Central nervous system prophylaxis with combined intravenous and intrathecal methotrexate in diffuse lymphoma of aggressive histologic type

Roman Perez-Soler, T. L. Smith, F. Cabanillas

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Abstract

With the use of a multivariate regression model, 21 patients with diffuse lymphoma were identified as having greater than 15% risk of experiencing relapse in the central nervous system (CNS). The efficacy of a combination of sequential intravenous methotrexate (MTX) (1 g/m2) and intrathecal MTX in preventing relapse in the CNS and improving survival times was assessed. A comparable historical control group of patients with similar risk of CNS relapse and who did not receive any CNS prophylaxis was used. The CNS relapse-free survival rate (RFS) was improved in patients who received CNS prophylaxis (95% versus 59% at 2 years; P = 0.01). Pretreatment serum lactic dehydrogenase (LDH) levels correlated with the incidence of relapse in the CNS in the control group (P = 0.01). In patients with high pretreatment serum LDH levels (>225 U/L), CNS RFS was improved in those who received CNS prophylaxis (RFS at 2 years: 91% versus 46%; P = 0.02). Both CNS RFS (100% versus 38% at 2 years; P = 0.03) and survival rates (100% versus 38% at 2 years; P = 0.02) were improved in six patients with histologic type other than large cell. In 15 patients with large cell lymphoma, no significant differences in CNS RFS (93% versus 75% at 2 years; P = 0.29) and survival rates (43% versus 44% at 2 years; P = 0.56) were observed. Cerebrospinal fluid MTX levels were above the therapeutic level of 1 x 10-6 M for at least 20 hours in 90% of courses of combined MTX. The MTX combination used is an effective and non-neurotoxic CNS prophylaxis method. Because the comparison between different methods of CNS prophylaxis is difficult to make without a precise idea of the expected CNS relapse rate, use of the multivariate regression technique is recommended.

Original languageEnglish (US)
Pages (from-to)971-977
Number of pages7
JournalCancer
Volume57
Issue number5
StatePublished - 1986
Externally publishedYes

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Methotrexate
Non-Hodgkin's Lymphoma
Central Nervous System
Recurrence
Survival Rate
Oxidoreductases
Milk
Control Groups
Serum
Cerebrospinal Fluid
Lymphoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Central nervous system prophylaxis with combined intravenous and intrathecal methotrexate in diffuse lymphoma of aggressive histologic type. / Perez-Soler, Roman; Smith, T. L.; Cabanillas, F.

In: Cancer, Vol. 57, No. 5, 1986, p. 971-977.

Research output: Contribution to journalArticle

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abstract = "With the use of a multivariate regression model, 21 patients with diffuse lymphoma were identified as having greater than 15{\%} risk of experiencing relapse in the central nervous system (CNS). The efficacy of a combination of sequential intravenous methotrexate (MTX) (1 g/m2) and intrathecal MTX in preventing relapse in the CNS and improving survival times was assessed. A comparable historical control group of patients with similar risk of CNS relapse and who did not receive any CNS prophylaxis was used. The CNS relapse-free survival rate (RFS) was improved in patients who received CNS prophylaxis (95{\%} versus 59{\%} at 2 years; P = 0.01). Pretreatment serum lactic dehydrogenase (LDH) levels correlated with the incidence of relapse in the CNS in the control group (P = 0.01). In patients with high pretreatment serum LDH levels (>225 U/L), CNS RFS was improved in those who received CNS prophylaxis (RFS at 2 years: 91{\%} versus 46{\%}; P = 0.02). Both CNS RFS (100{\%} versus 38{\%} at 2 years; P = 0.03) and survival rates (100{\%} versus 38{\%} at 2 years; P = 0.02) were improved in six patients with histologic type other than large cell. In 15 patients with large cell lymphoma, no significant differences in CNS RFS (93{\%} versus 75{\%} at 2 years; P = 0.29) and survival rates (43{\%} versus 44{\%} at 2 years; P = 0.56) were observed. Cerebrospinal fluid MTX levels were above the therapeutic level of 1 x 10-6 M for at least 20 hours in 90{\%} of courses of combined MTX. The MTX combination used is an effective and non-neurotoxic CNS prophylaxis method. Because the comparison between different methods of CNS prophylaxis is difficult to make without a precise idea of the expected CNS relapse rate, use of the multivariate regression technique is recommended.",
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