Mixed Chimerism and Secondary Graft Failure in Allogeneic Hematopoietic Stem Cell Transplantation for Aplastic Anemia

Biol Blood Marrow Transplant. 2020 Mar;26(3):445-450. doi: 10.1016/j.bbmt.2019.10.004. Epub 2019 Oct 13.

Abstract

Mixed chimerism (MC) and/or secondary graft failure (SGF) with recipient- or donor-type chimerism is a major obstacle in allogeneic transplantation for aplastic anemia (AA). From a registry database in Japan, patients with AA age >15 years who underwent a first allogeneic bone marrow or peripheral blood stem cell transplantation between 2000 and 2014 and achieved engraftment were included in this study. MC that did not require either granulocyte-colony stimulating factor (G-CSF) or transfusion support (group 1), MC (not SGF) that required G-CSF and/or transfusion support (group 2), SGF with MC or complete recipient-type chimerism (group 3), and SGF with complete donor-type chimerism (group 4) developed in 26, 16, 19, and 17 patients, respectively. The overall median duration of follow-up for survivors was 1727 days. The overall survival (OS) was 90.4% at 1 year and 83.5% at 5 years in patients without MC or SGF (n = 340), which was not different from the OS in groups 1 and 2. However, inferior OS was observed in group 3 (1 year, 52.1%; 5 years, 52.1%) and group 4 (1 year, 82.4%; 5 years, 56.3%). In multivariate analyses, the use of fludarabine (Flu) and the absence of irradiation in conditioning were associated with the development of SGF with MC or complete recipient-type chimerism, and the use of Flu in conditioning was associated with SGF with complete donor-type chimerism. In conclusion, the use of Flu may affect the occurrence of SGF with both recipient-type and donor-type chimerism.

Keywords: Allogeneic hematopoietic stem cell transplantation; Aplastic anemia; Mixed chimerism; Secondary graft failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anemia, Aplastic* / therapy
  • Chimerism
  • Graft vs Host Disease*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Japan
  • Transplantation Conditioning