Persistence of host-type hematopoiesis after allogeneic bone marrow transplantation for leukemia is significantly related to the recipient's age and/or the conditioning regimen, but it is not associated with an increased risk of relapse

Abstract

We investigated the chimerism pattern within flow-sorted peripheral blood- or bone marrow-derived cell populations after allogeneic bone marrow transplantation (BMT) for the treatment of leukemia in children. This study was performed to define the identity of persistent host-type cells, to identify prognostic variables for the persistence of host- type hematopoiesis, and to determine the prognostic significance of the chimerism pattern on the duration of the leukemia-free interval, the overall survival, and the leukemia-free survival. The patients received either HLA-identical non-T-cell-depleted (n = 46) or HLA nonidentical T- cell-depleted (n = 7) BMT. In the peripheral blood, the children showed either stable mixed chimerism (SMC; ie, persistent host-type hematopoiesis; n = 14), (transient) mixed T-lymphoid chimerism (MTLC; n = 9), or complete chimerism (CC; n = 30). In the bone marrow, only donor-type cells were found in children with either CC (n = 8) or MTLC (n = 2), and a mixture of donor- and recipient-type cells was found in children with SMC (n = 7). The persistence of host-type hematopoiesis (SMC) was significantly related to a lower age of the recipient, the type of conditioning regimen, a lower total body irradiation dose, T- cell depletion of the bone marrow graft, and the use of cyclosporine A for acute graft-versus-host disease prophylaxis. No significant differences were found between patients with (SMC) or without (CC/MTLC) persistent host-type hematopoiesis with respect to the duration of the leukemia-free interval, the overall survival, or the leukemia-free survival. We conclude that ablation of host-type hematopoiesis is not compulsory for long-term leukemia-free survival after allogeneic BMT for various hematologic malignancies.

Characterization of lineage‐specific chimaerism in patients with acute leukaemia and myelodysplastic syndrome after allogeneic stem cell transplantation before and after relapse

“…Studies on chimaerism analysis of cell subpopulations in patients with acute leukaemias and MDS are rare. van Leeuwen et al (1994) performed subset analysis in a cohort of 53 children transplanted for acute leukaemias.…”

Increasing hematopoietic microchimerism is a reliable indicator of incipient AML relapse

“…The question, whether chimerism status is somehow connected to the incipient relapse, or if it could be taken as an indicator of an impending relapse, has been disputed intensively during the last two decades. Several research groups found correlation between mixed chimerism (MC) and AML relapse (Lawler, Humphries & McCann, 1991;Bader et al, 1997Bader et al, , 1998, while such relationship was disapproved by others (Schattenberg et al, 1989;Roy et al, 1990;Bertheas et al, 1991;van Leeuwen et al, 1993van Leeuwen et al, , 1994Suttorp et al, 1993;Choi et al, 2000;Schaap et al, 2002). This controversy can be partially explained in context of dynamic process of MC: whereas reappearance or increase in autologous hematopoiesis is related with the impending AML relapse, stable MC is not (Formá nková et al, 2000(Formá nková et al, , 2003Wä sch et al, 2000;Mattsson et al, 2001;Pé rez-Simó n et al, 2002;Schaap et al, 2002;Barrios et al, 2003;Ferná ndez-Avilé s et al, 2003;Lamba et al, 2004;Scheffold et al, 2004;Huisman et al, 2007).…”

Comparative serial quantitative measurements of chimaerism following unmanipulated allogeneic transplantation of peripheral blood stem cells and bone marrow

“…Conversely, continuing complete donor chimaerism was associated with a low incidence of minimal residual disease (MRD) and relapse in patients with chronic myeloid leukaemia (Gardiner et al, 1997). In contrast, other studies have suggested that low level MC is not associated with a higher incidence of relapse (Petz et al, 1987;Suttorp et al, 1993;van Leeuwen et al, 1994). Thus the signi®cance of MC following unmanipulated allogeneic transplantation remains unclear.…”