title: Evidence of a graft-versus-leukemia effect in chronic lymphocytic leukemia after reduced-intensity conditioning and allogeneic stem-cell transplantation: the Cooperative German Transplant Study Group.
abstract: OBJECTIVE
  To study whether hematopoietic stem-cell transplantation (HSCT) after reduced-intensity conditioning is effective and tolerable in patients with advanced chronic lymphocytic leukemia (CLL).
  
  
  METHODS
  Thirty patients with advanced B-cell CLL were included into the study. After reduced-intensity conditioning with fludarabine, busulfan, and antithymocyte globulin, patients received a transplant from related (n = 15) or unrelated donors (n = 15). Minimal residual disease (MRD) was monitored with a clone-specific polymerase chain reaction.
  
  
  RESULTS
  After a median follow-up of 2 years, 23 patients are alive (to date). Neutrophil and platelet engraftment occurred after a median of 17.5 and 15 days, respectively. Acute graft-versus-host disease (GVHD) grade 2 to 4 was observed in 17 patients (56%), and chronic GVHD was observed in 21 patients (75%). Twelve patients (40%) achieved a complete remission (CR), and 16 patients (53%) achieved a partial remission. Late CR occurred up to 2 years after transplantation. MRD was monitored in eight patients with CR. All patients achieved a molecular CR. At last follow-up, six patients were in ongoing molecular CR. Causes of death were treatment-related complications in four patients and progressive disease in three patients. The probability of overall survival, progression-free survival, and nonrelapse mortality at 2 years was 72% (95% confidence interval [CI], 54% to 90%), 67% (95% CI, 49% to 85%), and 15% (95% CI, 1% to 29%), respectively.
  
  
  CONCLUSIONS
  Treatment-related mortality after reduced-intensity conditioning followed by allogeneic HSCT was low. The procedure induced molecular remissions in patients with advanced CLL. The observation of late remissions provided evidence of a graft-versus-leukemia effect.
authors.affiliation: Charité Campus Virchow Klinium, Berlin, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Schetelig
authors.forename: C
authors.initials: C
authors.lastname: Thiede
authors.forename: M
authors.initials: M
authors.lastname: Bornhauser
authors.forename: R
authors.initials: R
authors.lastname: Schwerdtfeger
authors.forename: M
authors.initials: M
authors.lastname: Kiehl
authors.forename: J
authors.initials: J
authors.lastname: Beyer
authors.forename: H G
authors.initials: HG
authors.lastname: Sayer
authors.forename: N
authors.initials: N
authors.lastname: Kroger
authors.forename: M
authors.initials: M
authors.lastname: Hensel
authors.forename: C
authors.initials: C
authors.lastname: Scheffold
authors.forename: T K
authors.initials: TK
authors.lastname: Held
authors.forename: K
authors.initials: K
authors.lastname: Hoffken
authors.forename: A D
authors.initials: AD
authors.lastname: Ho
authors.forename: J
authors.initials: J
authors.lastname: Kienast
authors.forename: A
authors.initials: A
authors.lastname: Neubauer
authors.forename: A R
authors.initials: AR
authors.lastname: Zander
authors.forename: A A
authors.initials: AA
authors.lastname: Fauser
authors.forename: G
authors.initials: G
authors.lastname: Ehninger
authors.forename: W
authors.initials: W
authors.lastname: Siegert
mesh_terms: D000328:Adult; D000368:Aged; D002066:Busulfan / Q000627:therapeutic use*; D002648:Child; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011336:Probability; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use*
chemical_list: D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine