Minimal residual disease is more common in patients who have mixed T- cell chimerism after bone marrow transplantation for chronic myelogenous leukemia

Abstract

Determining both lymphoid chimerism and the presence of minimal residual disease after allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML) could be helpful to the understanding of the biology of leukemic relapse in this disease. We prospectively investigated 32 patients with CML post-BMT by assessing T- cell chimerism and minimal residual disease using sensitive polymerase chain reaction (PCR) methodologies. Patients were studied between 1 and 24 months post-BMT. Thirty patients received a T-cell-depleted marrow grafts and 2 received unmanipulated marrow. All but 1 patient were conditioned with total body irradiation (TBI)+thiotepa+cyclophosphamide (Cy). The other patient received TBI+Cy as conditioning. The T cells were exclusively of donor origin in 12 of 16 patients who were tested at 1 month post-BMT, but were mixed chimeric in 11 of these patients by e or = 3 months. Once mixed T-cell chimerism was documented, no patient returned to having all donor T-cells. At a median follow-up of 12 months, minimal residual disease was present in 18 of 22 patients with mixed T-cell chimerism and in 3 of 10 patients with full donor chimerism. The actuarial molecular relapse rate at 24 months for the two groups is 91% and 33%, respectively (P < .02). The finding of BCR- ABL mRNA within the first 6 months of transplant or on two consecutive assays was highly predictive of subsequent cytogenetic or hematologic relapse (P = .032 and P < .02, respectively). Ten patients, 9 with mixed T-cell chimerism, have relapsed (4 clinical, 6 cytogenetic) at a median of 12 months post-BMT. These data suggest that mixed T-cell chimerism may be a marker for abrogation of graft-versus-leukemia activity that is thought to be pivotal in eradicating minimal residual disease after BMT for CML.

Reduced‐intensity conditioning for allogeneic haematopoietic stem cell transplantation in relapsed and refractory Hodgkin lymphoma: impact of alemtuzumab and donor lymphocyte infusions on long‐term outcomes

“…Firstly, the treatment of mixed chimerism with DLI could have reduced the risk of relapse. Mixed chimerism is recognized to be more common following T-cell depletion in fully ablative transplant protocols, and suggested to be associated with an increased risk of relapse (Mackinnon et al, 1994;Shaw et al, 2005). The rationale for the use of DLI to treat mixed chimerism is to prevent tolerance developing and therefore to maximize the graft-versus-tumour responses.…”

Lineage‐specific engraftment and outcomes after T‐cell‐depleted peripheral blood stem cell transplant with Flu/Cy/TBI conditioning

“…However, these investigators evaluated only whole blood chimaerism, and as a consequence, little is known about lineage-specific donor engraftment -especially in the context of myeloablative TCD transplants. Only one study (MacKinnon et al, 1994), specifically measured T-cell chimaerism after myeloablative T-depleted SCT. They found a correlation between mixed T-cell chimaerism and relapse at 12 months in patients with CML.…”

Immune reconstitution following haematopoietic stem cell transplantation

“…Theoretically, however, bilateral tolerance may also induce tolerance against the underlying malignancy such that the relapse risk may be higher. Mixed chimaerism in T cells, a compartment that would not be predicted to be involved in the neoplastic process in chronic myeloid leukaemia, is an independent marker for subsequent disease relapse/progression (Mackinnon et al, 1994). Administration of DLI can target this compartment, leading to conversion to full donor chimaerism.…”