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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mice infected with an immunosuppressive murine leukemia virus (MuLV) mixture, LP-BM5, displayed profound and selective deficits in spatial learning in a modified Morris water maze. These deficits appeared before the appearance of gross neurological impairment or histopathological changes in the central nervous system. Thus, LP-BM5-infected mice displayed deficits in several aspects of trained performance compared to controls. Furthermore, a failure to exhibit any evidence of task acquisition in this maze was observed almost twice as frequently (P less than 0.0005) in infected mice as in uninfected controls. Moreover, in the absence of gross visual, motoric, or motivational impairment, LP-BM5 MuLV-infected animals exhibited neither the target directed search pattern nor the spatial preference characteristic of controls. The spatial learning and memory deficit described here is the first report of cognitive impairment accompanying viral-induced immunosuppression in a nonprimate species.
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PMID:Spatial learning impairment in a murine model of AIDS. 164 64

The authors measured the cognitive function and physical growth of 51 children who had been treated for acute lymphoblastic leukemia with chemotherapy, cranial irradiation and intrathecal methotrexate, and who had remained disease-free for five to 12 years. A comparison group of 15 children treated for Wilms' tumor was also studied. Cognitive impairment and growth retardation were greater among the leukemia group. Of potentially greater significance, however, was the finding that female sex was the pre-eminent risk factor for central nervous system toxicity resulting from treatment. Cognitive impairment, short stature and excessive weight were all more prevalent among females than males. Approximately half the children were microcephalic, but there was no sex difference. Age at evaluation and diagnosis, as well as socio-economic status, were differentially related to outcomes for the two sexes. The authors believe the sex differences were indicative of a fundamental interaction between postnatal neural development and other biological processes.
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PMID:Late effects of central nervous system treatment of acute lymphoblastic leukemia in childhood are sex-dependent. 231 27

The cognitive sequelae of central nervous system treatments for leukemia have become a major concern as more leukemic children survive the initial consequences of the disease. A review of 28 neuropsychological outcome studies published in the past nine years shows that the preponderance of evidence from the better designed studies suggests that leukemic children who do not suffer overt Central Nervous System (CNS) complications, such as CNS relapse, do not experience significant cognitive deficits as a consequence of their treatment. Also, these studies do not unequivocally suggest that cranial irradiation as a treatment technique results in greater cognitive impairment than treatment without irradiation. Many studies are consistent in finding that leukemic children younger than 8 years of age have a worse outcome than older ones although both groups perform in the average to bright normal range. It is currently difficult to conclude that such differences in intellectual outcome were caused by the CNS treatment alone or other psychosocial aspects of acquiring leukemia. The confusion present in the literature could be greatly reduced by combining the research efforts on the psychosocial aspects of acquiring leukemia with the studies examining neuropsychological outcome.
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PMID:Central nervous system prophylactic treatment for childhood leukemia: neuropsychological outcome studies. 352 11

Children with leukemia receive CNS therapy to improve long-term survival. Neurotoxic effects, such as cognitive impairment, have been associated with this therapy. A rat model was developed to determine which agent, or combination of agents, in CNS therapy causes neurotoxicity. The agents examined were cranial irradiation (1000 cGy), methotrexate (2 or 4 mg/kg, intraperitoneally), and prednisolone (18 or 36 mg/kg, intraperitoneally). Young Sprague-Dawley rats were exposed to each agent alone or to two- or three-agent combinations. Each therapy had matched controls that received sham radiation and/or intraperitoneal saline. Subsequent to exposure, spontaneous behavior was tested using a computer pattern recognition system, which recorded and classified behavior in a novel environment. Behavioral initiations, total times, and time structures were compared in therapy and control groups. Combined rather than single-agent therapies had more behavioral effects, and these were dose- and sex-dependent. Synergistic interactions between agents caused behavioral deficits, and components of the combination determined the abnormality. Some combinations interacted antagonistically, and thus mitigated behavioral deficits. Prednisolone was clearly pivotal to behavioral outcome. A low prednisolone dose antagonized methotrexate preventing deficits, whereas a higher prednisolone dose altered behavior by enhancing effects of methotrexate and radiation. These findings emphasize that steroids are important in agent interactions. Their role in morbidity associated with leukemia treatment protocols may be equally important as that of methotrexate and cranial irradiation.
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PMID:Interactions of steroid, methotrexate, and radiation determine neurotoxicity in an animal model to study therapy for childhood leukemia. 816 51

110 children with malignant diseases (leukemia excepted) who survived 5-20 years (median 9) post-therapy were followed (1996-1998). Median age during follow-up was 15 years (range 5-23). The most common malignancies were brain tumors, lymphoma, retinoblastoma and Wilm's tumor. The 174 late side-effects included endocrine disorders (19%), cognitive impairment (14%), orthopedic dysfunction (12%), alopecia (12%), dental damage (11%), psychological (8%) and neurological (8%) disturbances, and azoospermia or amenorrhea (5%). There was no cardiac or renal damage and no second malignancy. 29% of side-effects were severe. There was significant reduction in quality of life in 54 (49%), in 27 of whom it was severe enough to require psychological intervention. Treatment of brain tumor caused 98 late side-effects in 28 patients (sequelae-to-patient ratio [SPR] 3.3). Most cognitive, endocrine and neurological disorders, and most cases of alopecia, dental and psychological difficulties were in these patients. There were frequent late complications in those treated for retinoblastoma (SPR 1.8), and bone or soft tissue sarcomas (SPR 0.8). Those treated for Wilm's tumor had few side-effects (SPR 0.4). Late side effects were most frequent after radiation, reaching as high as SPR 2.4. It averaged only 0.5 in those treated with chemotherapy alone or in combination with surgery. Reduction of late side-effects in these patients requires using less toxic modalities, as long as cure rate is not compromised. When considering secondary strategies, screening for early detection of late complications would enable immediate solutions, such as hormonal replacement or providing compensating skills for post-treatment disability.
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PMID:[Long-term sequelae of malignant tumors in childhood: consequences of late side-effects]. 1124 36

The role of adjuvant chemotherapy in treatment of breast cancers of 1 cm or less is controversial. Careful consideration must be given to the overall risk of recurrence and death and to the absolute benefit of adjuvant chemotherapy, given that risk. Studies in this group of patients indicate that their overall survival rate is 90% to 99%. The absolute benefit of chemotherapy in this setting is most likely 1% or less. Adjuvant chemotherapy has significant toxicities, including cognitive dysfunction, early menopause, leukemia, and even death. Following a realistic and detailed discussion between patient and oncologist, some patients may choose chemotherapy. However, for the majority of patients with breast cancers of 1 cm or less, the minimal benefit of adjuvant chemotherapy does not justify the risk of the treatment.
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PMID:Adjuvant chemotherapy for tumors of one centimeter or less: the law of diminishing returns. 1159 22

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.
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PMID:Hippocampal brain amines in methotrexate-induced learning and memory deficit. 1248 27

The cure and management of patients with cancer are constantly evolving. The rapid translation of scientific findings into clinical therapeutics has resulted in a variety of efficacious cancer agents. Results from recently completed and ongoing clinical trials continue to demonstrate the efficacy and tolerability of many of these new cancer therapies. This supplement aims to provide the oncology nurse with a better understanding of the pathophysiology and management of a variety of cancers. Each article provides practical information to the nurse treating cancer in clinical practice. At the conclusion of this educational activity, the participant should be able to discuss the most recent advances in the medical management of leukemia as well as lung, breast, and ovarian cancer; to describe the role and report the results of new molecular-targeted therapies in treating malignancies; to review new therapies for managing chemotherapy-related hematologic toxicities, cognitive impairment, fatigue, and pain; and to recognize the need and discuss the measures used to improve symptom control and supportive care in the palliative setting.
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PMID:Advances in cancer research and practice. 1502 5

The role of adjuvant chemotherapy in treatment of breast cancers < or = 1.0 cm is controversial. Careful consideration must be given to the patient's overall risk of recurrence and death given her tumor size and lymph node status. Studies indicate that overall survival for women with lymph node-negative breast cancers < or = 1.0 cm is 90-99%. Given the known relative benefit of adjuvant chemotherapy for breast cancer, the absolute benefit of chemotherapy in this setting is usually < or = 1%. The toxicities of adjuvant chemotherapy, including cognitive dysfunction, early menopause, cardiac dysfunction, and leukemia, are significant to patients. The decision to treat women who are already at a very low risk of recurrence with adjuvant chemotherapy must involve an honest and detailed discussion between the patient and her oncologist.
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PMID:When not to treat--chemotherapy for small (< or = 1 cm) breast cancers. 1568 20

We report a 47-year-old woman with progressive multifocal leukoencephalopathy (PML). She was a carrier of HTLV-I virus, and developed subacute right hemiparesis and marked motor aphasia. She had a malignant lymphoma in the left neck and basal cell carcinoma in the right inguinal region. Three months after the onset, she became unable to walk because of the right leg weakness or to speak because of motor aphasia. Magnetic resonance imaging (MRI) revealed multifocal T2-high lesions in the white matter of the left frontal lobe, and a brain biopsy revealed demyelinating pathology. A biopsy of the left parotid gland revealed a diffuse pleomorphic type large B cell lymphoma. Although anti-HTLV-I antibody was positive in the serum and cerebrospinal fluid (CSF), no adult T-cell leukemia (ATL) cells were found in the blood or CSF. The patient was then admitted to our hospital. Neurological examinations revealed severe motor aphasia, mild sensory aphasia/cognitive impairment, right hemiplegia, mild right hemihypesthesia, limb-kinetic apraxia in the left hand, idiomotor apraxia, agraphia, perseveration, marked spasticity and brisk tendon reflex in four extremities, and positive bilateral pathological reflexes. MRI showed multifocal T2-high lesions mainly in the cerebral white matter, predominantly in the left hemisphere, and partly in the cerebral cortex. No gadolinium enhancement was found. In addition, 99mTcECD-SPECT showed a broad decrease in cerebral blood flow (CBF) in the cortex. Anti-HTLV-I antibody was positive but anti-HIV antibody was negative in serum. ATL cells were found in 1-3% of the peripheral white blood cells after admission. CSF examination revealed that the cell count (1/microl), protein level (24 mg/dl), and IgG index (0.4) were all normal. However, the myelin basic protein level (321 pg/ml; normal < 102) was increased, JC virus DNA was detected by PCR, and anti-HTLV-I antibody (x 8) was detected in CSF. The regulatory region of the JC virus DNA in the CSF was partly deleted; immunostaining with anti-JC virus protein antibodies revealed the existence of JC virus in biopsied brain specimens, and these findings were consistent with PML. Her symptoms such as motor aphasia, cognitive dysfunction and left hemiparesis were subacutely progressive, and she developed akinetic mutism two weeks after admission. Since the efficacy of cytosine arabinoside for PML has been reported, she was administered 80 mg/day of the drug for five days. After treatment, her communication function was mildly improved but the efficacy was transient. Since it has been reported that HTLV-I, as well as HIV, activates the JC virus promoter and its proliferation, the latent infection of HTLV-I in the central nervous system (CNS) in this case might have stimulated the JC virus proliferation, promoting lesion extension over the cerebral cortex. There have been only a few reports of broad decreases in CBF by SPECT in PML patients. Further MRI and SPECT studies on PML patients are therefore necessary to evaluate the significance of HTLV-I in promoting the JC virus infiltration into the CNS.
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PMID:[A case of progressive multifocal leukoencephalopathy presenting white matter MRI lesions extending over the cerebral cortex and a marked decrease in cerebral blood flow on SPECT, and associated with HTLV-I infection]. 1602 67


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