Treatment of Meningeal Leukemia With Pyrimethamine

Geils, George F.; Scott, Charlie W.; Baugh, Charles M.; Butterworth, Charles E.

doi:10.1182/blood.v38.2.131.131

Cited by 52 publications

(2 citation statements)

References 21 publications

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“…In this regard, these preliminary data are encouraging. Moreover, the evaluation of Fansidar® in other diseases such as leukaemia, in which induction of apoptosis could be beneficial, might be considered (Geils et al , 1971).…”

Section: Discussionmentioning

confidence: 99%

Reversion of autoimmune lymphoproliferative syndrome with an antimalarial drug: preliminary results of a clinical cohort study and molecular observations

et al. 2002

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Autoimmune lymphoproliferative syndrome (ALPS) is a paediatric disease characterized by lymphoproliferation and autoimmunity. Most patients are known to carry heterozygous mutations of the TNFRSF6 gene leading to diminished Fas-mediated apoptosis and failure of activated lymphocytes to undergo apoptosis. A subgroup of patients without the TNFRSF6 gene mutation has similar defective apoptosis and clinical features. No effective treatment has been reported so far. Glucocorticoids, intravenous immunoglobulin and/or immunosuppressive drugs have usually led to only transient clinical improvement. Seven ALPS patients (two type Ia and five type III) were treated with the antimalarial drug Fansidar. No toxicity was observed. An objective response was seen in six of them and, in two, the treatment was stopped without reappearance of the symptoms. Moreover, a marked decrease in interleukin-10 levels was observed in two patients during the treatment. We found that the drug induced apoptosis in activated lymphocytes through activation of the mitochondrial apoptotic pathway.

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Section: Discussionmentioning

confidence: 99%

Reversion of autoimmune lymphoproliferative syndrome with an antimalarial drug: preliminary results of a clinical cohort study and molecular observations

et al. 2002

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“…2o Pyrimethamine has been used to effectively treat active meningeal leukemia. 5 A nitrosourea was added during maintenance for CNS prophylaxis based on the demonstrated effectiveness of 1, 3-bis-(2-chloroethyl)-Initrosourea (BCNU) in treating active meningeal leukemia in children. 12 CCNU was se-Combination therapy of adult ALL 241 lected because it is a stable oral preparation that causes less gastrointestinal toxicity than oral BCNU and has been shown to be at least as efficacious as intravenous BCNU in most clinical situations.…”

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confidence: 99%

Combination chemotherapy of adult acute lymphocytic leukemia

Smyth

Wiernik

1976

Clin Pharma and Therapeutics

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Seventeen adults with previously untreated acute lymphocytic leukemia (ALL) received thioguanine, vincristine, dexamethasone, and pyrimethamine for remission induction. Nine patients (53%) achieved complete and 5 (30%) partial remissions. Once in complete remission patients were given two closely separated consolidation courses followed by monthly maintenance courses of the same regimen with the addition of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) every other month during maintenance therapy. The median duration of complete remission was 176 days (range 38 to 605). The median survival for all patients was 405 days (range 30 to 1,058+). Oral pyrimethamine and CCNU were used for their potential activity as prophylactics against meningeal leukemia. Dexamethasone was used instead of prednisone because of the potential enhancement of granulocyte mobilization by the former. Six patients (35%) developed meningeal leukemia while on initial induction or maintenance therapy, 5 within 6 months of diagnosis. Life-threatening infections occured in 10 patients (59%) during induction. Whereas the regimen effectively induced complete remission in about half of previously untreated adults with ALL, it was not effective in maintenance. The incidence of meningeal leukemia and infection during induction was high. Oral pyrimethamine was inadequate prophylaxis for meningeal leukemia; dexamethasone did not reduce the incidence of serious infection.

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Parenchymatous degeneration of the central nervous system in childhood leukemia

Hendin¹,

DeVivo²,

Torack³

et al. 1974

Cancer

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A 7‐year‐old boy with acute lymphocytic leukemia suffered increasing dementia, seizures, ataxia, and spasticity. The neuropathologic findings appeared unique, and included extensive fibrillary gliosis, with lesser degrees of myelin loss and axonal dystrophy. Similar though less severe findings were observed on re‐examination of CNS tissues from 23 other children who died of leukemia. Subcortical fibrillary gliosis was particularly prominent in 22 of 23 cases, and occurred symmetrically in the subependymal and subpial regions, inferior olives, cerebellar roof nuclei, substantia nigra, internal and external capsules, subventricular nuclei, basis pontis, and ventral horns of the spinal cord. The subcortical fibrillary gliosis was out of proportion to the myelin pallor and was not associated with leukemic infiltration. Alzheimer Type II glia were also present diffusely in 22 of 24 cases. No clear etiologic association could be established between the severity of the neuropathologic alterations and the following actors: age at death, duration of illness, elevated intracranial pressure, or treatment regimens. However, the reported case demonstrated the most severe parenchymatous changes at autopsy and received the most intensive treatment of the CNS. This association suggests that the neurologic deterioration may be the consequence of antileukemic treatment. Additional studies to define the frequency of such CNS abnormalities and the factors leading to their development are needed.

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Treatment of Meningeal Leukemia With Pyrimethamine

Cited by 52 publications

References 21 publications

Reversion of autoimmune lymphoproliferative syndrome with an antimalarial drug: preliminary results of a clinical cohort study and molecular observations

Reversion of autoimmune lymphoproliferative syndrome with an antimalarial drug: preliminary results of a clinical cohort study and molecular observations

Combination chemotherapy of adult acute lymphocytic leukemia

Parenchymatous degeneration of the central nervous system in childhood leukemia

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