Biomedical subjects

F B Ruymann

Publications and source records attributed to F B Ruymann.

At least 37 records · Page 2Linked to original sources

PubMed1994

Cytosine arabinoside and mitoxantrone induction chemotherapy followed by bone marrow transplantation or chemotherapy for relapsed or refractory pediatric acute myeloid leukemia.

The purpose of this study was to determine the induction rate, duration of response and toxicity of cytosine arabinoside (1.0 gm/m2 i.v. over 2 h q 12 h x 8 doses days 1 through 4) and mitoxantrone (12 mg/m2 over 1 h daily x 4 doses days 3 through 6) in pediatric patients with acute myeloid leukemia (AML). Patients achieving a complete remission received either bone marrow transplantation or further chemotherapy. Twenty-seven of 37 evaluable patients (73% (95% confidence interval 59-87%)) achieved a complete remission. For all responding patients, the projected median time to relapse is 12 months. The projected 1 and 2 year disease-free survival is 47% (28-66) and 41% (21-61) with a range of follow-up of 0 to 48+ months. The major toxicity was bone marrow suppression and infection. This therapy is very active in pediatric AML and has acceptable toxicity. Some patients treated achieve prolonged survival.

Adolescent↗

PubMed1993

Aggressive chemotherapy, organ-preserving surgery, and high-dose-rate remote brachytherapy in the treatment of rhabdomyosarcoma in infants and young children.

BACKGROUND: External beam radiation therapy often is avoided in the treatment of rhabdomyosarcoma (RMS) in young children because of the long-term sequelae. Conventional brachytherapy can reduce these problems, but its use is limited in young children because of radiation exposure to parents and care-givers. This is the first reported use of high-dose-rate remote brachytherapy (HDR) to treat RMS in young children. METHODS: Seven young children with RMS were treated from January 1990 through September 1991 with multiagent chemotherapy, organ preserving surgery, and HDR. The primary tumor sites included the tongue, buccal mucosa, chest wall, vagina, and clitoris. A minimum peripheral dose of 36 Gy HDR was administered in 12 fractions (twice a day) at 3 Gy per fraction for a period of 3 days. The treatment was given on an outpatient basis without requiring prolonged patient sedation or immobilization. Each treatment lasted 2-5 minutes. RESULTS: All seven children are alive and without evidence of tumor with a median follow-up of 30 months (range, 18-35 months) from diagnosis. The treatments have been reasonably well tolerated with some acute skin toxicity. There has been relatively good organ growth and function during this short follow-up period. CONCLUSION: The use of HDR radiation in these patients eliminated radiation exposure to care-givers and permitted constant nursing care and interaction among the parents, nursing personnel, and child. Treatments can be given on an outpatient basis, without requiring prolonged patient sedation or immobilization. Local control of tumor with preservation of organ function was achieved. HDR in young children should be restricted to controlled clinical trials until long-term morbidity and efficacy results are obtained from pilot studies.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1993

Parents' use of cocaine and marijuana and increased risk of rhabdomyosarcoma in their children.

Parents' use of marijuana and cocaine was evaluated in a national (United States) case-control study of childhood rhabdomyosarcoma (RMS). Subjects were 322 RMS cases, aged 0-20 years, from the Intergroup Rhabdomyosarcoma Study, and 322 matched controls identified by random-digit telephone dialing. Parents of subjects were interviewed by telephone using a structured questionnaire. Mothers' marijuana use during the year before their child's birth was associated with a 3.0-fold increased risk of RMS in the child (95% confidence interval [CI] = 1.4-6.5) and maternal cocaine use was associated with a 5.1-fold increased risk (CI = 1.0-25.0). Risk was increased 3.1-fold (CI = 1.4-6.7) with use of any recreational drug. Fathers' marijuana use was associated with a 2.0-fold increased risk (CI = 1.3-3.3), cocaine use with a 2.1-fold increased risk (CI = 0.9-4.9), and use of any recreational drug with a 2.0-fold (CI = 1.3-3.3) increased risk. Case mothers' cocaine use and both parents' marijuana use were associated with their children being diagnosed at a significantly younger age. It was not possible to determine whether cocaine and marijuana have independent effects, since use of the two drugs was materially correlated. Similarly, mothers' and fathers' use of these drugs was highly correlated. In summary, parents' marijuana and cocaine use during the year preceding their child's birth may increase, by twofold to fivefold, the risk of RMS in their children.

Adolescent↗

PubMed1992

Vasoactive intestinal peptide receptor expression on human lymphoblasts.

This study was designed to determine which (if any) subtypes of leukemic blasts express a functional receptor for vasoactive intestinal peptide (VIP). Blasts harvested from bone marrow of 38 newly diagnosed patients were classified as acute lymphocytic leukemia (CALLA + pre-B-cell leukemia, CALLA-, pre-B-cell leukemia, T-cell leukemia) or acute myeloid leukemia based on cytochemical and histochemical markers. Of the 32 patients with lymphocytic leukemia, 22 expressed the VIP receptor as evidenced by VIP-mediated activation of adenylate cyclase in cell homogenates. Binding of 125I-VIP to ALL cells correlated with the ability of VIP to activate adenylate cyclase. The VIP receptor was not identified in myeloid blasts from any of six patients. Further correlation of 125I-VIP binding and VIP-mediated stimulation of adenylate cyclase was demonstrated in transformed cell lines: a pre-B-cell line (Nalm 6) and a T-cell line (Molt 4b) exhibited high-affinity binding of 125I-VIP and VIP-mediated activation of adenylate cyclase, whereas neither the histiocytic line (U937) nor the myelocytic line (HL60) appeared to express the VIP receptor. These observations suggest a role for VIP in the proliferation or differentiation of human T and B lymphocytes.

Adenylyl Cyclases↗

PubMed1992

Pharmacokinetics and safety of prochlorperazine in paediatric patients receiving cancer chemotherapy.

Nausea and vomiting are common clinical problems in patients receiving cancer chemotherapy. Metoclopramide is often used but frequently causes extrapyramidal reactions. As an alternative, prochlorperazine is prescribed but no data on its pharmacokinetics in paediatric patients are available to guide the choice of suitable dosages. The primary objective of this study was to evaluate the pharmacokinetics and safety of intravenous prochlorperazine in paediatric patients receiving cancer chemotherapy. Eleven patients (ages 1-9 years) who received high doses of cisplatin or cyclophosphamide were given three to four intermittent doses of 0.2 mg/kg prochlorperazine i.v. over a period of 6-9 h. Multiple blood samples were collected and prochlorperazine was quantified by a specific gas-liquid chromatographic method. The peak serum concentrations ranged from 402 to 5,608 ng/ml. The total clearance and elimination half-life ranged from 0.03 to 0.28 (mean: 0.12) litre/kg/h, and from 1.2 to 15.5 (mean: 5.6) h, respectively. No adverse effects were observed in our patients. Three patients had uncontrolled episodes of vomiting during prochlorperazine therapy. These data suggest: (i) that there was a substantial interpatient variability in prochlorperazine pharmacokinetics thus the dose requirement differed among patients; and (ii) that prochlorperazine appeared safe at the doses used but higher doses may be required to control nausea and vomiting in some paediatric patients receiving high-dose cisplatin or cyclophosphamide therapy.

Adolescent↗

PubMed1991

Second neoplasms after acute lymphoblastic leukemia in childhood.

BACKGROUND: Effective forms of treatment for acute lymphoblastic leukemia (ALL) in childhood now result in survival rates above 70 percent at five years, but the treatments are potentially carcinogenic. To determine the magnitude of this risk and identify possible risk factors for the development of second neoplasms, we studied a large cohort of children treated for ALL. METHODS AND RESULTS. We undertook a retrospective cohort study of 9720 children who had been given a diagnosis of ALL between June 1972 and August 1988 and had been treated according to the therapeutic protocols of the Children's Cancer Study Group. The median follow-up was 4.7 years (range, 2 months to 16 years). We found that 43 second neoplasms occurred among the children in the cohort, including 24 neoplasms of the central nervous system, 10 new leukemias and lymphomas, and 9 other neoplasms. This represented a 7-fold excess of all cancers and a 22-fold excess of neoplasms of the central nervous system. The estimated cumulative proportion of children in whom a second neoplasm developed was 2.53 percent 15 years after diagnosis (95 percent confidence limits, 1.74 percent and 3.38 percent). An even higher risk, particularly of central nervous system tumors, was evident in children five years of age or less at the time of the diagnosis of ALL (P = 0.012). All central nervous system neoplasms developed in children who had previously undergone irradiation. There was no association with exposure to cyclophosphamide or anthracyclines. CONCLUSIONS: There is a substantial excess of second neoplasms, especially of the central nervous system, among children treated for ALL. Children five years old or younger and those receiving radiation are at higher risk, especially for second tumors arising in the central nervous system.

Central Nervous System Neoplasms↗

PubMed1991

A comparison of induction and maintenance therapy for acute nonlymphocytic leukemia in childhood: results of a Pediatric Oncology Group study.

Two hundred fifty-six children with previously untreated acute nonlymphocytic leukemia (ANLL) were evaluated on a Pediatric Oncology Group (POG) phase III randomized trial of both induction and continuation chemotherapies. Induction therapy compared vincristine, cytarabine, and dexamethasone (VADx) with daunorubicin, cytarabine, and thioguanine (DAT). The complete remission (CR) rate using DAT was superior (82% v 61%, P = .02). Postremission therapy consisted of either "standard" two-cycle therapy or a more intensive four-cycle regimen given for 2 years. Overall, there was no difference in outcome for patients randomized to either continuation regimen. The overall complete continuous remission rate (CCR) for the "best" induction/continuation therapy combination at 2 years was .50 (SE = .06), at 3 years was .35 (.04), and at 4 years was .34 (.05). Analysis of selected clinical and laboratory parameters demonstrated differences in induction responses favoring DAT induction but did not impact eventual disease-free survival. There were two subgroups of patients who responded better to four-cycle continuation therapy. These were patients with French-American-British (FAB) M1/M2 (2-year CCR was .20 v .44, P = .01) and patients older than 10 years at diagnosis (.32 v .62, P = .004).

Agranulocytosis↗

PubMed1990

The role of timing of high-dose cytosine arabinoside intensification and of maintenance therapy in the treatment of children with acute nonlymphocytic leukemia.

The Children's Cancer Study Group instituted a pilot study to investigate the use of high doses of cytosine arabinoside (AraC) in the intensification phase of treatment for acute nonlymphocytic leukemia (ANLL). Patients achieving remission and not eligible for allogeneic bone marrow transplantation were treated with four doses of high-dose AraC and L-asparaginase. These drugs were repeated either on or after 28 days (q28 days), after recovery of hematologic parameters (for the first 49 patients entered onto this trial); or after 7 days (q7 days), despite dropping blood counts (for the last 53 patients enrolled). After completing an additional 3 months of intensification therapy, patients were then allocated by physician choice to either discontinue therapy or receive 18 28-day cycles of maintenance therapy, including the daily administration of 6-thioguanine. Despite three deaths associated with the toxicity of the aggressive (q7 days) AraC timing, patients receiving this approach demonstrated equal or better disease-free survival from the end of induction (55% versus 42% actuarially at 3 years [P = 0.52]). Maintenance therapy appeared to play no role in improving outcome for people who received the aggressive timing of AraC cycles. Fifty-nine percent were alive disease free actuarially at 3 years from the decision to not give maintenance therapy (n = 27) compared with 62% for those receiving maintenance therapy (n = 16; P = 0.49). On the other hand, patients who received the less aggressive AraC intensification timing (q28 days) had an improved survival rate if maintenance therapy was administered (n = 17) (65% versus 39% for patients not receiving maintenance therapy [n = 24] at 3 years [P = 0.07]). Maintenance therapy therefore may not improve outcome in patients receiving aggressive timing of high-dose AraC but may be important in less intensive postremission regimens in childhood ANLL.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1989

Primary reexcision for patients with 'microscopic residual' tumor following initial excision of sarcomas of trunk and extremity sites.

Among 404 patients with primary tumors of extremity-trunk sites entered in the Intergroup Rhabdomyosarcoma Study (IRS) (1972 to 1984), 154 were placed in clinical group IIa, ie, with negative nodes but with "microscopic residual" (MR) disease, following the initial excisional (not biopsy) procedure. An elective reexcision of the area of the primary tumor (PRE) was performed in 41 of these patients within 35 days (mean interval, 14 days; SE, 0.9) with no intervening therapy. These procedures consisted of wider excision of the tumor "bed," resulting in a technical transfer of these patients from group IIa to group I, ie, complete excision. This reduced intensity of nonsurgical therapy (irradiation and chemotherapy). Among the 41 patients who underwent PRE, the 3-year survival estimate (Kaplan-Meier) was 91% (SE, 4%). This may be compared with the results in 113 patients who remained in group IIa, in which the 3-year survival estimate was 74% (SE, 4%). A second group for comparison consisted of the 73 patients with trunk/extremity tumors who were placed in group I after a single excisional procedure, ie, no PRE, in whom the 3-year survival estimate was 74% (SE, 5%). Recognized prognostic factors influencing survival in these groups were comparable, with the exception of tumor size, ie, the largest tumors (greater than or equal to 10 cm in diameter) were concentrated in groups I and IIa. When patients with tumors greater than or equal to 10 cm in diameter (9.7% of the total) were removed from all three study groups, patients undergoing PRE had longer survival duration estimates than patients in the control groups.

Humans↗

PubMed1988

Congenital anomalies associated with rhabdomyosarcoma: an autopsy study of 115 cases. A report from the Intergroup Rhabdomyosarcoma Study Committee (representing the Children's Cancer Study Group, the Pediatric Oncology Group, the United Kingdom Children's Cancer Study Group, and the Pediatric Intergroup Statistical Center).

Congenital anomalies were identified in 37 of 115 (32%) children and adolescents autopsied with rhabdomyosarcoma. An analysis of sex, age, site, and histology of cases with or without congenital anomalies showed no significant differences. Of the 45 identified anomalies, 14 were considered major and 31 minor. The distribution of the anomalies by system included central nervous (9), genitourinary (10), gastrointestinal (13), and cardiovascular systems (4). Ten patients had complex or miscellaneous anomalies. There was one child with each of the following: Rubinstein-Taybi syndrome, neurofibromatosis, single horseshoe kidney, hemihypertrophy, and Arnold-Chiari malformation. Aniridia was not noted in any case of rhabdomyosarcoma. Individuals with rhabdomyosarcoma have an increased incidence of genitourinary anomalies similar to that in Wilms' tumor. Recent molecular genetic investigations have suggested that rhabdomyosarcoma, Wilms' tumor, and hepatoblastoma share a common pathogenetic mechanism involving chromosome 11. The uniquely increased association of central nervous system anomalies with rhabdomyosarcoma and absence of aniridia would support a different gene locus operative on chromosome 11 for individuals with rhabdomyosarcoma compared to Wilms' tumor. Extensive epidemiologic studies now in progress in patients with rhabdomyosarcoma should provide the incidence of congenital anomalies and potential linkage with prenatal events.

Cardiovascular Abnormalities↗

PubMed1987

Pediatric orofacial and laryngopharyngeal rhabdomyosarcoma. An Intergroup Rhabdomyosarcoma Study report.

Eighty-nine children with localized rhabdomyosarcoma of orofacial and laryngopharyngeal sites were treated in accordance with the first and second Intergroup Rhabdomyosarcoma Study (IRS) protocols (IRS-I and IRS-II) between 1972 and 1984. Treatment included surgery (or biopsy) and chemotherapy for all patients and radiotherapy in the majority. The actuarial estimate of the three-year survival rate for all patients was 83% and did not differ significantly by primary site, histologic findings, or presence of adenopathy. A trend for a worse survival rate was seen in clinical group III patients and in those less than 5 years of age at diagnosis. Factors associated with an increased risk of local/regional relapse included omission of radiotherapy and a radiation dose of less than 40 Gy (4000 rad). We conclude that treatment of these patients as recommended in the IRS-I and IRS-II protocols results in very good local and regional tumor control and survival rates. Salvage therapy for local/regional recurrence may yield long-term remission and possibly cure.

Adolescent↗

PubMed1987

Eight drugs in one day chemotherapy for brain tumors: experience in 107 children and rationale for preradiation chemotherapy.

The development of a new multidrug chemotherapy regimen for primary brain tumors was based upon the cellular heterogeneity within individual tumors, the Goldie-Coldman and Price-Goldie-Hill hypotheses, and known agonistic effects of certain drug combinations and sequences. Eight drugs (vincristine [VCR], hydroxyurea, procarbazine, CCNU, cisplatin, cytosine arabinoside [Ara-C] high-dose methylprednisolone, and either cyclophosphamide or dacarbazine) were administered within 12 hours in an attempt to minimize myelosuppression. Courses were repeated at 2- to 4-week intervals. The regimen was devised to include lipid and water soluble drugs, polar and nonpolar agents, phase-specific and cell-cycle independent agents, and antineoplastics with different mechanisms of action. More than 330 courses of the regimen were administered to 107 children with brain tumors whose tumor had recurred or had been incompletely resected at diagnosis. Tumor response according to protocol-specified criteria and independent review was evaluable in 78% of the patients. After just two cycles of chemotherapy and within a 4- to 6-week interval, 50% had an objective tumor response including 15.5% who had a complete response (CR). Nephrotoxicity and high-frequency hearing losses were noted after three to five courses of therapy in approximately half of the patients. Transfusions with red cells or platelets and use of antibiotics for fever and neutropenia were required in 10% to 25% of patients. The regimen appears satisfactory for preradiation chemotherapy in newly diagnosed patients with residual tumor after surgery, but it must be compared with standard therapeutic approaches in prospective controlled trials before its relative value can be established.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1987

Rhabdomyosarcoma in children and adolescents. A review.

Children and adolescents with RMS presently have an overall survival of 60 to 65 per cent when treated with multimodality therapy. Those individuals with favorable histologic features and either complete resection or microscopic residual have an 80 to 85 per cent probability of long-term survival. These accomplishments by the IRS committee of the Children's Cancer Study Group and the Pediatric Oncology Group have been extended to thousands of patients. Other investigators in the United States, Great Britain, and Europe, working both in collaboration and independently of the IRS, have been responsible for innovative therapies, which should further reduce the mortality and morbidity of this common soft tissue sarcoma. Increasing emphasis is being placed on the tumor biology, molecular genetics, and epidemiology of RMS, as well as on the quality of life in survivors. At the fifteenth anniversary of its inception, the IRS has fulfilled the expectations of its founders as a model for intergroup collaborative research. Credit for these accomplishments can only go to the hundreds of investigators and their patients who have participated in these studies.

Adolescent↗

PubMed1986

The prognostic significance of age and pattern of metastases in stage IV-S neuroblastoma.

Stage IV-S neuroblastoma is a unique disseminated neoplasia characterized by remote disease to the liver, skin, or bone marrow. Stage IV-S patients have frequent spontaneous remissions and a 60% to 90% survival rate. Many investigators have recommended minimal or no therapeutic intervention; however, some patients do experience progressive disease and ultimately die of neuroblastoma. Many authors have commented on single prognostic factors such as age and site of metastatic involvement. Five newborns were recently seen at Walter Reed Army Medical Center with Stage IV-S neuroblastoma. Four of these children died of mechanical complications associated with massive hepatomegaly, prompting this review of Stage IV-S neuroblastoma to determine prognostic factors.

Age Factors↗

PubMed1986

Progressive change in lymphocyte distribution and degree of hypergammaglobulinemia with age in children with hemophilia.

Fifty asymptomatic, pediatric hemophiliacs were examined for distribution of T-cell subsets, responsiveness to mitogen stimulation, interleukin-2 production, hypergammaglobulinemia, and the presence of antibody to virus including the human T-lymphotrophic virus type III (HTLV-III). Hemophilia A patients receiving factor VIII concentrate as replacement therapy had the most pronounced changes including decreased T4/T8 ratios and lower in vitro responsiveness to both phytohemagglutinin and pokeweed mitogen. Hemophilia A patients treated with cryoprecipitate and hemophilia B patients did not demonstrate these changes. Regardless of replacement therapy, hemophiliacs demonstrated a progressive decrease in the T4/T8 ratio and a progressive increase in the degree of IgG hypergammaglobulinemia as they aged. The amount of factor or cryoprecipitate or exposure to virus did not influence the T4/T8 ratio. These changes appear to be a result of chronic product exposure, which becomes more pronounced with increasing age.

Acquired Immunodeficiency Syndrome↗

PubMed1986

Effect of retinoic acid on myeloid antigen expression and clonal growth of leukemic cells from children with acute non lymphocytic leukemia--a Pediatric Oncology Group Study.

We have used a panel of 5 monoclonal antibodies against normal myeloid-differentiation antigens to determine retinoic acid-induced changes in cell surface antigens on ANLL bone marrow cells from 24 children at the time of diagnosis. Two of these antibodies (T5A7 and 5F1) detect antigens expressed on normal mature granulocytes and on all monocytes, respectively. The percentage of positive cells for each monoclonal antibody was determined by indirect immunofluorescence. After 5 days incubation with 1 microM RA in liquid culture, cells from 11 of 24 patients showed substantially increased expression of one or both antigens detected by T5A7 and 5F1. Leukemic bone marrow cells from these patients were also cultured in methylcellulose medium with and without 1 microM RA for one week, and cells from 16 of 24 patients showed clonal growth. Cultures from 10 of these 16 patients showed RA-induced inhibition of colony growth; of these 10 patients, cultures from six patients showed RA-induced increases in antigens associated with maturing myeloid cells. This suggests that the RA-induced inhibition of clonal growth observed with leukemic cells from these patients may be accompanied by the increased expression of maturation-associated myeloid antigens by these cells in the presence of RA.

Acute Disease↗

PubMed1986

HTLV-III status and abnormalities in T lymphocyte distribution in children with hemophilia A.

Children with hemophilia A are at risk for the acquired immunodeficiency syndrome (AIDS). Clinically asymptomatic hemophiliacs demonstrate many immune abnormalities that might represent exposure to the AIDS agent through blood products or be a natural reaction to their therapy. In this study, we examined lymphocyte subset distribution in children with hemophilia A who had been exposed to HTLV-III as determined by antibody seroconversion. Seroconversion to HTLV-III was confirmed using Western blot analysis. The lymphocyte subsets studied included T4+ and T8+ cells. The distribution of lymphocyte subsets in children with hemophilia A was independent of seroconversion to HTLV-III. Children with hemophilia A treated with commercial factor VIII concentrate had normal numbers of circulating T4+ lymphocytes and significantly increased numbers of circulating T8+ lymphocytes compared with their nontransfused age-matched counterparts. An increased number of T8+ lymphocytes was not observed, however, in children treated exclusively with cryoprecipitate. These results suggest that HTLV-III alone cannot account for changes in lymphocyte subsets in hemophiliacs. Higher antigenic protein loads in factor VIII concentrate or additional factors might account for the increased absolute numbers of T8+ lymphocytes and represent a natural response to therapy.

Acquired Immunodeficiency Syndrome↗

PubMed1985

Rhabdomyosarcoma of the biliary tree in childhood. A report from the Intergroup Rhabdomyosarcoma Study.

Ten cases of rhabdomyosarcoma of the biliary tree (RMS/BT) in children are reported in this review of the Intergroup Rhabdomyosarcoma Study (IRS) I and II. RMS/BT constitutes 0.8% of evaluable tumors on IRS I and II. Intermittent obstructive jaundice with or without abdominal distention, fever, and loss of appetite is the typical presentation. Attribution of these symptoms to hepatitis commonly delayed definitive treatment. Demonstration of a mass in the porta hepatitis by ultrasound led quickly to surgical consultation and an exploratory laparotomy. Intraoperative cholangiography was a valuable technique in establishing the level of biliary tree obstruction and verifying a functioning drainage procedure. Resection of the mass with only microscopic or minimal gross residual disease was possible at the initial surgery in six of the ten patients. Included in this group are all four of the surviving patients. The continuity of bile flow was usually maintained by variations of a Roux-en-Y jejunostomy. Histology was embryonal RMS with some botryoid elements. Consultation with a surgical pathologist during the course of the surgery was of invaluable assistance. Multi-drug chemotherapy and radiotherapy consistent with the IRS protocols were given postoperatively. A second-look surgery was useful in evaluating residual or recurrent disease. Four patients are surviving free of disease at 6 months, 3, 6 1/4, and 6 1/2 years from diagnosis, respectively. This review demonstrates that a multidisciplinary approach in RMS/BT can lead to long-term survival.

Bile Duct Neoplasms↗