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Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma.

Publication ,  Journal Article
Anasetti, C; Amos, D; Beatty, PG; Appelbaum, FR; Bensinger, W; Buckner, CD; Clift, R; Doney, K; Martin, PJ; Mickelson, E
Published in: N Engl J Med
January 26, 1989

We analyzed the relevance of HLA compatibility to sustained marrow engraftment in 269 patients with hematologic neoplasms who underwent bone marrow transplantations. Each patient received marrow from a family member who shared one HLA haplotype with the patient but differed to a variable degree for the HLA-A, B, and D antigens of the haplotype not shared. These 269 patients were compared with 930 patients who received marrow from siblings with identical HLA genotypes. All patients were treated with cyclophosphamide and total-body irradiation followed by the infusion of unmodified donor marrow cells. The rate of graft failure was 12.3 percent among the recipients of marrow from a donor with only one identical haplotype, as compared with 2.0 percent among recipients of marrow from a sibling with the same HLA genotype (both haplotypes inherited from the same parents) (P less than 0.0001). The incidence of graft failure correlated with the degree of donor HLA incompatibility. Graft failure occurred in 3 of 43 transplants (7 percent) from donors who were phenotypically HLA-matched with their recipient (haplotypes similar, but not inherited from the same parents), in 11 of 121 donors (9 percent) incompatible for one HLA locus, in 18 of 86 (21 percent) incompatible for two loci, and in 1 of 19 (5 percent) incompatible for three loci (P = 0.028). In a multivariate binary logistic regression analysis, independent risk factors associated with graft failure were donor incompatibility for HLA-B and D (relative risk = 2.1; 95 percent confidence interval, 1.7 to 2.5; P = 0.0004) and a positive crossmatch for anti-donor lymphocytotoxic antibody (relative risk = 2.3; 95 percent confidence interval, 1.8 to 2.8; P = 0.0038). Residual host lymphocytes were detected in 11 of 14 patients with graft failure, suggesting that the mechanism for graft failure could be host-mediated immune rejection. We conclude that donor HLA incompatibility and prior alloimmunization are significant risk factors for graft failure, and that a more effective immunosuppressive regimen than those currently used is needed for consistent achievement of sustained engraftment of marrow transplanted from donors who are not HLA-identical siblings.

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Published In

N Engl J Med

DOI

ISSN

0028-4793

Publication Date

January 26, 1989

Volume

320

Issue

4

Start / End Page

197 / 204

Location

United States

Related Subject Headings

  • Whole-Body Irradiation
  • Risk Factors
  • Middle Aged
  • Lymphoma
  • Leukemia
  • Infant
  • Humans
  • Histocompatibility Testing
  • HLA-D Antigens
  • HLA-B Antigens
 

Citation

APA
Chicago
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Anasetti, C., Amos, D., Beatty, P. G., Appelbaum, F. R., Bensinger, W., Buckner, C. D., … Mickelson, E. (1989). Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma. N Engl J Med, 320(4), 197–204. https://doi.org/10.1056/NEJM198901263200401
Anasetti, C., D. Amos, P. G. Beatty, F. R. Appelbaum, W. Bensinger, C. D. Buckner, R. Clift, K. Doney, P. J. Martin, and E. Mickelson. “Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma.N Engl J Med 320, no. 4 (January 26, 1989): 197–204. https://doi.org/10.1056/NEJM198901263200401.
Anasetti C, Amos D, Beatty PG, Appelbaum FR, Bensinger W, Buckner CD, et al. Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma. N Engl J Med. 1989 Jan 26;320(4):197–204.
Anasetti, C., et al. “Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma.N Engl J Med, vol. 320, no. 4, Jan. 1989, pp. 197–204. Pubmed, doi:10.1056/NEJM198901263200401.
Anasetti C, Amos D, Beatty PG, Appelbaum FR, Bensinger W, Buckner CD, Clift R, Doney K, Martin PJ, Mickelson E. Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma. N Engl J Med. 1989 Jan 26;320(4):197–204.
Journal cover image

Published In

N Engl J Med

DOI

ISSN

0028-4793

Publication Date

January 26, 1989

Volume

320

Issue

4

Start / End Page

197 / 204

Location

United States

Related Subject Headings

  • Whole-Body Irradiation
  • Risk Factors
  • Middle Aged
  • Lymphoma
  • Leukemia
  • Infant
  • Humans
  • Histocompatibility Testing
  • HLA-D Antigens
  • HLA-B Antigens