Primary central nervous system lymphoma natural history, complications, and prognosis

If left untreated, primary central nervous system lymphoma may progress to develop elevated intracranial pressure, ocular symptoms, focal neurological deficits, and neuropsychiatric problems. Common complications of primary central nervous system lymphoma include relapse, extracranial or subcutaneous metastasis, neuropsychiatric problems, and neurological toxicity. The prognosis of primary central nervous system lymphoma is generally poor.

• Primary central nervous system lymphoma is usually an aggressive lymphoma.^[1]

• The clinical course is rapidly fatal; these patients usually present with signs of elevated intracranial pressure, nausea, papilledema, vomiting, and neuropsychiatric symptoms.^[2]

Common complications of primary central nervous system lymphoma include:^[3][4][5]

• Relapse
• Extracranial or subcutaneous metastasis
• Neuropsychiatric problems

• Depression
• Apathy
• Slowed thinking
• Confusion

• Neurological toxicity

• As survival of patients with primary central nervous system lymphoma becoming long, the quality o life and mental function is now very important.^[5]
• Neurotoxicity typically is associated with significant cognitive, motor and autonomic dysfunction, and has a negative impact on quality of life.
• Delayed neurologic toxicity is a serious complication, especially occurring in patients older than 60 years.
• Methotrexate (MTX) is a known neurotoxin and has the potential of producing leukoencephalopathy as well as other types of neurotoxicities, such as microangiopathy. MTX is a folate antagonist inhibiting nucleic acid and methioine synthesis. Methionine is necessary for CNS myelination. The presence of a risk haplotype defined by polymorphisms influencing methionine metabolism referred a relative risk for CNS white matter changes. MTX in combination with whole brain radiotherapy (WBRT) relates to its potential for causing delayed leukoencephalopathy.^[5]
• Radiation therapy prior to MTX administration increase the risk of leukoencephalopathy. While intrathecal, intravenous MTX, and WBRT have the potential for producing leukoencephalopathy independently, when two or three of them are combined the risk will increase.
• Nguyen et al. reported late treatment-associated neurotoxicity in 15% of patients and was significantly associated with total radiation doses greater than 36 Gy.
• O`Brien et al. reported 30% of neurotoxicity risk who were treated with MTX (1g/m2) followed by WBRT.^[5]
• Correa et al. reported the neuropsychological evaluation of 28 patients. These were of sufficient severity to reduce quality of life in half of the patient sample. Patients treated with WBRT +/- chemotherapy revealed more pronounced cognitive impairement, particularly in the memory and attention/executive domain. Extent of white matter disease correlated with attention/executive, memory, and language impairment. Primary CNS lymphoma survivors treated with WBRT +/- chemotherapy displayed more pronounced cognitive dysfunction than patients treated with MTX-based chemotherapy alone.
• Delayed neurotoxicity may present as a rapidly progressive subcortical dementia characterized by psychomotor slowing, executive and memory dysfunction, behavioral changes, gait ataxia, and incontinence. Imaging findings may reveal diffuse white matter disease and cortical-subcortical atrophy.^[5]

• The prognosis of primary central nervous system lymphoma is generally poor.^[1][4]
• Poor prognostic factors for primary central nervous system lymphoma include:^[1][6]

• Elderly patient (>50 years)
• Poor performance status of the individual (PS > 1 or Karnofsky PS < 70)
• AIDS-related primary central nervous system lymphoma
• Elevated serum level of lactate dehydrogenase
• Elevated cerebrospinal fluid protein concentration
• Involvement of nonhemispheric areas of the brain (periventricular, basal ganglia, brainstem, and cerebellum)

• The initial response to radiotherapy is often excellent, and may result in a complete remission. However, the duration of response with radiotherapy alone remains short, with median survival after treatment with radiotherapy is 18 months.
• Methotrexate-based chemotherapy markedly improves survival, with some studies showing median survival after methotrexate chemotherapy reaching 48 months.^[7]

• Patients with AIDS and primary central nervous system lymphoma have a median survival of only 4 months with radiotherapy alone. Untreated, median survival is only 2.5 months, sometimes due to concurrent opportunistic infections rather than the lymphoma itself.^[7]
• Extended survival has been seen, however, in a subgroup of AIDS patients with CD4 counts of more than 200 and no concurrent opportunistic infections, who can tolerate aggressive therapy consisting of either methotrexate monotherapy or vincristine, procarbazine or whole brain radiotherapy.
• These patients have a median survival of 10–18 months. Of course, highly active antiretroviral therapy (HAART) is critical for prolonged survival in any AIDS patient, so compliance with HAART may play a role in survival in patients with concurrent AIDS and primary CNS lymphoma.^[7]

Template:WikiDoc Sources