Quality of life research in pediatric oncology. Research methods and barriers.
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Biomedical subjects
Publications and source records attributed to R T O'Brien.
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OBJECTIVE: To compare radiographic findings and determine useful criteria to differentiate between intranasal neoplasia and chronic rhinitis in cats. DESIGN: Retrospective study. ANIMALS: Cats with chronic nasal disease caused by neoplasia (n = 18) or by chronic rhinitis (n = 11). PROCEDURE: Radiographs were reviewed by 3 radiologists, followed by group review. Diagnosis was determined by intranasal biopsy or necropsy, and specimens were reviewed by a pathologist to confirm cause and histologic diagnosis. RESULTS: Lymphosarcoma was the most common (n = 5) of the 6 histopathologic types in the neoplasia group. Cats in the neoplasia and chronic rhinitis groups had a high prevalence of aggressive radiographic lesions. Prevalence of a facial mass in cats with neoplasia (8/18) versus in those with chronic rhinitis (4/11) and of deviation (9/18 vs 6/11, respectively) or lysis (12/18 vs 7/11) of the nasal septum was similar. However, significantly (P = 0.02) more cats with neoplasia than with chronic rhinitis (13/16 vs 3/7, respectively) had unilateral turbinate destruction/lysis. Additionally, unilateral lateral bone erosion and loss of teeth associated with adjacent intranasal disease were more prevalent in cats with neoplasia (7/8 and 5/18, respectively) than in cats with chronic rhinitis (1/3 and 0/11, respectively). CLINICAL IMPLICATIONS: Features that may assist in radiographic diagnosis of neoplasia include the appearance of unilateral aggressive lesions, such as lysis of lateral bones, nasal turbinate destruction, and loss of teeth. Bilaterally symmetric lesions are more suggestive of chronic rhinitis than of neoplasia.
Radiography will remain the most popular imaging modality in the near future for many reasons. It is economical, portable, and familiar to large animal practitioners. Contrast radiography allows evaluation of vascular and tract lesions. Other modalities may offer various advantages. Diagnostic sonography has the advantage of being able to evaluate soft tissue structure damage, fluid pockets, and lucent foreign bodies. Xeroradiography and CR use conventional, high-powered x-ray units for the production of images on nontraditional ionized film plate-cassette systems. Both systems provide superior bone-soft tissue contrast, by virtue of edge enhancement, than does conventional radiography. CT and MR imaging provide cross-sectional imaging of bones and adjacent structures, avoiding structures that may be superimposed on the area of interest with conventional radiography. The major limitation is the demand for a custom-engineered couch able to withstand the weight of an adult bovine. Scintigraphy provides important functional information for the clinical evaluation of orthopedic disease. It may be the most useful imaging tool to localize the cause of lameness.
PURPOSE: This study was designed to evaluate the effect on CNS relapse (CNSR) and overall relapse rates of blast cells in the CSF containing < or = 5 cells/microL at the time of diagnosis of intermediate-risk acute lymphoblastic leukemia (ALL) in children entered onto a large randomized multicenter prospective therapeutic trial (Childrens Cancer Group [CCG]-105). PATIENTS AND METHODS: We studied outcome in terms of CNSR and event-free survival (EFS) in 1,544 patients who successfully completed remission-induction therapy and had been randomized to one of four systemic chemotherapy regimens and to one of two CNS prophylaxis regimens. We compared outcome between 1,450 patients who had varying degrees of pleocytosis but no blasts in the CSF at diagnosis (blast-negative group) with 94 who had blasts detected in the CSF after cytocentrifugation but had a total CSF WBC count of < or = 5/microL (blast-positive group). RESULTS: No statistically significant differences in overall CNSR or EFS rates were observed between the two groups and no differences were found when analyzed according to age or WBC count at diagnosis, sex, or type of CNS prophylaxis (intrathecal [IT] methotrexate [MTX] alone v IT MTX plus 18 Gy cranial irradiation [CXRT]). CONCLUSION: In intermediate-risk ALL, there was no significant difference in CNSR and systemic relapse rates after standard presymptomatic CNS therapy between patients with a CSF WBC count < or = 5/microL and those without identifiable blasts in the CSF. These findings suggest that certain approaches to therapy, such as that used in this study, may eliminate the need for any additional special treatment directed at this subset of patients with CSF blasts.
PURPOSE: The Childrens Cancer Group (CCG) requires both a CSF WBC count of more than five cells per microliter and demonstration of blast cells in the cytocentrifuge specimen to support a diagnosis of CNS relapse. We reviewed the CSF examinations of patients with intermediate-risk acute lymphoblastic leukemia (ALL) to determine the clinical significance of blast cells reported in the cytocentrifuge when the total CSF cell count was normal. PATIENTS AND METHODS: Children treated on CCG-105 for ALL had CSF examinations every 12 weeks during maintenance therapy. The outcome of children who had a positive CSF cytocentrifuge examination without an elevated CSF WBC count was compared with that of children who did not have any CSF blast cells observed. RESULTS: Sixty-four patients had 81 CSF examinations with blast cells and a normal cell count. By Cox life-table regression analysis, patients with blasts had a different disease-free survival (DFS) distribution, with relapses tending to occur earlier (P = .008). However, the DFS for these patients was 63% +/- 9.6% at 5 years from the time of the abnormal cytocentrifuge result as compared with 69% +/- 1.5% for 1,490 children who did not have blasts in their CSF. This difference is not significant. CONCLUSION: Blast cells were infrequently identified in cytocentrifuge preparations of CSF when the cell count was normal. The majority of patients in whom such an event was observed have not experienced a subsequent relapse as measured by life-table analysis at 5 years. The data do not justify changing or augmenting therapy based on cytocentrifuge results alone.
PURPOSE: This study (Childrens Cancer Group [CCG]-105) was designed in part to determine in a prospective randomized trial whether intrathecal methotrexate (IT MTX) administered during induction, consolidation, and maintenance could provide protection from CNS relapse equivalent to that provided by cranial radiation (CXRT) in children with acute lymphoblastic leukemia (ALL) and intermediate-risk features. PATIENTS AND METHODS: We randomized 1,388 children with intermediate-risk ALL to the two CNS regimens. They received either IT MTX at intervals throughout their course of therapy or CXRT (18 Gy) during consolidation with IT MTX during induction, consolidation, and delayed intensification. Systemic therapy was randomized to one of four treatment regimens derived from a regimen used by CCG in recent studies for this patient population and three more intensive regimens based on the Berlin-Frankfurt-Munster trials. RESULTS: Life-table estimates at 7 years show a 93% and 91% CNS relapse-free survival rate for the CXRT and IT MTX groups, respectively. The corresponding event-free survival (EFS) rates are 68% and 64%. The differences are not significant. Patients who received more intensive systemic therapy had a 94% CNS relapse-free survival rate on either CXRT or IT MTX, while patients who received standard systemic therapy had 90% and 80% rates for CXRT and IT MTX, respectively (P < .0001). Patients less than 10 years of age who received CXRT or IT MTX had 72% and 71% EFS rates if they received more intensive systemic therapy. Patients 10 years or older who received CXRT had an improved EFS (61% v 53%) with a more intensive systemic program. This was primarily due to fewer bone marrow relapses (P = .04). CONCLUSIONS: IT MTX during induction, consolidation, and maintenance provides protection from CNS relapse in patients with intermediate-risk ALL equivalent to that provided by CXRT if more intensive systemic therapy is given. The CNS relapse rate with either CXRT or IT MTX is in part dependent on the associated systemic therapy. For intermediate-risk patients less than 10 years of age, IT MTX with an intensified systemic regimen provided CNS prophylaxis comparable to that provided by CXRT, whereas older patients had fewer systemic relapses if they received CXRT.
PURPOSE: The Berlin-Frankfurt-Munster (BFM) 76/79 trial of acute lymphoblastic leukemia (ALL) in children produced impressive disease-free survival (DFS) rates with a protocol that began with 8 weeks of intensive therapy, followed by 8 weeks of maintenance therapy, and then another 6 weeks of intensive treatment. The current study was conducted to determine the relative contributions of each of these periods of intense therapy on the DFS rates of ALL patients with intermediate presenting features. In addition, due to concerns regarding the toxicity of CNS irradiation, we compared cranial irradiation (CXRT) with intrathecal methotrexate (IT MTX) administered during induction and consolidation to IT MTX during all phases of the treatment program. PATIENTS AND METHODS: Between May 1983 and April 1989, more than 1,600 children with ALL and intermediate presenting features, as defined by the Childrens Cancer Group (CCG), were entered into a randomized trial that tested four systemic therapy regimens and two CNS programs. RESULTS: The results with a median follow-up of 57 months show that systemic regimens with a delayed intensification (Delint) phase of therapy had a 5-year event-free survival (EFS) rate of 73% compared with the control regimen EFS rate of 61% (p = .006). For children less than 10 years of age, standard three-drug induction and Delint produced a 77% 5-year EFS. IT MTX during all phases of therapy provided CNS protection comparable to the CXRT regimen in children less than 10 years of age. Children 10 years of age or older appear to have a better EFS rate with intensive induction, Delint, and CXRT. CONCLUSION: Delint improves the EFS rate of children with ALL and intermediate presenting features. Maintenance IT MTX can be safely substituted for CXRT for presymptomatic CNS therapy in children with intermediate-risk characteristics less than 10 years of age.
Current medical treatments for childhood acute lymphoblastic leukemia (ALL) have improved the outlook to where more than 50% can be expected to survive five years or more. The use of CNS prophylaxis has contributed in a significant way to these improved survival statistics by reducing the likelihood of CNS relapses. The literature relating to the potential adverse psychological consequences of CNS prophylaxis, which include cranial radiation therapy (CRT), is reviewed and analyzed. The majority of published papers of children in first remission report that CNS prophylaxis, which include both CRT and intrathecal methotrexate, results in a variety of learning problems in many children who were younger than age 5 when treated. The available literature on the social, emotional, and educational sequelae of childhood ALL is also reviewed.
Widespread organ distribution of malignant fibrous histiocytoma, including osseous involvement, was demonstrated in two dogs. Both cases had a storiform-pleomorphic pattern histologically and immunohistochemical stains were used to differentiate this from other types of neoplasms with the same histological pattern. Radiographically the lesions were predominantly lytic in the metaphysis of long bones, although periosteal proliferation and axial skeletal involvement were seen in one dog.
Sixty-four patients aged 2 to 18 years with advanced-stage Hodgkin's disease (HD) were treated on a Children's Cancer Study Group (CCSG) pilot toxicity study (521-P). Therapy consisted of 12 courses of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), bleomycin, vinblastine, and dacarbazine (ABVD), followed by low-dose (2,100 cGy in 12 fractions) regional irradiation (RT). All patients were monitored for toxicity with particular attention to the pulmonary system. Six patients (9%) developed grade 3 or 4 pulmonary toxicity. Three had grade 3 toxicity based solely on changes in carbon monoxide diffusing capacity (DLCO) and remained well for more than 3 years after diagnosis. There was one fatality among the three symptomatic cases. In five cases, toxicity occurred prior to RT. One occurred after seven courses of ABVD, one after nine courses, and three after 10 courses. In one of these five cases, ABVD was stopped. The patient was given nitrogen mustard (mechlorethamine), vincristine, prednisone, and procarbazine (MOPP). This patient subsequently developed recurrence of HD and died of overwhelming sepsis. The other four continued on study and completed their chemotherapy. Three patients had no further bleomycin, and one continued bleomycin at 50% of the assigned dose. They all received mantle RT following chemotherapy, one with a boost dose to the mediastinum to 3,800 cGy and one with added RT to both lungs (1,050 cGy). In the sixth case of pulmonary toxicity, symptoms were first noticed 2 weeks after mantle RT to 3,500 cGy. This patient died of progressive respiratory failure. The event-free survival (EFS) and overall survival is 87% at 3 years. These early results indicate that this therapy is effective in advanced HD in children but has a 9% incidence of acute pulmonary toxicity.
Retained yolk sacs are common in the domestic chicken and account for considerable morbidity and mortality during late embryonic development and within the first 10 days of life. What is believed to be the first recorded instance of a retained caseous yolk sac and its successful surgical removal from a Burmese python (Python molurus bivittatus) is reported. The snake experienced no post-operative complications and continues to be well 16 mo following surgery.
During detailed immunophenotypic analyses of marrow blasts from 336 acute lymphoblastic leukemia (ALL) patients, a very small percentage of cases reactive with B-cell-directed as well as T-cell-directed monoclonal antibodies (MoAbs) were identified. Five ALL cases were biphenotypic since they coexpressed CD2 (Tp50) and CD19 (Bp95) antigens at the single-cell level. The composite immunophenotype of these biphenotypic ALL cases was [TdT+HLA-ABC+CD2+CD3-CD10+CD13-CD14-CD16-CD19+CD20+ ++-CD21-CD33-CD34+Bgp95-C mu- slg-]. Low-molecular-weight B-cell growth factor (LMW-BCGF), recombinant interleukin-2 (rIL-2), and rIL-3 stimulated the proliferative activity of biphenotypic leukemic lymphocyte precursors without inducing differentiation. In the presence of the phorbol ester TPA, leukemic blasts from two cases differentiated along the B precursor pathway to the [CD2-CD10+CD19+CD20+C mu+slg-] pre-B cell stage. Biphenotypic ALL cases did not share a common configuration and gene rearrangement pattern of the immunoglobulin heavy chain genes or T-cell receptor (TCR) genes. Three cases had rearranged C mu genes but germline TCR genes, one case showed rearrangement of both C mu and TCR genes, and the remaining case had rearranged TCR genes but germline C mu genes. All five patients attained prompt remission after standard induction chemotherapy. Three to four years after initial diagnosis, four patients are now off chemotherapy and remain alive in their first remission. One patient relapsed at 3 years, 7 months, but promptly achieved complete remission after reinduction chemotherapy and remains in second remission off chemotherapy greater than 3 years after her reinduction therapy. With two-color immunofluorescence staining techniques and multiparameter flow cytometric analyses, we identified a small population of CD2+CD19+ lymphoid cells in fetal livers (FLs) and fetal bone marrows (FBMs), which may represent the putative normal counterparts of biphenotypic ALL blasts. A CD2+CD19+ normal biphenotypic lymphoid precursor cell line, designated FL 8.2 CD2+, was established from an FL of 8-weeks of gestational age by Epstein-Barr virus (EBV)-induced blastoid transformation. The composite immunophenotype of FL 8.2 CD2+ cell line was [TdT+HLA-ABC+HLA-DR+ CD2+CD5-CD7-CD10+/-CD13-CD19+CD20-CD21+ CD22+CD33-CD34+/-Bgp95-CDw40+C mu-slgD-slgM-]. FL 8.2 CD2+ cells showed germline patterns of immunoglobulin heavy-chain joining region, heavy-chain constant region, kappa light-chain constant region genes, and TCR beta-chain genes. Cross-linking of CD2 as well as CD19 antigens on FL 8.2 CD2+ cells caused an increase of intracellular ionized calcium.(ABSTRACT TRUNCATED AT 400 WORDS)
Idiopathic thrombocytopenic purpura is a disorder characterized by antibody-mediated platelet destruction. Other than thrombocytopenia and its consequences, the physical and laboratory examination of the child with ITP is normal. The prognosis in children is excellent; 90 percent will recover spontaneously within one year. Serious hemorrhage is uncommon and conservative management is appropriate. Aspirin and potential trauma should be avoided. Transfusions are rarely necessary or helpful. Corticosteroids may cause a more rapid rise in the platelet count but do not influence the long-term prognosis.
A retrospective study of thrombocytosis in children with Hemophilus influenzae meningitis was performed. Forty-five percent of patients had a platelet count greater than 500 X 10(9)/l during hospitalization. The mean platelet count was 284 X 10(9)/l on admission, and gradually increased to 648 X 10(9)/l on day 11 of hospitalization. These results document that thrombocytosis is common among children with H. influenzae meningitis and suggest that it is probably a recovery phenomenon.
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This report describes two cousins with Wilms' tumor and mucin detected in the sera with rapidly fatal courses. A review of the literature reveals five additional reported cases of Wilms' tumor where mucin was observed in the sera. The patients in this report are similar to those previously reported in that all had metastatic disease at diagnosis, and four of five died within one year of diagnosis. Both the extent of disease at diagnosis at the poor response to therapy in these two cases, and those from the literature suggest that evidence of mucin production may indicate poor prognosis in Wilms' tumor. In addition, evidence is reviewed that mucin itself may contribute to a rapid tumor growth and metastases. The genetics of Wilms' tumor and familial nature of these cases is also discussed.
Children with neuroblastoma treated in Salt Lake City from 1966 through 1982 were analyzed in an attempt to develop guidelines for external beam radiation. Particular attention was addressed to time-dose relationships in those patients with residual disease post-resection (Stages II and III). Altogether, 76 patients were analyzed and survival rates were: Stage I--100%; Stage II--84%; Stage III--69.2%; Stage IV--14.3%; Stage IV-S--71.4%. Survival rates were correspondingly better in younger children and in infants. Indications for postoperative radiation therapy in this population were: unresectable or gross remaining tumor; residual tumor in neural foramina; tumor spill during surgery; positive regional lymph nodes or positive surgical margins. Local control was achieved in a majority of patients undergoing surgery and radiation for limited disease. In children younger than 1 year of age, no local failures were observed at doses above 1200 rad. In children between 1-2 years of age, no local failures were observed with doses as low as 1440 rad. In children older than 3 years, local failures were observed up to 4500 rad.
Significant alterations in hemotologic function in cystic fibrosis are suggested by the observation that polycythemia is uncommon, even among cyanotic patients. To elucidate those factors that influence hematologic equilibrium, 39 stable patients with cystic fibrosis were evaluated with regard to hemoglobin, hematocrit, RBC indices, reticulocyte count, serum iron and total iron binding capacity, serum ferritin, vitamin E, and carboxyhemoglobin levels. Hemoglobin concentrations were below the 50th percentile for age in 90% of the patients, including the 23% who were cyanotic. Serum ferritin levels were below the mean for age in 85% and below 12 ng/mL in 33% of patients. Vitamin E levels were less than 5 micrograms/dL in 33%, indicating deficiency. Carboxyhemoglobin values were elevated in 64% of the patients. These data indicate that relative anemia is common in cystic fibrosis and suggest that iron and vitamin E deficiency may contribute to that anemia. Twenty-two patients with cystic fibrosis were then given 2 weeks of oral iron therapy followed by two to three additional weeks of iron and vitamin E. This therapeutic trial resulted in an increase in mean hemoglobin concentration from 13.87 to 14.50 g/dL (P less than 0.01) associated with a significant increase in levels of serum ferritin (P less than 0.001). The increase in hemoglobin occurred primarily during the second 2 weeks when patients were receiving both iron and vitamin E. However, we were unable to document evidence of increased hemolysis when patients were receiving iron therapy alone. This response to oral iron therapy is confirmation that iron deficiency contributes to the failure of some patients with cystic fibrosis to compensate hemotologically for hypoxia.