title: Terminal deoxynucleotidyl transferase-positive cells in trephine biopsies following bone marrow or peripheral stem cell transplantation reflect vigorous B-cell generation.
abstract: OBJECTIVE
  Bone marrow is the major site of B-cell generation in humans. While in early childhood a high number of B-cell precursors is found in the bone marrow, only very few such cells are usually detectable in adult bone marrow. To assess the number of immature B cells present after haematopoietic cell transplantation the number of terminal deoxynucleotidyl transferase (TdT)-positive cells in regenerating bone marrow of adult patients was analysed.
  
  
  RESULTS
  Bone marrow biopsy specimens were analysed from patients after allogeneic bone marrow transplantation (BMT; n = 14) or stem cell transplantation (SCT; n = 25) and autologous BMT (n = 9). Specimens from 11 untransplanted adult patients and 11 infants were also studied, as negative and positive controls, respectively. Immunohistochemistry was performed on paraffin-embedded bone marrow biopsy sections using TdT as a marker of lymphoid progenitors. Immunoreactivity for CD79a, CD20 and CD10 was used to confirm their B-cell origin. Using computer-assisted automated image analysis we quantitatively assessed the TdT+ cells present. We found a significant increase in the numbers of B-cell precursors in the bone marrow after allogeneic and autologous BMT/SCT compared with adult controls (P = 0.022). To analyse this in detail, we followed some patients after allogeneic BMT/SCT for up to 1445 days, when a marked B-cell increase was still detectable. However, the median number of TdT+ B cells after BMT/SCT was significantly lower than the number of equivalent B cells in infantile bone marrow biopsy specimens (P < 0.001).
  
  
  CONCLUSIONS
  Bone marrow of adult patients after BMT/SCT is capable of initiating vigorous precursor B-cell generation, which is not seen in untransplanted adults. However, the increase of immature B cells was variable in our study. Only in two young adult patients did it reach the magnitude of B-cell generation seen in infantile bone marrow where immunocompetent B cells are produced normally. A marked increase in number of immature B cells post-transplant may mimic B-cell acute lymphoblastic leukaemia (B-ALL). This is a potential problem in patients transplanted for B-ALL itself. Since reactive and neoplastic B-cell precursors share the same immunophenotype in paraffin-embedded tissue, additional tools, particularly molecular techniques, may have to be employed to establish the correct diagnosis.
authors.affiliation: Department of Pathology, University of Erlangen-Nuremburg, Erlangen, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Wolf
authors.forename: H
authors.initials: H
authors.lastname: Harms
authors.forename: J
authors.initials: J
authors.lastname: Winkler
authors.forename: U
authors.initials: U
authors.lastname: Reulbach
authors.forename: T
authors.initials: T
authors.lastname: Kirchner
authors.forename: G
authors.initials: G
authors.lastname: Niedobitek
authors.forename: I
authors.initials: I
authors.lastname: Baumann
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000166:cytology*; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D004253:DNA Nucleotidylexotransferase / Q000097:blood*; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000473:pathology / Q000628:therapy; D018655:Lymphocyte Count; D008223:Lymphoma / Q000473:pathology / Q000628:therapy; D038041:Lymphopoiesis; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000473:pathology / Q000628:therapy; D036102:Peripheral Blood Stem Cell Transplantation; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D004253:DNA Nucleotidylexotransferase