A new marrow T cell depletion method using anti-CD6 monoclonal antibody-conjugated magnetic beads and its clinical application for prevention of acute graft-vs.-host disease in allogeneic bone marrow transplantation: results of a phase I-II trial.
We established a simple method of T cell depletion using anti-CD6 monoclonal antibody-conjugated immunomagnetic beads. Preliminary experiments using this method demonstrated that CD3+ T cells could be partially depleted without depleting CD56+ NK cells. A phase I-II clinical study was performed to assess the safety and efficacy of this partial T cell depletion method for the prevention of acute graft-vs.-host disease (GVHD) in 10 leukemia patients at high risk for GVHD (defined as 1) unrelated transplant from MLC-positive or HLA-DRB1 mismatched donor or 2) related transplant from serologically HLA-A, -B, or -DR one-locus mismatched donor). Cyclosporine (CSP) and methotrexate (MTX) were used for additional prophylaxis against GVHD in all cases. Sustained engraftment occurred in 9 of the 10 patients. Although acute GVHD developed in 6 of the 9 evaluable patients, none developed more than grade III severe acute GVHD. Five patients were alive in remission at a median follow-up of 32 months after bone marrow transplantation, and no relapse of leukemia was observed. We conclude from this pilot study that selective T cell depletion with anti-CD6 monoclonal antibody coupled with CSP and MTX posttransplant immunosuppressive therapy is safe. Further analysis of the phase II-III study is needed to confirm the effectiveness of this protocol.
Sao
H
H
Department of Hematology, Meitetsu Hospital, Nagoya, Japan.
Kitaori
K
K
Kasai
M
M
Shimokawa
T
T
Kato
C
C
Yamanishi
H
H
Ueda
R
R
Morishima
Y
Y
D000208:Acute Disease; D000257:Adenoviridae Infections / Q000209:etiology; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000998:Antiviral Agents / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D016572:Cyclosporine / Q000627:therapeutic use; D003556:Cystitis / Q000209:etiology; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000209:etiology; D005260:Female; D016469:Fungemia / Q000209:etiology; D015774:Ganciclovir / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006648:Histocompatibility; D006801:Humans; D018189:Immunomagnetic Separation; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007938:Leukemia / Q000628:therapy; D017563:Lung Diseases, Interstitial / Q000209:etiology; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D012449:Safety; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous / Q000009:adverse effects*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000998:Antiviral Agents; C062279:CD6 antigen; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D015774:Ganciclovir; D008727:Methotrexate