title: Fractionated cyclophosphamide, vincristine, liposomal daunorubicin (daunoXome), and dexamethasone (hyperCVXD) regimen in Richter's syndrome.
abstract: Approximately 3 to 5% of patients with chronic lymphocytic leukemia (CLL) develop an aggressive large cell non Hodgkin's lymphoma (NHL) known as Richter's syndrome (RS). RS has a poor prognosis and a response rate of < 10% with fludarabine-based or other cytotoxic combination regimens. The aim of this study was to evaluate the efficacy and toxicity of the hyperCVXD regimen in RS. Twenty-nine patients, median age 61 years (36-75) 23 males, were treated. Prior diagnosis was CLL in 26 patients, NHL in 2, and Prolymphocytic leukemia in 1. Treatment consisted of fractionated cyclophosphamide, vincristine, daunoXome and dexamethasone. Six patients (20%) died while receiving study therapy, 4 (14%) during the first cycle of whom 2 had started therapy with overt pneumonia. Grade 4 granulocytopenia occurred in all 95 cycles of therapy with a median time to recovery of 14 days. Twenty three (24%) cycles were complicated by fever, and 15 (15%) by pneumonia. Sepsis was documented in 8 (8%) cycles, and neuropathy in 5 (5%) of cycles. Twenty three patients had a platelet count < 100 x 10(9)/l prior to therapy: a greater than 50% decrease in platelet count over pre-therapy level occurred in 79% of first cycles, overt bleeding occurred in 4 (4%) of all cycles. Eleven of 29 (38%) patients achieved complete remission (CR), 4 of whom have relapsed after 5, 6, 9, and 12 months of remission. Two of 11 CR patients presented with RS without any prior CLL therapy. One patient had a partial remission. Thus the overall response rate was 12/29 (41%). Overall median survival was 10 months, 19 months in patients who achieved CR, 3 months in those who did not (p = 0.0008). A landmark analysis performed at 2 months from start of therapy comparing patients alive in CR versus patients alive but not in CR showed a median survival of 19 months versus 6 months, respectively (p 0.0017). In conclusion the hyper CVXD regimen has a relatively high response rate, significant toxicity and a moderate impact on survival in RS.
authors.affiliation: Department of Leukemia, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 428, Houston, Texas 77030, USA.
authors.forename: B S
authors.initials: BS
authors.lastname: Dabaja
authors.forename: S M
authors.initials: SM
authors.lastname: O'Brien
authors.forename: H M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: J E
authors.initials: JE
authors.lastname: Cortes
authors.forename: D A
authors.initials: DA
authors.lastname: Thomas
authors.forename: M
authors.initials: M
authors.lastname: Albitar
authors.forename: E S
authors.initials: ES
authors.lastname: Schlette
authors.forename: S
authors.initials: S
authors.lastname: Faderl
authors.forename: A
authors.initials: A
authors.lastname: Sarris
authors.forename: M J
authors.initials: MJ
authors.lastname: Keating
authors.forename: F J
authors.initials: FJ
authors.lastname: Giles
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D004337:Drug Carriers; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality; D008081:Liposomes; D016403:Lymphoma, Large B-Cell, Diffuse / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D013577:Syndrome; D013997:Time Factors; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D014750:Vincristine; D003907:Dexamethasone; D003520:Cyclophosphamide