title: Stem cell transplantation after salvage therapy with high-dose cytarabine and amsacrine in adults with high-risk leukaemia.
abstract: Stem cell transplantation (SCT) may be the only curative option for patients with relapsed or refractory leukaemia, that is, high-risk (HR) leukaemia. Several salvage regimens have been used to cytoreduce disease before SCT, but disease progression or treatment toxicity limits numbers of patients receiving SCT. Here, we report our experience with high-dose cytarabine and amsacrine (Ara-amsa) to salvage patients with HR-leukaemia in the context of SCT. A total of 34 patients with HR-leukaemia (20 AML, 12 ALL, two advanced CML) received 3 g/m(2)/day cytarabine for 5 days and amsacrine 200 mg/m(2)/day for 3 days. Disease response was observed in 62% of patients. Toxicity was limited to neutropenic fever, one patient developed cerebellar toxicity and there was one treatment-related death. A total of 17 patients proceeded to SCT (12 allografts and five autografts). Median survival (OS) of all patients was 10.8 months (95% CI 7.8-21). Patients who were consolidated with SCT after salvage therapy had a superior median OS of 29.4 months (95% CI 12.5-upper limit not reached, n=17) than those who did not receive SCT (6.7 months, CI 1.5-8.6, P<0.0001). Median disease-free survival with SCT (23 months) was higher than after treatment with salvage chemotherapy alone (6.7 months, P=0.0002). Thus Ara-amsa can be used effectively to salvage HR-leukaemia, enabling further consolidation with SCT.
authors.affiliation: Bone Marrow Transplant Unit, University Hospital, Birmingham, UK.
authors.forename: S
authors.initials: S
authors.lastname: Tauro
authors.forename: P
authors.initials: P
authors.lastname: Shankaranarayana
authors.forename: I C
authors.initials: IC
authors.lastname: Nitu-Whalley
authors.forename: N
authors.initials: N
authors.lastname: Duncan
authors.forename: G
authors.initials: G
authors.lastname: Begum
authors.forename: J I O
authors.initials: JI
authors.lastname: Craig
authors.forename: R E
authors.initials: RE
authors.lastname: Marcus
authors.forename: C F
authors.initials: CF
authors.lastname: Craddock
authors.forename: P
authors.initials: P
authors.lastname: Mahendra
mesh_terms: D000293:Adolescent; D000328:Adult; D000677:Amsacrine / Q000008:administration & dosage* / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D003561:Cytarabine / Q000008:administration & dosage* / Q000633:toxicity; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D007938:Leukemia / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000677:Amsacrine; D003561:Cytarabine