Disease- or therapy-related bone marrow damage cannot be overcome by changes in stem cell source or dose in allogeneic transplantation

• Published in: European journal of haematology 2004-07, Vol.73 (1), p.1-9
• Main Authors: Novotny, J. R., Rosenthal, C., Elmaagacli, A. H., Dürig, J., Beelen, D. W., Dührsen, U.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; allogeneic stem cell transplantation; Bone Marrow Cells - cytology; bone marrow damage; Bone Marrow Diseases - etiology; Bone Marrow Diseases - therapy; bone marrow transplantation; Bone Marrow Transplantation - methods; Cell Count; cobble stone area forming cells; Female; Graft Survival; Hematopoietic Stem Cell Transplantation - methods; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - surgery; Leukemia, Myeloid, Acute - surgery; Male; Middle Aged; peripheral blood stem cell transplantation; Peripheral Blood Stem Cell Transplantation - methods; stem cell dose; stem cell source; Transplantation Conditioning - methods; Transplantation, Homologous
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1111/j.1600-0609.2004.00255.x

:  Objective:  To test whether the functional impairment of the host bone marrow (BM) microenvironment pre‐existing at the time of transplantation could be overcome by the increased content of immature cells in allogeneic peripheral blood stem cell transplantation (PBSCT) when compared with bone marrow transplantation (BMT). Methods:  Cobble stone area forming cells (CAFC) were assayed in normal BM and BM after allogeneic BMT and PBSCT after stable engraftment. Groups were compared by two‐tailed t‐test. Results:  While BM from 11 normal controls contained an average of 778.8 CAFC‐d35 per 106 low density bone marrow cells (LDBMC, range 453–1231 per 106 LDBMC), BM from patients after BMT contained an average of 123.7 CAFC‐d35 per 106 LDBMC (range 38–257) per 106 LDBMC. BM from patients transplanted with PBSC after myeloablative conditioning contained 128.3 (range 46–305) CAFC‐d35 per 106 LDBMC (P = 0.89 compared with BMT). Similar results were obtained when patients after PBSCT with non‐myeloablative conditioning were included (P = 0.62 compared with BMT). CAFC numbers in patients transplanted in early stages of myeloid leukaemia (acute myeloid leukaemia first remission, chronic myeloid leukaemia first chronic phase) were significantly higher than CAFC numbers in patients transplanted in more advanced stages (P = 0.008) or myelodysplastic syndrome (P = 0.023). The lowest CAFC numbers were found in two cases of retransplantation. Conclusion:  Our findings indicate that the functional state of the BM microenvironment rather than stem cell dose or source is limiting for the homing and engraftment of immature haemopoietic cells in clinical transplantation.