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Biomedical subjects

H E Grier

Publications and source records attributed to H E Grier.

At least 37 records · Page 2Linked to original sources
PubMed1996

Treatment of endodermal sinus tumor in children using a regimen that lacks bleomycin.

BACKGROUND: The EPO-VAC protocol was initiated to study 1) the efficacy of adding a cisplatin regimen (EPO) to VAC alone (the previous standard of care) and 2) the effect of replacing bleomycin with etoposide in the treatment of pediatric endodermal sinus tumors. METHODS: The eligibility requirements for entry included age <21 years at diagnosis, diagnosis of a primary gonadal or extragonadal tumor (excluding central nervous system tumors and stage I testicular tumors), and histological confirmation of endodermal sinus tumor. Children who met the eligibility criteria were treated with four courses of EPO (etoposide, cisplatin, vincristine) alternating with three courses of VAC (vincristine, dactinomycin, and cyclophosphamide). RESULTS: Eleven children were entered on the protocol. Six patients had extragonadal disease, five patients had ovarian primaries. Seven patients had low-stage tumor (I or II) and four had advanced-stage tumor (III or IV). Three of six evaluable patients attained a complete response at 21 weeks. Three patients with a residual soft tissue mass at restaging underwent further therapy. No patient has relapsed after a median of 51 (range 14-88) months of follow-up. CONCLUSIONS: The results of this protocol suggests that a cisplatin-containing regimen that lacks bleomycin is active in childhood endodermal sinus tumors.

Adolescent↗
PubMed1996

Patient-controlled analgesia for mucositis pain in children: a three-period crossover study comparing morphine and hydromorphone.

OBJECTIVES: (1) To test the safety and efficacy of a clinical protocol for administering opioid by using patient-controlled analgesia (PCA) for the management of mucositis pain in children after bone marrow transplantation, (2) to compare the efficacy, side-effect profile, and potency ratio of morphine with those of hydromorphone by using PCA as the method of opioid administration, and (3) to obtain pharmacokinetic data on hydromorphone and morphine in this population of children. METHODS: In this double-blind, three-period crossover study, patients were randomly assigned to receive either morphine (group 1) or hydromorphone (group 2) initially by means of PCA on days 1, 2, and 3 (period 1), to be followed on days 4, 5, and 6 (period 2) with the alternative opioid, followed by the opioid used at the commencement of the study on days 7, 8, and 9 (period 3). A clinical protocol for calculating the PCA commencement opioid dose and subsequent opioid-dose escalation was tested by measures of safety and efficacy. Measures of pain intensity and opioid side effects were made during the three periods. On the last study day (day 10), patients received a continuous infusion of opioid derived from the previous 24-hour PCA opioid requirement, and blood specimens were collected and stored for subsequent opioid analysis. RESULTS: Ten patients were enrolled in this study. Rapid escalation in opioid requirement commonly occurred at the commencement of PCA, followed by a variable plateau phase and then deescalation of opioid requirement after mucositis resolution. The measures demonstrated the safety and efficacy of the clinical protocol. In the concentrations used, there was no statistical difference between the mean daily pain, sedation, nausea and vomiting, and pruritus scores for both opioids (Friedman test). The analysis of variance of the log-total opioid doses per patient during periods 1, 2, and 3 indicated that patients used 27% more hydromorphone than expected from its presumed 7:1 ratio relative to morphine potency used in the PCA infusions. The mean plasma hydromorphone concentration was 4.7 ng/ml (range, 1.9 to 8.9 ng/ml), and the mean clearance was 51.7 ml/min per kilogram of body weight (range, 28.6 to 98.2 ml/min per kilogram). The mean plasma morphine, morphine-6-glucuronide, and morphine-3-glucuronide concentrations were 40.0 ng/ml (range, 15 to 62.5), 168.2 ng/ml (range, 54.4 to 231.9), and 391.0 ng/ml (range, 149.4 to 921.7), respectively. The mean morphine clearance was 34.3 ml/min per kilogram of body weight (range, 19.3 to 58.3). The mean molar ratios of morphine-6-glucuronide/morphine, morphine-3-glucoronide/morphine, and morphine-3-glucuronide/morphine-6-glucuronide were 2.48 (range, 1.4 to 3.3), 5.82 (range, 3.4 to 9.1), and 2.46 (range, 1.1 to 3.3), respectively. CONCLUSIONS: The safety and efficacy of a clinical protocol for the administration of opioids by means of PCA for mucositis pain after bone marrow transplantation was demonstrated. In this small study, hydromorphone was not superior to morphine in terms of analgesia or the side-effect profile: a larger study would be needed to show a difference. The clearances of hydromorphone and morphine in the children studied were generally greater than those previously recorded, but this finding may be related to disease or treatment variables. Apart from clearance, the morphine pharmacokinetics in the study population were similar to those previously recorded. Hydromorphone may be less potent in this population of children than indicated by adult equipotency tables.

Adolescent↗
PubMed1995

Etoposide, ifosfamide, and cisplatin therapy for refractory childhood solid tumors. Response and toxicity.

BACKGROUND: Etoposide, ifosfamide, and cisplatin (VIP) are each active in treating pediatric solid tumors, and this combination has been shown to be effective in treating adult germ cell tumors. Etoposide, ifosfamide, and cisplatin therapy was used to treat 11 patients, with ages ranging from 14 months to 22 years, with relapsed sarcoma, Wilm's tumor, and hepatoblastoma. METHODS: Etoposide, ifosfamide, and cisplatin therapy was administered daily for 3 days in doses of cisplatin 20 mg/m2 with mannitol 10 g/m2 for 1 hour, etoposide 100 mg/m2, and ifosfamide 1.5 g/m2 with MESNA 360 mg/m2 x 3 doses. A total of 65 courses (range, 3-10/patient) were administered, with 86% of the courses administered at full dose. Hematopoietic growth factors were not used. RESULTS: All 10 evaluable patients responded. Six patients had a complete response (CR) by computed tomographic or magnetic resonance imaging scan after one to three courses. The remaining four patients had a partial response (PR) (> 50% decrease in disease). One PR was converted to a CR by resection of the residual lesions. The major toxicity was myelosuppression. The median nadirs after full doses were as follows: leukocyte count of 900/mm3, absolute neutrophil count (ANC) of 156/mm3, platelet count of 61,000/mm3, and hemoglobin count of 8.6 g/dl; 75% of full dose courses led to an ANC of less than 500. Fever and neutropenia were observed after 8/55 (15%) full dose courses. Two episodes of bacteremia were noted, one with Staphylococcus epidermidis after full recovery of counts. The median time to hematologic recovery was 21 days (range, 14-29 days). No patient developed a decreased creatinine clearance level during therapy. Significant renal solute losses were observed in two patients, both of whom had been pretreated heavily with ifosfamide and had losses before VIP therapy. CONCLUSIONS: Etoposide, ifosfamide, and cisplatin appear to be active in treating childhood solid tumors. This therapy has predictable and tolerable myelotoxicity, and nephrotoxicity does not appear to be more severe than that observed after treatment with ifosfamide alone.

Adolescent↗
PubMed1995

A 10-year experience of pediatric brachytherapy.

PURPOSE: The purpose of this project was to review the brachytherapy experience in the pediatric population at the Joint Center for Radiation Therapy (JCRT) with respect to efficacy and morbidity. METHODS AND MATERIALS: Treatment outcome was reviewed for 18 children between the ages of 6 months and 23 years who received 19 implants between 1982 and 1992 at JCRT. Fourteen children received permanent Iodine-125 seed implants placed in the operative tumor bed at the time of resection. Two children received sterotactically placed afterloaded high-activity I-125 seed brain implants, and one child received a high-activity I-125 brain implant followed by a permanent I-125 seed brain implants 3 years later. One girl received a temporary Iridium-192 volume implant for a vulvar rhabdomyosarcoma. Among the 15 permanent I-125 implants, the cases included five primary brain tumors, one metastatic brain tumor, six sarcomas, and one each of the following: suprarenal neuroblastoma, hepatoblastoma, and adenocarcinoma of the pancreas. All patients underwent surgery and most patients (15 out of 18) received external beam radiotherapy to a field that included the implant. RESULTS: The median follow-up from the time of diagnosis for patients who remain alive is 55 months (range 24 to 119 months), and the median follow-up from the time of implant is 46 months (15 to 60 months). Disease was controlled in the area of the implant in 13 of 17 evaluable cases. Two patients experienced treatment-related morbidity; one patient developed severe desquamation related to an "adriamycin recall reaction," and one patient died of postoperative complications. CONCLUSION: Despite the heterogeneous mix of cases, the use of brachytherapy in this pediatric population resulted in several cases of long-term disease control, and the overall morbidity was very low. Therefore, in properly selected pediatric cases, brachytherapy appears to be an efficacious adjunct to multimodality cancer management.

Adolescent↗
PubMed1995

Control of severe pain in children with terminal malignancy.

OBJECTIVE: To identify the characteristics of the subset of children with malignancy in whom massive opioid infusions are needed during the terminal phase. DESIGN: Retrospective review of the records of the 199 patients who died of malignancy after treatment at Children's Hospital, Boston, from March 1989 to July 1993, identifying characteristics of patients who required massive opioid infusions (operationally defined as infusion of > 3 mg/kg per hour of morphine dose equivalent) during the terminal phase. RESULTS: Twelve patients (6%) required massive opioid infusions, and eight of these patients required extraordinary measures (epidural or subarachnoid infusion and/or sedation) to achieve adequate analgesia. The duration of epidural or subarachnoid infusions in three patients ranged from 3 to 9 days, and minimal complications occurred. The duration of sedation ranged from 1 to 15 days. Maximal intravenous opioid dosing ranged from 3.8 to 518 mg/kg per hour of morphine equivalent. The maximal infusion rate (exceeding all previous published reports) occurred in an infant with an isolated metastasis in the periaqueductal gray matter, a brain-stem site linked to mediating analgesia and defense reactions. The need for massive opioid dosing in 11 of 12 patients was associated with tumor spread to the spinal nerve roots, nerve plexus, large peripheral nerve, or spinal cord compression. CONCLUSIONS: Standard dosing of opioids adequately treats most cancer pain in children; however, a significant group requires more extensive management. These problems occur more commonly among patients with solid tumors metastatic to spine and major nerves.

Adolescent↗
PubMed1995

Treatment of patients with acute myelogenous leukemia: review of clinical trials of the past decade.

UNLABELLED: We discuss the history and progress of treatment for acute myelogenous leukemia (AML) in children as it has evolved over the past decade. We review the results of clinical trails for children with AML and examine the major strategies that have contributed to progresses in the treatment of this disease. Prior to the 1970's, nearly every child with AML died. Modern intensive chemotherapy, bone marrow transplantation, and advanced supportive care of critically ill patients have improved the outlook for children with this fatal disease. CONCLUSION: Although it represents only 15-20% of all childhood acute leukemias, > 30% of deaths from leukemia are still a consequence of AML, and only 30-40% of children with newly diagnosed AML are expected to achieve a long-term remission. Greater advances in treatment are expected as headway is made in understanding the complex biology of this heterogeneous disease.

Bone Marrow Transplantation↗
PubMed1994

Malignant small round cell tumor (Ewing's-PNET) of the chest wall in children.

From 1976 to 1989 the authors treated 21 infants and children with malignant tumors of the chest wall. Fifteen were classified as Askin's tumors or Ewing's sarcoma, which we now consider as a single entity of primitive neuroectodermal origin. They are infrequent but highly aggressive tumors that involve the chest wall in children. Five patients presented with metastatic disease; despite chemotherapy and radiotherapy, all succumbed to progressive disease. Ten patients with localized disease received combined modality therapy including surgical resection (three after initial chemotherapy), radiotherapy, and chemotherapy. Surgery involved resection of the mass and up to three ribs, with prosthetic mesh reconstruction in one patient. Six of the 10 patients with localized disease are continuously disease-free 3.5 to 9 years (median, 5 years) following diagnosis. No patient had local recurrence. Of the four whose treatment failed, one died (free of disease) from complications after resection of an extensive primary tumor. In the second patient, acute monocytic leukemia developed shortly after relapse in a distant bone site. The patient died during induction for the leukemia. In the other two patients, hilar and carinal lymph node relapse occurred 68 and 80 months after initial treatment. One of the patients is considered in second remission (now 105 months later) after further chemotherapy (Adria-VAC) and radiation; the other succumbed to secondary relapse 17 months after second remission was achieved through chemotherapy, radiation, and surgery. Initial percutaneous needle biopsy of the large lesions has provided adequate material for histological, immunohistochemical, cytogenetic and ultrastructural diagnosis, and permitted initial chemotherapy before proceeding to surgical resection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Ewing's sarcoma--routine diagnostic utilization of MIC2 analysis: a Pediatric Oncology Group/Children's Cancer Group Intergroup Study.

Ewing's sarcoma and peripheral neuroectodermal tumor (PNET) are small blue cell tumors with no reliable positive diagnostic markers. However, Ewing's sarcoma and PNET recently have been shown to strongly express an antigen determined by the MIC2 gene, whereas other blue cell tumors of childhood for the most part do not. MIC2 analysis therefore offers a distinctive addition to the panel of immunohistochemical stains used to differentiate among small blue cell tumors of childhood, since it represents the first positive marker for Ewing's sarcoma and PNET. This study addresses the reliability of MIC2 analysis using the monoclonal antibody 12E7 on tumors registered in the current Intergroup Ewing's Sarcoma protocol. Of 244 tumors, 221 (91%) showed a diffuse strong membranous pattern. The antibody appears to withstand all the fixation variables inherent in a multi-institutional study. We conclude that MIC2 expression is highly reliable as a positive marker for the Ewing's sarcoma/PNET family of tumors when the results are interpreted in the total context with clinical and pathologic parameters.

12E7 Antigen↗
PubMed1994

Fibrosarcoma in infants and children. Application of new techniques.

Fibrosarcomas occurring in infants and young children are intriguing tumors. Although biologically more benign than their counterparts occurring in old patients, they are histologically similar. Microscopically, they fit in one end of a spectrum of fibrous proliferations occurring in the pediatric population. Prompted by recent karyotypic reports of nonrandom gains of chromosomes 8, 11, 17, and 20 in infantile fibrosarcomas, we retrospectively analyzed 12 infantile fibrosarcomas utilizing fluorescence in-situ hybridization (FISH) with chromosome 8-, 11-, 17-, and 20-specific probes. Parallel studies were performed on fibrosarcomas occurring in older children and young adults and also on cellular fibromatoses, myofibromatoses, and fibromatoses. Gains of chromosomes 8, 11, 17, and 20 (in various combinations) were observed in 11 of 12 fibrosarcomas occurring in infants < 2 years of age. Extra copies of chromosomes 17 and 20 were observed in a fibrosarcoma occurring in a 5-year-old child but no abnormalities were detected by FISH in four additional fibrosarcomas occurring in patients aged 6-17 years. One of three cellular fibromatoses was characterized by extra copies of chromosome 8, 11, 17, and 20. Similar findings were not observed in any of the noncellular fibromatoses or in myofibromatoses.

Adolescent↗
PubMed1994

Chest wall tumors in infants and children.

Chest wall tumors are infrequent in infants and children, but a high proportion of these tumors are malignant. They present most frequently as a palpable mass, and less frequently with pain or respiratory distress. Radiographic evaluation should include chest radiographs followed by computed tomographic (CT) scan. In most cases an initial incisional biopsy is performed because of the significant risk of malignancy. The most frequent tumors are the malignant small round cell tumors (Ewing's sarcoma/primitive neuroectodermal tumor [PNET] family) followed by rhabdomyosarcoma, osteosarcoma, chondrosarcoma, and a spectrum of other sarcomas. Initial treatment with chemotherapy, particularly for the malignant small round cell tumors and osteosarcoma, may facilitate resection by decreasing the size of the tumor as well as its vascularity and friability. Cure requires successful local control and adjuvant chemotherapy and is particularly difficult to achieve in children presenting with metastases.

Child↗
PubMed1993

Posterior mediastinal masses.

Solid mediastinal masses in infancy and childhood occur most frequently in the posterior mediastinum. From 1972 to 1989, 63 patients presented with a posterior mediastinal mass. The median age at diagnosis was 6 years (range, 1 day to 26 years). Thirty patients were female. Forty-five percent of the patients presented with respiratory symptoms or chest pain; 13% had neurologic symptoms, one half of which were related to spinal cord compression; and 5% had a palpable mass. In 32% of patients the mass was an incidental finding. The tumors were of neurogenic origin in 89% of patients, of which neuroblastoma was the most common. Of all patients with posterior mediastinal masses, 60% had malignant tumors. Median follow-up for 62 of 63 evaluable patients was 45 months (range, 1 to 289 months). One patient was lost to follow-up. Of the 62 patients followed, 84% are alive and free of disease. All but 4 of the 32 patients with neuroblastoma are alive and free of disease with a median follow-up of 73 months (range, 7 to 289 months). Patients with neuroblastoma who were diagnosed in the first year of life had a significantly better survival pattern than those presenting after the first year. There were seven deaths in the series: four from neuroblastoma, two from primitive neuroectodermal tumor, and one from malignant schwannoma. Preoperative diagnostic evaluation of a posterior mediastinal mass should include posteroanterior and lateral chest roentgenograms, and either CT or MRI of the chest and abdomen to assess the extent of the mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Stage III neuroblastoma over 1 year of age at diagnosis: improved survival with intensive multimodality therapy including multiple alkylating agents.

PURPOSE: A nonrandomized, single-arm trial was conducted to assess the efficacy of multimodality therapy including intensive chemotherapy with multiple alkylating agents in the treatment of children with Evans stage III neuroblastoma older than 1 year at diagnosis. PATIENTS AND METHODS: Twenty-five patients with a median age of 18 months at diagnosis were treated with multimodality therapy including surgery and chemotherapy using either nitrogen mustard (mechlorethamine), doxorubicin, cisplatin, dacarbazine (DTIC), vincristine, and cyclophosphamide (MADDOC) or cisplatin and cyclophosphamide induction followed by maintenance MADDOC (induction MADDOC) protocols. Sixteen of 25 patients also received radiotherapy to the tumor bed and primary lymph nodes. Event-free survival (EFS) was compared with that reported previously in the literature. N-myc amplification was evaluated prospectively and the Shimada classification was evaluated retrospectively as potential prognostic factors. RESULTS: We report a 72% EFS (95% confidence interval +/- 18%) with a median follow-up of 85 months. EFS was significantly worse for patients with tumors demonstrating N-myc amplification (P = .018). Patients classified as favorable according to the Shimada system experienced a significantly better EFS (P = .04), but unfavorable patients still maintained a 60% EFS. CONCLUSION: Intensive multimodality treatment including MADDOC and induction MADDOC chemotherapy provides a very good EFS for children older than 1 year who have stage III neuroblastoma. Children classified as favorable according to the Shimada system have a better prognosis. Patients whose tumors demonstrate N-myc amplification have a poor prognosis despite therapy.

Alkylating Agents↗
PubMed1993

Detection of the (11;22)(q24;q12) translocation of Ewing's sarcoma and peripheral neuroectodermal tumor by reverse transcription polymerase chain reaction.

Ewing's sarcoma and the related primitive neuroectodermal tumor (PNET) share a unique and specific t(11;22)(q24;q12) chromosomal translocation. The breakpoints have recently been cloned and shown to involve the EWS gene on chromosome 22 and the FLI-1 gene on chromosome 11. Translocation results in the fusion of these genes on the der(22) chromosome, resulting in the production of a novel chimeric EWS/FLI-1 message. Using oligonucleotide primers derived from EWS and FLI-1 complementary DNAs, we were able to amplify a specific fusion transcript from 18 of 18 cases containing t(11;22) and 10 of 14 cases of Ewing's sarcoma/PNET that had unsuccessful cytogenetics. No EWS/FLI-1 fusion transcripts were detected in five cell lines derived from cases of pediatric sarcomas having a histological diagnosis other than Ewing's sarcoma/PNET. The sensitivity and specificity of this PCR analysis demonstrates the usefulness of this approach for the primary diagnosis of t(11;22)-containing Ewing's sarcoma/PNET and for the detection of metastatic or residual disease.

Amino Acid Sequence↗
PubMed1993

Prenatal detection of neuroblastoma: a ten-year experience from the Dana-Farber Cancer Institute and Children's Hospital.

OBJECTIVES: To assess the relative frequency of, the clinical and pathological correlates in, and the prognosis of the subset of infants with neuroblastoma who were identified initially by prenatal ultrasonography. DESIGN: Retrospective review of all patients with neuroblastoma evaluated between 1982 and 1992. SETTING: Large, urban, tertiary care children's hospital in Boston, Massachusetts. PATIENTS: Eleven infants with neuroblastoma initially detected with prenatal sonograms were identified. RESULTS: Nine patients had adrenal tumors; two had thoracic paraspinal tumors. Typical diagnostic evidence for neuroblastoma including a palpable abdominal mass and elevations in urinary catecholamines were not commonly seen postnatally. These patients had multiple favorable prognostic indicators including low stage of disease (10/11), favorable biological markers including cellular DNA content (5/5) and N-myc oncogene copy number (5/5), and histopathology suggestive for neuroblastoma in situ (7/11). All patients were treated by surgical resection. One patient exhibited progression of disease postoperatively, but demonstrated a complete clinical response to multiagent chemotherapy. Overall survival in our population was excellent with no deaths seen at a mean follow-up of 37 months (range 3 to 120 months). CONCLUSIONS: Patients with neuroblastoma identified by prenatal ultrasonography generally, although not exclusively, follow a clinically favorable course in which surgical resection is curative. Chemotherapy is not indicated unless substantial progression of disease occurs.

Adrenal Gland Neoplasms↗
PubMed1992

Intensive sequential chemotherapy for children with acute myelogenous leukemia: VAPA, 80-035, and HI-C-Daze.

Between 1976 and 1988 we treated 228 children age 18 years or less with AML on three consecutive protocols: Vapa, 80-035 and Hi-C Daze. All three protocols used intensive consolidation chemotherapy. VAPA and 80-035 used an anthracycline with standard dose cytosine arabinoside (ara-c) for remission induction followed by twelve to fourteen months of intensive sequential chemotherapy. Results were similar for these two treatment protocols. 90/125 (72%) of the patients achieved a complete remission with 45% projected disease free survival for the complete responders, and an event free survival of 31%. 8/26 (VAPA) and 3/21 (80-035) relapses were primary CNS. No factor significantly influenced the rate of complete remission, but M4 and M5 FAB subtypes and WBC greater than 100,000/ul predicted for shorter remission duration. 103 children received Hi-C DAZE. The protocol differed by utilizing high-dose ara-c during induction and consolidation and pairing VP-16 with azacytidine. Hi-C DAZE was modified after the first 33 patients (group 1) because of CNS toxicity; VP-16/azacytidine were substituted for high dose ara-c/daunorubicin as the second induction course for the next 70 patients (group 2). Twenty eight of 33 (85%) of group 1 and 54/70 (77%) of group 2 entered remission.

Adolescent↗
PubMed1991

Stage IV neuroblastoma in infants. Long-term survival.

Before the advent of multiagent chemotherapy, the prognosis for patients with Stage IV neuroblastoma of all ages was dismal. More recently, marked improvement in infants with Stage IV neuroblastoma has been reported. Twenty-four infants with Stage IV neuroblastoma have been treated at the Dana-Farber Cancer Institute/The Children's Hospital, and the Joint Center For Radiation Therapy, Boston, Massachusetts, between 1970 and 1988. Twenty-three of these patients were treated with multiagent chemotherapy and one with a single drug. In the initial report, ten of 11 patients were alive without evidence of disease after intensive therapy. In this report the authors update their initial series of patients and include 13 additional patients who subsequently presented to our institutions with Stage IV neuroblastoma younger than 1 year of age. The 5-year actuarial event-free survival for the 24 patients is 75%. No patient without bone metastases died from neuroblastoma, and 12 of 16 patients with bone metastases remained disease free. These results confirm that infants with Stage IV neuroblastoma have a very good prognosis when treated with intensive multiagent chemotherapy.

Adrenal Gland Neoplasms↗