title: Fluctuating lymphocyte chimerism, tolerance and anti-tumor response in a patient with refractory lymphoma receiving nonmyeloablative conditioning and a haploidentical related allogeneic bone marrow transplant.
abstract: A 51-year-old patient with refractory non-Hodgkin lymphoma (NHL) received non-myeloablative conditioning and a two of six (A, B, DR) human leucocyte antigen (HLA) mismatched donor BMT. Post-BMT lymphocytes showed fluctuating T- and natural killer (NK)-cell chimerism, which culminated in mainly donor lymphocytes by Day + 100. Changes in lymphocyte chimerism correlated with anti-donor and anti-host responses in mixed lymphocyte reaction (MLR). On Day + 100, a strong anti-host response was observed in MLR in the absence of graft-versus-host disease (GVHD), together with near complete regression of the patient's lymphoma. A mild chronic GVHD later developed and, eventually, by 680 days post-BMT, the lymphoma had relapsed and MLR reflected a state of global immune unresponsiveness. These observations demonstrate evolving host-versus-graft and graft-versus-host tolerance that correlates with fluctuating lymphoid chimerism and graft-versus-lymphoma (GVL) effects, in the absence of severe GVHD. Eventual lymphoma relapse temporally correlated with a generalised immunosuppressed state.
authors.affiliation: Bone Marrow Transplant Program, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
authors.forename: Han C
authors.initials: HC
authors.lastname: Toh
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Spitzer
authors.forename: Frederic
authors.initials: F
authors.lastname: Preffer
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Alexander
authors.forename: Steve
authors.initials: S
authors.lastname: McAfee
authors.forename: David
authors.initials: D
authors.lastname: Dombkowski
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Clark
authors.forename: Christine
authors.initials: C
authors.lastname: Colby
authors.forename: Susan
authors.initials: S
authors.lastname: Saidman
authors.forename: Robert
authors.initials: R
authors.lastname: Sackstein
authors.forename: Megan
authors.initials: M
authors.lastname: Sykes
mesh_terms: D016026:Bone Marrow Transplantation; D002986:Clinical Trials as Topic; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D016131:Lymphocyte Subsets; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D008223:Lymphoma / Q000276:immunology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D011993:Recombinant Fusion Proteins