title: Anti-tumour response despite loss of donor chimaerism in patients treated with non-myeloablative conditioning and allogeneic stem cell transplantation.
abstract: Based on a murine model, we conducted a series of trials of m-myeloablative human leucocyte antigen (HLA)-matched or mismatched related donor stem cell transplantation (SCT) with the intention of inducing mixed chimaerism (MC), then administering prophylactic donor lymphocyte infusions (DLIs), for the treatment of advanced haematologic malignancies. Preparative therapy consisted of cyclophosphamide, equine anti-thymocyte globulin (ATG) or MEDI-507 (an anti-CD2 monoclonal antibody) for in-vivo T-cell depletion, thymic irradiation on day -1 and cyclosporine alone for graft-versus-host disease (GVHD) prophylaxis. DLIs were given as early as 5 weeks post-SCT in patients with MC without evidence of GVHD. Twenty-two patients ultimately lost their graft (<1% donor cells) that could no be rescued by DLIs. Nine of 22 (41%) patients who lost donor chimaerism achieved an objective response, including three patients who showed evidence of disease regression following DLI, despite continued absence of macrochimaerism. Six patients were alive at 2.5-5.5 years following SCT, including four in continuous complete remission. In summary, it is possible to achieve sustained remission in patients with chemorefractory malignancies following non-myeloablative allogeneic SCT, even in the absence of sustained donor macrochimaerism; DLI may contribute to an ongoing anti-tumour effect in these patients. Immunological mechanisms that correlated with rejection of the graft may have a role in anti-tumour responses via a cell or cytokine-mediated pathway.
authors.affiliation: Department of Medicine Harvard Medical School Boston, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. bdey@partners.org
authors.forename: Bimalangshu R
authors.initials: BR
authors.lastname: Dey
authors.forename: Steven
authors.initials: S
authors.lastname: McAfee
authors.forename: Christine
authors.initials: C
authors.lastname: Colby
authors.forename: Kathy
authors.initials: K
authors.lastname: Cieply
authors.forename: Martin
authors.initials: M
authors.lastname: Caron
authors.forename: Susan
authors.initials: S
authors.lastname: Saidman
authors.forename: Frederic
authors.initials: F
authors.lastname: Preffer
authors.forename: Juanita
authors.initials: J
authors.lastname: Shaffer
authors.forename: Nancy
authors.initials: N
authors.lastname: Tarbell
authors.forename: Robert
authors.initials: R
authors.lastname: Sackstein
authors.forename: David
authors.initials: D
authors.lastname: Sachs
authors.forename: Megan
authors.initials: M
authors.lastname: Sykes
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Spitzer
mesh_terms: D000328:Adult; D006084:Graft Rejection; D006086:Graft vs Host Disease / Q000000981:diagnostic imaging / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D017710:Lymphocyte Transfusion; D008875:Middle Aged; D011877:Radionuclide Imaging; D012074:Remission Induction; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome