title: Hyper-CVAD and high-dose methotrexate/cytarabine followed by stem-cell transplantation: an active regimen for aggressive mantle-cell lymphoma.
abstract: OBJECTIVE
  Diffuse and nodular forms of mantle-cell lymphoma (MCL) are consistently associated with poor prognosis. In an effort to improve the outcome, we adopted a treatment plan that consisted of four courses of fractionated cyclophosphamide (CY) 1,800 mg/m2 administered with doxorubicin (DOX), vincristine (VCR), and dexamethasone (Hyper-CVAD) that alternated with high-dose methotrexate (MTX) and cytarabine (Ara-C). After four courses, patients were consolidated with high-dose CY, total-body irradiation, and autologous or allogeneic blood or marrow stem-cell transplantation.
  
  
  METHODS
  Forty-five patients were enrolled; 25 patients were previously untreated, 43 patients had Ann Arbor stage IV disease, and 42 patients had marrow involvement. Forty-one patients had diffuse histology, two patients had nodular, and two patients had blastic variants.
  
  
  RESULTS
  Hyper-CVAD/MTX-Ara-C induced a response rate of 93.5% (complete response [CR], 38%; partial response [PR], 55.5%) after four cycles of pretransplantation induction chemotherapy. All patients who went on to undergo transplantation achieved CRs. For the 25 previously untreated patients, the overall survival (OS) and event-free survival (EFS) rates at 3 years were 92% (95% confidence interval [CI], 80 to 100) and 72% (95% CI, 45 to 98) compared with 25% (95% CI, 12 to 62; P = .005) and 17% (95% CI, 10 to 43; P = .007), respectively, for the previously treated patients. When compared with a historic control group who received a CY, DOX, VCR, and prednisone (CHOP)-like regimen, untreated patients in the study had a 3-year EFS rate of 72% versus 28% (P = .0001) and a better OS rate (92% v 56%; P = .05). Treatment-related death occurred in five patients: all were previously treated and two received allogeneic transplants.
  
  
  CONCLUSIONS
  The Hyper-CVAD/MTX-Ara-C program followed by stem-cell transplantation is a promising new therapy for previously untreated patients with MCL.
authors.affiliation: Department of Hematology, The University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA. issafkhouri@mdanderson.org
authors.forename: I F
authors.initials: IF
authors.lastname: Khouri
authors.forename: J
authors.initials: J
authors.lastname: Romaguera
authors.forename: H
authors.initials: H
authors.lastname: Kantarjian
authors.forename: J L
authors.initials: JL
authors.lastname: Palmer
authors.forename: W C
authors.initials: WC
authors.lastname: Pugh
authors.forename: M
authors.initials: M
authors.lastname: Korbling
authors.forename: F
authors.initials: F
authors.lastname: Hagemeister
authors.forename: B
authors.initials: B
authors.lastname: Samuels
authors.forename: A
authors.initials: A
authors.lastname: Rodriguez
authors.forename: S
authors.initials: S
authors.lastname: Giralt
authors.forename: A
authors.initials: A
authors.lastname: Younes
authors.forename: D
authors.initials: D
authors.lastname: Przepiorka
authors.forename: D
authors.initials: D
authors.lastname: Claxton
authors.forename: F
authors.initials: F
authors.lastname: Cabanillas
authors.forename: R
authors.initials: R
authors.lastname: Champlin
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000628:therapy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D008727:Methotrexate