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Biomedical subjects

N Jaffe

Publications and source records attributed to N Jaffe.

At least 145 records · Page 8Linked to original sources

Lung function in adolescents receiving high-dose methotrexate.

Methotrexate (MTX) has been implicated as a cause of interstitial pneumonitis and/or fibrosis, but the mechanism by which the drug causes these processes is not known. The purpose of this study was to determine whether patients receiving high-dose MTX developed a consistent decrease in pulmonary function, which would implicate a role for total dose of MTX received in the pathogenesis of the lung toxicity. Pulmonary function studies, including spirometry, plethysmography, and diffusing capacity at two levels of alveolar PO2, were performed in 38 adolescents treated for osteogenic sarcoma. The patients were divided into three groups including 12 patients (group 1) studied before and during therapy, 15 patients (group 2) studied during therapy, and 11 patients (group 3) studied after completion of treatment. While total dose received at the time of the study varied from 0 to 256 gm/sq m, pulmonary function showed no change, with one exception. A mild restrictive defect and decrease in diffusing capacity due to unilateral pleural and diaphragmatic disease, whose relationship to MTX therapy is uncertain, developed in one patient. MTX, when administered in high dose to young patients by the described protocol, causes no dose-related decrease in pulmonary function.

Adolescent↗

Improved prognosis for patients with mediastinal lymphoblastic lymphoma.

Patients with diffuse lymphoblastic lymphoma (which includes convoluted lymphocytic lymphoma) with mediastinal involvement have predictable progression of disease to a leukemic phase that is cytologically indistinguishable from acute lymphoblastic leukemia (ALL). Therefore we treated 12 patients with diffuse lymphoblastic lymphoma involving the mediastinum with therapy that is effective in ALL. Treatment consisted of intermittent combination chemotherapy with adriamycin and preventive central nervous system therapy (craniocervical irradiation and intrathecal methotrexate). Mediastinal irradiation was given either for initial respiratory distress or to patients who had incomplete regression of disease following induction chemotherapy. Eleven patients achieve complete remission. With a median follow-up of 41 mo, and using life table analysis, 86% of these patients have remained in continuous complete remission. The results of this study demonstrate the efficacy of treating diffuse lymphoblastic lymphoma with mediastinal presentation as a disseminated lymphoid malignancy.

Adolescent↗

Esophagitis due to adriamycin and radiation therapy for childhood malignancy.

Esophagitis occurred in seven patients receiving mediastinal radiation and chemotherapy including adriamycin for non-Hodgkin's lymphoma, osteogenic sarcoma, and acute lymphocytic leukemia. Radiation doses were 500-2500 rad, below the reported esophageal tolerance dose. With subsequent adriamycin, recall esophagitis occurred in three of five patients at risk, two of whom developed strictures. Comparison to patients similarly treated without developing esophagitis revealed no specific risk factors, but suggested that the complication was less likely to occur if adriamycin therapy were completed more than two months before starting radiation. Adriamycin and radiation potentiate and recall each other's toxic effects on the esophagus. The interaction both increases the severity and lowers the radiation dose threshold for inflammation and stricture.

Adolescent↗

The role of radiation therapy in the treatment of soft tissue sarcomas of childhood.

The treatment of soft tissue sarcomas in children at the Joint Center for Radiation Therapy, Children's Hospital Medical Center, and the Sidney Farber Cancer Institute from 1970 to 1976 has been reviewed. Twenty-seven patients were diagnosed with rhabdomyosarcoma, and twenty patients were diagnosed with soft tissue sarcomas of other histologies. An aggressive, combined modality therapeutic approach was applied in the treatment of all patients with emphasis placed on conservation of function. Of irradiated patients, local control was achieved in 96% of those with rhabdomyosarcoma and 85% in other sarcomas. Cumulative relapse-free survival (actuarial) at 5 years is projected at 65% for the rhabdomyosarcoma patients and at 63% for the other sarcoma patients. Although there were differences in chemotherapy regimens (vincristine, actinomycin-D and cyclophosphamide for rhabdomyosarcoma and adriamycin and DTIC for other soft tissue sarcomas), the surgical and radiation therapeutic approaches are similar for both groups. The high probability of local control using function-conserving surgery and high dose radiation therapy supports this emerging approach. Improvements in survival will require better control of metastatic disease.

Adolescent↗

The role of radiation therapy in the treatment of pediatric non-Hodgkin's lymphomas.

Between 1971 and 1976, 64 patients less than 18 years of age with non-Hodgkin's lymphoma were treated at Boston's Children's Hospital Medical Center-Joint Center for Radiation Therapy. A multimodality approach was used, consisting of radiation therapy (3500--4500 rad), surgery, and chemotherapy. Since 1973, all patients have received a regimen initially comprising Adriamycin, Prednisone, 6-Mercaptopurine, Vincristine, and L-Asparaginase. Methotrexate was substituted for Adriamycin following a cumulative total dose of 450 mg/m2. The 5-year actuarial survival for all patients was 61% while relapse-free survival was 54%. The actuarial and relapse-free survival for patients presenting with localized disease was 75% and 72%, respectively. Median follow-up was 40 months and all relapses occurred within 24 months of initial therapy. A multidisicplinary approach, such as the current regimen, offers a good prognosis for this disease.

Adolescent↗

Meningeal seeding from rhabdomyosarcoma of the head and neck with base of the skull invasion: recognition of the clinical evolution and suggestions for management.

Rhabdomyosarcomas of the head and neck may spread by diffuse local invasion, resulting in erosion of the base of the skull with possible extension to the leptomeninges, brain, and cranial nerves, as well as invasion of the ventricular system with possible intradural, extramedullary metastases anywhere along the neuraxis. Meningeal spread of tumor is difficult to eradicate, and nearly all patients reviewed died soon after meningeal disease was evident. Patients with erosion of the base of the skull or abnormal cranial nerve findings seem to have a risk of seeding the meninges with tumor. The clinical evolution of this pattern of metastatic spread is reviewed, diagnostic studies are recommended, and therapeutic considerations are discussed. Tentative treatment guidelines are also offered.

Ataxia↗

Staging in childhood non-Hodgkin's lymphoma. What are its benefits? How extensive should it be?

A review of published reports of the management of childhood non-Hodgkin's lymphoma was undertaken to determine the extent to which a staging procedure should be implemented and the benefits which could be derived. A variety of clinical, radiographic, surgical, and laboratory investigations were performed by different investigators. Overall, similar results were obtained for the different stages. The utility of the individual studies was not defined in any single review. However, it appeared that bone marrow biopsy was superior to bone marrow aspirates, staging laparotomy was generally not required, and lymphangiography did not constitute a routine staging procedure. Staging permitted identification of patients with primary sites at high risk for the development of central nervous system disease or failure. The reviews did not specify the minimum number of procedures to be performed. It is concluded that each patient should receive individual consideration, and diagnostic evaluation should consist of a series of tests sequentially performed and interrupted whenever sufficient information has been assembled for institution of therapy.

Bone Marrow Examination↗

Pharmacokinetic and clinical studies of 24-h infusions of high-dose methotrexate.

Cytocidal activity of a drug is dependent on both drug dosage and duration of exposure. In contrast to the 'conventional" 6-h infusion and in an attempto to improve its efficacy, the high-dose methotrexate therapeutic regimen was given over a 24-h period with 10% of the dose administered in the first hour. Citrovorum factor was initiated at hour 24 and continued for 72 h. Treatment was administered every 2-3 weeks. 57 infusions were performed in twelve patients aged 7-20 years (six with osteogenic sarcoma and six with acute lymphoblastic leukemia). Determinations of serum methotrexate levels revealed that the levels were dependent on the dose. Levels assayed at 24 h revealed the following results: 4.4 +/- 1.4 x 10(-5) molar with 4.5 g/m(2), 2.04 +/- 0.34 x 10(-4) molar with 7.5 g/m(2) and 4.59 +/- 0.80 x 10(-4) molar with 12.5 g/m(2). Major toxicity was myelosuppression in 12 of 57 patients. There were no responses. The study demonstrates that 24-h infusions of high-dose methotrexate can be tolerated every 2-3 weeks in patients without bone marrow involvement and levels of at least 10(-4) molar can be maintained during the infusion.

Adolescent↗

The course of five-year survivors of cancer in childhood.

A follow-up study was made of two independent series of 1,807 and 425 children who were alive five years after diagnosis of a malignant neoplasm. Over the subsequent 20 years (5 to 24 years after initial diagnosis), actuarial survival rates for the cohorts were 83% and 79%, respectively, compared to 97% for matched control subjects in the general population (P less than 0.01). Cure was achieved in a large majority of the 5-year relapse-free survivors of cancer in this study.

Adolescent↗

The management of testicular tumors in children.

Of 43 testicular tumors in children seen at the Children's Hospital Medical Center and Sidney Farber Cancer Institute 33 were malignant. These tumors occurred primarily in young children. Any solid scrotal mass in an infant must be considered malignant until proved otherwise. Primary emphasis is placed on the 20 cases of embryonal cell carcinoma. Of 9 patients who underwent only orchiectomy 5 have died, whereas all 11 patients who received combination therapy have survived. We recommend radical inguinal orchiectomy, extended unilateral retroperitoneal lymphadenectomy and adjuvant chemotherapy in repeated courses for 2 years. Radiotherapy is withheld if the lymphadenectomy is negative.

Castration↗

Wilms' tumor--model of a curable pediatric malignant solid tumor.

Wilms' tumor is the model of the treatment of a pediatric solid tumor. Initially it appeared that multi-modality therapy, consisting of transabodominal nephrectomy, post-operative radiation therapy to the tumor bed and adjuvant, single agent chemotherapy provided the highest likelihood of disease-free survival. The identification of important prognostic factors, such as histology, tumor weight, lymph node involvement and age at diagnosis has led to a re-examination of the treatment of Wilms' tumor. Future therapeutic developments will include the administration of less therapy to some well defined groups of patients, and the exploration of new programs for patients who have been demonstrated to have a poor prognosis using currently accepted treatment techniques.

Adolescent↗

Serial studies of cardiac function in patients receiving adriamycin.

A total of 283 adult and pediatric patients treated with drug combinations which include adriamycin (ADM) had at least one cardiac evaluation; 103 patients had two or more serial studies after a baseline evaluation. Changes in systolic time intervals, echocardiographically determined ejection fractions, and electrocardiographic voltage correlated with increasing cumulative ADM dosage. However, the incidence of congestive heart failure among these patients was less than 2%. It is estimated that 22%-31% of these patients would not have completed a cumulative dose of greater than 450 mg/m2 of ADM if the drug had been discontinued on the basis of these tests, using previously published criteria for cessation of treatment. Thus far, however, no adverse effects have been observed from the completion of planned courses of therapy. The clinical significance of serial changes in noninvasive tests is therefore uncertain. While such changes may reflect subclinical anthracycline cardiotoxicity and clinical cardiotoxicity can reliably be diagnosed, the utility of routine, serial noninvasie testing in planning conventional-dose anthracycline therapy is questionable.

Adolescent↗