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Autologous stem cell transplant recipients tolerate haploidentical related-donor natural killer cell–enriched infusions

Authors

  • Hans Klingemann,

    Corresponding author
    1. From the Division of Hematology/Oncology, Tufts Medical Center, Boston, Massachusetts; the Division of Hematology/Oncology, Lahey Clinic Medical Center, Burlington, Massachusetts; the American Red Cross Blood Services, New England Region, Dedham, Massachusetts; and the Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, Minnesota.
      Hans Klingemann, MD, PhD, Division of Hematology/Oncology, Tufts Medical Center, 800 Washington Street, Number 245, Boston, MA 02111; e-mail: hklingemann@tuftsmedicalcenter.org.
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  • Carrie Grodman,

    1. From the Division of Hematology/Oncology, Tufts Medical Center, Boston, Massachusetts; the Division of Hematology/Oncology, Lahey Clinic Medical Center, Burlington, Massachusetts; the American Red Cross Blood Services, New England Region, Dedham, Massachusetts; and the Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, Minnesota.
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  • Elliott Cutler,

    1. From the Division of Hematology/Oncology, Tufts Medical Center, Boston, Massachusetts; the Division of Hematology/Oncology, Lahey Clinic Medical Center, Burlington, Massachusetts; the American Red Cross Blood Services, New England Region, Dedham, Massachusetts; and the Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, Minnesota.
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  • Marvin Duque,

    1. From the Division of Hematology/Oncology, Tufts Medical Center, Boston, Massachusetts; the Division of Hematology/Oncology, Lahey Clinic Medical Center, Burlington, Massachusetts; the American Red Cross Blood Services, New England Region, Dedham, Massachusetts; and the Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, Minnesota.
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  • Diane Kadidlo,

    1. From the Division of Hematology/Oncology, Tufts Medical Center, Boston, Massachusetts; the Division of Hematology/Oncology, Lahey Clinic Medical Center, Burlington, Massachusetts; the American Red Cross Blood Services, New England Region, Dedham, Massachusetts; and the Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, Minnesota.
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  • Andreas K. Klein,

    1. From the Division of Hematology/Oncology, Tufts Medical Center, Boston, Massachusetts; the Division of Hematology/Oncology, Lahey Clinic Medical Center, Burlington, Massachusetts; the American Red Cross Blood Services, New England Region, Dedham, Massachusetts; and the Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, Minnesota.
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  • Kellie A. Sprague,

    1. From the Division of Hematology/Oncology, Tufts Medical Center, Boston, Massachusetts; the Division of Hematology/Oncology, Lahey Clinic Medical Center, Burlington, Massachusetts; the American Red Cross Blood Services, New England Region, Dedham, Massachusetts; and the Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, Minnesota.
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  • Kenneth B. Miller,

    1. From the Division of Hematology/Oncology, Tufts Medical Center, Boston, Massachusetts; the Division of Hematology/Oncology, Lahey Clinic Medical Center, Burlington, Massachusetts; the American Red Cross Blood Services, New England Region, Dedham, Massachusetts; and the Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, Minnesota.
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  • Raymond L. Comenzo,

    1. From the Division of Hematology/Oncology, Tufts Medical Center, Boston, Massachusetts; the Division of Hematology/Oncology, Lahey Clinic Medical Center, Burlington, Massachusetts; the American Red Cross Blood Services, New England Region, Dedham, Massachusetts; and the Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, Minnesota.
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  • Tarun Kewalramani,

    1. From the Division of Hematology/Oncology, Tufts Medical Center, Boston, Massachusetts; the Division of Hematology/Oncology, Lahey Clinic Medical Center, Burlington, Massachusetts; the American Red Cross Blood Services, New England Region, Dedham, Massachusetts; and the Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, Minnesota.
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  • Neng Yu,

    1. From the Division of Hematology/Oncology, Tufts Medical Center, Boston, Massachusetts; the Division of Hematology/Oncology, Lahey Clinic Medical Center, Burlington, Massachusetts; the American Red Cross Blood Services, New England Region, Dedham, Massachusetts; and the Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, Minnesota.
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  • Richard A. Van Etten,

    1. From the Division of Hematology/Oncology, Tufts Medical Center, Boston, Massachusetts; the Division of Hematology/Oncology, Lahey Clinic Medical Center, Burlington, Massachusetts; the American Red Cross Blood Services, New England Region, Dedham, Massachusetts; and the Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, Minnesota.
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  • David H. McKenna

    1. From the Division of Hematology/Oncology, Tufts Medical Center, Boston, Massachusetts; the Division of Hematology/Oncology, Lahey Clinic Medical Center, Burlington, Massachusetts; the American Red Cross Blood Services, New England Region, Dedham, Massachusetts; and the Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, Minnesota.
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  • This project was supported in part by PACT that is federally funded by the National Heart, Lung, and Blood Institute under Contract N01-HB-37166 and HHSSN268201000008C. It was further funded in part by NIH Grant 1RO1HL093981-01A1.

Hans Klingemann, MD, PhD, Division of Hematology/Oncology, Tufts Medical Center, 800 Washington Street, Number 245, Boston, MA 02111; e-mail: hklingemann@tuftsmedicalcenter.org.

Abstract

BACKGROUND: In the setting of allogeneic stem cell transplantation (SCT), infusing natural killer (NK) cells from a major histocompatibility complex (MHC)-mismatched donor can mediate an antileukemic effect. The graft-versus-tumor effect after autologous stem cell transplantation (ASCT) may result in less disease relapse.

STUDY DESIGN AND METHODS: We performed a Phase I clinical trial to assess the safety and feasibility of infusing distantly processed donor NK-enriched mononuclear cell (NK-MNC) infusions from a MHC haplotype–mismatched (haploidentical) donor to patients who recently underwent ASCT for a hematologic malignancy. On Day 1, peripheral blood MNCs were obtained by steady-state leukapheresis and sent from Boston to the Production Assistance for Cellular Therapies (PACT) facility at the University of Minnesota, where immunomagnetic depletion of CD3 cells was performed on Day 2. NK-MNC products were then returned to Boston on Day 2 for infusion on Day 3. Toxicity, cellular product characteristics, and logistic events were monitored.

RESULTS: At a median of 90 days (range, 49-191 days) after ASCT, 13 patients were treated with escalating doses of NK-MNCs per kilogram from 105 to 2 × 107. Adverse effects included Grade 2 rigors and muscle aches, but no Grade 3 or 4 events and no graft-versus-host disease or marrow suppression. One air courier delay occurred. NK-MNC products were viable with cytotoxic activity after transport.

CONCLUSION: CD3-depleted, MHC-mismatched allogeneic NK-MNC infusions can be safely and feasibly administered to patients after ASCT after distant processing and transport, justifying further development of this approach.

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