Search PubMed⌕ Search

Biomedical subjects

W A Smithson

Publications and source records attributed to W A Smithson.

At least 55 records · Page 3Linked to original sources
PubMed1984

Hepatocellular toxicity during the treatment of refractory acute leukemia with indicine N-oxide.

Indicine N-oxide is the first member of the large class of compounds comprised of pyrrolizidine alkaloids and their N-oxides to be studied in the treatment of cancer in humans. Twenty-two patients with refractory acute leukemia received indicine N-oxide daily for 5 consecutive days in a dose-seeking study. Of eight patients with refractory acute lymphocytic leukemia, one had a complete remission, and one had a partial remission. Of 11 patients with refractory acute nonlymphocytic leukemia, 2 patients had complete remissions. Of three patients with blast crisis of chronic granulocytic leukemia, one patient had a partial remission. Five patients had severe hepatic toxicity, probably due to veno-occlusive disease induced by the drug. Whether hepatotoxicity and antileukemic activity are a result of the same mechanism of action of indicine N-oxide is not known.

Acute Disease↗
PubMed1984

Sequential half-body irradiation (SHBI) and combination chemotherapy as salvage treatment for failed Ewing's sarcoma--a pilot study.

This study was undertaken to evaluate the toxicity of sequential half-body irradiation (SHBI) and combination chemotherapy (5-FU, VM-26 and BCNU) in patients who had failed primary aggressive therapy for their Ewing's sarcoma. A secondary goal was to evaluate the response of these previously treated patients to the combination of systemic radiation and multi-agent chemotherapy. The first patient in the study was treated with SHBI only and died 139 days following retreatment. Four subsequent patients successfully received the first cycle of combination chemotherapy. However, only one completed both upper and lower half-body irradiation while the remaining three patients, because of rapid progression of their disease, completed either the upper or the lower portion of their half-body irradiation (HBI). The time from retreatment to disease progression in these four patients ranged from 45 to 97 days (mean 79 days) and the time from retreatment to death ranged from 72 to 193 days (mean 126 days). The combination chemotherapy was tolerated well by all the patients, and the SHBI was accompanied by mild nausea and some vomiting within the first few hours following treatment. Failure to give the second half of the half-body irradiation and to complete further chemotherapy in three of the patients was a result of the progressive nature of the patients' disease and not to any limitations imposed by poor blood counts. Half-body irradiation provided good pain relief within 24 hours for all of the patients. Systemic radiation contributes to the palliative treatment of patients with failed Ewing's sarcoma, but appears to be relatively ineffective when the tumor burden is high.

Adolescent↗
PubMed1984

Intraoperative irradiation: a new technique in pediatric oncology.

Adverse effects on normal tissue are the principal limiting factor in the use of radiation therapy. Maturing tissues are most susceptible to these side effects, so high-dose applications can be a particularly difficult challenge in children. Intraoperative radiation therapy (IORT) enables the radiation oncologist to displace or shield dose-limiting organs or structures. These first two cases of children treated with IORT suggest that IORT, used alone or in conjunction with external beam irradiation, may be useful in the pediatric age group.

Child↗
PubMed1984

Bone marrow transplantation for diseases of childhood.

Bone marrow transplantation in childhood is an established treatment modality for aplastic anemia, the acute and chronic leukemias, and severe combined immune deficiency. Recently, experience with this treatment has also been favorable with small numbers of children who have Wiskott-Aldrich syndrome, several types of inherited storage diseases, Fanconi's anemia, thalassemia, infantile malignant osteopetrosis, and selected cases of lymphoma and other solid tumors. The psychosocial impact and financial costs of bone marrow transplantation can be substantial. Multi-institutional, prospective, randomized trials that would compare transplantation and conventional therapy are necessary to establish the indications and precise timing for this procedure. Further development of monoclonal antibodies, a better understanding of the histocompatibility antigen systems, and improvement in pretransplantation conditioning regimens should increase the spectrum of effectiveness for bone marrow transplantation in the coming years.

Anemia, Aplastic↗
PubMed1984

A controlled pilot study of high-dose methotrexate as postsurgical adjuvant treatment for primary osteosarcoma.

Thirty-eight patients whose primary extremity or limb girdle osteosarcomas had been completely excised (37 amputations, one limb sparing procedure) were allocated at random to two treatment groups receiving respectively regular follow-up examinations plus a high-dose methotrexate (HDMTX) regimen or regular follow-up without primary adjuvant chemotherapy. Although the vincristine, HDMTX, leucovorin regimen was generally quite tolerable when given at three-week intervals for one year and most of the chemotherapy patients followed the planned HDMTX dose escalations from 3 to 6 to 7.5 g/m2, delayed methotrexate excretion limited dosage escalations in 25%. An estimated 52% of the 38 patients were surviving five years after randomization and an estimated 42% remained continuously relapse-free after five years. No significant differences between the outcomes of the 20 treated and the 18 untreated patients were apparent; however, power to detect differences was low. Furthermore, no significant differences in postmetastasis survival were apparent between the 12 treated and 10 untreated patients who relapsed. Approximately 20% of these failing patients appear to have been salvaged for long-term survival. This pilot study of HDMTX confirms the continuing need for controlled clinical trials in determining the therapeutic value of adjuvant chemotherapy programs for patients with primary osteosarcoma.

Adult↗
PubMed1983

Clinical features of central nervous system involvement in E-rosette-positive acute lymphocytic leukemia.

Involvement of the central nervous system (CNS) is a well-recognized complication of acute lymphocytic leukemia. We studied the patterns of such relapse in 56 children with acute lymphocytic leukemia whose disease was classified as E-rosette-positive or E-rosette-negative on the basis of whether their leukemic blasts formed rosettes with sheep erythrocytes. In the E+ group, CNS relapse was more frequent, and relapse occurred at, or sooner after, diagnosis and was more frequently followed shortly thereafter by bone marrow relapse. In addition, the E+ group was more likely to present with focal neurologic syndromes with or without blasts in the cerebrospinal fluid, in contrast to the more common features of diffuse meningeal leukemia with increase in intracranial pressure. These observations suggest that the E-rosette-positive lymphoblasts are more likely to infiltrate into nerve and brain tissue rather than invade the meninges diffusely. If confirmed, these findings imply that treatment of the CNS involvement may need to be different in patients with E+ acute lymphocytic leukemia than in patients with E- acute lymphocytic leukemia.

Adolescent↗
PubMed1982

Vindesine: a phase II study in childhood malignancies-a report for cancer and leukemia group B.

Vindesine, a semisynthetic derivative of vinblastine sulfate, was tested for antitumor activity and clinical toxicity in 36 children. The drug was administered to the initial 13 patients entered into the study a 2 mg/m2/day for five days by IV bolus. Because of severe neurotoxicity and life-threatening gastrointestinal toxicity, the regimen in 23 patients was modified to 4mg/m2 IV infusion over four hours, weekly. This latter regimen was well tolerated, with acceptable gastrointestinal, hematological, and neurotoxicity. One child with acute lymphocytic leukemia resistant to vincristine had a transient M1 remission bone marrow. Improvement or stable disease was noted in one patient each with Ewing's sarcoma, neuroblastoma, and Hodgkin's disease.

Adolescent↗
PubMed1982

Pharmacokinetic study of indicine N-oxide in pediatric cancer patients.

Pharmacokinetics of the experimental antitumor agent indicine N-oxide were investigated in a group of 23 pediatric cancer patients. Plasma elimination of indicine N-oxide was best described by a two-compartment open model. The mean plasma distribution phase half-life, plasma elimination phase half-life, and plasma clearance were 8 min, 84 min, and 62 ml/min/m2 (2.1 ml/min/kg), respectively. One patient with renal impairment had an abnormally long plasma elimination phase half-life (275 min) and reduced plasma clearance (17 ml/min/m2). Plasma elimination phase half-life values increased and plasma clearance values decreased with increasing age of the pediatric patients. Plasma elimination of indicine N-oxide was more rapid in this group of children than in adults who had previously received the drug.

Adolescent↗
PubMed1982

Primary mediastinal tumors in children.

Mediastinal masses in children constitute a heterogeneous group of malignant and benign neoplasms. The majority of malignant tumors in our series of 188 children with a mediastinal mass were Hodgkin's and non-Hodgkin's lymphoma (87 patients) arising in the anterior and middle mediastinum. Ganglioneuroma (17) arising in the posterior mediastinum made up the bulk of benign tumors (52). Infants less than 2 yr old presented with symptoms of tracheal compression, whereas older children had fewer symptoms but a far greater likelihood of having a malignancy. In the assessment of patients with mediastinal tumors, the posteroanterior and lateral chest roentgenograms were most often diagnostic, and computed tomography of the chest provided the most information concerning preoperative resectability. The excellent survival of patients with stage I and II Hodgkin's disease reflects the radiosensitivity of the tumor; in our series of 33 patients, survival was not increased by radical resection. Unlike lymphomatous tumors, neurogenic masses should be completely excised. When initial exploration reveals unresectability, biopsy followed by radiation therapy and second-look excision of the tumor can be accomplished. In patients with primary mediastinal sarcomas, total resection should be carried out if possible. In our series, adjuvant radiation therapy or chemotherapy was effective in only 1 of 15 children with sarcoma. Surgical treatment of all mediastinal masses except lymphoma should be complete excision. In cases of suspected lymphoma, cervical or supraclavicular node biopsy can yield adequate tissue for diagnosis.

Adolescent↗
PubMed1982

Use of subcutaneous deferoxamine in a child with hemochromatosis associated with congenital dyserythropoietic anemia, type I.

A 12-year-old girl with congenital dyserythropoietic anemia, type I, was diagnosed as having hemochromatosis. Deferoxamine was given subcutaneously for 14 months. Iron overload, as measured by liver iron and serum ferritin levels, was reduced substantially, liver function tests improved, and hepatomegaly decreased. Toxicity was negligible.

Anemia, Dyserythropoietic, Congenital↗
PubMed1981

Activity of indicine N-oxide in refractory acute leukemia.

Indicine N-oxide, the first pyrrolizidine alkaloid N-oxide to be studied in the treatment of cancer in humans, was administered to ten patients: four children and two adolescents with refractory acute lymphocytic leukemia and four adults with refractory acute nonlymphocytic leukemia (three acute myelocytic, one myelomonocytic). Two patients, a 4-year-old boy with acute lymphocytic leukemia and a 22-year-old man with acute myelocytic leukemia, achieved complete remission lasting 3 and 5+ months, respectively. Another 15-year-old male with acute lymphocytic leukemia had a partial remission for four months. Toxicities included bone marrow suppression, mild anorexia and nausea, and transient elevation of liver enzymes. Jaundice and liver failure, presumably induced by drug, occurred in two patients.

Adolescent↗
PubMed1981

Neuropsychologic performance among children in remission from acute lymphocytic leukemia.

Comprehensive neuropsychologic assessments were done for children in continuous remission from acute lymphocytic leukemia (ALL) following either chemotherapy alone (N = 14) or chemotherapy combined with prophylactic cranial radiation (N = 19). Only 5 of 75 neuropsychologic variables were found to differ at the .05 level for these two groups; trends were seen (p less than .10) on two additional variables. The data indicate few if any meaningful differences related to the presence of absence of radiation therapy, although the differences that were seen occurrred on tasks for which other authors have suggested diminished ability as a result of cranial radiation. Additional analysis failed to reveal any effects related to the age at which prophylactic radiation was received.

Adolescent↗