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Cancer. 2002 Aug 1;95(3):576-80.

Prophylactic intrathecal methotrexate and hydrocortisone reduces central nervous system recurrence and improves survival in aggressive non-hodgkin lymphoma.

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First Department of Internal Medicine, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-004, Japan.



Central nervous system (CNS) recurrence is almost invariably fatal in patients with aggressive non-Hodgkin lymphoma (NHL). Although some protocols are intended to prevent CNS disease, the value of CNS prophylaxis in patients with aggressive NHL remains to be determined.


We retrospectively analyzed a cohort of 68 adults with NHL who had been treated uniformly with systemic chemotherapy and had attained complete remission (CR) of disease. Patients ranged in age from 15 to 77 years (median, 56 years). Median follow-up after CR was 40 months. After CR was attained, 29 patients (Group A) received CNS prophylaxis consisting of four doses of intrathecal methotrexate 10 mg/m(2) and hydrocortisone 15 mg/m(2) as soon as they could tolerate it. The other 39 patients (Group B) did not receive CNS prophylaxis.


Although bulky mass (45% vs. 21%, P = 0.03) was more frequent in Group A than in Group B, none of the patients in Group A experienced CNS recurrence (0%), whereas CNS recurrence occurred in six patients in Group B (15%). This difference was significant (P = 0.03). Multivariate logistic regression analysis for CNS recurrence identified no CNS prophylaxis (P = 0.01) and bone marrow involvement (P = 0.02) as independent predictors. Among patients without CNS disease, systemic recurrence occurred in 5 patients in Group A and in 11 patients in Group B (P = 0.12). The 5-year overall survival rate from CR was 80% in Group A and 58% in Group B (P = 0.05). The 5-year recurrence-free survival rate from CR was 85% in Group A and 51% in Group B (P = 0.01).


Prophylactic intrathecal methotrexate and hydrocortisone injection reduces the incidence of CNS recurrence following CR in patients with aggressive NHL and improves the chance of long-term survival.

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