High risk of graft failure in patients with anti-HLA antibodies undergoing haploidentical stem-cell transplantation.
BACKGROUND.: Although donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) have been implicated in graft rejection in solid organ transplantation, their role in hematopoietic stem-cell transplantation remains unclear. METHODS.: To address the hypothesis that the presence of DSA contributes to the development graft failure, we tested 24 consecutive patients for the presence of anti-HLA antibodies determined by a sensitive and specific solid-phase/single-antigen assay. The study included a total of 28 haploidentical transplants, each with 2 to 5 HLA allele mismatches, at a single institution, from September 2005 to August 2008. RESULTS.: DSA were detected in five patients (21%). Three of four (75%) patients with DSA before the first transplant failed to engraft, compared with 1 of 20 (5%) without DSA (P=0.008). All four patients who experienced primary graft failure had second haploidentical transplants. One patient developed a second graft failure with persistent high DSA levels, whereas three engrafted, two of them in the absence of DSA. No other known factors that could negatively influence engraftment were associated with the development of graft failure in these patients. CONCLUSIONS.: These results suggest that donor-specific anti-HLA antibodies are associated with a high rate of graft rejection in patients undergoing haploidentical stem-cell transplantation. Anti-HLA sensitization should be evaluated routinely in hematopoietic stem-cell transplantation with HLA mismatched donors.
Department of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Stefan O
SO
Ciurea
Marcos
M
de Lima
Pedro
P
Cano
Martin
M
Korbling
Sergio
S
Giralt
Elizabeth J
EJ
Shpall
Xuemei
X
Wang
Peter F
PF
Thall
Richard E
RE
Champlin
Marcelo
M
Fernandez-Vina
D015703:Antigens, CD / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood; D005190:Family; D005260:Female; D000069585:Filgrastim; D006084:Graft Rejection / Q000276:immunology*; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006680:HLA Antigens / Q000276:immunology*; D006238:Haploidy; D006239:Haplotypes / Q000276:immunology; D019337:Hematologic Neoplasms / Q000601:surgery*; D006801:Humans; D007519:Isoantigens / Q000276:immunology; D008212:Lymphocyte Depletion; D011994:Recombinant Proteins; D033581:Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods*; D013601:T-Lymphocytes / Q000276:immunology; D014019:Tissue Donors / Q000706:statistics & numerical data; D017211:Treatment Failure
D015703:Antigens, CD; D018952:Antigens, CD34; D006680:HLA Antigens; D007519:Isoantigens; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim