Transient neurologic disturbances induced by high-dose methotrexate treatment

Jaffe, Norman; Takaue, Yoichi; Anzai, Takashi; Robertson, Resa

doi:10.1002/1097-0142(19850915)56:6<1356::aid-cncr2820560623>3.0.co;2-h

Cited by 99 publications

(49 citation statements)

References 9 publications

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“…In contrast, transient acute encephalopathy does not seem to contraindicate MTX resumption. 28,36 The incidence of spinal and peripheral neurotoxicity in our study was 1.2%, a figure compatible with the literature. In this group the number median of IT injections was 10, compared to six in patients with encephalopathy and three in patients with seizures, pointing to the possible role of cumulative toxicity.…”

Section: Discussionsupporting

confidence: 92%

Age and high-dose methotrexate are associated to clinical acute encephalopathy in FRALLE 93 trial for acute lymphoblastic leukemia in children

et al. 2006

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The objective of the study was to assess acute neurotoxicity associated with triple intrathecal therapy (TIT)7high-dose methotrexate (HD MTX) in children with acute lymphoblastic leukemia (ALL). 1395 children were enrolled on FRALLE 93 protocol from 1993 to 1999. Lower-risk group (LR, n ¼ 182) were randomized to weekly low-dose MTX at 25 mg/m 2 /week (LD MTX, n ¼ 81) or HD MTX at 1.5 g/m 2 /2 weeks Â 6 (n ¼ 77). Intermediate-risk group (IR, n ¼ 672) were randomized to LD MTX (n ¼ 290) or HD MTX at 8 g/m 2 /2 weeks Â 4 (n ¼ 316). Higherrisk group (HR, n ¼ 541) prednisone-responder patients received LD MTX and cranial radiotherapy. HR group steroid resistant cases were grafted (autologous or allogenic). TIT (MTX, cytarabine and methylprednisolone) was given every 2 weeks during 16-18 weeks and every 3 months during maintenance therapy in LR and IR patients. 52 patients (3.7%) developed neurotoxicity. Isolated seizures: n ¼ 15 (1.1%), peripheral and spinal neuropathy: n ¼ 17 (1.2%) and encephalopathy: n ¼ 20 (1.4%). Age 410 years was significantly associated with neurotoxicity (P ¼ 0.01) and use of HD MTX is associated with encephalopathy (P ¼ 0.03). Sequels are reported respectively in 60 and 33% of spinal neuropathy and encephalopathy cases. Current strategies tailoring risk of neurological sequels has to be defined.

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Section: Discussionsupporting

confidence: 92%

Age and high-dose methotrexate are associated to clinical acute encephalopathy in FRALLE 93 trial for acute lymphoblastic leukemia in children

et al. 2006

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“…[12][13][14][15] Most patients recover fully, although some suffer recurrences during subsequent courses of MTX. Evaluation usually reveals normal head CT or MRI scans, normal cerebrospinal fluid, and generalized slowing on EEG.…”

Section: Discussionmentioning

confidence: 99%

“…[7][8][9][10][11] By contrast, MTX can also cause acute or subacute neurotoxicity that is characterized by confusion, disorientation, seizures, and focal neurologic deficits. [12][13][14][15][16] Whereas chronic MTX-induced leukoencephalopathy is progressive and dose-limiting, acute While acute encephalopathy has been well-described in osteosarcoma patients, occurring in up to 15% of cases, 13 relatively little is known about this complication in children with ALL. Moreover, there are few data on continued treatment with HD-MTX in patients who developed encephalopathy.…”

Section: Introductionmentioning

confidence: 99%

Transient encephalopathy following high-dose methotrexate treatment in childhood acute lymphoblastic leukemia

et al. 1998

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The purpose of this study was to determine the incidence of and pharmacokinetic parameters associated with the development of transient encephalopathy following the administration of high-dose methotrexate and intrathecal chemotherapy in children with acute lymphoblastic leukemia (ALL). Two hundred and fifty-nine children with newly diagnosed ALL treated on one of two consecutive trials were analyzed. Presenting features in patients who developed transient encephalopathy were compared with those of patients who did not experience this event. For each patient who developed transient encephalopathy, methotrexate pharmacokinetic parameters were compared with those of matched controls. The cumulative incidence of acute encephalopathy was 3% (SE 1%) at 1 year and was associated with age greater than or equal to 10 years at diagnosis. Pharmacokinetic data did not differ between patients who developed transient encephalopathy and those who did not. The majority of patients had no long-term sequelae and were able to receive further courses of methotrexate without modification. Transient focal neurologic deficits occur in about 3% of children with ALL following the administration of intravenous and intrathecal methotrexate. These events cannot be predicted by pharmacokinetic parameters of methotrexate disposition. However, these events are generally benign, suggesting that patients who experience acute encephalopathy should continue to receive this important chemotherapeutic agent.

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“…The clinical features of this condition are variable ranging from transient headache and neurological deficits to life threatening paralysis and extrapyramidal symptomatology [3][4][5]. Dysphasia is well described while the ability to communicate by non-verbal means may be preserved [4].…”

Section: Discussionmentioning

confidence: 99%

“…Methotrexate induced encephalopathy occurs in 0.8-15 % of patients treated with high dose methotrexate (HDMtx) [1][2][3][4][5]. Mostly manifesting as a mild and transient neurological dysfunction, rarely it can be severe and lifethreatening [4,5].…”

Section: Introductionmentioning

confidence: 99%

Methotrexate Induced Acute Encephalopathy-Occurrence on Re-challenge and Response to Aminophylline

Ganesan

Bajpai

Shah

et al. 2013

Indian J Hematol Blood Transfus

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Methotrexate-induced acute encephalopathy is a serious complication of a common chemotherapy agent used in lymphoblastic leukemia. As this drug is considered vital for therapeutic success of leukemia therapy it is often rechallenged in these patients. A patient of acute lymphoblastic leukemia developed mild, transient hemiparesis after the 2nd dose of high dose methotrexate (5 g/m 2 ) during the consolidation phase of the BFM-95 protocol. When we repeated the drug in the 3rd cycle he developed severe life threatening quadriparesis and cranial nerve palsies. The toxicity was reversed after treatment with Aminophylline. The relevant literature is reviewed.

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Transient neurologic disturbances induced by high-dose methotrexate treatment

Cited by 99 publications

References 9 publications

Age and high-dose methotrexate are associated to clinical acute encephalopathy in FRALLE 93 trial for acute lymphoblastic leukemia in children

Age and high-dose methotrexate are associated to clinical acute encephalopathy in FRALLE 93 trial for acute lymphoblastic leukemia in children

Transient encephalopathy following high-dose methotrexate treatment in childhood acute lymphoblastic leukemia

Methotrexate Induced Acute Encephalopathy-Occurrence on Re-challenge and Response to Aminophylline

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