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Biomedical subjects

L F Sinks

Publications and source records attributed to L F Sinks.

At least 37 records · Page 2Linked to original sources

Combination chemotherapy in recurrent medulloblastoma.

Five children with recurrent medulloblastomas were treated with Vincristine, BCNU, Methotrexate and Dexamethasone. All five patients responded to therapy. Two of the patients are alive and well 30 and 48 months later; one died of disease 19 months after first recurrence; one developed a further recurrence at 18 months but responded to additional chemotherapy and is alive; and the fifth patient developed a second recurrence after 28 months but has responded to repeat chemotherapy and radiotherapy and is now asymptomatic. These results support the concept that medulloblastomas are sensitive to chemotherapy and suggest that chemotherapy should be considered in cases of recurrent medulloblastomas. In addition, the importance of trials now in progress which employ both adjuvant chemotherapy and radiotherapy in newly diagnosed medulloblastomas is apparent.

Adolescent↗

Intermediate dose methotrexate (IDM) in childhood acute lymphocytic leukemia (ALL).

We employed three courses of intermediate dose Methotrexate (IDM) added onto a standard induction and maintenance program with the concept of both central nervous system (CNS) prophylaxis and simultaneous systemic intensification. Cranial radiation (RT) was not employed as CNS prophylaxis. Fifty of 52 patients (to age 18) achieved complete remission. Time on study now ranges from 22-68 months with a median time of 33 months. We separated the children into standard risk and increased risk. We defined increased risk as a WBC over 30 000/mm3 at presentation and an age of less than two years or greater than 10 years at presentation. There have been 15 relapses on these 50 patients; 11 occurred in increased risk patients (of 22 increased risk patients) and four occurred in standard risk patients (of 28 standard risk patients). There were seven CNS relapses, six systemic relapses, one simultaneous systemic and CNS relapse and one testicular relapse. Toxicity to the IDM was small with the worst problem being mucositis. No leukoencephalopathy occurred. The control of hematological relapse is excellent and the avoidance of potential long-term complications notes is even of greater importance.

Adolescent↗

Correlation between volumetric CT imaging and autopsy measurements of glioblastoma size.

A three-dimensional reconstruction and display technique (THREAD SYSTEM) for serial computed tomography (CT) was employed in monitoring tumor volumes in two children under chemotherapy for glioblastoma multiforme of the cerebral hemispheres. Progressive diminution of tumor bulk was documented in the first patient and an increase in volume in the second. The first patient expired of the complications of his therapy and the second of transtentorial herniation. Independent measurements of the tumors as determined by a CT scan near the times of death and tumor dimensions measured at autopsy revealed good correlations between the radiographic and the anatomical data. The final CT measurement of tumor volume of 20 cm3 compared with an autopsy calculation of 13.3 cm3 in the first case. In the second case, CT volume was 417 cm3 and the actual volume of the primary tumor mass at autopsy was 437 cm3. The results suggest that the THREAD system is a practical method for monitoring the results of radiotherapy and chemotherapy in certain types of cerebral neoplasms.

Adolescent↗

Non-Hodgkin's lymphoma in children.

Until recently the prognosis of childhood non-Hodgkin's lymphoma has been poor. A program of combination chemotherapy and involved area radiotherapy was instituted in the Department of Pediatrics at Roswell Park Memorial Institute in 1971. Thirty-one biopsy proven untreated children entered this study. There were 4 Stage I, 9 Stage II, 6 Stage III, and 12 Stage IV. Initial site of presentation was neck and mediastinum in 16, abdomen in 12, and other sites in three. Nineteen were lymphocytic, seven histiocytic, three undifferentiated, and one was mixed. None had well differentiated or nodular histology. Chemotherapy consisted of vincristine and steroid induction along with intrathecal methotrexate followed by a maintenance phase consisting of daily oral 6-mercaptopurine, weekly oral methotrexate and monthly pulses of vincristine, cyclophosphamide and steroid. Because of initially poor results in Stage IV disease, the protocol was altered midway and high dose methotrexate on three occasions following induction was added. Twelve of 13 Stage I and II patients remain disease free. Four of 6 Stage III patients and 4 of 12 Stage IV patients remain disease free. Only 1/7 of the Stage IV patients prior to high dose methotrexate is disease free, whereas, 3/5 patients with high dose methotrexate are disease free. In total, 19/30 (63%) are disease free for a period ranging from 15+ to 63+ months with 19 patients being disease free for over one year and 12 for over two years.

Adolescent↗

Chemotherapy in recurrent noncystic low-grade astrocytomas of the cerebrum in children.

Six children with grade II astrocytomas were treated with combination chemotherapy consisting of 1,3 bis(2-chloroethyl) 1-nitrosourea (BCNU). Vincristine (VCR), intrathecal Methotrexate (i.t. MTX), and Dexamethasone. Of the children, 3 showed a partial remission, and 1 other showed clinical improvement. Our data suggest that chemotherapy is effective in low-grade astrocytomas, and there is now a need for larger trials in low-grade astrocytomas to document the role of chemotherapy accurately in these tumors. It is suggested that trials of chemotherapy as adjuvant to surgery and radiotherapy should be initiated.

Antineoplastic Agents↗

Profound radiosensitivity in "leukemic" T-cell lines and T-cell-type acute lymphoblastic leukemia demonstrated by sodium [51Cr]chromate labeling.

Radiation sensitivity was determined by measuring spontaneous release from 51Cr-labeled cells in various lymphoid cell populations. Among six leukemia T-cell lines originating from acute lymphoblastic leukemia, four such lines were found to be highly radiosensitive. In contrast, two of the leukemic T-cell lines and four normal control B-cell lines were not radiosensitive. Thymocytes from six patients and leukemia T-cell blasts from three patients with T-cell leukemia were likewise found to be highly radiosensitive, whereas leukemic blasts from six patients with null-cell (non-T, non-B-cell) acute lymphoblastic leukemia were not radiosensitive. Normal peripheral blood lymphocytes and mitogen-induced normal lymphoblasts were found not to be radiosensitive. The results indicate that measurement of the radiation sensitivity of acute leukemic blasts may have a therapeutic significance in coping with the heterogeneous nature of individual leukemia cases.

Animals↗

cis-Dichlorodiammineplatinum (II) in advanced osteogenic sarcoma.

Eight patients with advanced metastatic osteogenic sarcoma were treated with cis-dichlorodiammineplatinum(II) (DDP). Prior to DDP, seven patients had amputations and all had received adjuvant adriamycin (ADR) therapy. In addition, prior to DDP, six patients had received high-dose methotrexate. There was one complete response (pulmonary metastases) and four partial responses (three metastases in the lungs and one in the bone). One additional patient, with local recurrence of osteogenic sarcoma of the mandible following initial resection and adjuvant ADR, was retreated with surgery and DDP and is disease-free for greater than 3 years. The cumulative dose ranged from 300 to 660 mg/m2. Toxicity included irreversible kidney damage in two patients, transient severe hematologic suppression in two patients, and nausea and vomiting in all patients. DDP is a new effective agent in the treatment of osteogenic sarcoma.

Adolescent↗

Nonsurgical treatment of pelvic rhabdomyosarcoma: a case report.

A 2 1/2-year-old male child with rhabdomyosarcoma of the prostate was treated with radiation of the pelvis, consisting of 5,600 rads in 7 1/2 weeks, and combination chemotherapy of Vincristine and Actinomycin D. Surgery had been refused. The child is alive and disease-free more than 5 years after diagnosis, and over 2 years following the cessation of all therapy. Recent advances in radiotherapy and adjuvant chemotherapy have significantly improved the outlook in this aggressive childhood neoplasm and have made a less aggressive and less mutilating surgical approach often desirable. This, in turn, holds out the prospect of improved quality of survival in children so afflicted.

Antineoplastic Agents↗

Establishment and characterization of leukemic T-cell lines, B-cell lines, and null-cell line: a progress report on surface antigen study of fresh lymphatic leukemias in man.

Permanent human hematopoietic cell lines representing T-cell, B-cell and non T/non B (null-cell) leukemia have been established. Comparative analyses were made for their phenotype characteristics. A number of characteristics common within the 7 T-cell lines studied or distinct from other leukemia-type lines were described. Usefulness, validity and limitation of these findings are discussed in connection to the attempt at classification of ALL, CLL and blastic phase of CML. The great majority of CLL were SmIg+-B-cell leukemia and a single case of T-cell CLL was documented. Except 10% as T-cell ALL and a single case of B-cell ALL, the majority of ALL were found to be the non T/non B ALL. Nevertheless, little evidence was suggested from the present study in favor for a notion that the T-cell ALL and the non T/non B ALL are two distinct diseases.

Antigens, Neoplasm↗

High-dose methotrexate in acute lymphocytic leukemia.

A pharmacokinetic study of methotrexate (MTX) was performed in 60 patients who received high-dose MTX at 500 mg/m2 infused over 24 hours. MTX levels reached 1.2 X 10(-7) M in the cerebrospinal fluid (CSF) within 10 minutes and remained constant at that level for 24 hours. Forty of these 60 patients were children with acute lymphocytic leukemia. In these 40 patients, simultaneous intrathecal MTX was given along with high-dose MTX. The resultant CSF levels (lumbar area) were higher than those obtained with either high-dose MTX alone or simultaneous intrathecal MTX alone. To date, there have been one systemic and one central nervous system relapse in these 40 children, and the treatment program appears safe to administer.

Child↗

Clinical response and toxicity with cis-dichlorodiammineplatinum(II) in children.

cis-Dichlorodiammineplatinum(II) (DDP) was studied in 16 children with far-advanced malignancies. Three dosage schedules were tried: regimen A, 20 mg/m2/day x 5 days for 3-4 weeks (11 patients); regimen B, 50 mg/m2 once a week (four patients); and regimen C, 60 mg/m2/day x 2 days every 3-4 weeks (one patient). Four of 16 patients (25%) showed partial response, including one with osteogenic sarcoma, one with neuroblastoma, one with seminoma, and one with medullary carcinoma of the thyroid. Two patients showed clinical improvement. The major toxic manifestations included nausea and vomiting (16 of 16), renal toxicity (three of 16), transient pancytopenia (six of 12), and hearing loss (two of 16). It is apparent that DDP has activity in pediatric tumors; however, a more precise response rate must be delineated in a larger series of patients.

Adolescent↗

The treatment of Wilms' tumor: Results of the national Wilms' tumor study.

The National Wilms' Tumor Study, initiated in 1969, tested competing treatment strategems for patients with tumors ranging from Group (Gp) I (tumors confined to the kidney and totally removed) to Gp IV (remote metastases present at diagnosis). Three hundred and fifty-nine of 606 registered patients were randomized in the trial. Gp I patients under 2 years of age fared well whether postoperative radiation therapy (RT) was or was not added to 15 months' maintenance actinomycin D (AMD). Their prognosis was better than that for older cohorts similarly treated, in whom the difference in relapse rates between treatment groups were suggestive of an RT effect. Combined AMD and vincristine (VCR) gave better results than either agent alone in patients with more advanced tumors (Gps II and III) still confined to the abdomen, all of whom received postoperative RT as well. Preoperative VCR given Gp IV patients in addition to postoperative RT, AMD, and VCR did not improve results. The frequency of mesoblastic nephroma (1%), of bilateral tumors (5%), and of incorrect preoperative diagnosis of Wilms' tumor (5%), the toxicities of the various regimens, and other ancillary data are presented and discussed.

Age Factors↗

Hodgkin's disease in children.

From 1921 to 1973, 106 children with Hodgkin's disease under the age of 17 years were seen at Roswell Park Memorial Institute and were analyzed retrospectively. Evaluation was separated into three eras: 1921-1949 (early era), 1950-1964 (middle era), and 1965-1973 (recent era). In the early era, suboptimal radiation therapy was employed. In the middle era, radiation therapy techniques were improved, and single-agent chemotherapy was introduced. In the recent era, multiagent chemotherapy routines were frequently used; aggressive external megavoltage radiation therapy became routine in conjunction with improvement in staging procedures. The best survival was observed in the recent era where five-year survival of 96% was noted in early stage disease. Favorable prognostic features included: younger age group (5-9 years), female sex, lymphocytic predominant histology, early stage disease, and complete response to therapy. Nodular sclerosing and mixed cell types had an equal prognosis. The concept of involved area radiotherapy along with combination chemotherapy appears a reasonable approach in children and should be tested in a randomized study against more extensive radiotherapy techniques in early stage disease.

Adolescent↗

Receptors for sheep erythrocytes (E) and erythrocyte-antibody-complement complexes (EAC) on the lymphoblasts of childhood acute lymphocyblastic leukemia.

Two cell-surface markers, rosette formation with sheep erythrocytes (E-rosette) as a T-cell marker and rosette formation with bovine erythrocyte-antibody-complement complex (EAC-rosette) as a B-cell marker were determined on peripheral blood lymphocytes and lymphoblasts from normal and 89 children with acute lymphoblastic leukemia (ALL). In the majority of the patients (12/15 untreated patients and 6/11 patients in relapse), lymphoblasts exhibited neither E- nor EAC-rosette formation. Lymphoblasts from one untreated patient with mediastinal mass displayed E-(50%) and EAC-rosette formation (15%). In 3 of 11 patients in relapse, lymphoblasts displayed an increase in EAC-rosette formation with progressive disease. In the remaining patients with active disease, a small and variable proportion of lymphoblasts expressed E and/or EAC-rosette formation. In 63 patients in remission, percentages of E- and/or EAC-rosette were similar (p greater than 0.05) to those of control. The results indicate a wide heterogeniety with respect to expression of lymphocyte membrane markers in lymphoblasts and in normal lymphocytes in patients with active ALL.

Acute Disease↗