title: Control of relapsed or refractory acute myeloid leukemia by clofarabine in preparation for allogeneic stem cell transplant.
abstract: Allogeneic stem cell transplant is indicated for patients with refractory or relapsed acute myeloid leukemia (AML). Since elimination of the leukemic load is thought to be a prerequisite for treatment success, we here investigate toxicity and anti-leukemic activity of a clofarabine-AraC salvage protocol preceding transplant. In this retrospective analysis, we observed induction of objective remissions in 86% of patients receiving clofarabine-AraC as compared to 83% with sequential high dose AraC/mitoxantrone (S-HAM) and 50% after mitoxantrone/topotecane/AraC (MTC) salvage strategies. In addition, clofarabine conferred anti-leukemic activity to some patients who failed initial MTC or S-HAM therapy. For overall and leukemia-free survival, we identified cytogenetically defined adverse risk markers but not response to therapy to be a strong predictor. In summary, the clofarabine-AraC salvage strategy combines pronounced anti-leukemic activity with an acceptable toxicity profile and allows the majority of patients with relapsed or refractory AML to proceed to allo-SCT, even in cytogenetically defined high risk situations.
authors.affiliation: a Medical Hospital II, University of Wuerzburg , Wuerzburg , Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Loeffler
authors.affiliation: a Medical Hospital II, University of Wuerzburg , Wuerzburg , Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Kapp
authors.affiliation: a Medical Hospital II, University of Wuerzburg , Wuerzburg , Germany.
authors.forename: Goetz-Ulrich
authors.initials: GU
authors.lastname: Grigoleit
authors.affiliation: a Medical Hospital II, University of Wuerzburg , Wuerzburg , Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Mielke
authors.affiliation: a Medical Hospital II, University of Wuerzburg , Wuerzburg , Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Loeffler
authors.affiliation: b Institute for Clinical Epidemiology and Biometrics , Wuerzburg , Germany.
authors.forename: Peter U
authors.initials: PU
authors.lastname: Heuschmann
authors.affiliation: b Institute for Clinical Epidemiology and Biometrics , Wuerzburg , Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Malzahn
authors.affiliation: a Medical Hospital II, University of Wuerzburg , Wuerzburg , Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Hupp
authors.affiliation: a Medical Hospital II, University of Wuerzburg , Wuerzburg , Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.affiliation: a Medical Hospital II, University of Wuerzburg , Wuerzburg , Germany.|c DKD Helios Klinik , Wiesbaden , Germany.
authors.forename: Gernot
authors.initials: G
authors.lastname: Stuhler
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001087:Arabinonucleosides / Q000008:administration & dosage / Q000627:therapeutic use*; D000077866:Clofarabine; D019008:Drug Resistance, Neoplasm; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D019233:Retreatment; D012189:Retrospective Studies; D016879:Salvage Therapy; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000227:Adenine Nucleotides; D000964:Antimetabolites, Antineoplastic; D001087:Arabinonucleosides; D000077866:Clofarabine
keywords: Allogeneic stem cell transplant; clofarabine; cytarabine; relapsed and refractory AML; salvage therapy