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Donor bone marrow treatment with T101 Fab fragment-ricin A-chain immunotoxin prevents graft-versus-host disease.

Abstract
Thirty-eight patients with haematological malignancies were treated with bone marrow transplantation using histocompatible immunotoxin T cell-depleted marrow siblings. All patients received conventional postgraft immunosuppression (methotrexate and/or cyclosporin A). Donor bone marrow was treated ex vivo with T101 Fab fragment coupled to ricin A-chain (T101 Fab-RTA) at a concentration of 10(-8) M of A-chain in association with NH4Cl (2 x 10(-2) M) in pH adjusted (7.8) incubation medium. A median cytoreduction of 99.5% (91-99.5) was obtained. The median of follow-up was 300 days. Only three patients developed grade II acute graft-versus-host disease (GVHD) (actuarial rate of acute GVHD: 9.1%). No chronic GVHD occurred. All patients but one engrafted. Six out of the 37 patients developed a documented bone marrow rejection (actuarial rate of graft failure: 18%). Ten patients relapsed (actuarial rate of relapse: 36.9%). These findings demonstrate that treatment of donor marrow with T101 Fab-RTA in association with NH4Cl at critical pH value can achieve a high level of mature T cell depletion and greatly reduce the incidence of bone marrow rejection and relapse after T cell-depleted allogeneic bone marrow transplantation.
AuthorsG Laurent, D Maraninchi, E Gluckman, J P Vernant, J M Derocq, M H Gaspard, B Rio, M Michalet, J Reiffers, F Dreyfus
JournalBone marrow transplantation (Bone Marrow Transplant) Vol. 4 Issue 4 Pg. 367-71 (Jul 1989) ISSN: 0268-3369 [Print] England
PMID2789084 (Publication Type: Journal Article)
Chemical References
  • Immunoglobulin Fab Fragments
  • Immunotoxins
  • T101 FAB fragment-ricin A-chain immunotoxin
  • Ricin
Topics
  • Adolescent
  • Adult
  • Bone Marrow (drug effects)
  • Cell Survival (drug effects)
  • Child
  • Child, Preschool
  • Female
  • Graft vs Host Disease (prevention & control)
  • Humans
  • Immunoglobulin Fab Fragments (immunology, pharmacology, therapeutic use)
  • Immunotoxins (pharmacology, therapeutic use)
  • Male
  • Ricin (pharmacology, therapeutic use)

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