment rate in patients that were ABO matched, minor ABO mismatch, major ABO mismatch, and bidirectional mismatch; 94.1% vs 95.3% vs 88.1% vs 97.3%, P = 0.04
• Grade II–IV Acute Graft versus Host Disease (aGvHD) was significantly associated with bidirectional ABO mismatching (n = 38); HR = 2.38, P = 0.01
• Minor ABO mismatched patients transplanted with Bone Marrow (BM) grafts had increased risk of grade II–IV aGvHD; HR= 2.03, P = 0.047
• Major ABO mismatched patients transplanted with BM grafts had decreased Overall Survival (OS); HR = 1.82, P = 0.033

In summation, AML patients undergoing haplo-HCT with major ABO mismatch are associated with inferior engraftment and OS with the use of BM grafts. Furthermore, patients with minor ABO mismatch are more likely to experience increased aGvHD rates when transplanted with BM grafts.

The authors concluded by stating that “ABO incompatibility status may hold a prognostic significance and should be considered and assessed routinely during evaluation for the optimal donor prior to haplo-HCT”.

Abstract

A significant segment of hematopoietic stem cell transplantations are performed with ABO-mismatched donors. The impact of ABO-mismatch on outcome following transplantation remains controversial and there is no published data regarding the impact of ABO-mismatch in acute myeloid leukemia patients receiving haploidentical transplantation. Using the EBMT acute leukemia working group registry we identified 837 patients who underwent haploidentical transplantation. Comparative analysis was performed between patients receiving ABO-matched versus ABO-mismatched for common clinical outcome variables. Our cohort consisted of 522 ABO-matched pts and 315 ABO-mismatched patients including 150 minor, 127 major, and 38 bidirectional ABO mismatched. There were no significant differences between ABO matched and mismatched patients in terms of baseline disease and clinical characteristics. Major ABO mismatching was associated with inferior day 100 engraftment rate whereas multivariate analysis showed bi-directional mismatching to be associated with increased risk for grade II-IV acute graft versus host disease (hazard ratio [HR] of 2.387, 95% confidence interval [CI], 1.22-4.66; p=0.01). Non-relapse mortality, relapse incidence, leukemia free survival, overall survival, and chronic graft versus host disease rates were comparable between ABO matched and mismatched patients. Focused analysis for stem cell source showed that patients with minor mismatching transplanted with bone marrow grafts experienced increased grade II-IV acute graft versus host disease rates (HR of 2.03, 95% CI, 1.00-4.10; p=0.04). Patients with major ABO mismatching and bone marrow grafts had decreased survival (HR=1.82, CI 95%, 1.048-3.18; p=0.033). In conclusion, ABO incompatibility has a marginal but significant clinical effect in acute myeloid leukemia patients undergoing haploidentical transplantation.