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Biomedical subjects

J P Krischer

Publications and source records attributed to J P Krischer.

15 recordsLinked to original sources
PubMed1992

Acute myeloid leukemia (AML) in Down's syndrome is highly responsive to chemotherapy: experience on Pediatric Oncology Group AML Study 8498.

The treatment of acute myeloid leukemia (AML) in children with Down's syndrome (DS) has engendered considerable controversy. Because of the concerns for toxicity and increased rate of infections, treatment approaches varied considerably in the past with mixed results. However, experience on the recently completed Pediatric Oncology Group (POG) 8498 AML study suggests that DS children with AML constitute a distinct subgroup that responds well to therapy. Twelve of 285 children on POG 8498 (protocol for newly diagnosed AML) had DS. Children with DS and AML were predominantly male (9 of 12) and were quite younger at diagnosis (< 24 months in 10). The white blood cell count was less than 50 x 10(3)/microL in all 12 and French-American-British types M6 and M7 were frequent (5 of 12). An abnormal cytogenetic marker, in addition to constitutional trisomy 21, was present in 9 of 12 and involved chromosome 8 in 4 of 9. All cases studied (n = 5) were positive for myeloid cell surface markers (CD33, CD13, or CD11b) and, interestingly, were also positive for the CD7 antigen. Chemotherapy included daunorubicin, cytarabine (Ara-C), and 6-thioguanine for remission induction and featured high-dose Ara-C (3 g/m2 per dose) with or without L-asparaginase early in remission. Compared with children without DS, children with DS had a superior event-free survival (EFS at 4 years 100% v 28% +/- 6.2%; P = .003). The EFS remained superior even when compared with non-DS children less than 2 years of age with a white blood cell count less than 10 x 100,000/microL (100% v 48% +/- 17.3%; P = .01).

Acute Disease↗
PubMed1992

The incidence of pediatric cancer in Florida, 1981 to 1986.

Incidence rates for pediatric (ages, 0 to 14 years) cancer in the state of Florida were produced for the period 1981 to 1986 and compared with national data to investigate variations in pediatric cancer incidence. Overall, Florida had an incidence rate of 12.77 per 100,000; this was not significantly higher than expected based on national rates (standardized incidence ratio, 1.0; 95% confidence interval, 0.9 to 1.0). Compared with national rates, whites residing in Florida had an increased rate of acute lymphocytic leukemia and decreased rate for soft tissue sarcomas (other than rhabdomyosarcoma), "other leukemias," and "other" cancers. Nonwhites residing in Florida had increased rates for soft tissue sarcomas (other than rhabdomyosarcoma) and decreased rates of "other" cancers. Boys in Florida had increased rates for retinoblastoma and acute lymphocytic leukemia and decreased rates for "other leukemias" and "other" cancers. Rates for girls were decreased for neuroblastoma and "other leukemias."

Adolescent↗
PubMed1992

Treatment of children with progressive or recurrent brain tumors with carboplatin or iproplatin: a Pediatric Oncology Group randomized phase II study.

PURPOSE: The Pediatric Oncology Group (POG) conducted a randomized phase II study to evaluate the activity of carboplatin and iproplatin in children with progressive or recurrent brain tumors. PATIENTS AND METHODS: The study was designed to evaluate the activity of these agents and to compare the toxicities associated with their use. Treatment consisted of carboplatin 560 mg/m2 at 4-week intervals or iproplatin 270 mg/m2 at 3-week intervals. RESULTS: The major toxicity observed was myelosuppression, particularly thrombocytopenia, for both agents. Ototoxicity (grade 1 or 2) was seen in 2.5% of patients treated with carboplatin and 1.3% of patients treated with iproplatin. The majority of patients with low-grade astrocytic neoplasms treated with carboplatin (nine of 12 patients) or iproplatin (eight of 12 patients) demonstrated tumor response or prolonged stable disease that persisted off-therapy. The duration of stable disease produced by carboplatin was particularly striking, ranging from 2 months to 68 + months (median, 40 + months). Neither drug demonstrated appreciable activity in the treatment of medulloblastoma (two of 26 responses to carboplatin, one of 14 responses to iproplatin), ependymoma (two of 17 responses to carboplatin, none of seven responses to iproplatin), high-grade glioma (two of 19 responses to carboplatin, one of 14 responses to iproplatin), or brain-stem tumors (one of 23 responses to carboplatin, none of 14 responses to iproplatin). CONCLUSION: Carboplatin is active against low-grade gliomas. Further evaluation of the role of carboplatin in the preirradiation treatment of children with low-grade gliomas of the optic pathway is currently underway in a clinical trial.

Adolescent↗
PubMed1992

Expression of myeloid-associated and lymphoid-associated cell-surface antigens in acute myeloid leukemia of childhood: a Pediatric Oncology Group study.

PURPOSE: Although the expression of both myeloid- and lymphoid-associated cell-surface antigens in acute myeloid leukemia (AML) has been described, the clinical significance of such antigen expression remains unknown in the pediatric population. We sought to define an antibody panel for optimal diagnostic antigenic analysis and to test associations among antigen expression and a number of clinical features at presentation and prognosis in pediatric AML. PATIENTS AND METHODS: We reviewed the extensive immunophenotypic analysis performed at the time of diagnosis on 132 assessable patients registered on a single Pediatric Oncology Group AML protocol between 1984 and 1988. RESULTS: Eighty-eight percent of patients were identified by testing for expression of CD33 and CD13. Overall, 61% of patients expressed at least one lymphoid-associated antigen, most commonly CD4, CD7, or CD19. Expression of CD5, CD10, CD20, or CD22, commonly detected in T- or B-lineage pediatric acute lymphoid leukemia (ALL), was uncommon; coexpression of multiple lymphoid-associated antigens was also uncommon. Expression of the monocyte-associated antigen CD14 correlated with French-American-British (FAB) M4 or M5 morphology. Otherwise, no correlation between antigen expression and FAB classification was noted. None of the myeloid, lymphoid, natural-killer (NK), or progenitor-associated antigens were associated with significant differences in the likelihood of remission induction or event-free survival when expressor versus nonexpressor groups were compared. CONCLUSIONS: The distribution of cell-surface antigen expression in pediatric acute leukemia usually permitted the discrimination of AML from ALL by using a limited panel of antibodies. Although the expression of lymphoid-associated antigens was common, such expression did not seem to be associated with an adverse prognosis in pediatric AML.

Acute Disease↗
PubMed1991

Phase II trial of ICRF-187 in children with solid tumors and acute leukemia.

ICRF-187 is the (+) enantiomer of the racemic mixture razoxane (ICRF-159). This compound is much more water soluble and thus could be formulated for parental use. The maximum tolerated dose in children after phase I trials was determined to be 3500 mg/M2/day x 3 days. A phase II trial of ICRF-187 was done in 21 children with solid tumors and 35 children with acute leukemia. All these patients were less than 21 years of age, had recovered from previous chemotherapy, had normal liver and kidney functions, and had a life expectancy of greater than 4 weeks. ICRF-187 was administered at a dose of 3 g/M2/day for 3 days as a 4 hour infusion each day. In patients with leukemia, no objective response was seen in the bone marrow although a few patients had a decrease in peripheral blast count. There were no measurable responses seen in patients with a solid tumor. ICRF-187 was well tolerated. The major toxicity was hematopoietic depression. Significant but rare toxicities included moderate to severe nausea and vomiting, and elevation of bilirubin and transaminases. Although inactive in the current study, ICRF-187 might be more active in another schedule.

Acute Disease↗
PubMed1991

An automated patient registration and treatment randomization system for multicenter clinical trials.

This article describes an automated patient registration/treatment randomization system for multicenter clinical trials. Registrations take place centrally using telephone keypads (tone-dial) for data entry and synthesized speech (at the coordinating center) for confirmation. The system permits a wide variety of protocol designs and treatment assignment schemes and presently supports more than 85 protocols of the Pediatric Oncology Group. It is developed in modules to permit easy addition/deletion of studies and treating sites. The system permits uninterrupted, unattended operation at the coordinating center 7 days a week, 24 hours a day.

Clinical Protocols↗
PubMed1991

Interval between symptom onset and diagnosis of pediatric solid tumors.

Lag time (the interval between symptom onset and diagnosis) was described for 2665 children with lymphoma or a solid tumor who participated in Pediatric Oncology Group therapeutic protocols from 1982 until 1988. Median lag time ranged from 21 days for neuroblastoma to 72 days for Ewing sarcoma. Significant differences in lag time were found among diagnostic groups (p less than 0.001), even after adjustment for age, gender, and race. Age was significantly associated with lag time for all diagnoses (p less than 0.05) except Hodgkin disease. Girls had increased lag times for non-Hodgkin lymphoma (p = 0.02) but decreased lag times for Ewing sarcoma (p = 0.02). Differences in lag time related to race were significant only for children with osteosarcoma (p = 0.02), for which white children had longer lag times. Type of tumor and age were strongly associated with lag time. Within diagnostic groups, age, gender, and race failed to explain more than 16% of the variance in lag time, suggesting that other factors may play more prominent roles. Further study is necessary to identify these factors and to assess the relationship between lag time, stage of disease at diagnosis, and prognosis, especially before designing early-detection interventions for childhood cancer.

Adolescent↗
PubMed1991

Nitrogen mustard, vincristine, procarbazine, and prednisone as adjuvant chemotherapy in the treatment of medulloblastoma. A Pediatric Oncology Group study.

In a randomized postoperative trial, adjuvant post-irradiation chemotherapy, consisting of nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP), was tested versus radiation therapy alone for newly diagnosed medulloblastoma in patients between 1 and 21 years of age. Patients treated with irradiation plus MOPP had a statistically significant increase in overall survival rate at 5 years posttreatment compared to patients treated with radiation therapy alone (74% vs. 56%; p = 0.06, adjusted for race and gender). Although the overall study failed to show a statistically significant advantage for irradiation plus MOPP in event-free survival (p = 0.18), statistical significance was attained in children 5 years of age or older (p = 0.05). More severe hematological toxicities occurred in the group with irradiation plus MOPP; however, this hematotoxicity appeared to be tolerable and acceptable. These results suggest that patients may benefit from combined irradiation and chemotherapy following surgery for medulloblastoma.

Adolescent↗
PubMed1990

Aziridinylbenzoquinone (AZQ) in the treatment of recurrent pediatric brain and other malignant solid tumors. A Pediatric Oncology Group phase II study.

To assess the response rates and toxicity of AZQ in children with recurrent brain and other malignant solid tumors, a phase II study was implemented by the Pediatric Oncology Group. Eligible patients received AZQ 18 mg/M2/week i.v. for 4 doses followed by a 2 week rest period. Each dose was given over four hours (1/3 over the initial 20 minutes). After the first year, the dosage was reduced to 13 mg/M2 due to myelotoxicity resulting in treatment delays. No objective responses were observed in 73 evaluable children with various non-central nervous system tumors. Of the 91 patients with brain tumors, there were 4 CR's and 2 PR's in patients with astrocytoma, ependymoma, glioblastoma multiforme, oligodendroglioma, brain stem glioma and intracranial yolk sac tumor (median duration, 10 months; range, 2-20+ months). Three of 4 CR's were achieved with a dosage of 18 mg/M2/week. An additional 13 children with brain tumors experienced stable or improved disease (duration, 2-36 + months; median 7.5 months). The principal toxicity was myelosuppression which was cumulative but there were also 3 allergic reactions to AZQ. We conclude that for selected brain tumors, the rates of objective response and stable disease plus the duration of responses support further assessment of AZQ in combination with other agents. Furthermore, the 18 mg/M2 dosage may provide better responses.

Adolescent↗
PubMed1990

Nasopharyngeal carcinoma in children--a retrospective review and demonstration of Epstein-Barr viral genomes in tumor cell cytoplasm: a report of the Pediatric Oncology Group.

Twenty-seven nasopharyngeal carcinomas were entered in the Pediatric Oncology Group Rare Tumor Registry from 1973 to 1988 (15 males, 12 females; 10 white, 15 black, two unknown; aged 8 to 17 years). Eight tumors were non-keratinizing carcinomas (World Health Organization 2) and 19 were undifferentiated (World Health Organization 3). The overall 3-year survival rate was 70% (SE 11%). Nine children developed distant metastases and two were salvaged. We found that localized tumor (P = .02) and black race (P = .05) were associated with a better outcome. In situ hybridization using a biotinylated probe demonstrated Epstein-Barr virus DNA in the cytoplasm of the neoplastic epithelial cells in nine of 11 tumors examined, firmly establishing the presence of Epstein-Barr virus within the malignant cells of nasopharyngeal carcinomas of both World Health Organization 2 and World Health Organization 3 histology, rather than in the surrounding lymphocytes.

Adolescent↗
PubMed1979

Indexes of severity: conceptual development.

A discussion of severity index development is presented in relation to conceptual issues in index definition, analytic issues in index formulation and validation issues in index application. The CHOP index is discussed along with six severity indexes described in an earlier paper dealing with underlying concepts to illustrate the material presented. Replies are provided to specific questions raised in an accompanying paper discussing the Injury Severity Score. This conceptual material is presented to provide a foundation for severity index development, to suggest criteria to be used in their formulation and testing, and to identify analyses that can lead to the successful selection and application of an index for a defined purpose.

Abstracting and Indexing↗
PubMed1976

The mathematics of cleft lip and palate treatment evaluation: measuring the desirability of treatment outcomes.

A study was undertaken to investigate the applicability of utility theory to cleft lip and palate treatment decision making. Questionnaires were used to assess value judgements and attitudes toward risk from 119 individuals associated with seventeen cleft lip and palate treatment centers. Significant differences were found to exist between the values expressed by clinicians grouped according to their specialty or the facility to which they were affiliated. Fathers of cleft lip and palate children differed from cleft palate teams in their judgements regarding the relative values of speech and cosmetic treatment outcomes. No such differences were found between team members and mothers, however. It is suggested that these differences affect the desirability of treatment decisions and the outcomes that follow from them. Therefore, cleft lip and palate treatment planning and the evaluation of alternative therapeutic interventions might be based on a mathematical theory of decision making that explicitly incorporates the subjective assessment of a child's habilitative needs and the goals of the habilitative process.

Cleft Lip↗
PubMed1976

Indexes of severity: underlying concepts.

Six severity indexes proposed in the health services research literature are shown to be special cases of a class of ordinal ranking functions called additive value functions. Deficiencies manifest in each of the severity indexes are discussed in relation to the properties that additive value functions must satisfy. In that severity indexes are a subset of health status indexes, the properties that imply and are implied by additive value formulations are relevant to the larger class of indexes as well.

Disability Evaluation↗
PubMed1975

Changing cleft widths: a problem revisited.

A study was undertaken to evaluate changing cleft widths and the timing of surgical repair of the lip in so far as it affects the types of cross-bite occlussion that result in cases treated by presurgical orthopedics (as practiced at Tufts-New England Medical Center Hospitals) and by purely surgical intervention. On the basis of the analyses carried out, the following conclusions were reached: 1. Both the alveolar cleft width prior to lip surgery and the arch form following lip surgery are significantly related, and are predictors of, the type of cross-bite occlusion that will result from purely surgical intervention. 2. Neither the alveolar cleft width prior to lip surgery nor the arch form following lip surgery is significantly related to, or is a predictor of, the type of cross-bite occlusion that will result from presurgical orthopedics. 3. For both presurgical orthopedic treatment programs and purely surgical treatment programs, there is a significant relationship between the arch form following palate surgery and the type of cross-bite occlusion that will result. 4. In cases treated by presurgical orthopedics there is a higher probability of achieving favorable occlusal relationships than in cases treated by purely surgical intervention. 5. In a period of 6 months following birth, but prior to lip surgery, presurgical orthopedics results in a smaller percentage reduction in alveolar cleft width than does treatment without the use of an appliance. However, the posterior cleft widths and posterior palate widths show comparable changes in size. 6. The larger anterior cleft width maintained by the use of presurgical orthopedics prior to lip surgery is completely compensated for following lip surgery, so that no significant difference remains between cases treated by presurgical orthopedics and those treated by purely surgical intervention. 7. Since previous findings showed a larger reduction in posterior cleft width in cases treated by presurgical orthopedics than in cases treated by purely surgical intervention and these results show that there is a comparable reduction in posterior cleft width when lip surgery is delayed until the age of 6 months, then early lip surgery tends to limit the natural reduction of the posterior cleft width. 8. Additional studies are needed. These studies must be based on as complete a description of the cleft and the treatment program as possible. It is the total implication for patient rehabilitation that must be considered in the evaluation of treatment outcomes.

Alveolar Process↗