title: Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation.
abstract: OBJECTIVE
  We designed a minimal-intensity conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) in patients with advanced hematologic malignancies unable to tolerate high-intensity regimens because of age, serious comorbidities, or previous high-dose HCT. The regimen allows the purest assessment of graft-versus-tumor (GVT) effects apart from conditioning and graft-versus-host disease (GVHD) not augmented by regimen-related toxicities.
  
  
  METHODS
  Patients received low-dose total-body irradiation ± fludarabine before HCT from HLA-matched related (n = 611) or unrelated (n = 481) donors, followed by mycophenolate mofetil and a calcineurin inhibitor to aid engraftment and control GVHD. Median patient age was 56 years (range, 7 to 75 years). Forty-five percent of patients had comorbidity scores of ≥ 3. Median follow-up time was 5 years (range, 0.6 to 12.7 years).
  
  
  RESULTS
  Depending on disease risk, comorbidities, and GVHD, lasting remissions were seen in 45% to 75% of patients, and 5-year survival ranged from 25% to 60%. At 5 years, the nonrelapse mortality (NRM) rate was 24%, and the relapse mortality rate was 34.5%. Most NRM was a result of GVHD. The most significant factors associated with GVHD-associated NRM were serious comorbidities and grafts from unrelated donors. Most relapses occurred early while the immune system was compromised. GVT effects were comparable after unrelated and related grafts. Chronic GVHD, but not acute GVHD, further increased GVT effects. The potential benefit associated with chronic GVHD was outweighed by increased NRM.
  
  
  CONCLUSIONS
  Allogeneic HCT relying on GVT effects is feasible and results in cures of an appreciable number of malignancies. Improved results could come from methods that control progression of malignancy early after HCT and effectively prevent GVHD.
authors.affiliation: University of Washington, USA. rstorb@fhcrc.org
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
authors.forename: Boglarka
authors.initials: B
authors.lastname: Gyurkocza
authors.forename: Barry E
authors.initials: BE
authors.lastname: Storer
authors.forename: Mohamed L
authors.initials: ML
authors.lastname: Sorror
authors.forename: Karl
authors.initials: K
authors.lastname: Blume
authors.forename: Dietger
authors.initials: D
authors.lastname: Niederwieser
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Chauncey
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pulsipher
authors.forename: Finn B
authors.initials: FB
authors.lastname: Petersen
authors.forename: Firoozeh
authors.initials: F
authors.lastname: Sahebi
authors.forename: Edward D
authors.initials: ED
authors.lastname: Agura
authors.forename: Parameswaran
authors.initials: P
authors.lastname: Hari
authors.forename: Benedetto
authors.initials: B
authors.lastname: Bruno
authors.forename: Peter A
authors.initials: PA
authors.lastname: McSweeney
authors.forename: Michael B
authors.initials: MB
authors.lastname: Maris
authors.forename: Richard T
authors.initials: RT
authors.lastname: Maziarz
authors.forename: Amelia A
authors.initials: AA
authors.lastname: Langston
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bethge
authors.forename: Lars
authors.initials: L
authors.lastname: Vindeløv
authors.forename: Georg-Nikolaus
authors.initials: GN
authors.lastname: Franke
authors.forename: Ginna G
authors.initials: GG
authors.lastname: Laport
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Yeager
authors.forename: Kai
authors.initials: K
authors.lastname: Hübel
authors.forename: H Joachim
authors.initials: HJ
authors.lastname: Deeg
authors.forename: George E
authors.initials: GE
authors.lastname: Georges
authors.forename: Mary E D
authors.initials: ME
authors.lastname: Flowers
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Martin
authors.forename: Marco
authors.initials: M
authors.lastname: Mielcarek
authors.forename: Ann E
authors.initials: AE
authors.lastname: Woolfrey
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000209:etiology* / Q000401:mortality; D006086:Graft vs Host Disease / Q000209:etiology* / Q000401:mortality; D020350:Graft vs Tumor Effect; D006680:HLA Antigens / Q000378:metabolism; D019337:Hematologic Neoplasms / Q000150:complications* / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000401:mortality; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D006680:HLA Antigens