Erythropoietic reconstitution, macrophages and reticulin fibrosis in bone marrow specimens of CML patients following allogeneic transplantation

A clinicopathological study was conducted on 351 bone marrow trephine biops ies derived from 124 patients with chronic myeloid leukemia (CML) at standa rdized endpoints before and after allogeneic bone marrow transplantation (B MT). The purpose was to investigate quantitative changes of the nucleated e rythroid precursor cell population and other associated features such as re sident bone marrow macrophages and myelofibrosis and to elucidate their rel evance on engraftment parameters. Monoclonal antibodies were applied for th e identification of erythroid precursors and the labeling of mature macroph ages; argyrophilic (reticulin-collagen) fibers were demonstrated by a silve r impregnation technique. Following morphometric analysis of the pregraft b one marrow specimens statistical evaluation was in line with an adverse cor relation between early to moderate reticulin fibrosis and amount of erythro poiesis. Moreover, a significant relationship was calculable between number s of erythroid precursors and CD68(+) macrophages. After myelo-ablative the rapy and BMT a pronounced decrease in cellularity and in the quantity of er ythropoiesis was found. Comparable with the pregraft samples, a significant association between erythroid precursors and macrophages could be determin ed in the regenerating donor bone marrow. A pretransplant relevant reductio n of the red cell lineage and a manifest (reticulin) myelofibrosis indicati ng an advanced stage of disease were accompanied by a significant delay to reach transfusion independence. This result was further supported by compar able findings in trephine biopsies performed in the early post-transplant p eriod (second month after BMT). Corresponding examinations revealed an enha ncement of fiber density and a decrease in erythropoiesis in those patients who did not conform with the usually accepted criteria for successful engr aftment. In conclusion, compelling evidence has been produced that a signif icantly reduced amount of erythroid precursors, which is usually associated with myelofibrosis in the pretransplant bone marrow, exerts an impairment to undisturbed hematopoietic reconstitution. Moreover, a close spatial and numerical relationship between the erythroid lineage and resident (mature) macrophages is observable, in particular in the state of regeneration after BMT.