P131 : PLATELET SUPPORT FOLLOWING HAPLOIDENTICAL STEM CELL TRANSPLANT: BLURRED LINES BETWEEN SELF AND NONSELF

Abstract

As mismatched hematopoietic stem cell transplant (HSCT) becomes more common for treatment of hematologic malignancies, interpretation of HLA sensitization has become more complex. The patient is a 19 year old male with persistent, refractory Acute Myeloid Leukemia (AML), and a history of thrombocytopenia since one week of age. He was found to have a RUNX1 mutation, and a diagnosis of Familial Thrombocytopenia with Predisposition to AML (FT-AML). The patient was referred to St. Jude for haploidentical HSCT and NK cell therapy, using his mother as the donor. Although refractory to platelets, he was negative for anti-HLA antibodies prior to transplant. On day 62 post-HSCT, the patient had engrafted and his peripheral blood chimerism was 100% donor. However, platelet consumption was suspected, and a serum sample at that time was clearly positive for antibodies to B42, 82, 7, 81, 55, 54, 27, 56 (B7 CREG), B49, 62, 50 (B5 CREG), plus B67 and A36. The patient also had antibody to Cw8, and to 5 different DR4 specificities (DRB1 ∗ 04:01, 04:02, 04:03, 04:04, and 04:05). HLA Class I Cw and class II antigens are not expressed on platelets, but may be important in the setting of current or future HSCT. Importantly, the patient’s father has HLA-A1, B56, and DR4. The patient did not have antibodies to his own HLA antigens, or the unshared antigens from his donor, illustrating tolerance to those “self” antigens. The treatment team desired HLA-matched platelets, but these were unavailable, based on the patient’s original HLA type. Compatible platelets were selected based on his original HLA type and excluding donors with HLA antigens to which he had demonstrated antibody. Once HLA-compatible platelets were selected, the patient was no longer refractory and his condition improved. Questions arose during this process regarding which antigens should or should not be considered “self,” considering that this patient was mismatched with his donor at HLA-A, B, DR, and DQ loci. Selection of HLA-compatible platelets in the context of haploidentical HSCT is complex, given that a patient will potentially have multiple unshared donor HLA antigens expressed on blood-derived cells and his original HLA antigens on other body cells. Traditional algorithms for searching platelet donor registries may not be adequate, and may require additional manual review.