title: Partially matched, nonmyeloablative allogeneic transplantation: clinical outcomes and immune reconstitution.
abstract: OBJECTIVE
  Allogeneic transplantation is typically limited to younger patients having a matched donor. To allow a donor to be found for nearly all patients, we have used a nonmyeloablative conditioning regimen in conjunction with stem cells from a related donor with one fully mismatched HLA haplotype.
  
  
  METHODS
  Fludarabine, cyclophosphamide, and alemtuzumab were used as the preparatory regimen. Additional graft-versus-host disease (GVHD) prophylaxis included mycophenolate with or without cyclosporine. Patients with persistence of disease had a donor lymphocyte boost planned. Toxicities, engraftment, response, survival, and immune recovery are reported.
  
  
  RESULTS
  Forty-nine patients with hematologic malignancies or marrow failure and no other available donors were enrolled. Ninety-four percent of patients had successful engraftment, and 8% had secondary graft failure. The treatment-related mortality rate was 10.2%, and 8% of patients had severe GVHD. Encouraging evidence of quantitative lymphocyte recovery through expansion of transplanted T cells was noted by 3 to 6 months. Seventy-five percent of patients attained a complete remission, and 1-year survival rate was 31% (95% CI, 18% to 44%). A standard-risk group of 19 patients with aplasia or in remission at transplantation demonstrated a 63% 1-year survival rate (95% CI, 38% to 80%) and 2.9-year median overall survival time (95% CI, 6.2 to 48 months).
  
  
  CONCLUSIONS
  Nonmyeloablative therapy using haploidentical family member donors is feasible because the main obstacles of GVHD and graft rejection are manageable, allowing readily available stem-cell donors to be found for nearly all patients. Further qualitative and quantitative improvement in immune recovery is needed to address the high rate of relapse and risk of severe infections.
authors.affiliation: Department of Medicine, Division of Cellular Therapy, Duke University Medical Center, Durham, NC 27710, USA. rizzi003@mc.duke.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Rizzieri
authors.forename: Liang Piu
authors.initials: LP
authors.lastname: Koh
authors.forename: Gwynn D
authors.initials: GD
authors.lastname: Long
authors.forename: Cristina
authors.initials: C
authors.lastname: Gasparetto
authors.forename: Keith M
authors.initials: KM
authors.lastname: Sullivan
authors.forename: Mitchell
authors.initials: M
authors.lastname: Horwitz
authors.forename: John
authors.initials: J
authors.lastname: Chute
authors.forename: Clayton
authors.initials: C
authors.lastname: Smith
authors.forename: Jerald Z
authors.initials: JZ
authors.lastname: Gong
authors.forename: Anand
authors.initials: A
authors.lastname: Lagoo
authors.forename: Donna
authors.initials: D
authors.lastname: Niedzwiecki
authors.forename: Jeannette M
authors.initials: JM
authors.lastname: Dowell
authors.forename: Barbara
authors.initials: B
authors.lastname: Waters-Pick
authors.forename: CongXiao
authors.initials: C
authors.lastname: Liu
authors.forename: Dawn
authors.initials: D
authors.lastname: Marshall
authors.forename: James J
authors.initials: JJ
authors.lastname: Vredenburgh
authors.forename: Jon
authors.initials: J
authors.lastname: Gockerman
authors.forename: Carlos
authors.initials: C
authors.lastname: Decastro
authors.forename: Joseph
authors.initials: J
authors.lastname: Moore
authors.forename: Nelson J
authors.initials: NJ
authors.lastname: Chao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage; D011446:Prospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
chemical_list: D019653:Myeloablative Agonists