Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 23-year-old man is reported who had a connective tissue disorder with features of rheumatoid arthritis and systemic lupus erythematosus. Because of the development of severe myocarditis and acute cerebral dysfunction treatment with azathioprine and prednisone was instituted, with dramatic clinical improvement. Ten months later, when a total of some 52 g of azathioprine had been administered, acute myelomonocytic leukemia developed. Although acute myelogenous leukemia has been noted in several individuals receiving immunosuppressive drugs for treatment of lymphoreticular neoplasms, this complication has heretofore been rare in patients given azathioprine for non-neoplastic disease. The present case is documented because of the increasing use of immunosuppressive drugs in treatment of various rheumatic disorders and the need to establish the relationship, if any, between the use of such agents and malignancy.
 ...
PMID:Acute leukemia after azathioprine treatment of connective tissue disease. 26 41

The clinician should be alert to the possibility of cerebrovascular disease in cancer patients who develop signs of diffuse or focal cerebral dysfunction. The cause of cerebrovascular disease can usually be determined by knowing the primary tumor type, extent of metastatic disease, and type of antineoplastic treatment. Symptomatic infarctions are more common than hemorrhages in patients with carcinoma, and NBTE and cerebral intravascular coagulation are the most common causes of infarction. Brain hemorrhages in patients with carcinoma are usually from hemorrhage into metastatic tumor. Symptomatic hemorrhages are much more common than infarction in patients with leukemia, and hemorrhages may be caused by coagulopathy or central nervous system infiltration. Infarction in leukemia is usually due to septic embolism or intravascular coagulation. By determining the cause of cerebrovascular disease in the cancer patient, the clinician can often recommend appropriate treatment and predict the clinical outcome.
 ...
PMID:Cerebrovascular complications in cancer patients. 175 30

Methotrexate may cause seizures, dementia, and leukoencephalopathy when given in toxic doses to children with leukemia or solid tumors. Even in therapeutic doses, treatment with this drug is associated with an increased incidence of seizures in children with leukemia. To study mechanisms of injury, juvenile rats were given multiple intraventricular injections of methotrexate and the brains were analyzed for histopathology and biogenic amine metabolites of dopamine and serotonin. Disruption of monoamine metabolism has been proposed as a cause of brain dysfunction from this chemotherapy. Multiple injections (1 or 2 mg/kg) produced convulsions in an increasingly larger percentage of animals at higher cumulative doses, and five doses produced the neuropathological changes seen in human leukoencephalopathy. A single dose reduced the concentration of brain metabolites of dopamine, but not serotonin, six hours later. The effect was less pronounced after five doses. This rodent model should be useful for studying the metabolic basis of methotrexate encephalopathy.
 ...
PMID:A model of methotrexate encephalopathy: neurotransmitter and pathologic abnormalities. 359 35

Glutamic acid decarboxylase (GAD) activity in cerebrospinal fluid (CSF) was determined in 53 patients with neurological diseases as follows: Epilepsy (n:17), febrile convulsions (n:3), meningoencephalitis (n:17), encephalopathies (n:10), CNS leukemia (n:3), congenital hydrocephalus (n:2) and pseudoileus neonatorum (n:1). Compared with the mean normal value (5.2 +/- 2.5 pmol CO2 formed/hr/ml) reported in Part I, a significant increase of GAD activity in CSF was demonstrated in patients with uncontrolled epileptic seizures (11.4 +/- 3.9 pmol CO2 formed/hr/ml), febrile convulsions (13.5 +/- 8.7), viral meningitis with or without encephalitis (20.3 +/- 13.6), encephalopathies (30.0 +/- 25.9), CNS leukemia (11.1 +/- 5.0), congenital hydrocephalus (20.5 +/- 7.3) and pseudoileus neonatorum (28.6). Markedly high GAD activity was found in patients with CNS leukemia several days after intrathecal injection of methotrexate (39.8 +/- 18.0). On the other hand, significantly low GAD activity was shown in patients with bacterial meningitis or brain abscess (1.3 +/- 1.2). This suggests that some bacterial factors may be inhibitory toward GAD activity in CSF. High GAD activity in CSF may be useful as an indicator of aseptic brain dysfunction, although it was not always correlated with the severity of symptoms.
 ...
PMID:Glutamic acid decarboxylase in cerebrospinal fluid in infancy and childhood Part II. Glutamic acid decarboxylase activity in cerebrospinal fluid of children with neurological diseases. 666 Apr 21

We evaluated the neuropsychological and personality profiles of 25 patients with chronic myelogenous leukemia treated with interferon alfa (IFN-alpha). This group of persons performed well below expectation on tests of cognitive speed, verbal memory, and executive functions. Personality changes included depression, increased somatic concern, and stress reactions. A control group of leukemia patients not treated with IFN-alpha had significantly better cognitive speed and mood. The pattern of cognitive and personality changes in patients receiving IFN-alpha is highly suggestive of frontal-subcortical brain dysfunction.
 ...
PMID:Pattern of neurobehavioral deficits associated with interferon alfa therapy for leukemia. 871 Jan 13

Neurological toxicity occurred in 8/219 patients treated with fludarabine (FAMP), 30 mg/m2 per day and cytosine arabinoside (Ara-C), 0.5 g/m2 per hour for 2-6 hours for 5 days, for new or relapsed acute leukemia or myelodysplasia. Two patients developed severe, progressive cerebral dysfunction that was ultimately fatal. This toxicity was similar to that seen with high-dose fludarabine therapy and was limited to patients with serum creatine > or = 2.0 mg/dl and age over 60 years, occurring in 2/9 such patients compared to 0/210 among the other patients (p < 0.005). Since FAMP is partially excreted by the kidney, toxicity in these two patients was likely due to receiving an effectively high dose of FAMP. Five patients developed peripheral neuropathy but there was no association with age, creatinine, dose of Ara-C, or number of courses. A patient, who also received intrathecal Ara-C, developed myelopathy. At this dose rate and duration of Ara-C peripheral neuropathy rarely arises, and cerebral toxicity is not seen. Neither toxicity was observed in 481 chronic lymphocytic leukemia patients treated with FAMP alone, by the same dose and schedule, suggesting that combination with Ara-C is important for the development of at least the peripheral neuropathy. The incidence of neurotoxicity with FAMP/Ara-C is low especially in comparison with high-dose Ara-C therapy (3 g/m2 over 2 hours). Cerebral toxicity can likely be decreased by dose reduction of FAMP in patients with increased creatinine and peripheral neuropathy decreased by detailed neurological examination before courses of FAMP/Ara-C.
Leukemia 1993 Mar
PMID:Neurotoxicity associated with fludarabine and cytosine arabinoside chemotherapy for acute leukemia and myelodysplasia. 844 43

Intrathecal chemotherapy has been determined to cause transient or permanent paraparesis due to myelopathy in patients with leukemia or other malignancies. To systematically evaluate the effect of methotrexate on spinal cord function, somatosensory evoked potentials (SEP) were measured in children with acute lymphoblastic leukemia (ALL). A prospective evaluation was performed in 38 consecutive children aged 1.4-15.3 years with newly diagnosed ALL during treatment. Intrathecal methotrexate therapy was included in the therapy schedule of all patients as central nervous system (CNS) therapy in addition to intravenous chemotherapy in 19 standard risk patients and intravenous chemotherapy with cranial irradiation in 19 intermediate or high-risk patients. The measured conduction times were compared with those of 38 control children matched for age, height, and sex. A significant increase in the conduction time of the tibial nerve SEP was found between the Th12 level and the cortex in children with ALL after receiving intrathecal methotrexate therapy during the induction and CNS therapy phases when compared with their controls. The difference of the mean latencies was 1.45 ms (95% CI 0.39-2.51; P < 0.01). There was no significant delay in the median nerve SEP from the brain stem to the cortex, indicating that the conduction delay was in the area of the spinal cord exposed to intrathecal methotrexate. Moreover, the cortical amplitudes of the median nerve SEPs were significantly reduced when measured immediately after intravenous and intrathecal methotrexate and compared to the amplitudes measured after induction therapy in standard risk patients (P = 0.001). Intrathecal methotrexate with systemic chemotherapy causes a deterioration in the somatosensory pathways within the CNS, suggesting also spinal cord dysfunction in children with ALL in addition to the cerebral dysfunction described earlier.
 ...
PMID:Chemotherapy for acute lymphoblastic leukemia may cause subtle changes of the spinal cord detectable by somatosensory evoked potentials. 895 Mar 35

Intrathecal methotrexate in children with leukemia is known to cause seizures, dementia, leukoencephalopathy, and cognitive dysfunction after long-term treatment. To investigate the cognitive dysfunction, male Wistar rats were given multiple intracerebroventricular injections of methotrexate. Its effect on behaviour was tested in the two-compartment conditioned avoidance task and dark-bright arena test. Levels of brain amines in the hippocampal region of the brain were estimated by HPLC. The qualitative and quantitative histopathological changes in the different regions of the hippocampus were studied by cresyl violet staining. Multiple injections (1 or 2 mg/kg) produced convulsions and learning and memory impairment but did not induce anxiolytic activity. They also reduced concentrations of all three brain amines (norepinephrine, dopamine, and serotonin) and the serotonin metabolite 5-hydroxyindoleacetic acid. The CA4 region of the hippocampus was severely affected by intraventricular methotrexate. Disruption of brain monoamines has been proposed as a cause of brain dysfunction from this chemotherapy, and that disruption may in turn involve cytotoxic effects of methotrexate on brain tissue. The outcomes of this study may have therapeutic implications in the management of cancer conditions, particularly in childhood lymphoblastic leukemia.
 ...
PMID:Hippocampal brain amines in methotrexate-induced learning and memory deficit. 1248 27

Intrathecal methotrexate in children with leukemia is known to cause seizures, dementia, leukoencephalopathy and cognitive dysfunction. To investigate the role of brain amines in cognitive dysfunction, male Wistar rats were given multiple intracerebroventricular injections of methotrexate. Our earlier studies in this regard revealed disruption of brain monoamines in hippocampus with severe cytotoxic effect on CA4 hippocampal neurons. Further extending this study, the levels of brain monoamines in frontal cortex, hypothalamus and brainstem were estimated by HPLC method and histopathological study of the frontal cortex. The concentration of all three-brain amine (norepinephrine, dopamine and serotonin) levels was reduced in 2 mg/kg dose of methotrexate in frontal cortex and brain stem. Hypothalamus did not show any significant change in brain monoamine levels. No structural changes in the frontal cortex neurons were observed. Disruption of brain monoamines has been proposed as a cause of brain dysfunction from this chemotherapy. The outcome of the study may have therapeutic implications in the management of childhood lymphoblastic leukemia.
 ...
PMID:Effect of intracerebroventricular methotrexate on brain amines. 1657 96

Tumour lysis syndrome (TLS) is a constellation of meta- bolic complications due to the rapid destruction of malignant cells, causing renal, cardiac or cerebral dysfunction. Electrolyte abnormalities include hyperuricaemia, hyperphosphataemia, hyperkalaemia and hypocalcaemia. TLS-induced renal failure is mainly caused by uric acid and calcium phosphate crystal deposition and usually develops following cytotoxic chemotherapy. Here, we present a case of spontaneous TLS in a patient with chronic myelomonocytic leukaemia (CMML) with massive uric acid stone and crystal formation and rapidly worsening renal failure. Autopsy revealed underlying tumourous kidney infiltration. Risk factors for occurrence of TLS and current therapeutic management are discussed.
...
PMID:Massive uric acid nephrolithiasis with progressive renal failure due to spontaneous tumour lysis syndrome. 2598 19


1