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Biomedical subjects

J V Simone

Publications and source records attributed to J V Simone.

At least 55 records · Page 3Linked to original sources

Preventive central nervous system irradiation in children with acute nonlymphocytic leukemia.

In this study of children with acute nonlymphocytic leukemia an attempt was made to prevent central nervous system relapse and to determine whether this therapy, coupled with multiagent chemotherapy, would be successful in prolonging durations of complete remission. Central nervous system relapses were prevented by irradiation, although patients who received this therapy did no better than those who did not receive irradiation. A small group of patients received irradiation to the liver and spleen, but this modality also failed to improve the duration of remission. Control of extramedullary leukemia, in this study, failed to improve remission duration because bone marrow relapse was not prevented or delayed. It is unlikely that focal therapy will have a significant impact in acute nonlymphocytic leukemia until longer marrow remissions are achieved.

Acute Disease↗

Current progress in the treatment of the child with cancer.

Treatment for the child with cancer has increasingly been on a rational rather than an empiric basis. An understanding has developed of the importance for determining clinical and laboratory features present at diagnosis as an aid not only to establish a prognosis but also to design specific treatment regimens. A system has been developed for bringing new chemotherapeutic agents into clinical trials as effectively as possible. Through both clinical and laboratory studies, an increasing understanding of the biology of cancer is being developed. This understanding will provide the basis for more rational treatment programs in the future. Physicians of different specialty interests have learned to work together to develop coordinated programs of treatment so important to optimal care. By far the most important lesson learned, however, is that cancer in children is not of necessity a fatal disease, even when dissemination has occurred. For the furture, it will be necessary to develop even more effective methods of treatment, and research must provide a better understanding of this disease that may offer the opportunity for prevention, which, after all, is the number one interest of the pediatrician.

Adolescent↗

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↗

Acute nonlymphocytic leukemia in 171 children.

The initial features, response to therapy, complications, cause of death, and prognostic factors of 171 consecutive children with ANLL are described and compated to historical data for adults with ANLL and for children with ALL. Major differences between children and adults with ANLL include a higher frequency of CNS leukemia and a lower frequency of early deaths in the children. The most important differences between children with ANLL and ALL are the absence of a peak age of incidence in ANLL and the far better response to therapy in ALL. Among features present at 100,000/mm3 or above, and no palpable hepatomegaly had significantly longer survivals, while patients with platelet counts below 10,000/mm3 had significantly shorter survivals. The frequency and duration of remission were significantly better with three protocols used since 1968 than previously. However, even with these protocols, the results were far from satisfactory, with a complete remission frequency of 66%, a median duration of hematological remission of 6 months, and a median duration of survival of 10 months. The striking contrast of these results in childhood ANLL with current results in childhood ALL underscores the need for novel, imaginative therapeutic approaches for ANLL.

Acute Disease↗

Double-blind evaluation of 5-mum final filtration to reduce postinfusion phlebitis.

A double-blind study was conducted to determine the effectiveness of 5-mum final filtration in preventing phlebitis secondary to intravenous fluid administration. An experimental administration set which contained distal portion of the tubing was used for patients randomly assigned to receive filtered intravenous solutions. An identical administration set minus the filter was used in the control group to allow double-blind evaluation of the injection site. Data were collected on 49 patients whose average age was eight years and one month. Most patients had a primary diagnosis of acute lymphocytic or myelocytic leukemia or solid tumor. The patients' injection sites were evaluated daily for clinical findings of phlebitis (erythema, induration, heat, erythematous-streak and discomfort). The incidence of phlebitis was significantly lower (p less than 0.01) in patients receiving filtered intravenous solutions. For the patients in this study, filtration of intravenous fluids with a 5-mum mesh filter appeared to be a feasible and effective means of reducing postinfusion complications.

Drug Contamination↗

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↗

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↗

Initial features and prognosis in 363 children with acute lymphocytic leukemia.

The relationship of a variety of initial features and the outcome of therapy was analyzed for 363 children with acute lymphocytic leukemia (ALL). All had entered "total therapy" studies between 1962 and 1971. The standard for comparing outcome of therapy was whether patients with a given feature attained or exceeded the median duration of complete remission, hematologic remission or survival for the group. The results showed that, in general, the more massive or extensive the disease at diagnosis, the poorer the outcome. Factors associated with a significantly poorer prognosis included: initial leukocyte count above 100,000/mm; spleen enlargement greater than 5 cm; mediastinal involvement and early CNS involvement. Children over 10 years old at diagnosis and Negro children also had a poor prognosis. From another viewpoint features were examined for patients who attained at least 3 years of continuous complete remission. This confirmed some earlier findings and, in addition, showed that children under 2 years of age at diagnosis or with hepatomegaly over 5 cm were less likely to attain this goal. With the exception of early CNS involvement, however, patients with excellent responses to therapy were found with each factor of poor prognosis. Two major factors were not analyzed because their relationship to prognosis is generally accepted: therapeutic differences and acute nonlymphocytic leukemia.

Age Factors↗