Michigan Medicine Ann Arbor, Michigan, United States
Background/Case Studies: In ABO mismatched hematopoietic stem cell transplants (HSCT), the emergence of the patient’s original ABO type is associated with disease relapse and/or graft loss. We describe a case in which strong re-emergence of the patient’s ABO type was attributed to high levels of soluble ABO antigen in the setting of severe graft versus host disease (GVHD). Removal of red cell soluble A antigen was achieved using an older method described for Lewis antigen removal.
Study
Design/Methods: Patient history and engraftment analysis came from medical chart review. Column agglutination (Gel) and serologic tube tests were used for investigation. Lewis antigen typing was performed for secretor status prediction. Neutralization tests consisted of 0.5mL human high titer anti-A (h) mixed with 0.5mL patient plasma and 0.5mL saline as a control. A1 cells were incubated with doubling dilutions of neutralized plasma and saline control. To extract soluble A antigen, plasma (1mL) from an A1 non secretor was incubated with patient and control cells (100uL pRBCs) at 37C for 6 days with daily plasma replacement.
Results/Findings: The patient was a group A, RhD+ male with a history of B-ALL who received a related group O, RhD+ haploidentical HSCT in 2021. Full donor (100%) engraftment was confirmed for lymphoid (CD3+) and myeloid (CD33/CD66b+) lines at 1 & 2 years post-HSCT with transfusion-independence. On ABO typing, his RBC were predominantly group O with trace group A RBC present. At 20 months post-HSCT, he was admitted for chronic GVHD (cGVHD) of the gut and lung, confirmed by biopsy and CT chest. He was treated with extracorporeal photopheresis (ECP) x 15, steroids, and immunosuppressives. He required 3 units of O pRBCs for ECP blood prime. During admission, there was an unexpected increase in group A reactivity (Table 1). He typed Le (a-b-). Soluble A antigen was demonstrated through neutralization of human anti-A(h) by patient plasma at titers 1:32 IgM & 1:64 IgG versus saline control (1:512 IgM & IgG). Resolution of ABO was achieved by incubating plasma from a non-secretor over six days with patient red cells. Appropriate reactivity was seen with control cells. A follow-up visit demonstrated a decrease in soluble A antigen reactivity once cGVHD improved. Conclusions: A sudden course of cGVHD appears to have caused a temporary elevated A antigen reactivity in a post-HSCT patient with lung and GI cGVHD. This contributed to an unexpected forward typing problem that was resolved by exchanging soluble glycolipid lacking A antigen with patient soluble A antigen coating group O donor cells.
Importance of research: This report highlights a method for immunohematology to employ in working up an abnormality in blood type. In this case, after successful stem cell engraftment, a mismatched HSCT recipient’s course was complicated by cGVHD of the GI tract and liver and caused an abnormal forward blood type finding. In order to resolve this finding, a method to remove soluble A antigens from a patient’s red cells was employed to help distinguish recurrent A cells from group O cells with soluble A antigen.
