Hemolytic anemia due to passenger lymphocyte syndrome in solid malignancy patients treated with allogeneic natural killer cell products

Background Allogeneic natural killer (NK) cell products for treatment of solid organ malignancies were prepared by performing T (CD3+)-cell depletion on nonmobilized apheresis mononuclear cell collections. The products were not B-cell depleted. This report details two cases of passenger lymphocyte syndrome (PLS) after NK-cell infusion. Case Reports Patient 1 is a blood group A+ 56-year-old female with Stage IV ovarian carcinoma who received NK cells from an O+ donor. On Day +7 she developed new hemolytic anemia. Direct antiglobulin test (DAT) was positive for immunoglobulin G and C3, and the eluate contained anti-A. Subsequently, anti-A was identified on reverse typing. She was transfused with group O red blood cells (RBCs). By Day +12 she forward typed as O with anti-A and B on reverse typing. By Day +42, DAT was negative with only weak anti-A on reverse typing. Patient 2 is a blood group B+ 51-year-old female with metastatic lobular breast carcinoma who received NK cells from an O+ donor. On Day +7 she developed new hemolytic anemia. DAT was positive, and the eluate contained anti-A and -B. Anti-A reactivity was due to anti-A,B. The next day she developed new anti-B on reverse typing. She was transfused with O RBCs. Anti-B titer increased to a maximum of 512 on Day +12. At discharge on Day +29 her anti-B titer was still 32. Conclusions These patients developed PLS after infusion of NK cells. Because of these cases NK-cell products are now B (CD19+)-cell depleted at our institution, and this approach is recommended for other centers.