Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Successful reduced-intensity stem cell transplantation from an HLA haploidentical 3-loci-mismatched donor on the basis of fetomaternal microchimerism in a patient with advanced acute myeloid Leukemia

Abstract

A31-year-old woman with advanced acute myeloid leukemia underwent non-T-cell-depleted (TCD) peripheral blood stem cell transplantation (PBSCT) with a reduced-intensity conditioning regimen. The donor was an HLA haploidentical 3-loci-mismatched complementary sibling who had not inherited maternal HLA antigens. Long-term fetomaternal microchimerism was detected by nested polymerase chain reaction with specific primer typing. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus with minidose methotrexate. Durable engraftment was achieved without severe acute GVHD, and complete remission was obtained. Thus non-TCD HLA haploidentical reduced-intensity PBSCT based on fetomaternal immunological tolerance appears to be feasible. Our results have important implications in the selection of alternative donors and conditioning regimens for allogeneic hematopoietic stem cell transplantation.

This is a preview of subscription content, log in to check access.

References

  1. 1.

    Maloney S, Smith A, Furst DE, et al. Microchimerism of maternal origin persists into adult life.J Clin Invest. 1999;104:41–47.

  2. 2.

    Tokita K, Terasaki P, Maruya E, Saji H. Tumour regression following stem cell infusion from daughter to microchimeric mother.Lancet. 2001;358:2047–2048.

  3. 3.

    Maruya E, Terasaki PI, Ichinohe T, et al. Very common occurrence of long-term reciprocal feto-maternal microchimerism detected by nested PCR for HLA antigens.Hum Immunol. 2001; 62(suppl 1):S104.

  4. 4.

    Ichinohe T, Tamaki S, Arata W, et al. Feasibility of non-T-cell- depleted blood and marrow transplantation between haploidentical family members linked with long-term feto-maternal microchimerism [abstract].Blood. 2001;98:669a. Abstract 2804.

  5. 5.

    Slavin S, Nagler A, Naparstek E, et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases.Blood. 1998;91:756–763.

  6. 6.

    Corradini P, Tarella C, Olivieri A, et al. Reduced-intensity conditioning followed by allografting of hematopoietic cells can produce clinical and molecular remissions in patients with poor-risk hematologic malignancies.Blood. 2002;99:75–82.

  7. 7.

    Nosaka T, Ohno H, Doi S, et al. Phenotypic conversion of T lymphoblastic lymphoma to acute biphenotypic leukemia composed of lymphoblasts and myeloblasts.J Clin Invest. 1988;81:1824–1828.

  8. 8.

    Ogawa H, Tsuboi A, Tamaki H, et al. Successful donor leukocyte transfusion at molecular relapse for a patient with acute myeloid leukemia who was treated with allogeneic bone marrow transplantation: importance of the monitoring of minimal residual disease by WT1 assay.Bone Marrow Transplant. 1998;21:525–527.

  9. 9.

    Klingemann HG, Grigg AP, Wilkie-Boyd K, et al. Treatment with recombinant interferon (α-2α) early after bone marrow transplantation in patients at high risk for relapse.Blood. 1991;78:3306–3311.

  10. 10.

    Shaffer L, Giralt S, Champlin R, Chan KW. Treatment of leukemia relapse after bone marrow transplantation with interferon-alpha and interleukin 2.Bone Marrow Transplant. 1995;15:317–319.

  11. 11.

    Tamaki S, Ichinohe T, Matsuo K, et al. Superior survival of blood and marrow stem cell recipients given maternal grafts over recipients given paternal grafts.Bone Marrow Transplant. 2001;28:375–380.

  12. 12.

    Van Rood JJ, Loberiza FR Jr, Zhang MJ, et al. Effect of tolerance to noninherited maternal antigens on the occurrence of graft-versus- host disease after bone marrow transplantation from a parent or an HLA-haploidentical sibling.Blood. 2002;99:1572–1577.

  13. 13.

    Ochiai N, Shimazaki C, Fuchida S, et al. Successful non-T-cell-depleted HLA haploidentical 3-loci mismatched hematopoietic stem cell transplantation from mother to son based the feto-maternal microchimerism.Bone Marrow Transplant. 2002;30:793–796.

  14. 14.

    Giralt S, Thall PF, Khouri I, et al. Melphalan and purine analogcontaining preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation.Blood. 2001;97:631–637.

  15. 15.

    Martino R, Caballero MD, De la Serna J, et al. Low transplantrelated mortality after second allogeneic peripheral blood stem cell transplant with reduced-intensity conditioning in adult patients who have failed a prior autologous transplant.Bone Marrow Transplant. 2002;30:63–68.

  16. 16.

    Sykes M, Preffer F, McAfee S, et al. Mixed lymphohaemopoietic chimerism and graft-versus-lymphoma effects after nonmyeloablative therapy and HLA-mismatched bone-marrow transplantation.Lancet. 1999;353:1755–1759.

  17. 17.

    Ruggeri L, Capanni M, Urbani E, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplant.Science. 2002;295:2097–2100.

Download references

Author information

Correspondence to Nobuhiko Uoshima or Yuri Kamitsuji or Etsuko Maruya or Hiroh Saji.

About this article

Cite this article

Uoshima, N., Kamitsuji, Y., Maruya, E. et al. Successful reduced-intensity stem cell transplantation from an HLA haploidentical 3-loci-mismatched donor on the basis of fetomaternal microchimerism in a patient with advanced acute myeloid Leukemia. Int J Hematol 78, 69–72 (2003). https://doi.org/10.1007/BF02983243

Download citation

Key words

  • Advanced AML
  • HLA-haploidentical 3-loci-mismatched HSCT
  • Reduced-intensity conditioning
  • Long-term fetomaternal microchimerism