Elimination of alloantibodies by immunoablative high-dose cyclophosphamide.
BACKGROUND
Alloimmunization is a major problem for patients being considered for solid organ transplantation and in patients who require blood transfusion support. We previously demonstrated that high-dose cyclophosphamide (200 mg/kg) without hematopoietic stem cell transplantation leads to durable complete remissions in aplastic anemia and other autoimmune disorders. We now examine the ability of high-dose cyclophosphamide to eliminate alloreactivity.


METHODS
IgG-specific antibodies to HLA class I were assayed using enzyme-linked immunosorbent assays in 18 consecutive patients with severe aplastic anemia before and after treatment with high-dose cyclophosphamide.


RESULTS
Anti-HLA antibodies were detected before or shortly after therapy in 5 of the 18 patients studied. Complete remission of aplastic anemia was achieved in four of these five patients. High-dose cyclophosphamide markedly reduced anti-HLA antibody titers in these four patients; they were completely eradicated in three patients. Only one patient did not achieve significant reduction in the alloantibody titer after high-dose cyclophosphamide.


CONCLUSIONS
High-dose cyclophosphamide without stem cell transplantation can eradicate HLA-specific alloantibody.
Johns Hopkins Oncology Center, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. rbrodsky@jhmi.edu
R A
RA
Brodsky
A K
AK
Fuller
L E
LE
Ratner
M S
MS
Leffell
R J
RJ
Jones
D000328:Adult; D000741:Anemia, Aplastic / Q000276:immunology / Q000628:therapy; D000906:Antibodies / Q000097:blood; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007518:Isoantibodies / Q000187:drug effects*; D008297:Male; D008875:Middle Aged
D000906:Antibodies; D006680:HLA Antigens; D007074:Immunoglobulin G; D007518:Isoantibodies; D003520:Cyclophosphamide