Clofarabine in the treatment of poor risk acute myeloid leukaemia.
Clofarabine is a second generation nucleoside analogue. It inhibits DNA repair and activates the mitochondrial apoptotic pathway leading to cell death. In vitro clofarabine has demonstrated synergy with daunorubicin and Ara-C and in phase II clinical trials has shown promising activity in poor risk Acute myeloid leukaemia (AML) patients. In our institution over a 24 month period 22 AML patients (11 M, 11 F) with poor risk features, deemed unsuitable for standard therapy, were treated with clofarabine, alone (eight patients) or in combination (14 patients) for up to three cycles of treatment. The median age was 67.5 years (24-76) with 16 patients > 60 years. At the time of treatment 18 patients had active AML. Four patients intolerant of standard induction received clofarabine as consolidation. The overall response rate (ORR) for the 18 patients with active AML was 61%, nine patients (50%) achieving a complete response (CR). Induction and consolidation were well tolerated with no unexpected toxicities. Predictably, all patients developed grade 4 neutropenia but the median duration was only 20 days (17-120). Induction mortality was acceptable at 17%. In conclusion, clofarabine (alone or in combination) is active in poor risk AML with an acceptable safety profile and should be considered a potential option in poor risk AML patients.
Krawczyk
Janusz
J
Department of Haematology, Galway University Hospital and National University of Ireland, Galway, Ireland.
Ansar
Naeem
N
Swords
Ronan
R
Murphy
Tracy
T
MacDonagh
Barry
B
Meenaghan
Teresa
T
Hayden
Patrick
P
Hayad
Amjad
A
Murray
Margaret
M
O'Dwyer
Michael
M
D000227:Adenine Nucleotides / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000008:administration & dosage / Q000627:therapeutic use*; D000077866:Clofarabine; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D000077866:Clofarabine