Terminal deoxynucleotidyl transferase-positive cells in trephine biopsies following bone marrow or peripheral stem...

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.

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).

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.