myelin-basic-protein and Leukemia--Lymphoid

Topics: Adolescent; Asparaginase; Central Nervous System; Child; Clinical Trials as Topic; Electroencephalography; Humans; Injections, Intravenous; Injections, Spinal; Leukemia, Lymphoid; Leukocyte Count; Mercaptopurine; Methotrexate; Myelin Basic Protein; Prednisone; Prospective Studies; Random Allocation; Vincristine

Cranial computed tomography (CT) was used to estimate the frequency and permanence of brain abnormalities in 108 consecutive children with acute lymphoblastic leukemia (ALL). Fifty-five patients received cranial irradiation (1,800 rad) with intrathecal methotrexate (RT group) and 53 patients received intravenous and intrathecal methotrexate without irradiation (IVIT group). Continuation treatment included sequential drug pairs for the RT group and periodic IVIT methotrexate for the other group. After 12 to 24 months of serial evaluation, five (9%) of the 55 patients in the RT group have had CT scan abnormalities, compared to 10 (19%) of 52 in the IVIT group (p = 0.171). Fourteen of the 15 patients with CT scan abnormalities had focal or diffuse white-matter hypodensity; these have reverted to normal in most cases, reflecting a dynamic process. While such CT findings are of concern and may be an early indicator of central nervous system toxicity, this remains to be proven. Therapy should not be altered on the basis of abnormal CT scans alone but in the context of the entire clinical situation.

Topics: Adolescent; Brain; Child; Child, Preschool; Combined Modality Therapy; Humans; Injections, Intravenous; Injections, Spinal; Leukemia, Lymphoid; Meningeal Neoplasms; Methotrexate; Myelin Basic Protein; Tomography, X-Ray Computed

Myelin basic protein (MBP) was serially measured in 177 CSF samples of 33 patients with leptomeningeal metastases and in 34 cancer controls. The mean level in cancer controls (free of neural involvement) was 5.7 +/- 0.33 ng/ml (normal less than 5 ng/ml) with abnormal elevation of MBP detected in 17%. The activity of the leptomeningeal disease was classified as either acute-progressive, stable or in remission on the basis of clinical and CSF cytological findings. CSF MBP levels were analysed in each stage. Abnormal elevation of MBP was detected in 74% of the 68 samples obtained in the acute-progressive stage (mean +/- SEM: 18.25 +/- 1.4 ng/ml, P less than 0.0001), in 24% of the 79 samples in the stable phase (mean: 7.99 +/- 0.8 ng/ml, NS) and in 20% of the 30 samples in remission (mean 5.7 +/- 0.3 ng/ml, NS). Similar changes in levels of CSF MBP were also observed in longitudinal studies of patients responding to treatment or relapsing to the acute stage. Eight patients developed treatment induced necrotizing leukoencephalopathy with typical CT-scan findings; elevated levels of CSF MBP were detected in 7 of them (mean: 21 +/- 3 ng/ml) when measured within 2 weeks of diagnosis but not when measured 2 months earlier. Our study suggests that in leptomeningeal metastases, CSF MBP levels are indicators of the disease activity, particularly if longitudinal determinations are used.

Topics: Adolescent; Adult; Aged; Brain Diseases; Breast Neoplasms; Cerebrospinal Fluid Proteins; Female; Humans; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Male; Meningeal Neoplasms; Middle Aged; Myelin Basic Protein

Topics: Child; Humans; Leukemia, Lymphoid; Methotrexate; Myelin Basic Protein

Topics: Child; False Negative Reactions; Humans; Leukemia, Lymphoid; Methotrexate; Myelin Basic Protein; Paraplegia

Ascending myelopathy developed in a previously irradiated 10-year-old boy after intraventricular methotrexate and cytosine arabinoside were given for central nervous system relapse of acute lymphoblastic leukemia. The course was fatal in 10 weeks. Cerebrospinal fluid myelin basic protein levels, indicating a demyelinative process, rose prior to the onset of clinical symptoms and remained at very high levels until death. Myelin basic protein may be useful as a predictor of chemotherapy-associated neurotoxicity.

Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Combined Modality Therapy; Cytarabine; Humans; Hydrocortisone; Injections, Spinal; Leukemia, Lymphoid; Male; Methotrexate; Myelin Basic Protein; Prednisone; Radiotherapy Dosage; Recurrence; Spinal Cord Neoplasms; Testicular Neoplasms; Vincristine

Cerebrospinal fluid was examined from 70 children with acute lymphoblastic leukemia for evidence of active myelin breakdown based on the release of myelin basic protein (MBP). Fifty-three asymptomatic children were followed from diagnosis with serial MBP determinations. Eight (15.1%) of 53 children had abnormal elevations of MBP, six of eight before receiving presymptomatic central nervous system therapy. Long-term observations are in progress. For comparison, six children with clinical and radiologic findings of leukoencephalopathy had abnormal MBP determinations, whereas no abnormalities were detected in 11 children with meningeal leukemia.

Topics: Adolescent; Central Nervous System Diseases; Child; Child, Preschool; Humans; Leukemia, Lymphoid; Meningeal Neoplasms; Myelin Basic Protein; Necrosis; Prospective Studies

Normal CSF-MBP levels as determined by a RIA were less than 6.2 ng/ml CSF (mean 3.9). Eighty percent of patients with acute optic neuritis have CSF-MBP levels greater than 6.2 ng/ml (mean 7.6 ng/ml CSF). Five of 7 patients with acute internuclear ophthalmoplegia due to an initial exacerbation of demyelination have CSF-MBP levels above 6.2 ng/ml (mean 6.8 ng/ml). Fifty percent of MS patients with chronic progressive disease have CSF-MBP levels above 6.2 ng/ml (mean 6.7 ng/ml). MS patients experiencing monosymptomatic exacerbations show elevated CSF-MBP levels in 75% in 75% of cases (mean 8.2 ng/ml). MS patients experiencing polysymptomatic exacerbations show significantly higher levels of CSF-MBP (mean 22.3 ng/ml) than the patients with monosymptomatic exacerbations. Ninety-five percent of MS patients experiencing polysymptomatic exacerbations have elevated levels of CSF-MBP.

Topics: Acute Disease; Adolescent; Adult; Aged; Female; Humans; Leukemia, Lymphoid; Male; Middle Aged; Multiple Sclerosis; Myelin Basic Protein; Ophthalmoplegia; Optic Neuritis; Radioimmunoassay

To study how viruses interact with oligodendroglia and produce demyelination, we immunostained paraffin and epon sections of lesions from patients with progressive multifocal leukoencephalopathy (PML) with antisera to papovaviruses, oligodendroglial myelin-associated glycoprotein (MAG), and myelin basic protein (MBP) according to the peroxidase-antiperoxidase method. In paraffin sections from a rapidly progressive case of PML, hyperimmune JC virus antiserum stained single oligodendroglia which were located in white matter that appeared normal histologically and stained normally with MAG and MBP antisera. In zones surrounding areas of demyelination, virus containing oligodendroglia were most numerous and MAG staining of periaxonal regions was decreased, but there was little change in MBP staining. In demyelinated regions, both MAG and MBP staining were severely altered; also there was much less JC virus staining. In tissue from three other chronic cases, viral antiserum stained fewer oligodendrocytes and the differences in MAG and MBP staining were much less striking. In epon sections from two biopsies of central nervous system tissue, we studied the electron microscopic appearance of oligodendroglia that also had been stained by JC virus antiserum. Virions were present in all nuclei and in some cytoplasmic regions. The results suggest that changes in MAG distribution are useful indicators of early oligodendroglial abnormalities which can cause myelin breakdown.

Topics: Aged; Brain; Brain Chemistry; Female; Humans; Leukemia, Lymphoid; Leukoencephalopathy, Progressive Multifocal; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Myelin Basic Protein; Myelin P0 Protein; Myelin Proteins; Papillomaviridae; Polyomaviridae

Topics: Adolescent; Adult; Brain; Brain Diseases; Child; Child, Preschool; Demyelinating Diseases; Humans; Leukemia, Lymphoid; Methotrexate; Myelin Basic Protein

Lymphocyte sensitisation to encephalitogenic factor (EF) was determined in 131 children with the electrophoretic mobility test (EM-test) to find out, whether this test may be helpful in the diagnosis of malignant disease in children. None of 34 healthy controls showed a decrease of electrophoretic mobility of more than 5%, while all 10 children with malignant solid tumors showed a slowing of more than 5%. 3 of 54 patients with non malignant disease showed a slowing of more than 5% in the EM-test. Children with malignant solid tumors during therapy and children with leukemia during different stages of the disease often showed a slowing of less than 5% in the EM-test. The possible diagnostic help of the EM-test is shown in a case history. Finally some technical remarks are made on improving this test, and further studies are suggested.

Topics: Cell Movement; Child; Electrophoresis; Epilepsy; Humans; Infectious Mononucleosis; Leukemia, Lymphoid; Lymphocytes; Myelin Basic Protein; Neoplasms

A modified electrophoretic mobility (EM) test was performed in 150 children to examine their lymphocyte sensitization to myelin basic protein (encephalitogenic factor). Measurements in the cytopherometer were facilitated by using devitalized sheep erythrocytes as indicator particles instead of macrophages. A significant decrease in EM was found in 29/30 children with acute lymphoblastic leukaemia and in 67/75 children with solid tumours, thus giving a false negative rate in malignant disease of 9/105=8-6%, as compared to 6 false positives among 45 children with non-malignant disorders; 5 of the later "false/positive" 6 patients had autoimmune disease. Results of the EM test in the children with leukaemia were compared with those in 9 patients with non-Hodgkin's lymphoma and 2 with Hodgkin's disease at different stages, but no striking change was seen between different diseases, or after cessation of long-term immunosuppressive chemotherapy. Percentage of "slowing" ranged from 4 to 30%. These results indicate that patients with lymphoid malignancies still have lymphocytes which had been sensitized by a common antigen of the malignant cell clone at the beginning of the disease. The EM test, furthermore, could serve as an additional diagnostic aid in differentiating benign from malignant masses in the abdomen, extremities or intracranial disease.

Topics: Abdominal Neoplasms; Acute Disease; Antigens; Child; Electrophoresis; Humans; Leukemia, Lymphoid; Lymphocytes; Lymphoma; Myelin Basic Protein; Neoplasms

Lymphocyte sensitization to myelin basic protein (encephalitogenic factor, EF) was determined in 193 children by measuring the electrophoretic mobility of indicator particles which had been incubated with the supernatant of the lymphocyte-antigen (EF) mixture. A significant decrease in electrophoretic migration time was found in 77 of 85 children with malignant tumours localized in brain, abdomen and extremities, in 36 of 38 children with acute lymphoblastic leukaemia (all except one in hematological remission), and in all 17 patients with lymphoma, in contrast to only 1 of 10 healthy children and 14 of 48 patients with non-malignant disorders. 10 of these 14 "false positive" patients, however, had auto-immune diseases. Thus, with false negative and false positive rates of less than 10%, this test could be of diagnostic help in patients with suspected malignant or auto-immune disease. Two examples of preoperative application of the EM-test are demonstrated.

Topics: Abdominal Neoplasms; Adolescent; Age Factors; Autoimmune Diseases; Brain Neoplasms; Cell Movement; Child; Electrophoresis; Humans; Leukemia, Lymphoid; Lymphocytes; Lymphoma; Myelin Basic Protein; Neoplasms

Topics: Cytoplasm; Fluorescence; Humans; Lectins; Leukemia, Lymphoid; Lymphocytes; Myelin Basic Protein; Neoplasm Proteins; Neoplasms; Precancerous Conditions