title: Improved outcome of adult Burkitt lymphoma/leukemia with rituximab and chemotherapy: report of a large prospective multicenter trial.
abstract: This largest prospective multicenter trial for adult patients with Burkitt lymphoma/leukemia aimed to prove the efficacy and feasibility of short-intensive chemotherapy combined with the anti-CD20 antibody rituximab. From 2002 to 2011, 363 patients 16 to 85 years old were recruited in 98 centers. Treatment consisted of 6 5-day chemotherapy cycles with high-dose methotrexate, high-dose cytosine arabinoside, cyclophosphamide, etoposide, ifosphamide, corticosteroids, and triple intrathecal therapy. Patients >55 years old received a reduced regimen. Rituximab was given before each cycle and twice as maintenance, for a total of 8 doses. The rate of complete remission was 88% (319/363); overall survival (OS) at 5 years, 80%; and progression-free survival, 71%; with significant difference between adolescents, adults, and elderly patients (OS rate of 90%, 84%, and 62%, respectively). Full treatment could be applied in 86% of the patients. The most important prognostic factors were International Prognostic Index (IPI) score (0-2 vs 3-5; P = .0005), age-adjusted IPI score (0-1 vs 2-3; P = .0001), and gender (male vs female; P = .004). The high cure rate in this prospective trial with a substantial number of participating hospitals demonstrates the efficacy and feasibility of chemoimmunotherapy, even in elderly patients. This trial was registered at www.clinicaltrials.gov as #NCT00199082.
authors.affiliation: Department of Internal Medicine II, Hematology and Oncology, University Hospital, Frankfurt, Germany;
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoelzer
authors.affiliation: Department of Lymphoid Malignancies, Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland;
authors.forename: Jan
authors.initials: J
authors.lastname: Walewski
authors.affiliation: Department of Internal Medicine III, University Hospital, Ulm, Germany;
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.affiliation: Department of Internal Medicine III, University Hospital, Ulm, Germany;
authors.forename: Andreas
authors.initials: A
authors.lastname: Viardot
authors.affiliation: Department of Medicine III, Clinic Grosshadern, Munich, Germany;
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
authors.affiliation: Department of Medicine III, Clinic Grosshadern, Munich, Germany;
authors.forename: Karsten
authors.initials: K
authors.lastname: Spiekermann
authors.affiliation: Department of Internal Medicine II, Hematology and Oncology, University Hospital, Frankfurt, Germany;
authors.forename: Hubert
authors.initials: H
authors.lastname: Serve
authors.affiliation: Department of Hematology and Oncology, University Hospital, Essen, Germany;
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dührsen
authors.affiliation: Department of Hematology and Oncology, University Hospital, Essen, Germany;
authors.forename: Andreas
authors.initials: A
authors.lastname: Hüttmann
authors.affiliation: Department of Hematology, Oncology, and Tumorimmunology, Charité Campus Benjamin Franklin, Berlin, Germany;
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Germany;
authors.forename: Jolanta
authors.initials: J
authors.lastname: Dengler
authors.affiliation: Department of Internal Medicine II, University Hospital of Schleswig Holstein, Campus Kiel, Kiel, Germany;
authors.forename: Michael
authors.initials: M
authors.lastname: Kneba
authors.affiliation: Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany;
authors.forename: Markus
authors.initials: M
authors.lastname: Schaich
authors.affiliation: Department of Internal Medicine III, University of Bonn, Bonn, Germany;
authors.forename: Ingo G H
authors.initials: IG
authors.lastname: Schmidt-Wolf
authors.affiliation: Department of Medicine II, University Hospital, Mainz, Germany;
authors.forename: Joachim
authors.initials: J
authors.lastname: Beck
authors.affiliation: Department of Internal Medicine I, Clinic Bremen-Mitte, Bremen, Germany;
authors.forename: Bernd
authors.initials: B
authors.lastname: Hertenstein
authors.affiliation: Department of Hematology/Oncology, University Hospital, Regensburg, Germany;
authors.forename: Albrecht
authors.initials: A
authors.lastname: Reichle
authors.affiliation: Department of Lymphoid Malignancies, Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland;
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Domanska-Czyz
authors.affiliation: Institute for Radiotherapy, University Hospital, Erlangen, Germany; and.
authors.forename: Rainer
authors.initials: R
authors.lastname: Fietkau
authors.affiliation: Department of Internal Medicine II, University Hospital of Schleswig Holstein, Campus Kiel, Kiel, Germany;
authors.forename: Heinz-August
authors.initials: HA
authors.lastname: Horst
authors.affiliation: Institute for Human Genetics, University Clinic, Duesseldorf, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Rieder
authors.affiliation: Department of Hematology, Oncology, and Tumorimmunology, Charité Campus Benjamin Franklin, Berlin, Germany;
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwartz
authors.affiliation: Department of Hematology, Oncology, and Tumorimmunology, Charité Campus Benjamin Franklin, Berlin, Germany;
authors.forename: Thomas
authors.initials: T
authors.lastname: Burmeister
authors.affiliation: Department of Internal Medicine II, Hematology and Oncology, University Hospital, Frankfurt, Germany;
authors.forename: Nicola
authors.initials: N
authors.lastname: Gökbuget
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D018951:Antigens, CD20 / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002051:Burkitt Lymphoma / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007167:Immunotherapy / Q000379:methods; D007278:Injections, Spinal; D007938:Leukemia / Q000188:drug therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D000069283:Rituximab; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D003561:Cytarabine; D000069283:Rituximab; D005047:Etoposide; D003520:Cyclophosphamide; D007069:Ifosfamide; D008727:Methotrexate