title: Clofarabine/cyclophosphamide for debulking before stem cell transplantation.
abstract: BACKGROUND
  Allogeneic haematopoietic stem cell transplantation (HSCT) is the only curative rescue therapy for patients (pts) with chemotherapy-refractory acute leukaemia. Disease control prior to HSCT is essential for long-term disease-free survival after HSCT.
  
  
  METHODS
  We have retrospectively analysed the outcome of 20 pts aged 21-64 years with refractory leukaemia (acute myeloid leukaemia, n = 16; acute lymphatic leukaemia, n = 4) who received debulking therapy with clofarabine (10 mg/m², days 1-4) and cyclophosphamide (200 mg/m², days 1-4; ClofCy) prior to HSCT.
  
  
  RESULTS
  Clofarabine/cyclophosphamide (1-4 cycles) was well tolerated and resulted in a substantial reduction of leukaemic cells in all pts. HSCT was performed in 15 of 20 pts. After HSCT (myeloablative, n = 9; dose-reduced, n = 6), all pts showed engraftment and full donor chimerism (related donors, n = 4 or unrelated donors, n = 11) and all pts achieved complete haematologic remission (CR). The median survival after HSCT is 531 days (range: 48-1462 days), and six pts are still alive after a median of 1245 days. Seven pts died after they had relapsed between days +152 and +1496. One patient died from acute graft-versus-host disease (day +48) and one from systemic fungal infection (day +87).
  
  
  CONCLUSIONS
  Clofarabine/cyclophosphamide is a novel effective treatment approach for pts with chemotherapy-refractory acute leukaemia prior to HSCT. Whether this novel debulking protocol leads to improved long-term outcome in pts with refractory leukaemias remains to be determined in forthcoming clinical studies.
authors.affiliation: Bone Marrow Transplantation Unit, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria; Intensive Care Unit, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Rabitsch
authors.forename: Alexandra
authors.initials: A
authors.lastname: Böhm
authors.forename: Marija
authors.initials: M
authors.lastname: Bojic
authors.forename: Peter
authors.initials: P
authors.lastname: Schellongowski
authors.forename: Stefan
authors.initials: S
authors.lastname: Wöhrer
authors.forename: Thamer
authors.initials: T
authors.lastname: Sliwa
authors.forename: Felix
authors.initials: F
authors.lastname: Keil
authors.forename: Nina
authors.initials: N
authors.lastname: Worel
authors.forename: Hildegard
authors.initials: H
authors.lastname: Greinix
authors.forename: Alexander
authors.initials: A
authors.lastname: Hauswirth
authors.forename: Peter
authors.initials: P
authors.lastname: Kalhs
authors.forename: Ulrich
authors.initials: U
authors.lastname: Jaeger
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.forename: Wolfgang R
authors.initials: WR
authors.lastname: Sperr
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000008:administration & dosage; D000077866:Clofarabine; D003520:Cyclophosphamide / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000628:therapy*; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D000077866:Clofarabine; D003520:Cyclophosphamide
keywords: Debulking; haematopoietic stem cell transplantation; refractory leukaemia; survival