Central nervous system prophylaxis

The prevalence of methotrexate pneumonitis has been variably estimated from 0.3 to 18%, with a mean estimated prevalence of 3.3% (14,16). In a review of the respiratory complications of methotrexate, the authors concluded that pneumonitis occurs in 7% of patients, in 25% of whom it is fatal as a result of respiratory failure (18). This can occur with any dose of methotrexate, given via any route it has occurred after the intrathecal administration of 12 mg given for central nervous system prophylaxis (19). In a review of 194 patients with rheumatoid arthritis and 38 with psoriatic arthritis, the prevalences of pneumonitis were 2.1 and 0.03% respectively (14), which is similar to the 3.2% incidence in a prospective study of 124 patients with rheumatoid arthritis (20). Another analysis performed over 5 years showed that the estimated prevalence of definite or probable pneumonitis was only 0.86% in 1162 patients (10 patients, of whom three died), but this conclusion was based on a limited retrospective identification of cases (21). 

Because the risk of central nervous system (CNS) involvement is high, regardless of cerebrospinal fluid (CSF) cytology all patients with acute lymphocytic leukemia (ALL) receive intrathecal prophylaxis. 

Keyset LA, Karl M, Nafziger AN, Bertino JS Jr. (2000) Comparison of central nervous system adverse effects of amantadine and rimantadine used as sequential prophylaxis of influenza a in elderly nursing home patients. Arch Intern Med 160 1485-1488... 

The treatment of adult acute lymphoblastic leukemia (ALL) is typically divided into 4 broad categories induction therapy, intensification or consolidation therapy, maintenance therapy and central nervous system (CNS) prophylaxis. 

Efavirenz (Sustiva) is approved for the therapy of HIV infection of adults and children and is also used for postexposure prophylaxis. It is the only NNRTI approved for once-daUy dosing. Rash, although rarely severe, is a common adverse effect of efavirenz. Elevated liver enzymes and serum cholesterol also may occur. Central nervous system (CNS) effects in approximately half of patients may include dizziness, headache, insomnia, drowsiness, euphoria, agitation, impaired cognition, nightmares, vivid dreams, and hallucinations. These effects often subside after several weeks to months of therapy. 

Cefazolin penetrates well into most tissues. It is a drug of choice for surgical prophylaxis. Cefazolin may be a choice in infections for which it is the least toxic drug (eg, penicillinase-producing E coli or pneumoniae) and in persons with staphylococcal or streptococcal infections who have a history of penicillin allergy other than immediate hypersensitivity. Cefazolin does not penetrate the central nervous system and cannot be used to treat meningitis. Cefazolin is an alternative to an antistaphylococcal penicillin for patients who are allergic to penicillin. 

Therapy for ALL has historically been divided into three phases (1) remission induction (2) consolidation therapy and (3) maintenance therapy (Fig. 131-1). Central nervous system (CNS) prophylaxis is a mandatory component of any ALL treatment regimen and is administered longitudinally during the induction and consolidation phases. Recently more complex regimens have been explored. All patients still receive induction therapy to yield a CR. Post-remission therapy is needed to treat microscopic disease and may include intensive inpatient therapy (consolidation or intensification therapy) followed by less aggressive outpatient therapy (maintenance or continuation). Tables 131-9 and 131-10 illustrate representative treatment regimens for adult and pediatric ALL. ° ... 

It is the first ever antineoplastic agent that produced appreciable remissions in leukemia. It is extensively employed for the treatment of acute lymphoblastic leukemia. It is invariably used in combination cheotherapy for palliative management of limg eaneer, breast cancer and epidermoid cancers of the head. It is frequently recommended for the treatment and prophylaxis of meningeal leukemia based on its ability to penetrate the central nervous system. It is also of value in choricarcinoma and related trophoblastie tumours of women. 

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