Donor bone marrow treatment with T101 Fab fragment-ricin A-chain immunotoxin prevents graft-versus-host disease.
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.
Laurent
G
G
Sanofi Recherche, Montpellier, France.
Maraninchi
D
D
Gluckman
E
E
Vernant
J P
JP
Derocq
J M
JM
Gaspard
M H
MH
Rio
B
B
Michalet
M
M
Reiffers
J
J
Dreyfus
F
F
D000293:Adolescent; D000328:Adult; D001853:Bone Marrow / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D000922:Immunotoxins / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D012276:Ricin / Q000494:pharmacology / Q000627:therapeutic use*
D007140:Immunoglobulin Fab Fragments; D000922:Immunotoxins; C061184:T101 FAB fragment-ricin A-chain immunotoxin; D012276:Ricin