Hemolytic anemia due to passenger lymphocyte syndrome in solid malignancy patients treated with allogeneic natural killer cell products
Address correspondence to: David H. McKenna Jr, MD, Clinical Cell Therapy Laboratory, University of Minnesota Medical Center, Molecular & Cellular Therapeutics, 1900 Fitch Avenue, Saint Paul, MN 55108; e-mail: email@example.com.
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.
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.
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.