Prolonged myelosuppression with clofarabine in the treatment of patients with relapsed or refractory, aggressive non-Hodgkin lymphoma.
We evaluated the safety and efficacy of the purine nucleoside analogue, clofarabine, in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). Six patients with DLBCL (n = 5) or MCL (n = 1) and a median age of 68 years were treated with 40 mg/m(2) clofarabine IV over 2 h for 5 days, repeated every 28 days, for 1-2 cycles. The overall response rate was 50% (complete response = 1, complete response unconfirmed = 1, partial response = 1). Median progression-free survival was 3.5 months (range 1.5-10 months) and the median overall survival was 7.8 months (range 3-31 months). Grade 3-4 neutropenia and thrombocytopenia was universal, with a median of 34 (range 19-55) and 77 (range 0-275) days required for neutrophil and platelet recovery. Grade 3 non-hematologic toxicities included transaminitis, febrile neutropenia, non-neutropenic infections and orthostatic hypotension. Further accrual to the study was terminated due to prolonged Grade 3-4 myelosuppression and orthostatic hypotension in five of six patients. Clofarabine exhibits evidence of single agent activity in relapsed or refractory DLBCL. However, further study with novel administration schedules that maintain this efficacy and limit toxicity is warranted.
Blum
Kristie A
KA
Division of Hematology-Oncology, Department of Internal Medicine, Arthur G James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA. kristie.blum@osumc.edu
Hamadani
Mehdi
M
Phillips
Gary S
GS
Lozanski
Gerard
G
Johnson
Amy J
AJ
Lucas
David M
DM
Smith
Lisa L
LL
Baiocchi
Robert
R
Lin
Thomas S
TS
Porcu
Pierluigi
P
Devine
Steven M
SM
Byrd
John C
JC
D000227:Adenine Nucleotides / Q000008:administration & dosage* / Q000633:toxicity; D000368:Aged; D001087:Arabinonucleosides / Q000008:administration & dosage* / Q000633:toxicity; D000077866:Clofarabine; D005260:Female; D006410:Hematopoiesis; D006801:Humans; D007700:Kinetics; D016403:Lymphoma, Large B-Cell, Diffuse / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D020522:Lymphoma, Mantle-Cell / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage* / Q000633:toxicity; D009503:Neutropenia / Q000139:chemically induced; D012074:Remission Induction; D016879:Salvage Therapy / Q000379:methods*; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced
D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D019653:Myeloablative Agonists; D000077866:Clofarabine