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

Authors

  • Robert Skeate,

    1. Canadian Blood Services, Central Ontario, Toronto, Canada
    2. Department of Laboratory Medicine and Pathology, Division of Transfusion Medicine, University of Minnesota Medical School, Minneapolis, Minnesota
    3. Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, Minnesota
    4. Department of Obstetrics and Gynecology, University of Minnesota Medical School, Minneapolis, Minnesota
    5. Clinical Cell Therapy Laboratory, University of Minnesota Medical Center, Molecular and Cellular Therapeutics, Saint Paul, Minnesota
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  • Charanjeet Singh,

    1. Canadian Blood Services, Central Ontario, Toronto, Canada
    2. Department of Laboratory Medicine and Pathology, Division of Transfusion Medicine, University of Minnesota Medical School, Minneapolis, Minnesota
    3. Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, Minnesota
    4. Department of Obstetrics and Gynecology, University of Minnesota Medical School, Minneapolis, Minnesota
    5. Clinical Cell Therapy Laboratory, University of Minnesota Medical Center, Molecular and Cellular Therapeutics, Saint Paul, Minnesota
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  • Sarah Cooley,

    1. Canadian Blood Services, Central Ontario, Toronto, Canada
    2. Department of Laboratory Medicine and Pathology, Division of Transfusion Medicine, University of Minnesota Medical School, Minneapolis, Minnesota
    3. Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, Minnesota
    4. Department of Obstetrics and Gynecology, University of Minnesota Medical School, Minneapolis, Minnesota
    5. Clinical Cell Therapy Laboratory, University of Minnesota Medical Center, Molecular and Cellular Therapeutics, Saint Paul, Minnesota
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  • Melissa Geller,

    1. Canadian Blood Services, Central Ontario, Toronto, Canada
    2. Department of Laboratory Medicine and Pathology, Division of Transfusion Medicine, University of Minnesota Medical School, Minneapolis, Minnesota
    3. Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, Minnesota
    4. Department of Obstetrics and Gynecology, University of Minnesota Medical School, Minneapolis, Minnesota
    5. Clinical Cell Therapy Laboratory, University of Minnesota Medical Center, Molecular and Cellular Therapeutics, Saint Paul, Minnesota
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  • Joan Northouse,

    1. Canadian Blood Services, Central Ontario, Toronto, Canada
    2. Department of Laboratory Medicine and Pathology, Division of Transfusion Medicine, University of Minnesota Medical School, Minneapolis, Minnesota
    3. Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, Minnesota
    4. Department of Obstetrics and Gynecology, University of Minnesota Medical School, Minneapolis, Minnesota
    5. Clinical Cell Therapy Laboratory, University of Minnesota Medical Center, Molecular and Cellular Therapeutics, Saint Paul, Minnesota
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  • Julie Welbig,

    1. Canadian Blood Services, Central Ontario, Toronto, Canada
    2. Department of Laboratory Medicine and Pathology, Division of Transfusion Medicine, University of Minnesota Medical School, Minneapolis, Minnesota
    3. Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, Minnesota
    4. Department of Obstetrics and Gynecology, University of Minnesota Medical School, Minneapolis, Minnesota
    5. Clinical Cell Therapy Laboratory, University of Minnesota Medical Center, Molecular and Cellular Therapeutics, Saint Paul, Minnesota
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  • Arne Slungaard,

    1. Canadian Blood Services, Central Ontario, Toronto, Canada
    2. Department of Laboratory Medicine and Pathology, Division of Transfusion Medicine, University of Minnesota Medical School, Minneapolis, Minnesota
    3. Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, Minnesota
    4. Department of Obstetrics and Gynecology, University of Minnesota Medical School, Minneapolis, Minnesota
    5. Clinical Cell Therapy Laboratory, University of Minnesota Medical Center, Molecular and Cellular Therapeutics, Saint Paul, Minnesota
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  • Jeff Miller,

    1. Canadian Blood Services, Central Ontario, Toronto, Canada
    2. Department of Laboratory Medicine and Pathology, Division of Transfusion Medicine, University of Minnesota Medical School, Minneapolis, Minnesota
    3. Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, Minnesota
    4. Department of Obstetrics and Gynecology, University of Minnesota Medical School, Minneapolis, Minnesota
    5. Clinical Cell Therapy Laboratory, University of Minnesota Medical Center, Molecular and Cellular Therapeutics, Saint Paul, Minnesota
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  • David McKenna

    Corresponding author
    1. Department of Laboratory Medicine and Pathology, Division of Transfusion Medicine, University of Minnesota Medical School, Minneapolis, Minnesota
    2. Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, Minnesota
    3. Department of Obstetrics and Gynecology, University of Minnesota Medical School, Minneapolis, Minnesota
    4. Clinical Cell Therapy Laboratory, University of Minnesota Medical Center, Molecular and Cellular Therapeutics, Saint Paul, Minnesota
    • Canadian Blood Services, Central Ontario, Toronto, Canada
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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: mcken020@umn.edu.

Abstract

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.

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