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Biomedical subjects

R J Aur

Publications and source records attributed to R J Aur.

At least 37 records · Page 2Linked to original sources

Progression of methotrexate-induced leukoencephalopathy in children with leukemia.

From 1972-1974, 228 children began treatment for acute lymphocytic leukemia and were prospectively assessed for neurologic complications. After CNS irradiation (2,400 rad) and intrathecal methotrexate (MTX), they received weekly intravenous maintenance therapy with MTX alone (40-60 mg/m2; 20 patients) or MTX (10-30 mg/m2) with other drugs (208 patients). Signs of leukoencephalopathy appeared in 11 children (nine without CNS leukemia) after 4-15 months of IV MTX alone, and included lethargy, seizures, spasticity, paresis, drooling, and dementia. Before or during the clinical onset, EEG frequencies slowed (all ten patients tested). Radionuclide scans showed periventricular accumulation of 99mTc (9/11 patients) and remained abnormal for greater than or equal to six months in eight patients. Cranial computed tomograms or neuropathology findings (five patients each) demonstrated leukoencephalopathy (nine patients) and radiation-related microangiopathy (ten patients). Severe neurologic and neuropsychologic dysfunctions were present in four long-term survivors.

Brain↗

Risk factors for hyperglycemia in children with leukemia receiving L-asparaginase and prednisone.

We determined retrospectively the frequency and risk of hyperglycemia in 421 children with leukemia who had received L-asparaginase and prednisone as part of their remission induction therapy. Forty-one patients (9.7%) developed this complication, 39 within one week after the first dose of L-asparaginase. Hyperglycemia resolved in all patients and in 32 before the end of the four-week induction period. Age, obesity, and Down syndrome each had a significant bearing on the frequency of hyperglycemia. Children 10 years of age or older were more likely to develop the complication than were younger children. When more than one factor was present in a child, the risk of hyperglycemia increased significantly. A family history of diabetes mellitus also appeared related to an increased risk of hyperglycemia. Childhood leukemia patients with any of the risk factors identified here should be closely monitored for glucosuria while receiving prednisone and L-asparaginase for remission induction.

Adolescent↗

A clinical perspective on cell markers in acute lymphocytic leukemia.

Two hundred consecutive new patients, with acute lymphocytic leukemia (ALL) have been studied with a battery of five cell marker assays to determine if a classification system with prognostic significance can be developed; 182 have been classified among four groups as follows: 33 T-cell, 3 B-cell, 126 common, and 20 undifferentiated ALLs. Patients with T-cell disease are likely to have unfavorable clinical prognostic features and a poor response to therapy. Rare patients with B-cell disease are closely related clinically to non-Hodgkin's lymphoma. Those with common ALL infrequently have unfavorable clinical features and have a superior outcome to that of T-cell patients. Children with undifferentiated markers seem to respond less well to treatment than do those with common ALL, yet may not be identifiable as poor risk by clinical features. What remains to be resolved with further observation is whether these marker patterns are more reliable indicators of prognosis than the usual clinical determinants predisposing to treatment failure (high white blood cell count, mediastinal mass, and central nervous system disease). At the present time, it appears that in the absence of poor-risk clinical prognostic features, patients with common ALL are more likely to have lasting remissions than those with erythrocyte-rosette-positive T-cell disease or those with ALL that is undifferentiated by markers.

Antigens, Neoplasm↗

VM-26 and cytosine arabinoside combination chemotherapy for initial induction failures in childhood lymphocytic leukemia.

Combination chemotherapy with VM-26 and ara-C was given to 14 children with acute lymphocytic leukemia who had not responded to initial treatment with prednisone, vincristine, daunomycin, and asparaginase. Nine of these patients had also received ara-C. At diagnosis, five children were classified as having standard prognostic features and nine as being at high risk for treatment failure. The drug combination was administered by vein twice a week for four weeks at dosages of 165 mg/m2 for VM-26 and 300 mg/m2 for araC. Nine complete remissions, five in patients with high-risk leukemia, were induced with acceptable toxicity; all 9 subsequently were given continuation therapy with oral mercaptopurine and methotrexate. Four of the 9 patients have relapsed at 2--21 months. All treatment was stopped in 2 patients after 30 months of complete remission. Combinations of VM-26 and ara-C represent an alternative remission induction treatment for patients who fail to attain initial remission with agents of established effectiveness. These agents may especially benefit patients with prognostic features indicating a high risk of treatment failure.

Adolescent↗

Combined VM-26 and cytosine arabinoside in treatment of refractory childhood lymphocytic leukemia.

On the basis of previous findings at this institution, VM-26 and Cytosine Arabinoside (ara-C) were used in combination to treat 33 children with refractory acute lymphocytic leukemia (ALL). Chemotherapy was given by vein twice a week for four weeks at dosage of 300 mg/m2 for ara-C and 50, 75, 110, 165, or 200 mg/m2 for VM-26. Ten marrow remissions (nine complete and one partial) were induced, with hypotension (2/33) and bone marrow hypoplasia (20/33) the most significant side effects observed. Therapeutic responses were obtained with each dosage of VM-26 except 75 mg/m2; myelosuppression developed at all dosages, being most prolonged at 200 mg/m2. Ten of the 23 non-responders did not complete their planned courses of therapy. The significance of this information is that combinations of VM-26 and ara-C were effective in patients who were either in late stages of their leukemia or had never achieved an initial remission. All had been previously treated with prednisone, vincristine, daunomycin and L-asparaginase. In addition, seven of the 10 responders had previously received ara-C in other drug combinations. The use of VM-26 and ara-C in combination may be warranted for newly diagnosed patients who are at high risk for treatment failure with first-line drugs.

Adolescent↗

Chemoprophylaxis for Pneumocystis carinii pneumonitis: outcome of unstructured delivery.

Sulfamethoxazole-trimethoprim was administered prophylactically to 786 patients judged to be at sufficient risk for development of Pneumocystis carinii pneumonitis. The selection of patients, administration of the agents, and surveillance for compliance were the responsibility of the attending oncologists rather than specialists in infectious diseases, as in an earlier trial at this center. The recommended dosage was trimethoprim, 150 mg/sq m/day, and sulfamethoxazole, 750 mg/sq m/day. Over a three-year study period, nine cases of P carinii pneumonitis occurred at this institution, with none attributable to drug failure. Adverse reactions, skin rashes mainly, were noted in 43 patients, and one patient died with Stevens-Johnson syndrome. These results confirm the efficacy of sulfamethoxazole-trimethoprim in preventing P carinii pneumonitis in childhood cancer patients and illustrate the feasibility of large-scale unstructured delivery of the combination to patients with malignant diseases frequently associated with this pneumonia.

Adolescent↗

Long-term neurological implications of somnolence syndrome in children with acute lymphocytic leukemia.

A longitudinal study of 49 children with acute lymphocytic leukemia (ALL) assessed the long-term effects of central nervous system (CNS) prophylaxis on brain function. From 10 to 12 electroencephalograms (EEGs) were done before and at intervals during after 30 months of treatment that included 2,400 rads of CNS irradiation plus intrathecal methotrexate therapy. None of the children had CNS leukemia, and all remained in first complete remissions. All 49 had abnormally slow EEG background frequencies during the four-year study, and 29 (60%) developed somnolence syndrome six to eight weeks after CNS prophylaxis. During this syndrome, EEG background frequencies decreased more than 3 standard deviations below the expected mean values for normal children. Thereafter, 7 of the 29 began to show signs of learning disabilities and 7 developed recurrent seizures. Of the 20 children who did not have the syndrome, none showed later evidence of CNS dysfunction. Somnolence may be an early indicator of long-term neurological sequelae after cranial irradiation.

Brain↗

Effects of cranial radiation on hearing in children with acute lymphocytic leukemia.

We serially assessed the hearing sensitivity of 61 children with acute lymphocytic leukemia who were admitted to our Total Therapy IX study between December, 1975, and July, 1977. Their treatment included combined chemotherapy, 2,400 rads of cranial radiation, and intrathecal methotrexate. Subjects initially received an otologic examination and middle ear function testing. Audiometric testing was not done until ears were free of outer or middle ear pathology. If the child had no outer or middle ear disease, audiometric thresholds were obtained for the test frequencies: 500, 1,000, 2,000, 4,000, 6,000, and 8,000 Hz. Pure-tone thresholds were obtained before irradiation (61 patients) and at 6, 12, and 36 months thereafter (49, 46, and 22 patients, respectively). The median age at time of baseline testing was 10 years, 2 months. A paired sample test based on group data was used to test whether there were any significant changes from the threshold values at 6, 12, and 36 months after irradiation. Thresholds were not significantly affected for any test frequency at any test time. Assessments of individual audiograms indicated that none of the children had any significant reductions in hearing levels at the end of the third year after cranial irradiation.

Adolescent↗

A reappraisal of the results of stopping therapy in childhood leukemia.

We examined the results of stopping therapy in children with acute lymphocytic leukemia. Of 639 patients in eight consecutive "total therapy" studies, 278 (44 per cent) had all treatment stopped, usually after 2 1/2 years of complete remission. About one fifth (55 of 278) of this group have relapsed, mainly in the bone marrow. The relapse rate for the first year off therapy was higher than that for the next three years (0.16 vs. 0.04, P less than 0.01). The life-table estimates of the four-year relapse rates were 0.24 for all patients and 0.22 for patients receiving adequate central-nervous system prophylaxis. Boys had a higher relapse rate than girls (0.33 vs. 0.15 P less than 0.01). None of the 79 patients who remained in complete remission for at least four years off therapy have yet relapsed. Acute lymphocytic leukemia appears curable in over one third of all newly diagnosed patients who receive treatment for approximately 2 1/2 years.

Antineoplastic Agents↗

Childhood acute lymphocytic leukemia: study VIII.

This controlled study of children with ALL was designed to test the efficacy and toxicity of one-, two-, three- and four-drug therapy during remission and whether more aggressive therapy in the first eight weeks prolongs remission in patients with features associated with a particularly poor prognosis. After inducing remission with prednisone, vincristine and asparaginase, patients received cranial irradiation and IT methotrexate and were randomized to receive: 1--methotrexate alone; 2--methotrexate plus mercaptopurine; 3--same as in group 2 plus cyclophosphamide; and 4--same as in group 3 plus arabinosyl cytosine. Patients with CNS leukemia at diagnosis received IT methotrexate weekly during the induction period and a higher dose of CNS irradiation. Patients with anterior mediastinal enlargement at diagnosis received radiotherapy to the mass during the induction period. Patients who failed to attain bone marrow remission after four weeks of therapy were given daunorubicin and prednisone for 2--4 additional weeks. Of the 282 patients entering this study between January 1972 and November 1975, 268 (95%) attained complete remission and 228 (85%) were randomized to receive continuation chemotherapy with 1, 2, 3 or 4 drugs. In Group 1 (methotrexate alone), 14 of 20 patients relapsed and 9 developed leukoencephalopathy without antecedent CNS leukemia apparently due to higher doses of intravenous methotrexate; in Groups 2, 3 and 4 the results were equivalent, but without leukoencephalopathy in initial CR. The addition of cyclophosphamide and arabinosyl cytosine increased toxicity and complications without demonstrably increasing the leukemocidal effect. In the 40 patients given additional early therapy, the modalties employed in this study did not prolong remission.

Adolescent↗

Phase I study of neocarzinostatin in children with cancer.

Twenty-three children with advanced cancer refractory to conventional therapy received weekly iv doses of neocarzinostatin for 5 weeks. Doses were escalated from 500 to 6750 units/m2/week. Four types of toxic manifestations occurred: acute reactions consisting of shaking chills with or without fever and cyanosis (rigor), hypersensitivity, vomiting, and marrow depression. Evidence of oncolytic activity was limited to patients with acute leukemia in whom phase II trials at doses between 3000 and 4500 units/m2 appear warranted.

Adolescent↗