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Information from PDQ -- for Health Professionals
Primary central nervous system lymphoma
208/04272
** DISEASE DESCRIPTION **
Primary central nervous system (CNS) lymphoma is defined as lymphoma limited to
the cranial-spinal axis without systemic disease. An increasing incidence of
this disease has been seen among patients with acquired immunodeficiency
syndrome (AIDS) and among other immunocompromised persons. The natural history
of this disorder differs between patients with AIDS and those without AIDS.
Computed tomographic (CT) scans may show ring enhancement in one half of the
AIDS patients while patients without AIDS almost always show only homogeneous
enhancement.[1] Both groups do equally poorly without therapy (1-3 month mean
survival), but the overall survival for treated patients is much better for
patients without AIDS (18.9 months) than for those with AIDS (2.6 months).[1,2]
Nonambulatory performance status and age older than 60 years are considered
important poor prognostic indicators. In addition, presence of multiple
neurological dysfunctions, elevated cerebrospinal fluid protein level, and
nonhemispheric location of the tumor have been associated with a worse
prognosis.[3] When tumor progression occurs, it is usually confined to the CNS
and/or the eye. Occult systemic disease can be excluded by staging with bone
marrow biopsy and CT scans of the chest, abdomen, and pelvis.[4]
Because of the diffuse nature of CNS lymphomas, aggressive surgical
decompression with partial or gross total removal of the tumor is of no benefit
to the patient. Median survival with surgery alone is in the range of only 1-5
months. Until recently, radiation therapy has been the standard treatment,
with doses of up to 45 Gy using standard fractionation. When the Radiation
Therapy Oncology Group used 40 Gy whole-brain irradiation and a 20 Gy boost to
the tumor, the results were no better than had been previously reported, with
median survival of 1 year and 28% surviving 2 years.[3,5] Disease recurs in
the brain in 92% of patients despite the high doses of radiation. The addition
of spinal axis radiation does not affect survival because it does not prevent
cerebral relapse.
Two multicenter prospective trials used pre-irradiation cyclophosphamide,
doxorubicin, vincristine, and dexamethasone followed by whole-brain
irradiation.[6,7] Median survival times were no better than for radiation
therapy alone. The failure of these and other combined modality trials [8-11]
has been attributed to poor penetration of standard drugs through the blood-
brain barrier and to increased neurotoxicity.[6,9-14] A retrospective review
of 226 patients suggested improved results using high-dose methotrexate or
cytarabine with radiation therapy over other combination regimens[15]
Due to the unsatisfactory results of whole-brain irradiation alone and to the
neurologic toxic effects of chemotherapy and radiation therapy, there is now a
major focus on trials with chemotherapy alone. There are now several single-
institution reports in which systemic chemotherapy has been employed alone or
with osmotic blood-brain barrier disruption.[8,12,13,16-18] Currently, most
regimens are employing high-dose methotrexate and require
hospitalization.[8,13,17,18] For patients who do not respond to chemotherapy
alone or with radiation therapy, but are still responsive to salvage
chemotherapy with cytarabine and etoposide, intensive chemotherapy with
autologous peripheral stem cell transplantation is under evaluation.[19]
Severe cognitive deficits are reported with all intensive therapies due to
iatrogenic leukoencephalopathy. Retrospective data suggest a decreased risk of
dementia when chemotherapy is employed prior to radiation therapy and even less
when radiation therapy is avoided.[1,2,15] The use of systemic chemotherapy
alone, with or without osmotic blood-brain barrier disruption, may avoid the
cognitive loss observed with radiation therapy.[2,15-17] Comparative trials
with validated measures of cognitive function will be necessary to determine
the value of delaying radiation therapy until relapse after high-dose
chemotherapy.[2,20,21] Glucocorticoids can also produce substantial but
short-lived remissions. Steroid efficacy may complicate the diagnostic
evaluation by obscuring the histologic findings. New drugs that cross the
blood-brain barrier are under clinical evaulation.[22]
Patients with AIDS-associated primary CNS lymphoma usually have very advanced
human immunodeficiency virus (HIV) infections, with CD4+ counts less than 50
cells per milliliter.[23] Consequently, most patients die of opportunistic
infections irrespective of therapy for the lymphoma. Groups that benefit most
from radiation therapy (with or without antecedent chemotherapy) include those
HIV-seropositive patients with no prior opportunistic infections or tumors for
whom the CNS lymphoma is the AIDS-defining illness and those patients with a
good performance status, high CD4 lymphocyte count (>100/mm3), and symptoms
referable only to the CNS lymphoma.[1,24] Treatment of these patients requires
special consideration. (Refer to the PDQ summary on AIDS-Related Lymphoma
Treatment for more information.)
References:
1. Fine HA, Mayer RJ: Primary central nervous system lymphoma. Annals of
Internal Medicine 119(11): 1093-1104, 1993.
2. Nasir S, DeAngelis LM: Update on the management of primary CNS lymphoma.
Oncology (Huntington NY) 14(2): 228-234, 2000.
3. Pollack IF, Lunsford LD, Flickinger JC, et al.: Prognostic factors in the
diagnosis and treatment of primary central nervous system lymphoma.
Cancer 63(5): 939-947, 1989.
4. O'Neill BP, Dinapoli RP, Kurtin PJ, et al.: Occult systemic non-Hodgkin's
lymphoma (NHL) in patients initially diagnosed as primary central
nervous system lymphoma (PCNSL): how much staging is enough? Journal of
Neuro-Oncology 25(1): 67-71, 1995.
5. Nelson DF, Martz KL, Bonner H, et al.: Non-Hodgkin's lymphoma of the
brain: can high dose, large volume radiation therapy improve survival?
Report on a prospective trial by the Radiation Therapy Oncology Group
(RTOG): RTOG 8315. International Journal of Radiation Oncology,
Biology, Physics 23(1): 9-17, 1992.
6. O'Neill BP, O'Fallon JR, Earle JD, et al.: Primary central nervous system
non-Hodgkin's lymphoma: survival advantages with combined initial
therapy? International Journal of Radiation Oncology, Biology, Physics
33(3): 663-673, 1995.
7. Schultz C, Scott C, Sherman W, et al.: Preirradiation chemotherapy with
cyclophosphamide, doxorubicin, vincristine, and dexamethasone for
primary CNS lymphomas: initial report of Radiation Therapy Oncology
Group protocol 88-06. Journal of Clinical Oncology 14(2): 556-564,
1996.
8. Brada M, Dearnaley D, Horwich A, et al.: Management of primary cerebral
lymphoma with initial chemotherapy: preliminary results and comparison
with patients treated with radiotherapy alone. International Journal of
Radiation Oncology, Biology, Physics 18(4): 787-792, 1990.
9. Chamberlain MC, Levin VA: Primary central nervous system lymphoma: a role
for adjuvant chemotherapy. Journal of Neuro-Oncology 14(3): 271-275,
1992.
10. Fine HA: Treatment of primary central nervous system lymphoma: still
more questions than answers. Blood 86(8): 2873-2875, 1995.
11. Bessell EM, Graus F, Lopez-Guillermo A, et al.: CHOD/BVAM plus
radiotherapy in patients with primary CNS non-Hodgkin's lymphoma.
International Journal of Radiation Oncology, Biology, Physics 50(2):
457-464, 2001.
12. Abrey LE, DeAngelis LM, Yahalom J: Long-term survival in primary CNS
lymphoma. Journal of Clinical Oncology 16(3): 859-863, 1998.
13. Blay JY, Bouhour D, Carrie C, et al.: The C5R protocol: a regimen of
high-dose chemotherapy and radiotherapy in primary cerebral
non-Hodgkin's lymphoma of patients with no known cause of
immunosuppression. Blood 86(8): 2922-2929, 1995.
14. O'Brien P, Roos D, Pratt G, et al.: Phase II multicenter study of brief
single-agent methotrexate followed by irradiation in primary CNS
lymphoma. Journal of Clinical Oncology 18(3): 519-526, 2000.
15. Blay JY, Conroy T, Chevreau C, et al.: High-dose methotrexate for the
treatment of primary cerebral lymphomas: analysis of survival and late
neurologic toxicity in a retrospective series. Journal of Clinical
Oncology 16(3): 864-871, 1998.
16. Dahlborg SA, Henner WD, Crossen JR, et al.: Non-AIDS primary CNS
lymphoma: first example of a durable response in a primary brain tumor
using enhanced chemotherapy delivery without cognitive loss and without
radiotherapy. Cancer Journal from Scientific American 2(3): 166-174,
1996.
17. Gabbai AA, Hochberg FH, Linggood RM, et al.: High-dose methotrexate for
non-AIDS primary central nervous system lymphoma: report of 13 cases.
Journal of Neurosurgery 70(2): 190-194, 1989.
18. Sandor V, Stark-Vancs V, Pearson D, et al.: Phase II trial of
chemotherapy alone for primary CNS and intraocular lymphoma. Journal of
Clinical Oncology 16(9): 3000-3006, 1998.
19. Soussain C, Suzan F, Hoang-Xuan K, et al.: Results of intensive
chemotherapy followed by hematopoietic stem-cell rescue in 22 patients
with refractory or recurrent primary CNS lymphoma or intraocular
lymphoma. Journal of Clinical Oncology 19(3): 742-749, 2001.
20. DeAngelis LM: Primary central nervous system lymphoma: curable without
toxicity? Cancer Journal from Scientific American 2(3): 137-139, 1996.
21. Bessell EM, Lopez-Guillermo A, Villa S, et al.: Importance of
radiotherapy in the outcome of patients with primary CNS lymphoma: an
analysis of the CHOD/BVAM regimen followed by two different radiotherapy
treatments. Journal of Clinical Oncology 20(1): 231-236, 2002.
22. Reni M, Ferreri AJ, Landoni C, et al.: Salvage therapy with temozolomide
in an immunocompetent patient with primary brain lymphoma. Journal of
the National Cancer Institute 92(7): 575-576, 2000.
23. Levine AM: Acquired immunodeficiency syndrome-related lymphoma. Blood
80(1): 8-20, 1992.
24. Corn BW, Donahue BR, Rosenstock JG, et al.: Performance status and age as
independent predictors of survival among AIDS patients with primary CNS
lymphoma: a multivariate analysis of a multi-institutional experience.
Cancer Journal from Scientific American 3(1): 52-56, 1997.
Date Last Modified: 07/2002
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