title: Relapse risk after autologous transplantation in patients with newly diagnosed myeloma is not related with infused tumor cell load and the outcome is not improved by CD34+ cell selection: long term follow-up of an EBMT phase III randomized study.
abstract: OBJECTIVE
  This European Group for Blood and Marrow Transplantation (EBMT) multicentre randomized phase III study was designed to assess the safety and efficacy of CD34+ selection in newly diagnosed myeloma patients undergoing autologous transplantation.
  
  
  METHODS
  One hundred and eleven patients responsive to initial chemotherapy were randomized to receive CD34+ selected (arm A) or unselected PBPC (arm B) after conditioning with high-dose melphalan and TBI. ASO-PCR was used to assess purging efficacy and reinfused tumor load. Tumor load could be assessed in 59 patients.
  
  
  RESULTS
  CD34+ selection gave a median tumor cell depletion of 2.2 logs (0.77-5.96). No tumor cells were detected in products infused in 17/26 (A) and 5/33 (B) patients. The five year overall survival (OS), event free survival (EFS) and relapse rate (RR) were 51%, 20% and 80% in arm A and 45%, 18% and 80% in arm B respectively with no significant difference between the two groups. Thirteen patients in arm A and 2 in arm B experienced episodes of serious early infection (p=0.02). There were 3 early transplant related deaths in A but none in B.
  
  
  CONCLUSIONS
  Despite significant tumor cell reduction, CD34+ selection does not reduce RR and increases the risk of severe post-transplant infections. There was also no difference in RR between patients in either arm who received grafts with detectable tumor cells and those receiving grafts with no detectable tumor cells, suggesting that reinfused tumor cells may not be the main cause of relapse after autologous transplant in myeloma.
authors.affiliation: Division of Hematology, Department of Medicine, Institut Gustave Roussy, 94800 Villejuif, France. jhb@igr.fr
authors.forename: Jean-Henri
authors.initials: JH
authors.lastname: Bourhis
authors.forename: Yasmina
authors.initials: Y
authors.lastname: Bouko
authors.forename: Serge
authors.initials: S
authors.lastname: Koscielny
authors.forename: Marleen
authors.initials: M
authors.lastname: Bakkus
authors.forename: Hildegard
authors.initials: H
authors.lastname: Greinix
authors.forename: Gunter
authors.initials: G
authors.lastname: Derigs
authors.forename: Gilles
authors.initials: G
authors.lastname: Salles
authors.forename: Walter
authors.initials: W
authors.lastname: Feremans
authors.forename: Jane
authors.initials: J
authors.lastname: Apperley
authors.forename: Diana
authors.initials: D
authors.lastname: Samson
authors.forename: Bo
authors.initials: B
authors.lastname: Björkstrand
authors.forename: Dietger
authors.initials: D
authors.lastname: Niederwieser
authors.forename: Gösta
authors.initials: G
authors.lastname: Gahrton
authors.forename: José-Luis
authors.initials: JL
authors.lastname: Pico
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D016465:Bone Marrow Purging / Q000379:methods*; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000401:mortality / Q000601:surgery*; D036102:Peripheral Blood Stem Cell Transplantation / Q000401:mortality / Q000706:statistics & numerical data; D011183:Postoperative Complications / Q000453:epidemiology; D011379:Prognosis; D012008:Recurrence; D012306:Risk; D016019:Survival Analysis; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods; D014182:Transplantation, Autologous / Q000706:statistics & numerical data; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D018952:Antigens, CD34; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin