title: Detection and outcome of occult leptomeningeal disease in diffuse large B-cell lymphoma and Burkitt lymphoma.
abstract: The benefit of intrathecal therapy and systemic rituximab on the outcome of diffuse large B-cell lymphoma at risk of central nervous system disease is controversial. Furthermore, the effect of intrathecal treatment and rituximab in diffuse large B-cell and Burkitt lymphoma with occult leptomeningeal disease detected by flow cytometry at diagnosis is unknown. Untreated diffuse large B-cell (n=246) and Burkitt (n=80) lymphoma at clinical risk of central nervous system disease and having had pre-treatment cerebrospinal fluid were analyzed by flow cytometry and cytology. Spinal fluid involvement was detected by flow cytometry alone (occult) in 33 (13%) diffuse large B-cell and 9 (11%) Burkitt lymphoma patients, and detected by cytology in 11 (4.5%) and 5 (6%) patients, respectively. Diffuse large B-cell lymphoma with occult spinal fluid involvement had poorer survival (P=0.0001) and freedom from central nervous system relapse (P<0.0001) compared to negative cases. Burkitt lymphoma with occult spinal fluid involvement had an inferior freedom from central nervous system relapse (P=0.026) but not survival. The amount of intrathecal chemotherapy was quantitatively associated with survival in diffuse large B-cell lymphoma with (P=0.02) and without (P=0.001) occult spinal fluid involvement. However, progression of systemic disease and not control of central nervous system disease was the principal cause of treatment failure. In diffuse large B-cell lymphoma, systemic rituximab was associated with improved freedom from central nervous system relapse (P=0.003) but not with survival. Our results suggest that patients at risk of central nervous system disease should be evaluated by flow cytometry and that intrathecal prophylaxis/therapy is beneficial.
authors.affiliation: Lymphoid Malignancy Branch, National Cancer Institute, Bethesda, MD, USA wilsonw@mail.nih.gov.
authors.forename: Wyndham H
authors.initials: WH
authors.lastname: Wilson
authors.affiliation: Department of Neuro-Oncology, Daniel den Hoed Cancer Center, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Jacoline E C
authors.initials: JE
authors.lastname: Bromberg
authors.affiliation: Lymphoid Malignancy Branch, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Maryalice
authors.initials: M
authors.lastname: Stetler-Stevenson
authors.affiliation: Lymphoid Malignancy Branch, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.affiliation: Department of Medicine and Centro de Investigacion del Cancer (IBMCC-CSIC/USAL) and Department of Hematology, University Hospital, IBSAL and University of Salamanca, Salamanca, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Martin-Martin
authors.affiliation: Department of Medicine and Centro de Investigacion del Cancer (IBMCC-CSIC/USAL) and Department of Hematology, University Hospital, IBSAL and University of Salamanca, Salamanca, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Muñiz
authors.affiliation: Department of Hematology, Hospital German Trias i Puyol, University of Barcelona, Spain for the Spanish Group for the Study of CNS Disease in NHL.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Sancho
authors.affiliation: Department of Medicine and Centro de Investigacion del Cancer (IBMCC-CSIC/USAL) and Department of Hematology, University Hospital, IBSAL and University of Salamanca, Salamanca, Spain.
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Caballero
authors.affiliation: Department of Hematology, Daniel den Hoed Cancer Center, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
authors.forename: Marjan A
authors.initials: MA
authors.lastname: Davidis
authors.affiliation: Department of Medical Immunology, Daniel den Hoed Cancer Center, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
authors.forename: Rik A
authors.initials: RA
authors.lastname: Brooimans
authors.affiliation: Department of Hematology, Hospital del Mar, Barcelona, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Sanchez-Gonzalez
authors.affiliation: Department of Hematology, Hospital del Mar, Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Salar
authors.affiliation: Department of Hematology, Hospital Duran i Reynals, Institut Catala d'Oncologia, IDIBELL, University of Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: González-Barca
authors.affiliation: Department of Hematology, Hospital German Trias i Puyol, University of Barcelona, Spain for the Spanish Group for the Study of CNS Disease in NHL.
authors.forename: Jose Maria
authors.initials: JM
authors.lastname: Ribera
authors.affiliation: Lymphoid Malignancy Branch, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Shovlin
authors.affiliation: Lymphoid Malignancy Branch, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Armando
authors.initials: A
authors.lastname: Filie
authors.affiliation: Lymphoid Malignancy Branch, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Kieron
authors.initials: K
authors.lastname: Dunleavy
authors.affiliation: Mundipharma International Limited, Cambridge, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mehrling
authors.affiliation: Division of Medical Oncology A, National Cancer Institute, Aviano, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Spina
authors.affiliation: Department of Medicine and Centro de Investigacion del Cancer (IBMCC-CSIC/USAL) and Department of Hematology, University Hospital, IBSAL and University of Salamanca, Salamanca, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002051:Burkitt Lymphoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D002555:Cerebrospinal Fluid / Q000166:cytology; D002648:Child; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007278:Injections, Spinal; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D008297:Male; D008577:Meningeal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality / Q000556:secondary*; D008875:Middle Aged; D009367:Neoplasm Staging; D012307:Risk Factors; D000069283:Rituximab; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab
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