Effective dose of L-asparaginase for induction of remission in previously treated children with acute lymphocytic leukemia: a report from Childrens Cancer Study Group.

L-Asparaginase, in the dose of greater than or equal to 6000 IU/sq m three times weekly, was demonstrated to be an effective agent in reinduction of remissions in childhood leukemia. Four hundred thirteen children with acute lymphocytic leukemia were treated with L-asparaginase. Doses i.m. ranged from 300 to 12,000 IU/sq m. None of the patients had received prior asparaginase therapy. 6-Mercaptopurine was given p.o. concurrently. All of the patients had experienced several previous relapses, and their disease was not responsive to 6-mercaptopurine. L-Asparaginase was found to be effective in reinducing remissions at the following rates: 9.5% for 300 IU/sq m; 35.1% for 3,000 IU/sq m; 53.5% for 6,000 IU/sq m; and 62.5% for 12,000 IU/sq m. The drug was given three times weekly for four weeks. Hypersensitivity reactions occurred in 6.5% of patients.

Detection of two anaerobic periodontopathogens in children by means of the BANA and ELISA assays.

The mouths of young children become colonized by a variety of bacteria, but there have been only a few studies that have sought the presence of periodontopathic species in this population. Almost all of these studies used culturing techniques rather than the newer detection methodologies for various periodontopathogens. Studies in adults have shown that Treponema denticola and Porphyromonas (Bacteroides) gingivalis can be detected in dental plaque by use of the BANA and ELISA diagnostic tests. In the present study, plaque samples from four subgingival sites in each of 157 children (aged from two to 18 years) were tested for BANA hydrolysis with a BANA reagent card, and for T. denticola and P. gingivalis with an ELISA assay. Anaerobic periodontopathogens hydrolyzing the BANA substrate were found to be present in at least one of four plaque samples in 88 children (56%). T. denticola and/or P. gingivalis were detected by ELISA in at least one plaque sample in each of 135 children (86%). This study shows that children are widely colonized by these micro-organisms. A higher proportion of Black children than Caucasian children was colonized by these BANA-positive organisms. Also, children having a parent with a documented history of periodontal disease were more likely to be BANA-positive than were children of parents with unknown periodontal status.

Brain-stem tumors in childhood: a prospective randomized trial of irradiation with and without adjuvant CCNU, VCR, and prednisone. A report of the Childrens Cancer Study Group.

Seventy-four children with a brain-stem tumor diagnosed between 1977 and 1980 were entered into a prospective study in which exploration and assessment for resection were optional, radiation treatment using standard methods was required, and randomization occurred with regard to the use of adjuvant chemotherapy (1-(2-chloroethyl)-1-nitrosourea, vincristine, and prednisone) or no further treatment. The overall 5-year survival rate was 20% and was not improved by the adjuvant chemotherapy program. An increased risk of infection was associated with the adjuvant therapy.

The treatment of medulloblastoma. Results of a prospective randomized trial of radiation therapy with and without CCNU, vincristine, and prednisone.

In a prospective randomized trial designed to study the effectiveness of adjuvant chemotherapy following standard surgical treatment and radiation therapy, 233 eligible patients with medulloblastoma were treated by members of the Children's Cancer Study Group and the Radiation Therapy Oncology Group. Eligible patients were randomly assigned to receive radiation therapy with or without adjuvant chemotherapy consisting of 1-(2-chloroethyl)-3-cyclohexyl-nitrosourea (CCNU), vincristine, and prednisone. The estimated 5-year event-free survival probability was 59% for patients treated with radiation therapy and chemotherapy and 50% for patients treated with radiation therapy alone, a difference which is not statistically significant. The 5-year survival probability was 65% for both groups. Although the treatment difference was not statistically significant when all patients were combined, in the small number of patients with more extensive tumors, event-free survival was better in the group receiving chemotherapy (48% vs. 0%, p = 0.006). In these latter patients the survival time is also significantly prolonged. Extent of disease (as measured by the M staging criteria described by Chang) and age at diagnosis were significantly associated with outcome; advanced disease and young age had a worse prognosis. The extent of tumor resection was not an independent prognostic factor. It is concluded that chemotherapy does not benefit patients with low-stage medulloblastoma, but may benefit those with more advanced stages of disease.

The relationship of various aspects of surgical management to outcome in childhood nonmetastatic osteosarcoma: a report from the Childrens Cancer Study Group.

Recently, much attention has been focused on the role of adjuvant chemotherapy in the treatment of osteosarcoma. Surgery, however, remains the primary modality for the ablation of this disease. In this report, we examine the relationship of various aspects of surgical management of osteosarcoma to prognosis for disease-free survival (DFS) in a randomized study of 234 pediatric patients. Attention is restricted to 166 patients with nonmetastatic disease confined to an extremity and who were randomized to receive one of two chemotherapeutic regimens. No advantage with respect to DFS was attributable to the various aspects of surgical management considered: interval from first symptoms to definitive surgery, surgical sequence, and type of surgery. Only two local recurrences were seen. One occurred in an above knee amputation stump and the other occurred in a patient receiving a tibial allograft. One of these patients died of pulmonary metastases within 6 months of recurrence; the other patient is alive without evidence of disease at last contact after resection of the recurrence followed by chemotherapy.

Brain tumors in children.

Brain tumors are relatively common cancers among children, just as they are among adults. Unlike the tumors of adults, however, they have a predilection for the posterior fossa. The most common types of tumors among children are astrocytomas, ependymomas, and medulloblastomas. The definitive diagnosis of these lesions can usually be made with relative ease by CT scans of the brain. Treatment typically consists of the surgical removal of all or as much tumor as possible, followed by radiation therapy, and occasionally also by chemotherapy with one of the nitrosoureas combined with vincristine and/or other antitumor drugs. Recurrence-free survival may be expected for about half of the children past infancy who develop brain tumors. The substantial progress recently made in both the diagnosis and treatment of brain tumors in childhood has heightened, not diminished, the clinical responsibilities of primary care clinicians throughout the management of this disease. Since tumor-free survival so heavily depends upon an early diagnosis, a high index of suspicion must be maintained for commonplace non-specific symptomatology. The primary physician must pursue critical aspects of the medical history at the first suggestion of an atypical course. A skillful physical examination is then needed to detect subtle clinical signs that are indicators for the prompt performance of definitive diagnostic tests. Further, since there are now so many therapeutic modalities that can be brought into the comprehensive management of children with brain tumors, the primary clinician should maintain close contact with the patient not only to provide medical and psychological support, but also to monitor the clinical response or side effects of therapeutic agents and to serve as the patient advocate at times of great personal and family need.

Residents' evaluation of behavioural paediatrics instruction.

This study sought to explore the following questions: (1) Do residents perceive training focused on infancy and early childhood care issues as more clinically applicable than training focused on care of older children and adolescents? (2) Do residents at different training levels differ in their evaluation of behavioural paediatrics instruction? (3) What is the strength of the association between instructional style and clinical impact dimensions? and (4) Compared to the instruction provided by instructors from other medical and academic disciplines, do paediatric residents perceive differences in the teaching efficacy and clinical relevance of instruction provided by paediatricians? Data were drawn from 1341 residents' evaluations of 116 required behavioural paediatrics sessions over 3 years. The data demonstrated that house officers recognize the value of acquiring knowledge in behavioural paediatrics, regardless of the level of the house officers' training, or whether the focus concerned infants or older children. However, residents were more likely to perceive the presentations provided by paediatricians as providing instruction that was slightly more applicable to their practice needs than instruction that other faculty presented. The study results further demonstrated that the clarity and organization of instruction influences, but does not supercede, the residents' perception of the merit of instruction. The findings suggest that international recommendations for greater inclusion and acceptance of behavioural paediatric instruction can be achieved in programmes that, by requiring participation, confer equal status to behavioural paediatrics and traditional residency training. The results support residents' acceptance of a health team approach to behavioural paediatric instruction.(ABSTRACT TRUNCATED AT 250 WORDS)

5-(3,3-Dimethyl-1-triazeno)imidazole-4-carboxamide (NSC-45388) in the treatment of solid tumors in children.

5-(3,3-Dimethyl-1-triazeno)imidazole-4-carboxamide (NSC-45388) was administered to 46 children with various solid tumors which were resistant to conventional therapy. Two or more courses of NSC-45388 were administered to 13 of 18 children with neuroblastoma, seven of 11 children with rhabdomyosarcoma, three of four children with Wilms' tumor, one of three children with Ewing's tumor, and six of ten children with miscellaneous neoplastic disorders. Major toxic effects included nausea, vomiting, decreased hemoglobin level, thrombocytopenia, and leukopenia. A therapeutic regimen of 200-450 mg/m2/day for 5 consecutive days can be administered safely every 22 days. Objective responses were observed in three children with neuroblastoma and in one child with rhabdomyosarcoma. This drug has minimal but definite activity as a single agent in children with advanced neuroblastoma and rhabdomyosarcoma and should be evaluated further in combination therapy.

L-Asparaginase as a single agent in acute lymphocytic leukemia: survey of studies form Childrens Cancer Study Group.

A series of studies were undertaken by the Childrens Cancer Study Group between 1968 and 1972 to evaluate the optimum schedule and dosage of L-asparaginase as a single agent in induction and maintenance of children with previously treated acute lymphocytic leukemia. Six different dosages of enzyme were administered (3600-840,000 IU/4 wk/m2). The optimal dose of L-asparaginase was found to be 12,000 IU/m2 given three times per week for a total dose of 144,000 IU/m2. Sixty-three percent of children treated with this dosage achieved a bone marrow remission. The intramuscular method of administration is as effective and produced less significant sensitivity reactions than the intravenous method. Reinduction, after an unmaintained remission, with L-asparaginase was possible in 32% of the cases. L-Asparaginase used as a maintenance agent did not result in a significant increase in remission duration when compared to no maintenance therapy. However, patients who received L-asparaginase maintenance had a median remission duration of 66 days as compared to 41 days for the no-maintenance group.

Effective combination treatment of advanced acute lymphocytic leukemia with cytosine arabinoside (NSC-63878) and L-asparaginase (NSC-109229).

The combination of cytosine arabinoside and L-asparaginase induced remission in 15 of 22 children (68%) with previously treated acute lymphocytic leukemia (ALL). Eight of these patients were in remission after the second week of treatment and seven were in remission after the fourth week. The combination was well tolerated. These preliminary results suggest that these two agents have an additive therapeutic effect in inducing remissions in children with advanced ALL.

A double-blind, placebo-controlled study of the efficacy of Lactinex in the prophylaxis of amoxicillin-induced diarrhea.

The disruption of the natural flora of the gastrointestinal tract (especially Lactobacillus acidophilus) may occur during antibiotic therapy. This may lead to diarrhea, dehydration, and electrolyte imbalances. It has been suggested that replacement of the lactobacilli with a commercially available product may prevent the diarrhea. The efficacy and safety of prophylactically administered Lactinex (culture of L. acidophilus and L. bulgaricus) was compared with placebo for the prevention of amoxicillin-induced diarrhea in pediatric patients. Lactinex or placebo was administered four times a day for ten days to coincide with the antibiotic therapy. The Lactobacillus preparation did not appear to consistently prevent diarrhea in this patient population. Patients' age, diet, and parental definition of diarrhea were factors that may have influenced the results.

Tumors of the pineal and suprasellar region: Childrens Cancer Study Group treatment results 1960--1975: a report from Childrens Cancer Study Group.

Tumors of the pineal and suprasellar region form a rare and interesting group of lesions with germinomas accounting for over 50% of all lesions in this anatomic region. The Brain Tumor Committee of Childrens Cancer Study Group (CCSG) recently surveyed all CCSG member institutions to determine treatment parameters and assess the techniques. A total of 140 patients were seen during the period from 1960 to 1975; 118 patients were evaluable, having adequate treatment records. One hundred and one patients were less than 30 years of age with a 2:1 male predominance. Thirty-six of the 57 biopsied patients (63%) were found to have germinomas. The survival of patients in the germinoma group (72%) was comparable to that of the patients without biopsy (71%). The overall survival rate for all patients (biopsied and unbiopsied) was 65% with follow-up times ranging from 2 to 15 years. Nine patients developed spinal cord metastases (8%), two of whom also had simultaneous primary recurrence; none of these patients had received adjunctive spinal irradiation.

A randomized study comparing high-dose methotrexate with moderate-dose methotrexate as components of adjuvant chemotherapy in childhood nonmetastatic osteosarcoma: a report from the Childrens Cancer Study Group.

Methotrexate (MTX) has demonstrated significant activity against relapsed and metastatic osteosarcoma. However, there is little published data to indicate the appropriate dose for MTX when given as a component of a multidrug regimen for the treatment of osteosarcoma. Therefore, the investigators at the Childrens Cancer Study Group undertook a randomized clinical trial that compared Adriamycin and vincristine given with either high-dose methotrexate or moderate-dose methotrexate as postoperation chemotherapy in the treatment of childhood osteosarcoma. We report here the results for 166 patients with completely resected nonmetastatic disease of an extremity. The two therapies demonstrated equivalent disease-free survival (DFS). Further, no therapy prejudices survival after relapse. Approximately 38% of patients remain disease free 4 years after diagnosis. Two relapses occurred in patients free of disease at least 36 months after initiation of treatment. Some factors found by other investigators to be prognostic of poorer DFS, namely, male sex, primary tumor in the humerus or femur, and larger primary tumors, demonstrated similar though not statistically significant trends. The presence of spontaneous necrosis in the tumor sample from the definitive surgery was associated with poor prognosis for DFS. We postulate that this feature represents rapidly growing tumors with increased potential for metastases.