The impact of ABO incompatibility on the outcomes of AML patients undergoing mismatched unrelated donor transplantation

HLA-mismatched Unrelated Donor (MMURD) is an alternative donor source for Acute Myeloid Leukemia (AML) patients lacking a matched related donor or a fully HLA matched unrelated donor for allogenic Stem Cell Transplantation (SCT). However, MMURD SCT are often associated with increased risk of transplant complications. The effect of ABO incompatibility on the clinical outcome of AML patients receiving MMURD is not yet elucidated.

Jonathan Canaani from the Chaim Sheba Medical Center, Tel Aviv, Israel, and colleagues, on behalf of the European Society for Blood and Transplantation (EMBT), retrospectively studied the clinical effects of ABO incompatibility on the outcomes of adult AML patients undergoing MMURD transplantation. The results of the study were published ahead of print in the American Journal of Hematology on 25^th April 2017.

Using the EMBT registry, the authors identified 1,013 AML patients who underwent HLA mismatched allogenic SCT between 2005–2014. The authors focused on patients that were transplanted with peripheral blood mobilized grafts (n = 876) and they were either ABO-matched (n = 349) or ABO-mismatched (n = 527). ABO-mismatched patients were further divided into patients that were either minor ABO mismatch (n = 241), major ABO mismatch (n = 215), or bidirectional ABO mismatch (n = 71).

The key results of the study were:

• Day 30 engraftment rate in patients that were ABO matched, major ABO mismatch, minor ABO mismatch, and bidirectional mismatch; 96% vs 95% vs 98% vs 97%, P = 0.32
• Grade II–IV Acute Graft versus Host Disease (aGvHD) was significantly lower in patients with major ABO mismatching; HR = 0.7, P = 0.049
• 3-year Relapse Incidence (RI) in patients that were ABO matched and ABO mismatched; 34% vs 36%, P = 0.32
• 3-year Non-Relapse Mortality (NRM) in patients that were ABO matched and ABO mismatched; 28% vs 25%; P = 0.2
• 3-year Overall Survival (OS) in patients that were ABO matched and ABO mismatched; 40.7% vs 43.7%; P = 0.35
• 3-year Leukemia Free Survival (LFS) in patients that were ABO matched and ABO mismatched; 37.6% vs 38.3%; P = 0.87

In summation, “ABO incompatibility has no major impact” on the clinical outcomes of patients undergoing MMURD allogenic SCT.

Abstract

ABO incompatibility is commonly observed in stem cell transplantation and its impact in this setting has been extensively investigated. HLA-mismatched unrelated donors (MMURD) are often used as an alternative stem cell source but are associated with increased transplant related complications. Whether ABO incompatibility affects outcome in MMURD transplantation for acute myeloid leukemia (AML) patients is unknown. We evaluated 1013 AML patients who underwent MMURD transplantation between 2005 and 2014. Engraftment rates were comparable between ABO matched and mismatched patients, as were relapse incidence [34%; 95% confidence interval (CI), 28-39; for ABO matched vs. 36%; 95% CI, 32-40; for ABO mismatched; P=0.32], and non-relapse mortality (28%; 95% CI, 23-33; for ABO matched vs. 25%; 95% CI, 21-29; for ABO mismatched; P=0.2). Three year survival was 40% for ABO matched and 43% for ABO mismatched patients (P=0.35), Leukemia free survival rates were also comparable between groups (37%; 95% CI, 32-43; for ABO matched vs. 38%; 95% CI, 33-42; for ABO mismatched; P=0.87). Incidence of grade II-IV acute graft versus host disease was marginally lower in patients with major ABO mismatching [Hazard ratio (HR) of 0.7, 95% CI, 0.5-1; P = 0.049]. ABO incompatibility probably has no significant clinical implications in MMURD transplantation.