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

The objective of the study was to assess acute neurotoxicity associated with triple intrathecal therapy (TIT)+/-high-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=182) were randomized to weekly low-dose MTX at 25 mg/m(2)/week (LD MTX, n=81) or HD MTX at 1.5 g/m(2)/2 weeks x 6 (n=77). Intermediate-risk group (IR, n=672) were randomized to LD MTX (n=290) or HD MTX at 8 g/m(2)/2 weeks x 4 (n=316). Higher-risk group (HR, n=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=15 (1.1%), peripheral and spinal neuropathy: n=17 (1.2%) and encephalopathy: n=20 (1.4%). Age >10 years was significantly associated with neurotoxicity (P=0.01) and use of HD MTX is associated with encephalopathy (P=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.
Leukemia 2007 Feb
PMID:Age and high-dose methotrexate are associated to clinical acute encephalopathy in FRALLE 93 trial for acute lymphoblastic leukemia in children. 1717 Jul 21

Polymorphisms of the ABCB1 (MDR1) and ABCG2 (BCRP) genes were reported to alter the expression and function of these drug transporters. Both proteins are present at the main pharmacokinetic barriers including the blood-brain barrier. Data from 291 children with acute lymphoblastic leukaemia were analysed in this retrospective study. ABCB1 3435T>C, 2677G>T/A, 1236C>T and ABCG2 421C>A, 34G>A genotypes were determined. Encephalopathy episodes were more frequent among those with ABCB1 3435TT genotype than in the 3435CC/CT group (odds ratio (OR) 3.5; P=0.03). Patients with the ABCG2 421A allele tended to have more complications than wild type homozygotes (OR=2.0; P=0.25). The rate of the adverse effect was similar in those harbouring no or only one of the predisposing genotypes, that is, either ABCB1 3435TT or ABCG2 421AA/AC. However, significantly more children suffered encephalopathy in the group with both predisposing genotypes (OR=12.3; P=0.005). In conclusion, these variations exert synergistic effect in predisposing patients to toxic neurological complications of chemotherapy.
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PMID:Synergistic interaction of ABCB1 and ABCG2 polymorphisms predicts the prevalence of toxic encephalopathy during anticancer chemotherapy. 1793 43

The tyrosine kinase receptor ErbB4 (erythroblastic leukemia viral oncogene homolog 4) plays a crucial role in numerous neurobiological processes in the developing and adult brain. Moreover, recent molecular genetics studies implicate ErbB4 in the pathophysiology of schizophrenia. However, the phenotypic consequences of haploinsufficiency of ErbB4 are not known, as no coding mutations have been identified until now. Here, we present a patient with early myoclonic encephalopathy and profound psychomotor delay with a de novo reciprocal translocation t(2;6)(q34;p25.3), disrupting the ErbB4 gene. This patient represents the first case of haploinsufficiency for one of the ErbB family members of tyrosine kinase receptors.
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PMID:Early myoclonic encephalopathy caused by a disruption of the neuregulin-1 receptor ErbB4. 1885 70

This report describes four patients with acute lymphoblastic leukaemia, suffering from posterior reversible encephalopathy syndrome during the induction period of treatment. A review of the literature on posterior reversible encephalopathy syndrome in paediatric leukaemia is given. The exact mechanism of posterior reversible encephalopathy syndrome is not clear and seems to be multifactorial. Hypertension is likely to play a major role in the development but could be also secondary. All patients in this case series presented after introduction of the new induction protocol for acute lymphoblastic leukaemia. Treatment of hypertension is likely to have a favourable role and posterior reversible encephalopathy syndrome is most often reversible. It is important to consider this diagnosis during the induction phase of leukaemia treatment in the presence of neurological symptoms. The incidence of PRES in the induction scheme should be investigated, in order to optimize the ALL treatment.
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PMID:Posterior reversible encephalopathy syndrome in paediatric leukaemia. 2081 Feb 97

Intracerebral hemorrhage (ICH) contributes significantly to the morbidity and mortality of patients suffering from acute leukemia. While ICH is often identified in autopsy studies of leukemic patients, it is rare for ICH to be the presenting sign that ultimately leads to the diagnosis of leukemia. We report a patient with previously undiagnosed acute precursor B-cell lymphoblastic leukemia (ALL) who presented with diffuse encephalopathy due to ICH in the setting of an acute blast crisis. The diagnosis of ALL was initially suspected, because of the hyperleukocytosis observed on presentation, then confirmed with a bone marrow biopsy and flow cytometry study of the peripheral blood. Furthermore, detection of the BCR/ABL Philadelphia translocation t(9:22)(q34:q11) in this leukemic patient by fluorescent in situ hybridization permitted targeted therapy of the blast crisis with imatinib (Gleevec). Understanding the underlying etiology of ICH is pivotal in its management. This case demonstrates that the presence of hyperleukocytosis in a patient with intracerebral hemorrhage should raise clinical suspicion for acute leukemia as the cause of the ICH.
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PMID:Diagnosis of acute lymphoblastic leukemia from intracerebral hemorrhage and blast crisis. A case report and review of the literature. 2049 28

Posterior reversible encephalopathy syndrome (PRES) is a clinico-neuroradiological entity with typical symptoms and symmetric high-signal intensity lesions in the bilateral parieto-occipital lobes on T2-weighted or fluid-attenuated inversion recovery (FLAIR) MRI. We described three patients with PRES of varied etiologies. Patient 1 was a young man with severe hypertension who presented with headache and visual disturbance. Patient 2 had leukemia and was receiving umbilical cord blood cell transplantation with immunosuppressant, and developed PRES with convulsions. Patient 3 was a pregnant woman with renal failure, who repeatedly developed PRES with convulsions. FLAIR and apparent diffusion coefficient mapping were useful in detecting PRES lesions in our patients, although diffusion-weighted imaging and CT scans had limited use in the diagnosis. Adequate and prompt treatment with antihypertensive medication immediately ameliorated the symptoms, with improvement of abnormal MRI findings. In previous reports, delayed diagnosis might have affected the prognosis. Further work on the clinical manifestations of PRES and its therapy is required.
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PMID:Posterior reversible encephalopathy syndrome. 2123 81

Posterior reversible encephalopathy syndrome (PRES) has been reported in childhood leukemia patients increasingly frequently. However, the development of PRES in adult leukemia patients during chemotherapy is very rare. We present a case of PRES in an adult patient with acute lymphoblastic leukemia (ALL) after remission induction chemotherapy. A 28-year-old woman with ALL was administered remission induction chemotherapy consisting of cyclophosphamide, daunorubicin, vincristine, prednisone, and L-asparaginase. After initiation of chemotherapy, the patient developed paralytic ileus and hypertension, and on day 30, she suddenly developed generalized convulsions, loss of visual acuity, and muscle weakness in the legs. Magnetic resonance imaging findings and her signs and symptoms were typical of PRES. The symptoms gradually improved following treatment with an anticonvulsant and an antihypertensive agent, and the patient underwent allogeneic bone marrow transplantation. She has completely recovered from PRES and has been asymptomatic without leukemia relapse. During remission induction chemotherapy for ALL, PRES may be caused by multiple drugs, such as L-asparaginase, vincristine, and corticosteroids, with different mechanisms of action. PRES should be recognized as an important complication, which will occur more frequently with the increased intensity of chemotherapy for adult ALL patients.
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PMID:Posterior reversible encephalopathy syndrome in an adult patient with acute lymphoblastic leukemia after remission induction chemotherapy. 2216 Aug 36

Intracranial hemorrhage (ICH) is a common neurological emergency in patients with cancer, typically occurring late in the disease course, although it occasionally heralds the cancer diagnosis. ICH in these patients often occurs from unique mechanisms, especially intratumoral hemorrhage or coagulopathy, whereas hypertensive hemorrhage is rare. Lung, melanoma, breast, and glioblastoma multiforme are the most commonly associated solid tumors, partly because of their ubiquity and frequent brain involvement, whereas leukemia is the most commonly associated hematological cancer. Patients typically present with focal neurological deficits, headache, and encephalopathy, and their initial diagnostic evaluation and management should follow standard guidelines, although steroids and/or surgical resection should be strongly considered in those with intratumoral hemorrhage. Short-term outcomes are comparable to ICH in the community, whereas long-term outcomes are generally poor, corresponding to the prognosis of the underlying cancer. This review focuses on the recent advances and special considerations in cancer-related intracranial hemorrhage.
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PMID:Intracranial hemorrhage in patients with cancer. 2252 22

A retrospective chart review was performed on 19 patients aged <18 years who developed posterior reversible encephalopathy syndrome as a complication during treatment of acute childhood leukemia. Posterior reversible encephalopathy syndrome was most often observed during acute lymphoblastic leukemia induction chemotherapy (n = 9, 47.4%) and after hematopoietic stem cell transplantation (n = 8, 42.1%). Among eight patients with the complication of posterior reversible encephalopathy syndrome after hematopoietic stem cell transplantation, five (62.5%) had a history of hypertension. In contrast, among 11 patients with the complication of posterior reversible encephalopathy syndrome without hematopoietic stem cell transplantation, only one (9.1%) had a history of hypertension. Moreover, unlike other leukemia induction chemotherapy, posterior reversible encephalopathy syndrome developed only in patients who received acute lymphoblastic leukemia induction chemotherapy. Posterior reversible encephalopathy syndrome patients required long-term anticonvulsant therapy (n = 9, 50.0%) and manifested intractable seizures (n = 3, 16.7%). Sequelae were evident in long-term follow-up magnetic resonance images (n = 5, 26.3%). Acute lymphoblastic leukemia chemotherapy regimens apparently comprised the main predisposing factors for posterior reversible encephalopathy syndrome complicated during induction chemotherapy, compared with hypertension and immunosuppressive agents after hematopoietic stem cell transplantation.
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PMID:Predisposing factors of posterior reversible encephalopathy syndrome in acute childhood leukemia. 2312 65

Of 71 acute lymphoblastic leukemia survivors at our hospital over the past 10 years, 2 children developed mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). This is the first report to describe the clinical course of MTLE-HS observed longitudinally by EEG and MRI. Patient 1 experienced a seizure during chemotherapy involving intrathecal methotrexate. Postseizure MRI suggested methotrexate encephalopathy or leukemic invasion. Anticonvulsant therapy was initiated; subsequent EEGs and MRIs revealed normal results. Three years after chemotherapy, a diffuse, irregular spike-and-wave pattern was observed on interictal EEG. Five years after chemotherapy, the patient developed MTLE-HS comprising complex partial seizures, typical temporal spikes on EEG, and hippocampal sclerosis (HS). Patient 2 did not experience seizures during chemotherapy. Four years later, the patient started experiencing complex partial seizures, and a diffuse, irregular spike-and-wave pattern was observed on interictal EEG. A clinical picture of MTLE-HS developed 2 years later. In both patients, nonspecific EEG abnormalities (ie, diffuse, irregular spike-and-wave activity) preceded the appearance of HS on MRI by 2 years, suggesting an insidious advance of HS during the latent period. Such atypical EEG findings may indicate MTLE-HS during follow-up of leukemia patients. MTLE-HS develops several years after an initial precipitating incident such as prolonged seizures, central nervous system infection, and brain trauma. In our cases, the initial precipitating incident may have been chemotherapy and/or prolonged seizures. Thus, MTLE-HS associated with leukemia may not be as rare as generally believed. A large cohort study of late neurologic complications is warranted.
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PMID:Temporal lobe epilepsy with hippocampal sclerosis in acute lymphoblastic leukemia. 2377 22


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