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Biomedical subjects

R J Aur

Publications and source records attributed to R J Aur.

At least 55 records · Page 3Linked to original sources

Successful chemoprophylaxis for Pneumocystis carinii pneumonitis.

In a randomized, double-blind, placebocontrolled study to evaluate the efficacy of trimethoprim-sulfamethoxazole for the prevention of Pneumocystis carinii pneumonia, we studied 160 patients with cancer who were at high risk for this pneumonia over a two-year period. Seventeen of the 80 patients receiving a placebo acquired P. carinii pneumonitis, whereas none of the 80 given 150 mg of trimethoprim and 750 mg of sulfamethoxazole per square meter per day had the infection P less than 0.01). Bacterial sepsis, pneumonia other than that caused by P. carinii, acute otitis media, upper-respiratory-tract infections, sinusitis and cellulitis occurred less frequently in recipients of the drug than in the placebo group (P less than 0.01 in each case). Oral candidiasis was the only adverse effect ecountered from trimethoprim-sulfamethoxazole administration. The study shows the combination to be highly effective in the prevention of P. carinii pneumonitis.

Adolescent↗

Hodgkin's disease occurring during acute leukaemia in remission.

Three patients with acute lymphoblastic leukaemia are reported in whom Hodgkin's disease developed during chemotherapy-maintained remission. This association has been reported only once before. The pathogenesis of the Hodgkin's disease in these patients is discussed, including the possible role of anti-leukaemic therapy.

Adolescent↗

Radiotherapy in leukemia and lymphoma of children.

Radiotherapy is important in the treatment of leukemia and lymphoma of children. In acute lymphocytic leukemia administration of cranial irradiation early during chemotherapy-induced remission prevents initial meningeal relapse. When cranial irradiation is combined with a 3-year course of multiple drug systemic chemotherapy approximately one-half of the children remain in complete remission for 5 years or more and are at little risk of relapse. Preventive cranial irradiation is effective in children with acute myelocytic leukemia, also, but this does not affect survival because of the inadequacy of chemotherapy in controlling bone marrow disease. Low dose palliative irradiation can be helpful in caring for some children with obstructive, painful or disabling leukemic lesions. In Hodgkin's disease of children radiotherapy is effective in curing stages IA, IIA, and IIIA disease and contributes to chemotherapy control of stages IIIB and IV disease. The role of radiotherapy in non-Hodgkin's lymphoma is less clear. Children with T-lymphoblastic lymphoma tend to have rapid dissemination to bone marrow and meninges and appear to benefit more from multiple agent chemotherapy and preventive meningeal irradiation. Children with B-lymphoblastic lymphoma usually benefit from cyclophosphamide therapy; the value of irradiation is yet to be established. However, radiotherapy is frequently curative in stage I B-lymphocytic nodular and histiocytic lymphomas. The indications for radiotherapy in children with leukemia and lymphoma are constantly changing. Before each child is treated the multi disciplinary evaluation and treatment team must consider the rationale in relation to the specific child and current knowledge.

Antineoplastic Agents↗

Initial prognostic factors and lymphoblast-erythrocyte rosette formation in 109 children with acute lymphoblastic leukemia.

Bone marrow lymphoblasts from 109 children admitted with untreated acute lymphoblastic leukemia (ALL) were tested for spontaneous rosette formation with sheep erythrocytes. Twenty-six children (24%) had lymphoblasts that formed rosettes (E+). Of 13 initial clinical characteristics, 8 were significantly associated with E+ lymphoblasts: mediastinal enlargement (86% of patients E+), leukocyte counts over 100 X 10(9)/liter (65% E+), nodes greater than 2 cm in any diameter (65% E+), age over 5 yr (46% E+), hemoglobin over 8 g/dl (44% E+), hepatomegaly greater than 5 cm (38% E+), boys (35% E+), and lymph node enlargement outside of the cervical area (28% E+). Spleen size, initial platelet counts, and periodic acid-Schiff scores did not distinguish E+ from E- patients. Since few patients were black and few presented with central nervous system leukemia, the association of these two characteristics with E+ blasts could not be determined. A hierarchical classification scheme and a linear logistic regression model were used to define the patterns of characteristics associated with E+ lymphoblasts. The initial clinical characteristics and the poorer course of E+ patients suggest that ALL comprises at least two biologically and clinically distinct types. The E+ ALL may result from a leukemic transformation of a non-Hodgkin lymphoma.

Adolescent↗

Pretreatment cytokinetic studies in 94 children with acute leukemia. Relationship to other variables at diagnosis and to outcome of standard treatment.

The relationship of the pretreatment bone marrow mitotic index (MI) and in vitro 3H-thymidine labeling index (LI) to other variables present at diagnosis and to the outcome of standard therapy was examined in a series of 94 children with acute leukemia (71 ALL, 23 AML). The range of observed values at diagnosis was extremely broad, from less than 1% labeled cells to more than 25%. The median LI% for all patients studied was 5.2%; the median MI% was 0.3%. The values for AML and ALL did not differ significantly despite older age, higher initial white blood cell (WBC) counts, and poorer response to therapy of AML patients. The initial MI and LI were positively correlated with each other, but unrelated to age or initial WBC count in either ALL or AML. However, the LI and MI were significantly higher (p less than 0.01) in the group of 10 children of 54 studied with ALL whose blasts formed spontaneous rosettes with sheep red blood cells at 37 degrees C. The initial LI and MI were not shown to be related to the likelihood of attaining a complete response or to the length of remission in either ALL or AML. There was thus no evidence that either the initial MI or LI% of marrow blasts was of any prognostic significance in children with acute leukemia.

Age Factors↗

Recurrent childhood lymphocytic leukemia following cessation of therapy: treatment and response.

A unique population of patients--children who developed recurrent acute lymphocytic leukemia (ALL) following cessation of initial prolonged therapy--was studied. During a 2-year period, 17 such children were admitted to a planned combination chemotherapy program. Complete bone-marrow remissions were achieved in 16 patients, and the median duration of second hematologic remissions was 216 days. These responses were significantly better than those obtained in seven patients who relapsed during the administration of continuation chemotherapy. Although the rate and duration of induced remissions were notably high, 9 of the 17 patients who relapsed off therapy have again developed recurrent leukemia. This result, together with the moderate toxicity encountered during treatment, indicates that more therapy is needed. The equal proportion of bone marrow and meningeal relapses was interpreted to mean that a secon course of preventive central nervous system therapy early in remission may be especially useful.

Adolescent↗

Childhood acute lymphocytic leukemia.

Childhood ALL is a potentially curable disease. All children suffering from this ailment should be given an opportunity to live by receiving therapy aimed at permanent cure. The disease requires extensive, complex, and costly diagnostic study and treatment. Specialized care is more efficiently given in centers dedicated to treating patients with malignant diseases. The referring physicians are an essential part of the working team delivering care to the children with acute leukemia. Despite improved results, a significant number of patients fail to develop permanent remission. The risk of relapse after cessation of therapy is greatest in the first year and in patients given no specific CNS therapy. However, modern therapy produces a substantial number of long-term leukemia-free survivals in children with ALL, a majority of which persist after cessation of therapy. After cessation of therapy the quality of survival of the vast majority of patients is excellent.

Ambulatory Care↗

Combined modality therapy of acute lymphocytic leukemia.

The progressive improvement in the prognosis of acute lymphocytic leukemia has been a result of two major developments: 1) the more efficient use of chemotherapeutic agents, particularly the use of combinations of agents and the discovery that agents effective at one stage of disease may be inappropriate at another stage, and 2) the prevention with irradiation of central nervous system relapse. As many as one-half of children with this disease may enjoy long-term leukemia-free survival. However, further studies are needed to improve the efficacy and reduce the toxicity of therapy. This paper reviews the evolution of some of these studies.

Age Factors↗

Acute lymphocytic leukemia in children.

An overview is presented of the improvements in the prognosis of acute lymphocytic leukemia due to combined modality therapy. With the best available regimens, approximately 50% of these children have remained leukemia-free for 5 years or more. Because of these results, there is growing concern for the quality of survival and for the side effects of therapy. A case in point is a completely unexpected side effect in a current study. Nonleukemic leukoencephalopathy has developed in 8 of 20 children given intravenous methotrexate, 50-80 mg/m2 per week, as the sole agent following remission induction and CNS therapy. Thus, with longer remissions and survivals now commonly observed, a concerted effort is needed to minimize side effects while trying to improve further the efficacy of therapy.

Child↗

Cyclophosphamide-induced hemorrhagic cystitis in children with leukemia.

The records of 314 children with acute lymphocytic leukemia (ALL) were reviewed to determine the frequency, clinical and laboratory features; contributing factors; and prognosis of cyclophosphamide-induced hemorrhagic cystitis. Twenty-five well-documented cases of hemorrhagic cystitis were identified. While most of the affected children suffered a mild transient illness, 1 patient died as a result of bladder hemorrhage. The doses of cyclophosphamide received by these children ranged widely and did not correlate with the severity of the cystitis. The frequency of this complication did not differ significantly with sex, age or route of administration. However, cystitis was over twice as frequent in black children as in white. Nineteen of 25 cases occurred in the spring and summer months. The group of affected children did not differ significantly from a matched control group in terms of total drug dosage received, incidence of systemic toxicity, mean urine specific gravity, or overall survival.

Adolescent↗

Intensity of immunosuppressive therapy and the incidence of Pneumocystis carinii pneumonitis.

One hundred and forty-nine children with acute lymphocytic leukemia treated according to a prospective protocol were randomized after induction of remission and central nervous system (CNS) irradiation to receive maintenance chemotherapy with 1, 2, 3, or 4 chemotherapy agents. The incidence of P. carinii pneumonitis (PCP) was 5.0, 2.3, 2.2, and 22.4%, respectively, during the period of maintenance therapy. An additional 31 patients enrolled in the same study were placed in special categories to receive three drugs for maintenance plus supplemental chemotherapy or irradiation because of CNS leukemia on admission, remission failure, ediastinal mass, or generalized lymphosarcoma without bone marrow involvement. The incidences of PCP in these groups were 16.7, 30.0, 35.7, and 0%, respectively, during the period of maintenance therapy.

Antineoplastic Agents↗

Non-Hodgkin's lymphoma in children.

The clinical and pathological features of 64 children with non-Hodgkin's malignant lymphoma seen between April 1962 and June 1973 are described. Forty-one children had diffuse, undifferentiated, non-Burkitt lymphoma (lymphoblastic lymphoma). They tended to be boys under 10 years of age and their median survival was 1 year. Almost one-third are surviving for 1-11 years, most in initial complete remission. Nineteen children had diffuse, poorly differentiated, histiocytic lymphoma. They tended to be boys more than 10 years of age, their median survival was only 6 months, and only the 3 patients with Stage I peripheral node tumour survived. Two children had nodular, lymphocytic, poorly differentiated lymphoma and 2 had lymphoma resembling the Burkitt type. From our clinical and pathological observations, we conclude that non-Hodgkin's malignant lymphomata in children cannot be separated from the acute lymphocytic, histiocytic and unclassified leukaemias by cytological or histological methods. What is called diffuse, undifferentiated, non-Burkitt type, or lymphoblastic lymphoma is actually acute lymphocytic leukaemia without apparent invasion of marrow and peripheral blood by neoplastic lymphocytes at time of diagnosis. What is termed diffuse, histiocytic lymphoma is acute histiocytic leukaemia without apparent infiltration of marrow and peripheral blood at initial presentation. One could say just as well that acute lymphocytic leukaemia is Stage IV lymphoblastic lymphoma and that acute histiocytic leukaemia is Stage IV histiocytic lymphoma. Further classification of lymphocytic and histiocytic cancers by newer functional, chemical and morphological methods should include both what is called lymphocytic or histiocytic leukaemia and what is called non-Hodgkin's lymphoma as one group of diseases, susceptible to subclassification by the new methods. We recommend that Stage I lymphocytic and histiocytic cancers be treated with local irradiation. Patients with Stages II-IV tumours should receive anti-leukaemic forms of therapy including prolonged multiple agent chemotherapy and preventive central nervous system irradiation. Staging laparotomy should be considered in patients with Stage I tumour in low cervical, axillary and inguinal nodes.

Adolescent↗