Dynamics of CD34+ progenitor cells following allogeneic bone marrow transplantation in Ph1+CML--an immunohistochemical study on 113 patients with sequential trephine biopsies.
A retrospective immunohistological and morphometric study was performed on bone marrow trephine biopsies derived from 113 patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph(1+)-CML) before and at standardized intervals following allogeneic transplantation (BMT) with full unmanipulated marrow specimens. The purpose of this investigation was to quantify CD34+ progenitor cells and to determine their dynamics during the post-transplant period. Moreover, we tried to correlate their number with corresponding changes in the amount of nucleated erythroid precursors and megakaryocytes including pro- and megakaryoblasts and the fiber content. Monitoring the quantity of precursors after BMT revealed a very rapid recovery in comparison to a control group. However, a more detailed evaluation showed that at day 22 +/- 6 a higher number of progenitor cells was significantly associated with an earlier independence for platelet transfusion and also with a more pronounced growth of erythro- and megakaryopoiesis including their precursor cells. Furthermore, a slight increase in the density of the fibrous matrix (reticulin fibers) was present in these patients that were characterized by a more favorable engraftment. The latter feature sheds some light on the complex pathomechanisms of homing and differentiation of progenitors. In confirmation with in vitro findings, this phenomenon is dependent on proper anchoring sites to the fibrous bone marrow stroma. Finally, the size of a full BM graft exerted a distinctive influence on the number of CD34+ precursors in the early post-transplant period. In conclusion, the present study has validated a number of BM features by focusing on the CD34+ progenitor cells and associated hematopoietic reconstitution including reticulin fibers and precursor cells of the erythroid and megakaryocyte lineage, which are not readily evaluable by fluorescence-activated cell sorting (FACS) analysis.
Institute of Pathology, University of Cologne, D-50924 Cologne, Germany. j.thiele@uni-koeln.de
Juergen
J
Thiele
Hans Michael
HM
Kvasnicka
Dietrich Wilhelm
DW
Beelen
Guelken
G
Cicek
Lutz-Dietrich
LD
Leder
Ulrich Wilhelm
UW
Schaefer
D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34; D001706:Biopsy; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D016022:Case-Control Studies; D002450:Cell Communication; D002452:Cell Count; D005260:Female; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011336:Probability; D012189:Retrospective Studies; D017154:Stromal Cells; D014184:Transplantation, Homologous
D018952:Antigens, CD34