title: Successful treatment of incipient graft rejection with donor leukocyte infusions, further proof of a graft versus host lymphohaemopoietic effect.
abstract: Graft rejection is a major cause of treatment failure after T-cell-depleted stem cell transplantation (TCD-SCT) and remains a therapeutic challenge. Donor leukocyte infusions (DLIs) have an efficient graft versus host effect, which has been successfully used to treat recipient relapses. We hypothesized that this effect could be exploited to counteract the host versus graft reactions responsible for graft rejection. We report two adult patients with haematological malignancies who underwent sex-mismatched TCD-SCT from HLA-identical sibling donors. Peripheral blood (PB) counts and bone marrow (BM) cellularity were studied on a serial basis. Sequential chimaerism and minimal residual disease analysis were performed by FISH on PB and BM samples as well as on leukocyte lineages (T and B lymphocytes and myeloid cells) purified from PB using immunomagnetic technology. Both patients were diagnosed with incipient graft rejection 2-3 months after engraftment, based on persistently decreasing PB counts and BM cellularity together with the observation of decreasing mixed chimaerism (increasing percentage of recipient cells), mostly in whole PB and T lymphocytes. Both patients were successfully treated with a single DLI (1 x 10(7) CD3+ cells/kg), thereafter achieving normal PB counts and BM cellularity as well as complete chimaerism. Interestingly, the only side effect observed was mild graft versus host disease that did not require treatment. In conclusion, provided that an early diagnosis is made, the graft versus host lymphohaemopoietic effect harboured by immunocompetent donor cells can be successfully used for the treatment of incipient graft rejection.
authors.affiliation: Unidad de Trasplante de Médula Osea, Hosp. G.U. Gregorio Marañón, Doctor Esquerdo 46, 28007 Madrid, Spain. jdiez.hgugm@salud.madrid.org
authors.forename: J L
authors.initials: JL
authors.lastname: Díez-Martín
authors.forename: A
authors.initials: A
authors.lastname: Gómez-Pineda
authors.forename: D
authors.initials: D
authors.lastname: Serrano
authors.forename: R
authors.initials: R
authors.lastname: Carrión
authors.forename: P
authors.initials: P
authors.lastname: Balsalobre
authors.forename: I
authors.initials: I
authors.lastname: Buño
mesh_terms: D018952:Antigens, CD34 / Q000096:biosynthesis / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D017252:CD3 Complex / Q000096:biosynthesis; D017690:Cell Transplantation; D005260:Female; D006084:Graft Rejection / Q000628:therapy*; D006086:Graft vs Host Disease; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D017404:In Situ Hybridization, Fluorescence; D017708:Leukocyte Transfusion / Q000379:methods*; D007962:Leukocytes / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D035781:Siblings; D033581:Stem Cell Transplantation; D013997:Time Factors; D014184:Transplantation, Homologous; D019737:Transplants; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34; D017252:CD3 Complex; D007166:Immunosuppressive Agents; D016179:Granulocyte Colony-Stimulating Factor