Has ABO Mismatch Rate Decreased in AML and ALL Transplant Recipients over the Years, a Trend Analysis Using CIBMTR Data

Background:

ABO major mismatch (ABOMM) is defined as a condition when donor antigens cross-react with recipient antibodies. ABO matching, a part of donor selection algorithms for allogeneic hematopoietic stem cell transplant (allo-HSCT), is preferable whenever possible as ABOMM may be associated with negative outcomes. Kollman et al. (2016) found an increased mortality associated with ABOMM for the 1998–2006 cohort (n = 6,349, HR: 1.13, p: 0.01) but not for the 2007–2011 cohort (n = 4,690, HR: 1.01, p: 0.83). A meta-analysis (n = 1,208) found no association between ABOMM and mortality (HR: 1.03, p: 0.81). Given disease heterogeneity and conflicting results of these studies, a CIBMTR (Center for International Blood and Marrow Transplant Research) study by Subramanian et al. (2023) determined the association of ABOMM with increased primary graft failure (OR: 1.60, p: 0.01) and overall mortality (HR: 1.16, p: 0.005) among patients with acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL). Given ABOMM clinical implications and mortality association, we decided to perform ABOMM rates over years using the CIBMTR data.

Methods:

We used CIBMTR publicly available data (https://cibmtr.org/CIBMTR/Resources/Publicly-Available-Datasets#, Subramanian et al. 2023) in accordance with CIBMTR terms and conditions. Data contained AML and ALL adults who received allo-HSCT from HLA-matched siblings (HMS) or matched unrelated donors (MUDs) between 2008 and 2018 and had ABO mismatch status available. Descriptive statistics were performed. ABOMM rates per year per 100 transplants were calculated using the formula: no. of ABOMM cases/total transplants * 100. For year-to-year variation, we calculated the annual percent change (APC) between rates of two consecutive years [APC: (Current year rate-Previous year rate/Previous year rate) *100]. A scatter plot was used to visualize the ABOMM trend from 2008 to 2018. As the rate variable was normally distributed, we selected a linear regression model (LRM) for association between the transplant year and ABOMM rate. Analysis was performed using SAS, version 9.3, Copyright (c) 2016 by SAS Institute Inc., Cary, NC, USA.

Results:

Total sample included 4,946 recipients (AML:79.2%, ALL: 20.9%; 54.6% men; 87.1% Whites). Median age was 52.5, range: 18.0-81.5. 65.3% received transplant from MUD vs. 34.7% from HMS. Graft type was peripheral blood in 83.9% of cases. About 18.2% (n= 899) of recipients had major ABO mismatch, 20.8% had minor and 5.5% had bidirectional mismatch (both major and minor). ABOMM rates per 100 transplants were 22 (Yr. 2008), 21(2009), 18(2010), 21(2011), 15(2012), 18(2013), 17(2014),18(2015), 17(2016), 11(2017), 17(2018). APC for years 2009, 2010, 2011, 2012, 2013, 2014, 2015, 2016, 2017 and 2018 when compared with their respective preceding years were -3.7, -16.6, 15.1, -28.1, 22.1, -7.1, 4.6, -3.6, -33.7 and 51.2 percent, indicating a negative change occurring most often, 6/10 times. The scatter plot also showed rate datapoints around a downward regression line, indicating a decreasing trend over years. The LRM showed a negative association between year and ABOMM rate; with each passing year, there was an average decline of 0.67± 0.21(SE) in ABOMM rate, p: 0.0118 (p<0.05, significant).

Conclusion:

Use of ABO mismatched grafts in acute leukemias have decreased significantly over the last ten years. Advances in our understanding of the complications of ABO-mismatched transplants, improvement in immunohematology techniques, and implementation of accreditation policies may have contributed to this decline. Further research may help determine the impact of ABO-matching on transplant survival and transplant costs.