Mixed hematologic chimerism after allogeneic marrow transplantation for severe aplastic anemia is associated with a higher risk of graft rejection and a lessened incidence of acute graft-versus-host disease

Abstract

Ninety-six patients with severe aplastic anemia who received a sex- mismatched, HLA-identical allogeneic sibling marrow transplant had sequential cytogenetic analyses performed to determine the incidence and implications of posttransplant mixed hematologic chimerism. Of the 96 patients, 56 (58.3%) became mixed chimeras with coexisting host and donor cells detected in peripheral blood or marrow 14 days or later after transplant, and 40 patients (41.7%) were complete chimeras with 100% donor-type hematopoietic cells. The incidence of mixed chimerism was independent of prior blood production transfusions and infusion of donor buffy coat. The rejection rate was significantly increased in the mixed chimeric group, particularly in patients not receiving buffy coat (14 of 36 rejecting), although overall, the majority (69.7%) retained their first graft. Rejection was seen almost exclusively in patients exposed to multiple transfusions before transplantation. If patients who reject their first graft are censored, the overall incidence of grades II through IV acute graft-v-host disease (GVHD) was significantly reduced in those with mixed chimerism. Transfused patients with mixed chimerism in particular were less likely to develop grades II through IV acute GVHD. The incidence of chronic GVHD was similar in the two groups and did not significantly influence survival. In this study, mixed chimerism persisted for up to 395 days posttransplant, either the first graft being rejected or, more commonly, hematopoiesis reverting to 100% donor-type cells. Mixed lymphohematopoietic chimerism may persist in patients with aplastic anemia who have received matched allogeneic marrow transplants for significant periods before hematopoiesis reverts to donor cell type.

Serial chimerism analyses indicate that mixed haemopoietic chimerism influences the probability of graft rejection and disease recurrence following allogeneic stem cell transplantation (SCT) for severe aplastic anaemia (SAA): indication for routine assessment of chimerism post SCT for SAA

“…A small number of studies have assessed chimerism in SAA or FA with results on significant numbers of patients. Hill et al (1986) reported on a group of 96 patients who received SCT for SAA with a conditioning regimen that did not include irradiation. Cytogenetic analysis was performed and indicated a high level of MC (56 of 96 patients) in the first year post-SCT.…”

Chimaerism following allogeneic bone marrow transplantation: detection of residual host cells using the polymerase chain reaction

“…the treatment of choice for many haematological disorders, can now be monitored successfully using DNA probes (Blazar et al, 1985: Knowlton et al, 1986. Recent studies have indicated that a mixed chimaeric state may occur, particularly following T cell depleted BMT (Hill et al, 1986;Petz et al, 1987;deWitte et al, 1987;Bretagne et al, 1987;Bertheas et a1, 1988). The influence of a mixed chimaeric state on subsequent graft rejection or relapse is as yet unknown.…”

Molecular monitoring of T‐cell chimerism early after allogeneic stem cell transplantation may predict the occurrence of acute GVHD grades II–IV

“…In the present study, we investigated whether chimerism patterns during the early post‐transplantation period may be used to predict the occurrence of severe acute GVHD after SCT. Several studies have shown that MC is correlated to a lower risk for developing moderate to severe acute GVHD after allogeneic SCT (5, 16), especially for patients transplanted for aplastic anemia (7, 17). We hypothesized that the clearance rate of host T cells between days 7 and 10 may be used to evaluate and monitor the recipient specific alloreactivity of donor T cells in vivo irrespective of diagnosis and pre‐treatment regimens.…”