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Biomedical subjects

N Jaffe

Publications and source records attributed to N Jaffe.

At least 163 records · Page 9Linked to original sources

Concomitant presence of tumor-specific cytotoxic and inhibitor lymphocytes in patients with osteogenic sarcoma.

The lack of detectable tumor-specific cytotoxicity by the peripheral blood lymphocytes of patients with cancer may be due to a lack of cytotoxic lymphocytes or the presence of suppressor lymphocytes that inhibit cytotoxic cells. Unfractionated peripheral blood lymphocytes from 12 of 28 patients with osteogenic sarcoma were cytotoxic to osteogenic sarcoma cells in vitro (P less than 0,001). When the peripheral blood lymphocytes from patients whose lymphocytes were not cytotoxic underwent fractionation, a tumor-specific cytotoxic subpopulation was isolated from 11 of 13 patients (P less than 0.0001). Lymphocytes that inhibited cytotoxic activity of autologous tumor-specific cytotoxic lymphocytes were found in four of 10 patients with osteogenic sarcoma but not in six normal controls. Inhibitor lymphocytes form rosettes with sheep erythrocytes and adhere to nylon, whereas cytotoxic lymphocytes have a receptor for C3 but no surface immunoglobulin. The lack of tumor-specific lymphocytotoxicity in some patients can be due to inhibitor lymphocytes.

Cell Fractionation↗

Weekly high-dose methotrexate-citrovorum factor in osteogenic sarcoma: pre-surgical treatment of primary tumor and of overt pulmonary metastases.

Vincristine-high-dose methotrexate-citrovorum factor (VCR-MTX-CF) was administered preoperatively at weekly intervals to eight patients, four with primary tumors and four with pulmonary metastases. These patients had not received prior VCR-MTX-CF treatment. A similar treatment program was administered to five patients with pulmonary metastases who had received prior VCR-MTX-CF. Among the eight patients who had not received prior VCR-MTX-CF, complete responses were obtained in three with primary tumors (this was followed by surgical excision) and two with pulmonary metastases. Partial responses occurred in two additional patients. Partial responses were also obtained in two patients who had received VCR-MTX-CF. Chemotherapy and surgery in one patient with an extremity lesion resulted in preservation of the limb and useful function. The major toxicity was anorexia and weight loss. Other side effects included stomatitis, myelosuppression, hepatitis and transient renal impairment. The weekly program was highly effective when compared to responses obtained with the tri-weekly schedule utilized in previous studies.

Bone Neoplasms↗

The role of radiation therapy in localized resectable intestinal non-Hodgkin's lymphoma in children.

Forty children with localized resectable intestinal non-Hodgkin's lymphoma were seen between 1948 and 1974. Survival was related to the extent of disease at presentation and to therapy. No deaths occurred after 15 months and no recurrences occurred after 13 months after diagnosis. Six of eight stage IE patients (75%) and nine of 29 stage IIE patients (31%) have survived a minimum of 2 years; one of the three stage IVE patients has survived 17 years. Unfavorable prognostic findings at surgery were serosal involvement, presence of tumor at the surgical margins, mesenteric nodal involvement, and the presence of abdominal fluid or blood. Paraortic nodal involvement or multiple primary foci were universally fatal. Eight of 11 patients (73%) treated with surgery and whole abdominal irradiation (greater than or equal 2000 rad) with or without chemotherapy have survived. Seven of 18 patients (39%) treated with surgery and low dose chemotherapy have survived. One of seven patients treated with surgery and localized or low dose radiation therapy with or without chemotherapy has survived. Four patients treated with surgery alone died. Bone marrow and central nervous system involvement occurred after previous disease relapse elsewhere.

Adolescent↗

The increasing importance of radiation therapy in the improved prognosis of children with Wilms' tumor.

Treatment results for 32 children with Wilms' tumor seen at the JCRT, CHMC and SFCI from January 1, 1971, through December 31, 1975, are presented. Indications for and technical details of irridation are discussed. The uniform efficacy of irradiation in preventing local relapse in all patients presenting with unilateral disease despite tumor spill in nine is stressed. Actuarial survival of nearly 80% of all patients seen and followed for more than 2 years has been achieved. Eight of 14 patients with documented pulmonary relapse have been controlled with irradiation, chemotherapy and surgery. The importance of an aggressive multidisciplinary approach to this tumor is stressed.

Child↗

Stages I--III Hodgkin's disease in children: results of staging and treatment.

Fifty-two children with clinical stages I-III Hodgkin's disease were evaluated for disease extent between April 1969 and March 1975. All underwent laparotomy and splenectomy. Two patients with liver involvement were excluded. Thirty of 31 patients with pathologically staged IA-IIA disease have been continuous complete remission after mantle and para-aortic irradiation. There have been no extensions into the untreated pelvis. Fourteen of 15 patients with pathologic stages IIB and IIIB disease show no evidence of relapse after TNI and MOPP. Three of four patients with stage IIIA disease developed nodal relapse after irradiation; all are alive without evidence of disease after re-irradiation (3) and MOPP (2). Thus 45 of 50 patients (90%) have remained continuously free of disease after completion of the planned treatment, and overall 49 of 50 (98%) are alive, without evidence of disease. Such results justify continuation of our staging and treatment philosophy in children with Hodgkin's disease.

Adolescent↗

Parenteral nutritional support in children with cancer.

Acute and chronic starvation is often associated with childhood cancer. Total parenteral nutrition (TPN) with 20% glucose and 3.0% amino acids, and minerals and vitamins was instituted to treat or prevent malnutrition in 41 children with cancer, ages three months to 18 years. TPN was required for anorexia, vomiting and diarrhea associated with anti-cancer therapy in 33 patients for intestinal complications or surgery in nine, and for preoperative correction of malnutrition in two. During TPN, general nutrition and appearance improved in all patients. Weight gain was noted in most. Despite gastrointestinal complications which usually require the interruption of chemotherapy and irradiation, in 21 children treatment could be continued at full dose with nutritional support by TPN. TPN was discontinued in six patients when blood cultures became positive. Sepsis was treated successfully by removal of the central venous catheter in all six and administration of antibiotics in three. No metabolic complications were noted. TPN appears to be a safe and effective means of combating the malnutrition which may occur with cancer and its therapy.

Adolescent↗

Preliminary results of aggressive multimodality therapy for metastatic osteosarcoma.

Ten patients with metastatic osteosarcoma were treated at the Joint Center for Radiation Therapy, the Sidney Farber Cancer Institute, and the Children's Hospital Medical Center from 1973 to 1976. Patients were treated with an aggressive multimodality approach with included surgery, chemotherapy, and radiation therapy. Three of 10 patients are alive with no evidence of disease, five are alive, with disease, and two are dead of disease. The median survival is 12+ months. Local control data for radiation combined with high dose methotrexate in metastatic osteosarcoma is shown.

Adolescent↗

Clinical and cytokinetic aspects of remission induction of childhood acute lymphoblastic leukemia (ALL): addition of an anthracycline to vincristine and prednisone.

Fifty-six untreated patients with childhood with acute lymphoblastic leukemia (ALL) were randomized to receive one of three remission induction regimens: vincristine and prednisone (VP), vincristine, prednisone and daunorubicin (VPD), or vincristine, prednisone and adriamycin (VPA). The complete remission rate was similar for all three groups. Although the anthracycline regimens caused somewhat more rapid leukemic cell reduction than the VP only group, this difference was not significant. Labeling index reduction between study days 1 and 5 was significantly greater (p less than 0.001) with an anthracycline than for the VP group, but there was no difference between the two anthracyclines. Granulocytopenia during induction was significantly increased (p less than 0.05) in both the VPD and VPA groups as compared with VP alone. A significantly higher rate of infectious morbidity (p less than 0.01) was associated with the addition of either anthracycline, but to date no significant differences in remission duration or survival have been observed. The addition of anthracyclines to VP for remission induction in childhood ALL has theoretical advantages, but may be undesirable because of increased morbidity.

Child, Preschool↗

Chemotherapy with cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP) in childhood acute lymphoblastic leukemia (ALL).

Three groups of children with acute lymphoblastic leukemia (ALL) were treated with intermittent cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP). Group A (no prior relapse) and Group B (prior single-agent relapse) received COAP after 12 months on another chemotherapy regimen. Children in Group C (prior relapse on multiagent regimens) received COAP following A-COAP (asparaginase plus COAP) reinduction. Median disease-free survival after beginning COAP was not reached for Group A, but was only 7 months for Groups B and C. As of November 1976, there were 8 of 15 Group A patients, 1 of 12 Group B patients, and 1 of 28 Group C patients who had remained disease-free from 38 to 60 (median 54.5) months and were off chemotherapy. COAP has activity in childhood ALL. However, effectiveness is markedly diminished in patients with prior bone marrow relapse.

Child↗

Multidisciplinary treatment for childhood sarcoma.

Surgical extirpation of the primary tumor has traditionally been utilized as initial treatment for sarcomas in children. The present report, however, demonstrates that sarcomas are optimally treated by means of a coordianted multidisciplinary approach. The latter offers the potential for achieving improved survival and preservation of organs and limbs, particularly for structures of the head and neck, for extremities, and in the genitourinary system.

Adolescent↗

Prognosis for children with neuroblastoma presenting with paralysis.

Since 1947, we have treated 19 children with neuroblastoma whose first symptoms were paralysis or weakness of an extremity, and/or incontinence due to tumor in the spinal canal. In 18 patients, the spine tumor was part of a dumbbell tumor which was present in the adjacent paravertebral area and in one, no extraspinal tumor was found. Aggressive treatment was employed for all. In 17 children, the intraspinal tumor was treated by laminectomy and irradiation with and without chemotherapy. Radiation and chemotherapy were used for two. The extraspinal tumor was excised totally in six and partially in six. All 12 children received postoperative radiation and chemotherapy. In 6 children, the extraspinal tumor was treated only with radiation and chemotherapy. Nine of 19 children are alive without evidence of neuroblastoma. Thirteen patients showed either partial (6) or full (7) neurologic recovery. Survival was related to the child's age at diagnosis and the extent of disease. While 8 of 9 children under 1 yr of age survived, only 1 of 10 children over 1 yr survived. None of the 5 children with Stage IV disease at diagnosis could be saved. The degree and frequency of neurologic recovery were greatest in children whose neurologic symptoms had been present the shortest times and were equal among those who survived and those who died. The outlook for children who became paralyzed by neuroblastoma is not hopeless; therapy aimed at saving life or neurologic function is both worthwhile and rewarding.

Age Factors↗

Metastases in malignant childhood tumors-the role of "adjuvant" therapy and the utility of multidisciplinary treatment.

Patients with tumors which appear localized at diagnosis frequently develop metastases after primary definitive therapy. This suggests that occult (microscopic) dissemination of tumor has occurred prior to presentation. This is optimally treated early with chemotherapy after primary definitive treatment. The rationale for this approach is based on cytokinetic studies: micrometastases are more sensitive to anticancer agents thatn larger primary tumors from which they were derived and treatment administered when the tumor burden is at its nadir avoids the necessity to escalate doses and affect host tolerance. The application of these concepts to clinical practice has resulted in significant increases in survivals. Investigations to facilitate early detection of clinical metastases and the integrated use of multidisciplinary treatment for eradication of metastases are outlined.

Antineoplastic Agents↗

High-dose methotrexate with citrovorum factor in osteogenic sarcoma--progress report II.

Vincristine (VCR), high-dose methotrexate (MTX), and citrovorum factor (CF) were administered to 12 patients with classic osteogenic sarcoma with local control. Seven patients (58%) are free of pulmonary metastases for 2+-31/2+ years. With a second adjuvant program incorporating adriamycin (VCR, MTX, CF, and adriamycin), 16 of 20 patients are free of pulmonary metastases for 6+-18+ months. Five patients who developed pulmonary metastases were rendered free of disease by surgical resection. The VCR, MTX, and CF program was also administered at weekly intervals to eight patients with pulmonary metastases or unresected primary lesions. Two complete and one partial response were obtained in four patients with pulmonary metastases and three complete and one partial response were obtained in patients with primary lesions. This program was also administered in combination with radiation therapy to four patients who relapsed on conventional VCR, MTX, CF, and adriamycin therapy following surgical resection of pulmonary metastases. They remain free of recurrent disease for 2+-14+ months. There was no alteration in the incidence of toxicity when compared to earlier investigations. The results indicate that the VCR, MTX, and CF program has had a major impact on the management of osteogenic sarcoma.

Doxorubicin↗

Current concepts in the management of disseminated malignant bone disease in childhood.

Disseminated malignant disease should be approached with the intention of curing the patient. This requires a multidisciplinary approach. Essential to the successful application of multidisciplinary treatment is the administration of effective chemotherapy, which may achieve reduction in both microscopic disease and overt tumour. In Ewing's sarcoma, the latter should be treated also by irradiation. Limited areas of bulk tumour that have failed to respond or have responded only partially may be removed surgically. Chemotherapy and radiation therapy should be used extensively for palliation; surgery may be required occasionally for control of pain. The decision to treat palliatively should be reached only after patients have received multidisciplinary consultation.

Bone Neoplasms↗

Role of staging in childhood non-Hodgkin's lymphoma.

Childhood non-Hodgkin's lymphoma is characterized by a high incidence of leukemic transformation. A retrospective analysis of this incidence in 227 children is provided. In an attempt to identify factors associated with this phenomenon, the extent of disease in 30 recently diagnosed patients was determined by means of a modified Ann Arbor staging system. Concurrently, the staging system was utilized for the delivery of a new treatment program: chemotherapy was administered to all patients, and those with stage I and II disease also received radiation therapy to sites of bulk tumor. An overall disease-free survival of 75% was achieved. No patient with stage I disease converted to acute leukemia. The data suggest that the major utility of staging is the delineation of anatomic sites of bulk tumor. The chemotherapeutic program utilized in these patients is outlined.

Adolescent↗

Multidisciplinary treatment for macrometastatic osteogenic sarcoma.

Using a co-ordinated multidisciplinary approach with surgery, radiation therapy, and chemotherapy, 14 out of 21 patients with metastases from osteogenic sarcoma were rendered free of disease for over two to over 18 months. Most patients had pulmonary metastases, two had bony metastases, and one had metastases in the iliac nodes. As part of this multidisciplinary approach weekly high-dose methotrexate was given and caused tumour regression in seven out of 15 patients. After all clinical evidence of disease had been removed high-dose methotrexate was administered every two to three weeks as maintenance treatment. To assess the efficacy of treatment the results were compared with those in a historical control group of 82 consecutive patients who developed pulmonary or other metastases. The results in the study group were significantly better. This experience may be similar to that in Wilms's tumour, where actinomycin D has increased the cure rate when administered as adjuvant therapy after treatment of localised or overt metastatic disease.

Adolescent↗