Dynamics of lineage-restricted mixed chimerism following sex-mismatched allogeneic bone marrow transplantation

J. Thiele1, C. Wickenhauser1, H.M. Kvasnicka1, E. Varus1, D.W. Beelen2 and U.W. Schaefer2

1Institute of Pathology, University of Cologne, Cologne and
2Department of Bone Marrow Transplantation, University of Essen, Essen, Germany

Offprint requests to: J. Thiele, M.D., Institute of Pathology, University of Cologne, Joseph-Stelzmann-Str. 9, D-50924 Cologne, Germany. Fax: +49-0221/4786360. e-mail: j.thiele@uni-koeln.de

 

Summary. Scant knowledge is available about the dynamics of lineage-specific mixed chimerism (Ch) following bone marrow transplantation (BMT). This review is focused on findings derived from bone marrow (BM) biopsies in patients with chronic myeloid leukemia (CML) including a sex-mismatched host/donor constellation. Appropriate techniques involved immunophenotyping by monoclonal antibodies to identify the various cell lineages, dual color fluorescence in situ hybridization (FISH) with x- and y-chromosome-specific DNA-probes and a proper detection system for a simultaneous labeling of the bcr/abl locus. A significant degree of Ch with more than 20% host CD34+ progenitors was found in the early and late (up to 200 days after BMT) posttransplant period. However, only 10% of these cells harbored the bcr/abl translocation gene. This result fits well with corresponding molecularbiological findings of so-called minimal residual disease. Conversion of Ch evolved during leukemic relapse with 90% host progenitors of which 50% revealed the bcr/abl locus. A Ch of nucleated erythroid percursors (5%) and CD68+ macrophages (8%) was expressed to a significantly lower degree. The slightly increased frequency found in CD61+ megakaryocytes (16%) was probably due to the polyploid state of these cells. Similar to the CD34+ progenitor cells abrupt changes from donor to host type was associated with an insidious transformation into recurrent leukemia. The CD34+ endothelial cells showed a minor degree of Ch, because donor-derived elements ranged from 18% to 25%. Leukemic relapse was characterized by an almost complete conversion of the endothelial cells to a host type. These findings point towards a CD34+ progenitor cell origin of the (leukemic) endothelial cell layer and suggests that their dysfunction may contribute to an expansion of the neoplastic clone. Histol. Histopathol. 18, 557-574 (2003)

Key words: Mixed chimerism, CD34+ progenitor cells, Erythroid precursors, Megakaryopoiesis, Endothelial cells, BCR/ABL translocation, Macrophages, Bone marrow transplantation, CML

DOI: 10.14670/HH-18.557