title: Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem-cell transplantation.
abstract: OBJECTIVE
  Patients with advanced myeloid malignancies who experience relapse after allogeneic bone marrow transplantation (BMT) have a poor prognosis. Long-term survival after chemotherapy alone, second myeloablative transplant, or donor leukocyte infusions (DLIs) alone is unusual. DLIs may have minimal effectiveness in advanced disease because adequate cellular responses are not able to develop in the presence of bulky, fast-growing disease. A chemotherapy strategy was used to debulk disease before administration of granulocyte colony-stimulating factor (G-CSF)-primed DLIs.
  
  
  METHODS
  Sixty-five patients experiencing hematologic relapse of myeloid malignancy after HLA-matched sibling BMT were prospectively treated with cytarabine-based chemotherapy, then G-CSF-primed DLIs. No prophylactic immunosuppression was provided.
  
  
  RESULTS
  Twenty-seven of 57 assessable patients experienced a complete response. Graft-versus-host disease (GVHD) was observed in 56% of the patients. Treatment-related mortality was 23%. Overall survival at 2 years for the entire cohort was 19%. Patients with a complete response were more likely to survive, with 1- and 2-year survival rates of 51% and 41%, respectively, with a median follow-up of more than 2 years. The 1-year survival for nonresponders was 5%. A posttransplant remission lasting more than 6 months before relapse was associated with a higher likelihood of response. GVHD was not required for durable remission.
  
  
  CONCLUSIONS
  Salvage treatment with chemotherapy before DLI can help some patients with advanced myeloid relapse and is not dependent on GVHD. Patients with short remissions after BMT are unlikely to benefit from this approach, and the approach is associated with significant treatment-related mortality. Modifications of this approach or entirely different approaches will be required for most patients with this difficult clinical problem.
authors.affiliation: University of Michigan, Ann Arbor, MI, USA. jelevine@umich.edu
authors.forename: John E
authors.initials: JE
authors.lastname: Levine
authors.forename: Thomas
authors.initials: T
authors.lastname: Braun
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Penza
authors.forename: Patrick
authors.initials: P
authors.lastname: Beatty
authors.forename: Kenneth
authors.initials: K
authors.lastname: Cornetta
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Martino
authors.forename: William R
authors.initials: WR
authors.lastname: Drobyski
authors.forename: A John
authors.initials: AJ
authors.lastname: Barrett
authors.forename: David L
authors.initials: DL
authors.lastname: Porter
authors.forename: Sergio
authors.initials: S
authors.lastname: Giralt
authors.forename: Jose
authors.initials: J
authors.lastname: Leis
authors.forename: Houston E
authors.initials: HE
authors.lastname: Holmes
authors.forename: Matthew
authors.initials: M
authors.lastname: Johnson
authors.forename: Mary
authors.initials: M
authors.lastname: Horowitz
authors.forename: Robert H
authors.initials: RH
authors.lastname: Collins
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001782:Blood Donors; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007223:Infant; D007279:Injections, Subcutaneous; D007951:Leukemia, Myeloid / Q000473:pathology / Q000628:therapy*; D007962:Leukocytes; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012008:Recurrence; D016879:Salvage Therapy; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D016179:Granulocyte Colony-Stimulating Factor