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Biomedical subjects

S A Feig

Publications and source records attributed to S A Feig.

At least 91 records · Page 5Linked to original sources

The role of timing of high-dose cytosine arabinoside intensification and of maintenance therapy in the treatment of children with acute nonlymphocytic leukemia.

The Children's Cancer Study Group instituted a pilot study to investigate the use of high doses of cytosine arabinoside (AraC) in the intensification phase of treatment for acute nonlymphocytic leukemia (ANLL). Patients achieving remission and not eligible for allogeneic bone marrow transplantation were treated with four doses of high-dose AraC and L-asparaginase. These drugs were repeated either on or after 28 days (q28 days), after recovery of hematologic parameters (for the first 49 patients entered onto this trial); or after 7 days (q7 days), despite dropping blood counts (for the last 53 patients enrolled). After completing an additional 3 months of intensification therapy, patients were then allocated by physician choice to either discontinue therapy or receive 18 28-day cycles of maintenance therapy, including the daily administration of 6-thioguanine. Despite three deaths associated with the toxicity of the aggressive (q7 days) AraC timing, patients receiving this approach demonstrated equal or better disease-free survival from the end of induction (55% versus 42% actuarially at 3 years [P = 0.52]). Maintenance therapy appeared to play no role in improving outcome for people who received the aggressive timing of AraC cycles. Fifty-nine percent were alive disease free actuarially at 3 years from the decision to not give maintenance therapy (n = 27) compared with 62% for those receiving maintenance therapy (n = 16; P = 0.49). On the other hand, patients who received the less aggressive AraC intensification timing (q28 days) had an improved survival rate if maintenance therapy was administered (n = 17) (65% versus 39% for patients not receiving maintenance therapy [n = 24] at 3 years [P = 0.07]). Maintenance therapy therefore may not improve outcome in patients receiving aggressive timing of high-dose AraC but may be important in less intensive postremission regimens in childhood ANLL.

Antineoplastic Combined Chemotherapy Protocols↗

Bone marrow transplantation using unrelated donors for patients with advanced leukemia or bone marrow failure.

Thirty-four patients received bone marrow transplants from unrelated donors. Donors and recipients were phenotypically matched for 6 of 6 HLA-A, B, and DR antigens in 27 cases and at 5 of 6 antigens in 7 cases. Twenty-three patients had leukemia, six had myelodysplasia, and five had aplastic anemia. Twenty-four patients had durable engraftment. Five died of sepsis prior to engraftment. Five patients failed to engraft; 2 of these patients had autologous bone marrow recovery. Seventeen patients developed grade greater than or equal to II acute graft-versus-host disease for an actuarial probability of 67 +/- 20%. The severity of acute graft-versus-host disease and its mortality appeared increased for recipients matched for 5 of 6 HLA-A, B, and DR antigens. Of the 34 patients, 13 (38%) are alive; actuarial survival beyond 6 months is 44 +/- 17%. None of the 25 leukemia and myelodysplasia patients achieving engraftment have relapsed. For leukemia and myelodysplasia recipients of 6 of 6 HLA-matched grafts, actuarial survival at 6 months was 55 +/- 21% compared with 14 +/- 26% for recipients matched for 5 of 6 HLA loci (P = 0.19). Infection and acute graft-versus-host disease were the primary causes of death in the engrafted patients. Survival for aplastic anemia patients was 20%. Late deaths due to pneumonia and bronchiolitis obliterans occurred after one year in 2 patients. Closely matched unrelated donor bone marrow transplants are associated with a higher incidence of graft failure and graft-versus-host disease than typically reported for transplants from HLA-identical siblings, but these preliminary data suggest a lower rate of relapse.

Acute Disease↗

Transtentorial herniation caused by an intracranial mass lesion following high-dose methotrexate.

A patient with intracranial osteosarcoma that arose 16 years after radiation therapy for hereditary retinoblastoma developed fatal cerebral edema and brainstem herniation after she received a single dose of intravenous methotrexate. Autopsy demonstrated extensive necrosis of the tumor mass, as well as necrotizing vascular damage within the neoplasm. Although high-dose methotrexate has been shown to be useful in the treatment of primary osteogenic sarcoma, the tumoricidal effects of therapy appear to have caused a fatal rise in intracranial pressure.

Adolescent↗

Estimation of radiation risk from screening mammography: recent trends and comparison with expected benefits.

On the basis of recent epidemiologic studies, the National Institutes of Health in 1985 provided a new estimate for radiation risk to the breast that employed a relative risk model and acknowledged greater dependence on age at exposure. Lifetime risks from a single mammogram may be calculated from this estimate and are lower than those based on the previous 1977 National Cancer Institute estimate. Possible years of life expectancy lost from annual mammography beginning at age 40 years may also be calculated and are negligible compared with estimates for years of life expectancy gained from such screening.

Age Factors↗

Heterogeneity of intraductal carcinoma of the breast.

Fifty-one women (29 to 75 years of age) with 55 cancers (ductal carcinoma in situ [DCIS] or ductal carcinoma in situ with microinvasion [DCISM] were studied by comparing biopsy specimens with mastectomy specimens. Presentation, histologic type, nuclear grade, microscopic duct counts, multicentricity, and microinvasion were correlated. Forty-seven percent of the cancers (26 of 55) were detected by mammography, 18% (ten of 55) were incidental to benign disease, and 35% (19 of 55) were palpable or exhibited nipple abnormality. Incidental tumors were all DCIS, averaged seven ducts, and showed no residual tumor during mastectomy. Mammographic lesions averaged 117 ducts (31% [eight of 26] were DCISM and 42% [11 of 26] were multicentric). Most comedocarcinomas that showed a high incidence of microinvasion were in this group. Clinical lesions averaged 110 ducts (42% [eight of 19] were DCISM and 68% [13 of 19] were multicentric). Three had nodal metastases. Mammographic and clinical tumors in the quantitative range of the incidental group (50 ducts) showed significant differences from it for all variables studied. Histologic and quantitative study of these tumors is necessary to best guide treatment. Incidental tumors, however, may only need observation.

Adult↗

Nonpalpable in situ ductal carcinoma of the breast. Predictors of multicentricity and microinvasion and implications for treatment.

Fifty breasts with nonpalpable ductal carcinoma in situ (DCIS) were examined for the presence of microinvasion, multicentricity, and number of involved ducts to see if the biopsy specimen could have predicted the findings in the remainder of the breast. When DCIS was an incidental finding, fewer ducts were involved and no evidence of either microinvasion or multicentricity was found. Solid and cribriform DCIS were rarely multicentric or microinvasive; micropapillary DCIS was often multicentric, rarely microinvasive; comedocarcinoma was more likely to be both microinvasive and multicentric. Ductal carcinoma in situ as an incidental finding may be treated by excision alone; papillary and micropapillary DCIS are best treated by therapy aimed at the entire breast, although axillary dissection may not be required. Therapy for comedocarcinomas should include the entire breast and the axillary nodes.

Adult↗

Remission induction in children with acute non-lymphocytic leukemia using cytosine arabinoside and doxorubicin or daunorubicin: a report from the Childrens Cancer Study Group.

Four hundred ninety evaluable patients were treated on an induction regimen consisting of two to four courses of cytosine arabinoside plus an anthracycline. Overall, 78% of patients went into remission, 10% died during induction, and 12% were induction failures. For the first 152 patients, courses consisted of 7 days continuous infusion with cytosine arabinoside (Ara-C, 100 mg/m2) and 3 days of doxorubicin (30 mg/m2). Because of unacceptable toxicity, particularly for children less than 3 years of age, the anthracycline was changed to daunorubicin, and the doses of both induction drugs for children under 3 was reduced. For children aged 3 years and older the change in anthracycline was associated with a significant increase in induction failures (7% to 16%, P = .04) and a decrease in deaths (15% to 8%, P = .09). For younger children, for whom doses were also changed, the effect was greater; Mortality decreased from 29% to 1% (P less than .0001), and the remission induction rate increased from 66% to 88% (P = .005). The therapy modifications also influenced survival following remission induction: Daunorubicin-treated patients, aged 3 years and over, did significantly better than those given doxorubicin (P = .03), but the opposite was seen in younger children (P = .06). Gastrointestinal and skin toxicities and septicemia were significantly more common when doxorubicin was being used, but the extent of myelosuppression was similar for the two anthracyclines.

Age Factors↗

Accuracy of diagnostic imaging as determined by delayed operative intervention for advanced neuroblastoma.

Current treatment of newly diagnosed widespread neuroblastoma may include chemotherapy, delayed surgical resection, marrow ablative chemoradiotherapy, and bone marrow transplantation. Diagnostic imaging (DI) with computerized tomography (CT) or magnetic resonance imaging (MRI) has been used to determine response to therapy and timing of delayed resection. We assessed the accuracy of DI in 25 patients (26 total cases) treated over 21 months. Tumor size and location were estimated prior to surgical resection by DI, and the sensitivity and specificity of these studies were determined from operative findings. DI consisted of CT (15), MRI (8), and MRI and CT (3). Discordance between DI and operative findings was found in ten patients (38%). This included three errors of sensitivity (12%), including two false-positives and one false-negative. Seven errors of specificity were noted; they included a positive scan with no viable tumor identified (3), much more extensive disease (3), or less extensive disease (1). Viable tumor was identified in 18 cases, and in 11 patients, complete resection of macroscopic tumor at the primary site was carried out. Ten of 13 patients operated on within 5 months of beginning chemotherapy were rendered grossly free of neuroblastoma at the primary site after surgery. Eight of 12 patients operated on 6 months or longer after starting chemotherapy were rendered grossly free of tumor at the primary site. Bone marrow transplantation was performed in 21 patients, ten of whom are alive with a median follow up of 20 months. Survival was similar for patients who underwent surgical resection at less than or equal to 5 v greater than 6 months after starting chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Neoplasms↗

Secondary leukemia following successful treatment of Wilms' tumor.

Leukemia accounts for 15-20% of the secondary malignancies among survivors of Wilms' tumor. We report three patients who developed leukemia after the successful treatment of Wilms' tumor, each of whom demonstrates the importance of close long-term medical surveillance. The first patient developed Philadelphia chromosome positive chronic myelogenous leukemia (CML) 6 years after the diagnosis of Wilms' tumor. This is the second report of CML occurring after Wilms' tumor. The other two patients developed acute nonlymphocytic leukemia (ANLL) 3 and 18 years after successful treatment of Wilms' tumor. In one patient, the clinical manifestations were subtle, and in the other the latency period was the longest reported for secondary leukemia following Wilms' tumor. We conclude that survivors of childhood cancer require frequent medical surveillance even in their adult years.

Alkylating Agents↗

Normal neurodevelopment in four young children treated with bone marrow transplantation for acute leukemia or aplastic anemia.

Longitudinal neurodevelopmental studies of four consecutive young children treated by bone marrow transplantation for acute leukemia or aplastic anemia are presented. The children, the only four children less than 2 years of age who have received bone marrow transplants for these diseases at UCLA Medical Center, ranged in age from 36 weeks to 24 months at the time of transplantation. Conditioning involved high-dose cyclophosphamide treatment; three also had total body irradiation prior to bone marrow transplantation. Their respective outcomes after follow-up times of 28 months to 71 months posttransplantation are remarkable for normal somatic growth and normal development of intelligence, language, perception, and motor coordination. These findings indicate that future therapeutic studies of infants and young children with acute leukemia or aplastic anemia using total body irradiation, cyclophosphamide, and bone marrow transplantation are not contraindicated by risks of debilitating neurodevelopmental sequelae.

Anemia, Aplastic↗