Evaluation of anti-CD5 ricin A chain immunoconjugate for prevention of acute graft-vs.-host disease after HLA-identical marrow transplantation.
Anti-CD5 ricin A chain immunoconjugate (XZ-CD5) is an immunotoxin that inhibits proliferative and cytotoxic responses to alloantigen in vitro and has activity in the treatment of acute graft-vs.-host disease (GVHD). To determine if XZ-CD5 could be used to prevent acute GVHD, 11 adult recipients of HLA-identical allogeneic marrow received XZ-CD5 0.1 mg kg-1 day-1 intravenously with high-dose methyl-prednisolone for 10, 14 or 17 doses early post-transplant. Six additional patients received 17 doses of XZ-CD5 and cyclosporine (CSA). All patients engrafted. Severe capillary leak syndrome was the most common serious toxicity and occurred more frequently in patients receiving CSA (5/5 vs. 3/11, P = 0.03). All evaluable patients developed acute GVHD; 88% had grade II-IV GVHD. Flow cytometric analysis demonstrated a substantial number of circulating CD5+ and CD3+ lymphocytes during and early after administration of XZ-CD5. These results suggest that the immunotoxin did not eliminate alloreactive T cells in this setting.
Przepiorka
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Section of Bone Marrow Transplantation, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
LeMaistre
C F
CF
Huh
Y O
YO
Luna
M
M
Saria
E A
EA
Brown
C T
CT
Champlin
R E
RE
D000208:Acute Disease; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000379:methods*; D018956:CD5 Antigens / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D000922:Immunotoxins / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012276:Ricin / Q000009:adverse effects / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000911:Antibodies, Monoclonal; D018956:CD5 Antigens; D000922:Immunotoxins; C068230:zolimomab aritox; D012276:Ricin