Mixed T-lymphoid chimerism after allogeneic bone marrow transplantation for hematologic malignancies of children is not correlated with relapse

Abstract

We performed polymerase chain reaction-variable number of tandem repeats analysis of flow-sorted peripheral blood T-, B-, natural killer- , and myeloid cell populations (van Leeuwen et al, Br J Haematol 79:218, 1991) in 32 children following allogeneic bone marrow transplantation (BMT) for leukemia to evaluate the relationship between mixed lymphoid chimerism and leukemia relapse. Five patients showed a stable mixed chimerism pattern characterized by the presence of both recipient as well as donor type cells in all cell populations up to 1 year posttransplantation. Five others showed transient mixed chimerism in the T-lymphoid cell lineage. In one patient, host T cells persisted until leukemia relapse. The remaining 21 patients showed a complete chimerism throughout the period of investigation. Twenty-five of these patients were classified according to the presence (n = 10) or absence (n = 15) of recipient type T cells. Statistical analysis did not show significant differences in the distribution of a number of clinical variables between the two groups, nor in the actuarial survival (P = .11) and leukemia-free interval (P = .97). Therefore, these results suggest that persistence of recipient type T lymphoid cells after allogeneic BMT for hematologic malignancies is not correlated with leukemia relapse. In addition, we observed that persistence of host cells within the original leukemia cell lineage and at the correct maturational stage was predictive for leukemia relapse in one case.

Incidence of mixed chimaerism and clinical outcome in 101 patients after myeloablative conditioning regimens and allogeneic stem cell transplantation

“…The role of residual recipient lymphohaematopoietic cells after allogeneic transplantation is controversial (Bertheas et al , 1991; Mackinnon et al , 1992, 1994; van Leeuwen et al , 1993, 1994; Bader et al , 1998). Residual recipient cells may reflect at best healthy haematopoiesis or residual lymphocytes that survived chemotherapy, or at worst cells derived from the malignant clone.…”

“…With the increased sensitivity of new detection methods, MC has been found to be more frequent than initially thought (Mangioni et al , 1997), however microchimaerism of 0·7% or less 1–5 years after transplantation was not predictive of relapse (Najfeld et al , 1997). In recent studies, no correlation between MC and risk of relapse was found (van Leeuwen et al , 1993), whereas others confirmed the hypothesis of a higher risk of relapse in MC patients (Mackinnon et al , 1994). The occurrence of MC after allogeneic transplantation is influenced by several factors, such as the conditioning regimen, graft‐versus‐host disease (GVHD) prophylaxis and the kind of graft.…”

Translational Mini-Review Series on B cell subsets in disease. Reconstitution after haematopoietic stem cell transplantation – revelation of B cell developmental pathways and lineage phenotypes

“…As the numbers of CD8 + T cells increase earlier than CD4 + T cells, the CD4/CD8 ratio is initially reversed [9]. This early expansion is dependent on homeostatic peripheral proliferation of memory T cells, both of rare recipient‐derived T cells surviving the conditioning regimen and of donor‐derived co‐transferred T cells, rather than from thymic production [10,11].…”

Relapse after bone marrow transplantation: evidence for distinct immunological mechanisms between adult and paediatric populations

“…Several studies identified MC as a prognostic indicator of relapse (Mackinnon et al , 1994; Molloy et al , 1996; Bader et al , 1997, 1998). Nevertheless, others could not find an association between MC and relapse (Roy et al , 1990; van Leeuwen et al , 1993, 1994; Huss et al , 1996; Palka et al , 1996). Although several methodological and clinical discrepancies could be responsible for these differences, we hypothesized that a major factor was the difficulty in continually assessing the chimaerism status of transplant patients.…”