title: A high antithymocyte globulin dose increases the risk of relapse after reduced intensity conditioning HSCT with unrelated donors.
abstract: The study included 110 consecutive patients with hematological malignancies receiving fludarabine-based reduced intensity conditioning (RIC) and hematopoietic stem cell transplantation (HSCT) from matched unrelated donors. The median age was 55 yr (range 11-68) and all but 15 patients received peripheral blood stem cell grafts. Antithymocyte globulin (ATG) (Thymoglobulin, Genzyme) at a total dose of 6 mg/kg (n = 66) or 8 mg/kg (n = 44) was given to all patients according to protocol. The ATG dose did not affect time-to-neutrophil or platelet engraftment. The incidences of acute GVHD grades II-IV were 34% and 18% (p = 0.11) and of chronic GVHD were 40% and 26% (p = 0.46) in patients receiving 6 and 8 mg/kg of ATG, respectively. The five-yr relapse-free survival (RFS) was 61% and 36% (p = 0.14) in patients, given low and high ATG dose, respectively. In patients given low-dose ATG, the incidence of relapse was lower compared to those given high-dose ATG, 19% vs. 41% (p = 0.04). In multivariate analysis, age >50 yr (p < 0.001), absence of acute (p < 0.001) and chronic GVHD (p = 0.001) were correlated to relapse, and low-dose ATG was associated with improved RFS (p < 0.05). A high dose (8 mg/kg) of ATG in RIC HSCT with unrelated donors increased the risk for relapse and reduced the RFS.
authors.affiliation: Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Stockholm, Sweden. Mats.remberger@ki.se
authors.forename: Mats
authors.initials: M
authors.lastname: Remberger
authors.forename: Olle
authors.initials: O
authors.lastname: Ringdén
authors.forename: Hans
authors.initials: H
authors.lastname: Hägglund
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Svahn
authors.forename: Per
authors.initials: P
authors.lastname: Ljungman
authors.forename: Michael
authors.initials: M
authors.lastname: Uhlin
authors.forename: Jonas
authors.initials: J
authors.lastname: Mattsson
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000009:adverse effects*; D016022:Case-Control Studies; D002648:Child; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology*; D019337:Hematologic Neoplasms / Q000150:complications* / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000209:etiology*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D019172:Transplantation Conditioning; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents
keywords: MUD; allogeneic; antithymocyte globulin; hematopoietic stem cell transplantation; reduced intensity conditioning