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Biomedical subjects

M P Link

Publications and source records attributed to M P Link.

102 records · Page 6Linked to original sources

Acute nonlymphocytic leukemia developing during the course of Ewing's sarcoma.

Two children with Ewing's sarcoma developed acute nonlymphocytic leukemia (ANLL) during the course of their illness. One patient developed ANLL after apparently successful treatment of his primary malignancy with radiation therapy and multiagent chemotherapy. In the second patient, acute leukemia developed before the administration of radiotherapy or systemic chemotherapy. The development of secondary ANLL after Ewing's sarcoma has been reported only twice previously, most likely representing a therapy-induced complication. The occurrence of ANLL in Patient 2 prior to therapy suggests that these two disorders may have a more than treatment-related association. Close follow-up of long-term survivors of Ewing's sarcoma with surveillance for secondary acute leukemia is advised.

Acute Disease↗

A unique human B lymphocyte antigen defined by a monoclonal antibody.

We produced a hybridoma designated 4G7 from a mouse immunized with chronic lymphocytic leukemia cells. The 4G7 hybridoma secretes an IgG1 antibody that is specific for normal and malignant B lymphocytes. Using dual color immunofluorescence staining, this antibody reacted with all immunoglobulin-positive cells but no T cells in normal peripheral blood. There was no detectable 4G7 antigen on monocytes, platelets, red cells, granulocytes, or phytohemagglutinin-activated T cells. When PBL were depleted of 4G7 positive cells and stimulated with pokeweed mitogen, secreted immunoglobulin levels fell to less than 10% of control values on Day 5 and less than 1% of control on Day 7. This antibody was reactive with 155 of 176 B lineage neoplasms on which it was screened. Thirty-five cases of myeloid or T-lymphoid malignancy were negative. Our studies show that the 4G7 antigen modulates in the presence of excess antibody. Free 4G7 antigen was not found circulating in human serum. The cell surface antigen identified by 4G7 was sensitive to pronase proteolysis but resistant to trypsin and chymotrypsin digestion. A comparison of 4G7 with other known B-cell antibodies indicates that the 4G7 antigen has not been previously identified. This antibody is of use for the identification of normal B lymphocytes, the study of B-cell differentiation, and the characterization of lymphoid malignancies.

Animals↗

Monoclonal antibody and enzymatic profiles of human malignant T-lymphoid cells and derived cell lines.

Recently, four distinct cell lines were established from patients whose malignancies had been defined by immunological and biochemical markers. Each patient had a distinct subtype of a T-cell cancer, and each possessed elevated adenosine deaminase and reduced nucleoside phosphorylase activity. Cell lines cultured in vitro possessed the same basic immunophenotype and biochemical enzyme activity as the patients' original malignant cells. In a direct comparison of the immunophenotype of the cell lines and the patients' malignant cells, full concordance existed for 48 of 52 paired antibody tests performed. However, when compared to the corresponding patient's sample, each cell line showed some minor changes in antigen expression or enzyme level. Antigen loss, de novo antigen expression, or elevated adenosine deaminase levels occurred in the cell lines, and these changes were stable on repeated analysis. While there was good general concordance between the patient's cancer and the established cell line, minor biological differences in the cell lines may reflect cellular maturation or subpopulation selection in vitro.

Adenosine Deaminase↗

Identification and significance of cell markers in leukemia and lymphoma.

The identification of markers of human hematopoietic cell differentiation and function has revealed the nature of the proliferating cell in many lymphoid neoplasms and demonstrated marked phenotypic heterogeneity in traditional subgroups. Selected markers are described that define common subgroups of lymphoid leukemia and non-Hodgkin's lymphoma. The identification of cell markers has significant implications for accuracy of diagnosis, for predicting clinical characteristics, and for understanding the biology of these diseases.

Antibodies, Monoclonal↗

Cranial nerve involvement in children with leukemia and lymphoma.

Between 1965 and 1982, 52 children with acute lymphoblastic leukemia or non-Hodgkin's lymphoma were found to have central nervous system involvement of their disease. Of this group, 20 developed clinically apparent cranial nerve paresis or palsy. The cranial nerve most frequently affected was No. VII. With therapy, 16 of the patients had objective control of their central nervous system disease. Among these 16 patients, cranial nerve palsies resolved completely in 14, and only two children were left with residual cranial nerve dysfunction. Seven patients received intrathecal chemotherapy before radiation therapy was instituted in an attempt to control their cranial nerve palsies. Cranial nerve palsy resolved in only two of these seven patients. However, the addition of whole-brain irradiation in the remaining five patients reversed cranial nerve dysfunction in four of them. The combination of intrathecal chemotherapy and central nervous system irradiation was successful in reversing cranial nerve dysfunction in 11 of 13 patients in whom central nervous system disease was ultimately controlled. As cranial nerve dysfunction is associated with distressing signs and symptoms, the combination of central nervous system irradiation and intrathecal chemotherapy is important palliative therapy to initiate promptly. Intrathecal therapy alone appears to be inadequate therapy for prompt and durable reversal of symptoms in this group of patients.

Adolescent↗

Cutaneous lymphoblastic lymphoma with pre-B markers.

Two children with cutaneous convoluted lymphoblastic lymphoma are reported. Malignant cells from both patients contained cytoplasmic Mu heavy chains characteristic of pre-B-cells and expressed CALLA and la antigens as well. Most cases of convoluted lymphoblastic lymphoma are T-cell-derived neoplasms. The non-T, non-B phenotype found in these two children demonstrates that histology does not necessarily predict immunophenotype. The association of the pre-B phenotype with cutaneous lymphoma has not been previously reported, but may represent a unique clinical-histopathologic-immunologic entity that occurs in young children.

Antibodies, Monoclonal↗

Fetal-like erythropoiesis during recovery from transient erythroblastopenia of childhood (TEC).

Fetal-like erythropoiesis frequently accompanies marrow stress conditions such as Diamond-Blackfan syndrome and aplastic anemia. In contrast, patients with transient erythroblastopenia of childhood have erythrocytes which lack fetal characteristics at the time of diagnosis. This report describes nine children with transient erythroblastopenia of childhood in whom transient, fetal-like erythropoiesis was observed during the period of recovery. These patients initially presented with anemia, reticulocytopenia, erythrocytes of normal size for age, low levels of fetal hemoglobin, and i-antigen. During the recovery period, however, erythrocytes manifested one or more fetal characteristics. These included an increased fetal hemoglobin (in three of five patients), the presence of i-antigen (in four of six patients), and macrocytosis (in seven of nine patients). These fetal characteristics persisted more than 2 wk after the reticulocyte count returned to normal. Within one year from diagnosis, red blood cells contained no fetal characteristics.

Anemia, Aplastic↗

High-dose methotrexate in osteogenic sarcoma.

From 1972 to 1979, high-dose methotrexate (HDMTX) and 3 adjuvant regimens were used at the Sidney Farber Cancer Institute and Children's Hospital Medical Center. In the first regiment, HDMTX was used alone; the second, HDMTX and adriamycin, and the third, weekly courses of HDMTX and combination. Actuarial disease-free survival achieved with these regimens in patient with local control of the primary lesion varied from 42 to 75% at 3 years. This compared favorably with historical control patients, of whom 50% were free of disease at 6 months and only 20% at 12 months. Among 41 patients with established pulmonary metastases, 14 were alive and free of disease from more than 4 to over 60 months. The most efficacious method of administering HDMTX was a weekly schedule which produced an overall response rate of 48% in the treatment of pulmonary metastases and primary tumor in patients previously not exposed to HDMTX. Urinary alkalinization was not a standard procedure, and investigations failed to demonstrate any significant effect of alkalinization on HDMTX pharmacokinetics.

Antineoplastic Agents↗

Thyroid carcinoma after successful treatment of osteosarcoma: a report of three patients.

We report three cases of papillary thyroid carcinoma occurring after successful treatment of osteosarcoma. Only one of the three patients received radiation therapy (to the chest) as part of the primary treatment of osteosarcoma. The onset of thyroid carcinoma occurred between 8 and 16 years from the cessation of osteosarcoma therapy. All patients are alive and disease-free from both malignancies. Whereas the association between osteosarcoma and thyroid carcinoma has not previously been recognized, there have been five case reports of these two entities occurring in the same patient. Three of these cases occurred in patients with Werner syndrome. None of the patients reported here had physical stigmata of Werner syndrome or a family history consistent with a hereditary cancer syndrome. Thyroid carcinoma occurs infrequently in patients with osteosarcoma, but in view of the rarity of these two disorders, this association may represent an inherited predisposition to these malignancies.

Adolescent↗

Presurgical window of carboplatin and surgery and multidrug chemotherapy for the treatment of newly diagnosed metastatic or unresectable osteosarcoma: Pediatric Oncology Group Trial.

PURPOSE: Relapse remains a significant problem in patients with metastatic osteosarcoma. The response to carboplatin of patients with newly diagnosed metastatic or unresectable osteosarcoma was assessed in an upfront phase II window, which was followed-up by surgery and intensive multiagent chemotherapy. PATIENTS AND METHODS: Thirty-seven patients, ages 3 to 23 years with histologically confirmed diagnoses of osteosarcoma, were treated between January 1992 and November 1994 with carboplatin 1,000 mg/m2 per dose administered as a 48-hour continuous infusion. Two courses were administered in 3-week intervals, depending on marrow recovery. After radiographic reevaluation, patients underwent surgical removal of tumor (if feasible) and then 40 weeks of chemotherapy with high-dose methotrexate, ifosfamide, doxorubicin, and cisplatin. RESULTS: One of the 37 evaluable patients demonstrated a partial response to carboplatin; there were no complete responses. Patients were additionally analyzed by the response of pulmonary metastases to therapy and the extent of tumor necrosis of the primary lesion. By these criteria, 8 of 37 (22%) of patients showed a response at one or more sites, whereas 20 of 37 (54%) had unequivocal disease progression. Severe myelosuppression was the major toxicity. The projected 3-year event-free and overall survival rates were 23.9% and 31.9%, respectively. Only 1 of 17 patients with unresectable disease or distant bone metastases remains alive, in contrast to 6 of 17 patients with the lung as their only metastatic site and two of three patients with resected regional bone metastases. CONCLUSIONS: Continuous-infusion carboplatin demonstrated limited activity as an upfront agent in patients with metastatic osteosarcoma at diagnosis, even at doses that result in severe and prolonged myelosuppression. Patients with isolated pulmonary metastases or resectable bone metastases have a longer median survival time and greater chance of long-term survival than do patients with unresectable bone disease, for whom the prognosis remains dismal.

Adolescent↗