Anti-tumour response despite loss of donor chimaerism in patients treated with non-myeloablative conditioning and allogeneic stem cell transplantation.
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.
Dey
Bimalangshu R
BR
Department of Medicine Harvard Medical School Boston, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. bdey@partners.org
McAfee
Steven
S
Colby
Christine
C
Cieply
Kathy
K
Caron
Martin
M
Saidman
Susan
S
Preffer
Frederic
F
Shaffer
Juanita
J
Tarbell
Nancy
N
Sackstein
Robert
R
Sachs
David
D
Sykes
Megan
M
Spitzer
Thomas R
TR
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