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Antibody incubation of human marrow graft for prevention graft versus host disease

Knochenmarktransplantation nach Vorinkubation mit antihumanem Anti-T-Zell-Globulin

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Zusammenfassung

Tierexperimentelle Befunde ergaben den Hinweis, daß bei Knochenmarktransplantation mit inkompatiblem Spendermark eine Vorinkubation des Spendermarkes mit xenogenem Anti-T-Zell-Globulin eine sonst toxisch verlaufende Graft versus Host-(GvH)Erkrankung vermeidet. Bei drei Patienten mit akuter lymphatischer Leukämie wurde dieses Prinzip bei der Knochenmarktransplantation erfolgreich klinisch angewandt. Zur Anwendung gelangte ein spezifisches antihumanes Anti-T-Zell-Globulin (ATCG-H), das durch mehrere Absorptionsschritte aus rohem antihumanem Globulin (ATG) gewonnen wurde. Eine Vortestung des Serums ergab eine unveränderte Reaktion gegen menschliche T-Zell-Lymphozyten ohne toxische Nebenwirkungen auf in vitro nachweisbare Vorläuferzellen der Hämopoese (CFU-C).

Die Knochenmarktransplantation wurde bei allen drei Patienten nach üblicher Chemotherapie („Konditionierung“) und Ganzkörperbestrahlung mittels vorinkubiertem Spendermark von HLA-identischen Geschwisterndurchgeführt. Toxische Nebenwirkungen durch die Vorinkubation traten nicht auf. Anzeichen einer GvH wurden bisher (24, 7, 6 Monate) bei den Empfängern nicht beobachtet. Die in vitro -Vorinkubation von Spenderknochenmark kann somit als ungefährlicher neuer Versuch zur Vermeidung einer GvH beim Menschen empfohlen werden.

Summary

An in vitro incubation of incompatible donor bone marrow by xenogenic anti-T-cell globulin (ATG) suppressed an otherwise lethal GvH reaction in animal models. An application of this principle to clinical bone marrow transplantation was successfully tried in three patients with acute lymphoblastic leukemia. Preparation of the specific anti-human T-cell globulin (ATCG-H) was carried out by absorption of anti-human thymocyte globulin with liver-kidney homogenate, chronic lymphocytic leukemia cells of B-cell type, and erythrocytes. Subsequent testing revealed that the serum still reacted with human T-cells but no longer reduced the number of colony-forming units in culture (CFU-C).

All three bone marrow recipients were treated by chemotherapeutic conditioning and total body irradiation followed by grafting of in vitro treated bone marrow from HLA-identical siblings. The transplantation of the bone marrow was well tolerated and no major side effects were encountered. No patient so far (24, 7, 6 months) has shown any signs of GvHD. The in vitro pretransplantation treatment of bone marrow with anti T-globulin may be a new approach to the prevention for GvHD in man.

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Authors and Affiliations

  1. Kinderklinik der Universität München (Dr. von Haunersches Kinderspital), D-8000, München 2, Germany

    R. J. Haas, G. Janka, B. Netzel, M. Helmig, R. Eife, B. H. Belohradsky & K. Betke

  2. Institut für Hämatologie, Abt. Immunologie, Gesellschaft für Strahlen-,und Umweltforschung München, D-8000, München 2

    H. Rodt & S. Thierfelder

  3. III. Medizinische Klinik der Universität München, D-8000, München

    H. J. Kolb

Authors
  1. R. J. Haas
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  2. G. Janka
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  3. B. Netzel
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  4. H. Rodt
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  5. S. Thierfelder
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  6. M. Helmig
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  7. R. Eife
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  8. B. H. Belohradsky
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  9. H. J. Kolb
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  10. K. Betke
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Supported by Deutsche Krebshilfe, Bonn and Deutsche Forschungsgemeinschaft, SFB 37, B 7, E 9

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Haas, R.J., Janka, G., Netzel, B. et al. Antibody incubation of human marrow graft for prevention graft versus host disease. Blut 40, 387–397 (1980). https://doi.org/10.1007/BF01029680

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  • DOI: https://doi.org/10.1007/BF01029680

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