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Haematologica. 2014 Jul;99(7):1228-35. doi: 10.3324/haematol.2013.101741. Epub 2014 Apr 11.

Detection and outcome of occult leptomeningeal disease in diffuse large B-cell lymphoma and Burkitt lymphoma.

Author information

1
Lymphoid Malignancy Branch, National Cancer Institute, Bethesda, MD, USA wilsonw@mail.nih.gov.
2
Department of Neuro-Oncology, Daniel den Hoed Cancer Center, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
3
Lymphoid Malignancy Branch, National Cancer Institute, Bethesda, MD, USA.
4
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.
5
Department of Hematology, Hospital German Trias i Puyol, University of Barcelona, Spain for the Spanish Group for the Study of CNS Disease in NHL.
6
Department of Hematology, Daniel den Hoed Cancer Center, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
7
Department of Medical Immunology, Daniel den Hoed Cancer Center, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
8
Department of Hematology, Hospital del Mar, Barcelona, Spain.
9
Department of Hematology, Hospital Duran i Reynals, Institut Catala d'Oncologia, IDIBELL, University of Barcelona, Spain.
10
Mundipharma International Limited, Cambridge, UK.
11
Division of Medical Oncology A, National Cancer Institute, Aviano, Italy.

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.

PMID:
24727817
PMCID:
PMC4077085
DOI:
10.3324/haematol.2013.101741
[Indexed for MEDLINE]
Free PMC Article

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