title: Sustained remissions of high-risk acute myeloid leukemia and myelodysplastic syndrome after reduced-intensity conditioning allogeneic hematopoietic transplantation: chronic graft-versus-host disease is the strongest factor improving survival.
abstract: OBJECTIVE
  Reduced-intensity conditioning (RIC) for allogeneic stem-cell transplantation (allo-SCT) reduces nonrelapse mortality (NRM). This reduction makes it possible for patients who are ineligible for high-dose myeloablative conditioning allo-SCT to benefit from graft-versus-leukemia reaction. In this multicenter, prospective study of patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), we investigated the efficacy of RIC allo-SCT from a human leukocyte antigen-identical sibling by using a regimen that uses fludarabine and busulfan.
  
  
  METHODS
  Ninety-three patients with AML (n = 59) and MDS (n = 34) were included, and the median age was of 53 years. Follow-up for survivors was 43 months (range, 3 to 89 months). The conditioning regimen consisted of fludarabine (150 mg/m(2)) and oral busulfan (8 to 10 mg/kg). All except one patient received mobilized peripheral blood stem cells. Graft-versus-host disease (GVHD) prophylaxis consisted of cyslosporine and methotrexate or mycophenolate mofetil.
  
  
  RESULTS
  The 100-day, 1-year, and 4-year incidences of NRM were 8, 16%, and 21%, respectively. The 1- and 4-year relapse cumulative incidences were 23% and 37%, respectively, and leukemia recurrence was the main cause of death. The 4-year disease-free survival (DFS) and overall survival (OS) rates were 43% and 45%, respectively. The 4-year cumulative incidence of chronic GVHD was 53% (45% extensive), and its development was the major factor associated with lower relapse incidence and improved DFS and OS.
  
  
  CONCLUSIONS
  Our results confirm the capacity of this RIC regimen to obtain long-term remissions in patients ineligible for a conventional allo-SCT. The results suggest an important role of the development of chronic GVHD in reducing relapse and improving DFS and OS.
authors: Hospital de la Santa Creu i Sant Pau, Universitat Autonoma Barcelona, Barcelona, Spain. dvalcarcel@santpau.es
authors: David
authors: D
authors: Valcárcel
authors: Rodrigo
authors: R
authors: Martino
authors: Dolores
authors: D
authors: Caballero
authors: Jesus
authors: J
authors: Martin
authors: Christelle
authors: C
authors: Ferra
authors: Jose B
authors: JB
authors: Nieto
authors: Antonia
authors: A
authors: Sampol
authors: M Teresa
authors: MT
authors: Bernal
authors: Jose L
authors: JL
authors: Piñana
authors: Lourdes
authors: L
authors: Vazquez
authors: Jose M
authors: JM
authors: Ribera
authors: Joan
authors: J
authors: Besalduch
authors: Jose M
authors: JM
authors: Moraleda
authors: Dolores
authors: D
authors: Carrera
authors: M Salut
authors: MS
authors: Brunet
authors: Jose A
authors: JA
authors: Perez-Simón
authors: Jorge
authors: J
authors: Sierra
mesh_terms: D000328:Adult; D000368:Aged; D002066:Busulfan / Q000008:administration & dosage; D002908:Chronic Disease; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D015470:Leukemia, Myeloid, Acute / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019653:Myeloablative Agonists / Q000008:administration & dosage; D009190:Myelodysplastic Syndromes / Q000401:mortality* / Q000628:therapy*; D011446:Prospective Studies; D012074:Remission Induction; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine