title: A prospective randomized toxicity study to compare reduced-intensity and myeloablative conditioning in patients with myeloid leukaemia undergoing allogeneic haematopoietic stem cell transplantation.
abstract: BACKGROUND
  To our knowledge, no randomized toxicity studies have been conducted to compare myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC) in allogeneic haematopoietic stem cell transplantation (HSCT).
  
  
  METHODS
  Adult patients ≤60 years of age with myeloid leukaemia were randomly assigned (1 : 1) to treatment with RIC (n = 18) or MAC (n = 19) in this Phase II single-centre toxicity study.
  
  
  RESULTS
  There was a maximum median mucositis grade of 1 in the RIC group compared with 4 in the MAC group (P < 0.001). Haemorrhagic cystitis occurred in eight of the patients in the MAC group and none in the RIC group (P < 0.01). Results of renal and hepatic tests did not differ significantly between the two groups. RIC-treated patients had faster platelet engraftment (P < 0.01) and required fewer erythrocyte and platelet transfusions (P < 0.001) and less total parenteral nutrition (TPN) than those treated with MAC (P < 0.01). Cytomegalovirus (CMV) infection was more common in the MAC group (14/19) than in the RIC group (6/18) (P = 0.02). Donor chimerism was similar in the two groups with regard to CD19 and CD33, but was delayed for CD3 in the RIC group. Five-year transplant-related mortality (TRM) was approximately 11% in both groups, and rates of relapse and survival were not significantly different. Patients in the MAC group with intermediate cytogenetic acute myeloid leukaemia had a 3-year survival of 73%, compared with 90% among those in the RIC group.
  
  
  CONCLUSIONS
  Reduced-intensity conditioning had several advantages compared with MAC, including less mucositis, less haemorrhagic cystitis, faster platelet engraftment, the need for fewer transfusions and less TPN, and fewer CMV infections. Both regimens were tolerated and TRM was low.
authors: Division of Therapeutic Immunology and Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden. Olle.Ringden@ki.se
authors: O
authors: O
authors: Ringdén
authors: T
authors: T
authors: Erkers
authors: J
authors: J
authors: Aschan
authors: K
authors: K
authors: Garming-Legert
authors: K
authors: K
authors: Le Blanc
authors: H
authors: H
authors: Hägglund
authors: B
authors: B
authors: Omazic
authors: P
authors: P
authors: Svenberg
authors: G
authors: G
authors: Dahllöf
authors: J
authors: J
authors: Mattsson
authors: P
authors: P
authors: Ljungman
authors: M
authors: M
authors: Remberger
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002066:Busulfan / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000379:methods; D016896:Treatment Outcome
chemical_list: D003520:Cyclophosphamide; D002066:Busulfan
keywords: acute myeloid leukaemia; haematopoietic stem cell transplantation; myeloablative conditioning; randomized trial; reduced-intensity conditioning; toxicity