title: CNS disease in younger patients with aggressive B-cell lymphoma: an analysis of patients treated on the Mabthera International Trial and trials of the German High-Grade Non-Hodgkin Lymphoma Study Group.
abstract: BACKGROUND
  To describe incidence, risk factors, and influence of treatment on occurrence of central nervous system (CNS) relapse or progression in younger patients with aggressive B-cell lymphoma.
  
  
  METHODS
  We analyzed 2210 patients with aggressive B-cell lymphoma treated on various studies for CNS relapse/progression. Treatment consisted of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) ± etoposide. Six hundred and twenty patients also received rituximab. CNS prophylaxis was intrathecal methotrexate on High-CHOEP and MegaCHOEP phase III studies if upper neck, head, bone marrow, or testes were involved.
  
  
  RESULTS
  Fifty-six of 2196 patients (2.6%) developed CNS disease. It occurred early (median 7.0 months), median survival was 5.0 months. Patients with age-adjusted International Prognostic Index (aaIPI) 0 or 1 treated with rituximab showed a low risk for CNS disease (2-year rates: 0% or 0.5%), and rituximab decreased the risk (relative risk 0.3, 95% confidence interval 0.1-0.9, P = 0.029). Patients with aaIPI 2 or 3 showed a moderate risk (4.2%-9.7%) and no significant reduction of CNS disease with rituximab. CNS prophylaxis was of no significant benefit.
  
  
  CONCLUSIONS
  In younger patients with aaIPI 0 or 1, CNS relapse/progression is very rare; in patients with aaIPI 2 or 3, the risk is higher (up to 10%) and requires new diagnostic strategies and treatment.
authors: Department of Hematology, Oncology and Stem Cell Transplantation, Asklepios Hospital St. Georg, Hamburg. Electronic address: n.schmitz@asklepios.com.
authors: N
authors: N
authors: Schmitz
authors: Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig.
authors: S
authors: S
authors: Zeynalova
authors: Department of Hematology, Oncology and Stem Cell Transplantation, Asklepios Hospital St. Georg, Hamburg.
authors: B
authors: B
authors: Glass
authors: Internal Medicine II-Oncology Center, Hematology, Immunology, Internal Oncology, Palliative Medicine, St. Bernward Hospital, Hildesheim, Germany.
authors: U
authors: U
authors: Kaiser
authors: Department of Oncology, University of Lund, Lund, Sweden.
authors: E
authors: E
authors: Cavallin-Stahl
authors: Peter MacCallum Cancer Institute, Division of Haematology, East Melbourne, Australia.
authors: M
authors: M
authors: Wolf
authors: Internal Medicine III, Department of Hematology, Oncology, Stem Cell Transplantation, Klinikum Chemnitz, Chemnitz.
authors: M
authors: M
authors: Haenel
authors: Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig.
authors: M
authors: M
authors: Loeffler
authors: Department of Hematology and Oncology, University of Göttingen, Göttingen.
authors: L
authors: L
authors: Truemper
authors: Department of Internal Medicine I, Saarland University, Homburg/Saar, Germany.
authors: M
authors: M
authors: Pfreundschuh
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000556:secondary; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007391:International Cooperation; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D008297:Male; D008495:Medical Oncology / Q000458:organization & administration; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000069283:Rituximab; D012955:Societies, Medical / Q000458:organization & administration; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone; D011241:Prednisone; D008727:Methotrexate