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. 1977 Apr;59(4):625–632. doi: 10.1172/JCI108680

Treatment of aplastic anemia by marrow transplantation from HLA identical siblings. Prognostic factors associated with graft versus host disease and survival.

R Storb, R L Prentice, E D Thomas
PMCID: PMC372266  PMID: 14972

Abstract

73 consecutive patients with severe aplastic anemia were treated by marrow transplantation from hematologically normal HLA identical siblings. 68 patients lived long enough to document marrow engraftment. 21 rejected the graft and 19 of these died. 47 sustained engraftment and 18 of these died. In 16 patients, death was associated with graft versus host disease. 29 patients with sustained engraftment are alive with complete hematologic restoration between 8 mo and 5 yr. This analysis, by using a proportional hazards regression model, was directed at identifying factors that predicted survival (and absence of graft versus host disease). Of the 24 factors entered into the analysis only two strongly correlated with survival: (a) sex match of donor and recipient (P less than 0.01), and (b) absence of refractoriness to random donor platelets at the time of transplantation (P less than 0.05). Refractoriness adversely influenced the survival of the sex mismatched patients, These data suggest that X and Y-associated transplantation antigen systems are important determinants of the outcome of marrow grafts between HLA identical siblings for the treatment of aplastic anemia. The machanism by which refractoriness to random donor platelets influences survival is currently unclear.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BAILEY D. W. Histoincompatibility associated with the X chromosome in mice. Transplantation. 1963 Jan;1:70–74. doi: 10.1097/00007890-196301010-00009. [DOI] [PubMed] [Google Scholar]
  2. BILLINGHAM R. E., HODGE B. A., SILVERS W. K. An estimate of the number of histocompatibility loci in the rat. Proc Natl Acad Sci U S A. 1962 Feb;48:138–147. doi: 10.1073/pnas.48.2.138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BILLINGHAM R. E., SILVERS W. K., WILSON D. B. A SECOND STUDY ON THE H-Y TRANSPLANTATION ANTIGEN IN MICE. Proc R Soc Lond B Biol Sci. 1965 Aug 24;163:61–89. doi: 10.1098/rspb.1965.0060. [DOI] [PubMed] [Google Scholar]
  4. Bailey D. W. Allelic forms of a gene controlling the female immune response to the male antigen in mice. Transplantation. 1971 Apr;11(4):426–428. doi: 10.1097/00007890-197104000-00017. [DOI] [PubMed] [Google Scholar]
  5. Bailey D. W., Hoste J. A gene governing the female immune response to the male antigen in mice. Transplantation. 1971 Apr;11(4):404–407. doi: 10.1097/00007890-197104000-00008. [DOI] [PubMed] [Google Scholar]
  6. Camitta B. M., Thomas E. D., Nathan D. G., Santos G., Gordon-Smith E. C., Gale R. P., Rappeport J. M., Storb R. Severe aplastic anemia: a prospective study of the effect of early marrow transplantation on acute mortality. Blood. 1976 Jul;48(1):63–70. [PubMed] [Google Scholar]
  7. Chai C. K. The effect of inbreeding in rabbits. Skin transplantation. Transplantation. 1968 Aug;6(5):689–693. doi: 10.1097/00007890-196808000-00001. [DOI] [PubMed] [Google Scholar]
  8. DE VRIES M. J., VOS O. Treatment of mouse lymphosarcoma by total-body x-irradiation and by injection of bone marrow and lymph-node cells. J Natl Cancer Inst. 1958 Dec;21(6):1117–1129. [PubMed] [Google Scholar]
  9. Eichwald E. J., Silmser C. R. Skin. Transplant Bull. 1955;2:148–149. [PubMed] [Google Scholar]
  10. Gasser D. L., Silvers W. K. Genetic control of the immune response in mice. 3. An association between H-2 type and reaction to H-Y. J Immunol. 1971 Mar;106(3):875–876. [PubMed] [Google Scholar]
  11. Gasser D. L., Silvers W. K. Genetics and immunology of sex-linked antigens. Adv Immunol. 1972;15:215–247. doi: 10.1016/s0065-2776(08)60686-0. [DOI] [PubMed] [Google Scholar]
  12. Gasser D. L., Silvers W. K. The genetic basis of male skin rejection in mice. Transplantation. 1971 Nov;12(5):412–414. doi: 10.1097/00007890-197111000-00017. [DOI] [PubMed] [Google Scholar]
  13. Glucksberg H., Storb R., Fefer A., Buckner C. D., Neiman P. E., Clift R. A., Lerner K. G., Thomas E. D. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974 Oct;18(4):295–304. doi: 10.1097/00007890-197410000-00001. [DOI] [PubMed] [Google Scholar]
  14. Hildemann W. H., Cooper E. L. Transplantation genetics: unexpected histoincompatibility associated with skin grafts from F2 and F3 hybrid donors to F1 hybrid recipients. Transplantation. 1967 Jul;5(4):707–720. [PubMed] [Google Scholar]
  15. Hildemann W. H., Pinkerton W. Alloantibody production measured by plaque assay in relation to strong and weak histoincompatibility. J Exp Med. 1966 Nov 1;124(5):885–900. doi: 10.1084/jem.124.5.885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mickelson E. M., Fefer A., Storb R., Thomas E. D. Correlation of the relative response index with marrow graft rejection in patients with aplastic anemia. Transplantation. 1976 Sep;22(3):294–302. doi: 10.1097/00007890-197609000-00011. [DOI] [PubMed] [Google Scholar]
  17. Prentice R. Use of the logistic model in retrospective studies. Biometrics. 1976 Sep;32(3):599–606. [PubMed] [Google Scholar]
  18. Rosenau W., Horwitz C. Graft rejections in paternal to F1 hybrid and reciprocal hybrid grafts indicating a histocompatibility gene on the mouse X chromosome. Lab Invest. 1968 Mar;18(3):298–303. [PubMed] [Google Scholar]
  19. Storb R., Gluckman E., Thomas E. D., Buckner C. D., Clift R. A., Fefer A., Glucksberg H., Graham T. C., Johnson F. L., Lerner K. G. Treatment of established human graft-versus-host disease by antithymocyte globulin. Blood. 1974 Jul;44(1):56–75. [PubMed] [Google Scholar]
  20. Storb R., Thomas E. D., Buckner C. D., Clift R. A., Fefer A., Fernando L. P., Giblett E. R., Johnson F. L., Neiman P. E. Allogeneic marrow grafting for treatment of aplastic anemia: a follow-up on long-term survivors. Blood. 1976 Oct;48(4):485–490. [PubMed] [Google Scholar]
  21. Storb R., Thomas E. D., Buckner C. D., Clift R. A., Johnson F. L., Fefer A., Glucksberg H., Giblett E. R., Lerner K. G., Neiman P. Allogeneic marrow grafting for treatment of aplastic anemia. Blood. 1974 Feb;43(2):157–180. [PubMed] [Google Scholar]
  22. Storb R., Thomas E. D., Weiden P. L., Buckner C. D., Clift R. A., Fefer A., Fernando L. P., Giblett E. R., Goodell B. W., Johnson F. L. Aplastic anemia treated by allogeneic bone marrow transplantation: a report on 49 new cases from Seattle. Blood. 1976 Dec;48(6):817–841. [PubMed] [Google Scholar]
  23. Thomas E. D., Storb R., Clift R. A., Fefer A., Johnson L., Neiman P. E., Lerner K. G., Glucksberg H., Buckner C. D. Bone-marrow transplantation (second of two parts). N Engl J Med. 1975 Apr 24;292(17):895–902. doi: 10.1056/NEJM197504242921706. [DOI] [PubMed] [Google Scholar]
  24. Thomas E. D., Storb R., Fefer A., Slichter S. J., Bryant J. I., Buckner C. D., Neiman P. E., Clift R. A., Funk D. D., Lerner K. E. Aplastic anaemia treated by marrow transplantation. Lancet. 1972 Feb 5;1(7745):284–289. doi: 10.1016/s0140-6736(72)90292-9. [DOI] [PubMed] [Google Scholar]
  25. Thomas E. D., Storb R. Technique for human marrow grafting. Blood. 1970 Oct;36(4):507–515. [PubMed] [Google Scholar]
  26. Uphoff D. E. Male-specific antigens. Evidence for allelic differences in reciprocal hybrid mice. Transplantation. 1975 Jul;20(1):78–81. [PubMed] [Google Scholar]
  27. Wikstrand C. J., Haughton G., Bailey D. W. The male antigen. II. Regulation of the primary and secondary responses to H-Y by H-2 associated genes. Cell Immunol. 1974 Feb;10(2):238–247. doi: 10.1016/0008-8749(74)90115-4. [DOI] [PubMed] [Google Scholar]
  28. Wikstrand C. J., Haughton G. The murine male antigen. 3. Variable expression of H-Y by murine tumors. J Natl Cancer Inst. 1974 Aug;53(2):527–532. doi: 10.1093/jnci/53.2.527. [DOI] [PubMed] [Google Scholar]
  29. Wikstrand C. J., Haughton G. The murine male antigen. I. Sensitive detection by the PEC transfer system. Cell Immunol. 1974 Feb;10(2):226–237. doi: 10.1016/0008-8749(74)90114-2. [DOI] [PubMed] [Google Scholar]

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