Publication: Bone marrow engraftment: histopathology of hematopoietic reconstitution following allogeneic transplantation in CML patients
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Date
2001
Authors
Thiele, J. ; Kvasnicka, H.M. ; Beelen, D.W. ; Leder, L.D. ; Schaefer, U.W.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Following myelo-ablative treatment and
allogeneic bone marrow transplantation (BMT) in
chronic myelogenous leukemia (CML) histopathological
features assumed to exert a sienificant i m ~ a c ot n
engraftment have been rarely inve;igated systekatically.
This review is focused on immunohistochemical and
morphometric techniques involving nucleated erythroid
precursors, resident macrophages and their various
subsets, megakaryocytes and finally argyrophilic
(reticulin-collagen) fibers. Regarding standardized
intervals of examination in the postgraft sequential
trephine biopsies a pronounced reduction in cellularity
was obvious and accompanied by a decrease in the
quantity of erythro- and megakaryopoiesis. A significant
correlation between the number of erythroid precursors
and CD68+-macrophages could be determined in the
areas of regenerating hematopoiesis. This finding is in
keeping with the important functional role of the
centrally localized mature macrophages during
erythropoiesis. A relevant pretransplant reduction of the
red cell lineage and an early to advanced reticulin
fibrosis were correlated with a low hemoglobin leve1
(anemia) and splenomegaly and furthermore associated
with a significant delay to reach transfusion
independence. This result was supported by
corresponding findings in biopsy specimens performed
shortly after day 30 following BMT (standard interval
for assessment of engraftment). Samples revealed an
enhancement of fiber density and a conspicuous decrease
in the amount of erythropoiesis in the small fraction of
patients who did not conform with the usually accepted
criteria for successful hematopoietic reconstitution.
Considering the compartment of histiocytic reticular
cells the recurrence of Pseudo-Gaucher cells (PCGs) in
the engrafted donor marrow was remarkable and most
prominently expressed in the first two months following
BMT. This feature was presumed to be functionally linked with a pronounced degradation of cell debris in
the seque1 of myelo-ablative therapy (scavenger
macrophages). According to planimetric measurements
in the postgraft bone marrow the atypical dwarf-like
CD61+-megakaryocytes characteristic for CML
disappeared. On the other hand, normalization of
megakaryocyte size and nuclear lobulation were absent
in sequential examination of the few patients developing
a leukemic relapse. In a number of patients with
manifest myelofibrosis at onset, an initial regression
after BMT was followed by an insidiously occurring
retrieval which was concentrated on the areas of
reconstituting hematopoiesis. Similar to its relevant
pretransplant association the postgraft reappearance of
myelofibrosis was significantly correlated with the
quantity of CD61+-megakaryocytes. Altogether a
number of histological features in the pre-and postgraft
bone marrow exhibited significant correlations with each
other and thus indicated functional relationships.
Moreover, quantity of erythropoiesis and amount of
reticulin fibers (myelofibrosis) exerted a significant
impact on engraftment status.
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