Norma Wollner

Desmoplastic small round-cell tumor: prolonged progression-free survival with aggressive multimodality therapy.

PURPOSE To test intensive alkylator-based therapy in desmoplastic small round-cell tumor (DSRCT). PATIENTS AND METHODS Patients received the P6 protocol, which has seven courses of chemotherapy. Courses 1, 2, 3, and 6 included cyclophosphamide 4,200 mg/m2, doxorubicin 75 mg/m2, and vincristine (HD-CAV). Courses 4, 5, and 7 consisted of ifosfamide 9 g/m2 and etoposide 500 mg/m2 for previously untreated patients, or ifosfamide 12 g/m2 and etoposide 1,000 mg/m2 for previously treated patients. Courses started after neutrophil counts reached 500/microL and platelet counts reached 100,000/microL. Tumor resection was attempted. Post-P6 treatment options included radiotherapy and a myeloablative regimen of thiotepa (900 mg/m2) plus carboplatin (1,500 mg/m2), with stem-cell rescue. RESULTS Ten previously untreated and two previously treated patients have completed therapy. The male-to-female ratio was 11:1. Ages were 7 to 22 years (median, 14). The largest masses were infradiaphragmatic (n = 11) or intrathoracic (n = 1). Other findings included serosal implants (n = 11), regional lymph node invasion (n = 8), ascites or pleural effusion (n = 7), and metastases to liver (n = 5), lungs (n = 4), distant lymph nodes (n = 3), spleen (n = 2), and skeleton (n = 2). Tumors uniformly responded to HD-CAV, but there were no complete pathologic responses. One patient died at 1 month from tumor-related Budd-Chiari syndrome. Of seven patients who achieved a complete remission (CR), five remain in CR 9, 12, 13, 33, and 38 months from the start of P6, one patient died of infection at 12 months (autopsy-confirmed CR), and one patient relapsed 4 months off therapy. Of four patients who achieved a partial remission (PR), one remains progression-free at 34 months and three developed progressive disease. Five patients received local radiotherapy: three were not assessable for response, but in two patients, antitumor effect was evident. Four patients received thiotepa/carboplatin: two were in CR and remain so, and two patients had measurable disease that did not respond. CONCLUSION For control of DSRCT, our experience supports intensive use of HD-CAV, aggressive surgery to resect visible disease, radiotherapy to high-risk sites, and myeloablative chemotherapy with stem-cell rescue in selected cases.

Non‐Hodgkin's lymphoma in children. A comparative study of two modalities of therapy

Eighty‐six children with non‐Hodgkins lymphoma were studied from 1964 to January 31, 1975. Seventy‐six percent of the 43 patients in the nonprotocol group had far advanced disease, and 76% had Rappaports diffuse histology. Only 11% of these patients survived free of disease. The second group of 43 patients received the LSA2L2 protocol. Seventy‐six percent had advanced disease and 86% diffuse histology. Of these patients 76% are surviving free of disease with a median observation time of 25+ months. Fifty‐one percent of the survivors are off therapy and without evidence of disease. Prognostic factors such as primary sites, stages, histology, and others are discussed. The most important prognostic factor is early and aggressive therapy, and the achievement of a complete response status within 1–2 months from onset of therapy.

Transfusion-Associated Acute Chagas Disease Acquired in the United States

Excerpt Although a significant problem in Latin America (1), the transmission ofTrypanosoma cruziinfection by transfusion has not been unequivocally documented in the United States. We report a cas...

Disease‐free survival in children with Ewing's sarcoma treated with radiation therapy and adjuvant four‐drug sequential chemotherapy

Adjuvant chemotherapy was added to local radiation therapy for patients with Ewings sarcoma to treat widespread microfoci of disease presumed to be present at the time of diagnosis. Since June 1970, 12 children have been treated with radiation therapy and sequential adjuvant chemotherapy: dactinomycin, adriamycin, vincristine, and cyclophosphamide, continued for 2 years. Two children developed reversible congestive heart failure after cumulative adriamycin doses of 905 mg/m2 in one patient and 720 mg/m2 in another patient who had mediastinal irradiation. Adriamycin is now generally limited to cumulative doses of 720 mg/m2 but is further limited to 500 mg/m2 in children who receive mediastinal or pulmonary irradiation. Of 12 children entered into this study and followed for from 10 to 37 months, all continue in disease‐free remission without evidence of recurrent tumor, metastatic tumor, or central nervous system disease.

Very-high-dose short-term chemotherapy for poor-risk peripheral primitive neuroectodermal tumors, including Ewing's sarcoma, in children and young adults.

PURPOSE To improve the prognosis of patients with poor-risk peripheral primitive neuroectodermal tumors (pPNETs; including peripheral neuroepithelioma and Ewings sarcoma), while testing the feasibility of intensive use in adolescents and young adults of high-dose cyclophosphamide, doxorubicin, and vincristine (HD-CAV). PATIENTS AND METHODS This report concerns previously untreated patients with newly diagnosed pPNET deemed poor-risk because of a tumor volume more than 100 cm3 or metastases to bone or bone marrow. The P6 protocol consists of seven courses of chemotherapy. Courses 1, 2, 3, and 6 include 6-hour infusions of cyclophosphamide on days 1 and 2 for a total of 4,200 mg/m2 per course (140 mg/kg per course for patients < 10 years old), plus 72-hour infusions of doxorubicin 75 mg/m2 and vincristine 2.0 mg/m2 beginning on day 1 (HD-CAV). Courses 4, 5, and 7 consist of 1-hour infusions of ifosfamide 1.8 g/m2/d and etoposide (VP-16) 100 mg/m2/d, for 5 days. Granulocyte colony-stimulating factor (G-CSF) and mesna are used. Courses start after neutrophil counts reach 500/microL and platelet counts reach 100,000/uL. Surgical resection follows course 3 and radiotherapy follows completion of all chemotherapy. RESULTS Among the first 36 consecutive assessable patients (median age, 17 years), HD-CAV achieved excellent histopathologic or clinical responses in 34 patients and partial responses (PRs) in two patients. For 24 patients with locoregional disease, the 2-year event-free survival rate was 77%; adverse events were two locoregional relapses, one distant relapse, and one secondary leukemia. All six patients with metastatic disease limited to lungs achieved a complete response (CR) and did not relapse; one is in remission 36+ months from diagnosis, but the other patients are not assessable in terms of long-term efficacy of the P6 protocol because of short follow-up time (n = 3), additional systemic therapy (bone marrow transplantation), or septic death (autopsy showed no residual pPNET). All six patients with widespread metastases had major responses, including eradication of extensive bone marrow involvement, but distant relapses ensued. Myelosuppression was severe, but most patients received the first three courses of HD-CAV within 6 to 7 weeks. Major nonhematologic toxicities were mucositis and peripheral neuropathy. CONCLUSION Excellent antitumor efficacy and manageable toxicity support the dose-intensive use of HD-CAV for pPNET in children, as well as in young adults. Consolidation of remissions of pPNET metastatic to bone and bone marrow remains a therapeutic challenge.

Pediatric desmoid tumor : retrospective analysis of 63 cases

PURPOSE This study was conducted to evaluate clinical prognostic factors predictive of the probability of recurrence of desmoid tumor (DT). PATIENTS AND METHODS Sixty-three patients with histologically confirmed diagnosis of DT were retrospectively studied. Median age at diagnosis was 13 years. Patient distribution by site was as follows: 61% extremities, 18% head and neck, 13% trunk (including 5% intraabdominal), and 8% multicentric lesions. All patients had partial or complete resections; 20 patients also received radiotherapy and/or chemotherapy. RESULTS At a median follow-up time of 6 years since first treatment, the overall actuarial probability of having one or more recurrences was 75%. Age, sex, site, size, or number of previous recurrences had no significant impact on the likelihood of recurrence. The only factor associated with an increased proportion of recurrence-free patients was a negative margin of resection (70% v 15% with positive margins; P = .006). Of the four patients with more than 3 years follow-up since chemotherapy, two recurred, and of the 11 patients with the same follow-up after radiotherapy, four recurred, including two of five patients who received a dose of 50 Gy or more. No deaths directly related to tumor invasion were observed. CONCLUSION A surgical approach aiming at clear margins is presently the best treatment option. When this cannot be accomplished without severe disfigurement or function impairment, partial resection is an acceptable alternative, but one associated with a high risk of regrowth. Whether adjuvant strategies should be used in this situation remains to be addressed.

The cardiotoxicity of adriamycin and daunomycin in children.

Eight (16%) of 50 children receiving adriamycin and 2 (3%) of 60 receiving daunomycin had severe cardiomyopathy with congestive heart failure. All 110 patients received cumulative doses of over 500 mg/m2. The incidence was significantly higher in those who also had incidental cardiac radiation. The electrocardiogram, with few exceptions, provided the first indication of cardiac abnormality. There were no deaths from heart failure. Two had thromboembolic episodes. Recommendations are discussed.

Vancomycin-resistant Enterococcus faecium on a pediatric oncology ward : duration of stool shedding and incidence of clinical infection

OBJECTIVE To determine the duration of stool shedding and incidence of clinical infection among pediatric oncology patients colonized with vancomycin-resistant Enterococcus faecium (VRE) in our institution. METHODS Stool cultures were obtained from all patients admitted from May 15 to August 2, 1994. Patients were followed for evidence of clinical VRE infection and surveillance stool results through August 15, 1995. Genetic relatedness of stool-clinical isolate pairs and serial stool samples was evaluated using pulsed field gel electrophoresis. RESULTS Twenty-three (32%) of 73 screened patients were colonized with VRE. Eight (35%) of the colonized patients cleared VRE from stool; 10 (43%) were persistent carriers, excreting organisms for 19 to 331 days (median, 112 days); and 5 patients had an insufficient number of stools to determine length of carriage. Persistent carriers had a median of 6 hospital readmissions; 8 of 10 were positive at first or second readmission Clinical VRE infection developed in 6 of 73 patients (annual incidence, 8.2%). Clinical cases had more days of neutropenia between colonization and infection than colonized patients during a comparable follow-up (49 vs. 16 days, P = 0.04). Five of 6 stool-clinical isolate pairs were identical by pulsed field gel electrophoresis. Serial stools from 6 of 7 patients (collected 20 to 343 days apart) were identical by pulsed field gel electrophoresis. CONCLUSION Persistent gastrointestinal colonization with VRE is common among pediatric oncology patients. Carriage of the same VRE clone for up to 1 year was demonstrated. In the majority of cases invasive and colonizing isolates were identical by DNA fingerprinting techniques, suggesting that the colonizing VRE was the source of infection. Intermittent excretion of organisms in stool makes vigilant tracking and immediate isolation of such patients crucial to control efforts. Prolonged neutropenia may increase the risk of developing clinical infection among VRE-colonized patients.

Non‐Hodgkin's lymphoma in children. A progress report on the original patients treated with the LSA2‐L2 protocol

This report is a follow‐up of the initial group of 39 children with non‐Hodgkins lymphoma treated with the LSA2‐L2 protocol as previously reported in Cancer (37:123–134, 1976). The disease‐free actuarial survival is 73%. All surviving patients are off therapy and have shown no evidence of recurrence with a median observation time of 70+ months. Their survival times range from 56+ to 88+ months from diagnosis. An analysis of successes and failures is discussed and modifications in the role of radiation therapy and surgery in the multidisciplinary management of children with non‐Hodgkins lymphoma are advocated. The results in the present series indicate that the LSA2‐L2 protocol has substantially improved the prognosis for children with non‐Hodgkins lymphoma. We have concluded that age, sex, primary site (perhaps with the exception of primary skeletal), and histology are not of prognostic significance. The amount of bulky widespread disease at initial presentation, early and aggressive therapy, and the achievement of a complete remission status within 1–2 months from onset of therapy are the most important prognostic factors.

High risk of leukemia after short-term dose-intensive chemotherapy in young patients with solid tumors.

PURPOSE To help fill the gap in knowledge about the risk of leukemia from repetitive high-dose use of alkylating agents and topoisomerase-II inhibitors in young patients with solid tumors. METHODS Poor-risk solid tumors were treated with four courses of cyclophosphamide (4,200 mg/m2)/ doxorubicin (75 mg/m2), and three courses of ifosfamide (9,000 mg/m2)/etoposide (500 mg/m2). The cumulative incidence of treatment-related myelodysplasia/ leukemia (t-AML) was calculated using the method of competing risks. The expected number of leukemic events was calculated by applying national incidence rates to person-years classified by age and sex. RESULTS Among 86 patients (median age, 17 years) monitored for 6 to 88 months (median, 24), five cases of t-AML were detected at 10 to 37 months (median, 17). The expected number of leukemic events in this cohort was .001. Clinical and cytogenetic findings implicated prior alkylator therapy in three cases and prior treatment with topoisomerase-II inhibitors in two. At 40 months, the cumulative incidence of t-AML was 8% (SE 7%). CONCLUSION Repetitive high-dose use of alkylating agents given with topoisomerase-II inhibitors is strongly leukemogenic, even with modest cumulative doses of each drug. This finding is notable for the following reasons: (1) it undermines predictions that limited use of high-dose chemotherapy might be minimally leukemogenic, and (2) it contrasts strikingly with the previously reported low risk of t-AML following treatment of pediatric solid tumors with chemotherapy lacking the alkylator dose-intensity and prominence of etoposide that are hallmarks of current regimens.