Search PubMed⌕ Search

Biomedical subjects

J Otten

Publications and source records attributed to J Otten.

At least 37 records · Page 2Linked to original sources
PubMed1998

Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia. European Organization for Research and Treatment of Cancer--Childhood Leukemia Cooperative Group.

BACKGROUND AND METHODS: The implications of the detection of residual disease after treatment of acute lymphoblastic leukemia (ALL) are unclear. We conducted a prospective study at 11 centers to determine the predictive value of the presence or absence of detectable residual disease at several points in time during the first six months after complete remission of childhood ALL had been induced. Junctional sequences of T-cell-receptor or immunoglobulin gene rearrangements were used as clonal markers of leukemic cells. Residual disease was quantitated with a competitive polymerase-chain-reaction (PCR) assay. Of 246 patients enrolled at diagnosis and treated with a uniform chemotherapy protocol, 178 were monitored for residual disease with one clone-specific probe (in 74 percent) or more than one probe (in 26 percent). The median follow-up period was 38 months. RESULTS: The presence or absence and level of residual leukemia were significantly correlated with the risk of early relapse at each of the times studied (P<0.001). PCR measurements identified patients at high risk for relapse after the completion of induction therapy (those with > or =10(-2) residual blasts) or at later time points (those with > or =10(-3) residual blasts). Multivariate analysis showed that as compared with immunophenotype, age, risk group (standard or very high risk), and white-cell count at diagnosis, the presence or absence and level of residual disease were the most powerful independent prognostic factors. CONCLUSIONS: Residual leukemia after induction of a remission is a powerful prognostic factor in childhood ALL. Detection of residual disease by PCR should be used to identify patients at risk for relapse and should be taken into account in considering alternative treatment.

Adolescent↗
PubMed1998

Genetic heterogeneity of neuroblastoma studied by comparative genomic hybridization.

Comparative genomic hybridization (CGH) analysis was performed on 36 neuroblastomas of both low and high stage of disease. This study significantly increases the number of neuroblastoma tumors studied by CGH. Analysis of larger series of tumors is particularly important in view of the different clinical subgroups that are recognized for this tumor. The present data and a comparison with all published CGH data on neuroblastoma provide further insights into the genetic heterogeneity of neuroblastoma. Stage 1, 2, and 4S tumors showed predominantly whole chromosome gains and losses. A similar pattern of whole chromosome imbalances, although less frequent, was observed in stage 3 and 4 tumors, in addition to partial chromosome gains and losses. An increase in chromosome 17 or 17q copy number was observed in 81% of tumors. The most frequent losses, either through partial or whole chromosome underrepresentation, were observed for 1p (25%), 3p (25%), 4p (14%), 9p (19%), 11q (28%), and 14q (31%). The presence of 3p, 11q or 14q deletions defines a genetic subset of neuroblastomas and contributes to the further genetic characterization of stage 3 and 4 tumors without MYCN amplification (MNA) and 1p deletion. The present study also provides additional evidence for a possible role of genes at 11q13 in neuroblastoma. In a few cases, 1p deletion or MNA detected by FISH or Southern blotting was not found by CGH, indicating that the use of a second, independent technique for evaluation of these genetic parameters is recommended.

Adolescent↗
PubMed1998

Treatment of non-metastatic rhabdomyosarcomas in childhood and adolescence. Results of the second study of the International Society of Paediatric Oncology: MMT84.

The second International Society of Paediatric Oncology (SIOP) study for rhabdomyosarcoma (MMT84) had several goals. The two principal aims were: (1) to improve the survival of children with rhabdomyosarcoma; and (2) to reduce the late effects from therapy by restricting the indications for surgery and/or radiotherapy after good response to initial chemotherapy. A further aim was to investigate the role of high-dose chemotherapy in young patients with parameningeal primary tumours. 186 previously untreated eligible patients entered the study. Patients with completely resected primary tumour received three courses of IVA (ifosfamide, vincristine and actinomycin D). Patients with incompletely resected tumour received six to 10 courses of IVA according to stage. Patients achieving complete remission with chemotherapy alone did not usually receive radiotherapy or undergo extensive surgery, but patients remaining in partial remission received local therapy with surgery and/or radiotherapy. Only patients over 5 years of age with parameningeal disease and patients over 12 years with tumours at any site were given systematic irradiation. Complete remission was achieved in 91% (170/186) of all patients. With a median follow-up of 8 years, the 5-year overall survival was 68% (+/- 3% standard error of the mean (SEM) and the 5-year event-free survival 53% (+/- 4% SEM). These results show an improvement over previous SIOP study (RMS75) in which survival was 52% and event-free survival was 47%. Among the 54 patients who exhibited isolated local relapse, 35% (19/54) survived in further remission longer than 2 years after retreatment, including local therapy (surgery +/- radiotherapy). Analysis of the overall burden of therapy received by all surviving children (including primary treatment and treatment for relapse if required) showed that 24% (28/116) were treated by limited surgery followed by three courses of IVA, 29% (34/116) were treated by chemotherapy alone (after initial biopsy) and 13% (15/116) received chemotherapy plus conservative local treatment (limited surgery or radiotherapy for residual disease). Only 34% (39/116) received intensive local therapy defined as radical wide field radiotherapy or radical surgery or both. Compared with the results obtained in the previous SIOP study, treatment in MMT84 was based on response to initial chemotherapy and, despite an overall reduction of the use of local therapy, significantly improved survival for patients with non-metastatic disease. This trial, also for the first time, provides evidence that retreatment after local relapse can achieve long-term second remissions.

Adolescent↗
PubMed1998

The use of the anti-malaria drug Fansidar (pyrimethamine and sulphadoxine) in the treatment of a patient with autoimmune lymphoproliferative syndrome and Fas deficiency.

Fas is a protein that plays a major role in the apoptotic mechanism of several cell types, including white blood cells (WBC). Mutations of the Fas gene in humans are known to lead to autoimmune lymphoproliferative syndrome (ALPS). Glucocorticoids or cytostatic drugs are sometimes used to treat the lymphoproliferation in these patients. When treated with the anti-malaria drug Fansidar, a patient with ALPS showed a marked shrinkage of the lymph node masses, decrease in peripheral blood lymphocytes (PBL) and an increase in neutrophil numbers. In addition, an increased Fas expression was seen on all types of leucocytes.

Antimalarials↗
PubMed1998

Radiographic findings and patterns in multidrug-resistant tuberculosis.

Multidrug-resistant tuberculosis (MDR TB) is prevalent in urban areas with large HIV-positive populations. We retrospectively evaluated the chest radiographs of MDR TB patients at presentation and compared them to patients with drug-sensitive tuberculosis (DS TB). Although the overall radiographic findings and patterns of MDR TB and DS TB were similar, there were significant differences among the MDR TB patients depending on how MDR TB was acquired. Patients who developed MDR TB during an outbreak showed noncavitary consolidations, pleural effusions, and a primary radiographic pattern (70%). On the other hand, patients who acquired MDR TB due to noncompliance with antituberculous therapy often had cavitary consolidations (50%) and generally demonstrated a postprimary radiographic pattern. Cavitation occurred equally in patients with MDR TB who are HIV positive regardless of CD4 cell count. Chest radiographic findings and patterns in MDR TB are most accurately interpreted in conjunction with clinical history, specifically prior TB treatment. Nevertheless, approximately one-third of patients did not show the "expected" radiographic pattern.

AIDS-Related Opportunistic Infections↗
PubMed1998

Unusual evolution of a benign-looking cortical defect of the proximal humerus. A case of intracortical osteosarcoma?

A case of an osteosarcoma following a pathological fracture through a small benign-looking cortical lesion of the proximal humerus is described. The unusual evolution from a small cortical lesion to a malignant lesion raises the question whether this is a case of an intracortical osteosarcoma that has some distinct features from those of previously reported cases.

Bone Cysts↗
PubMed1997

How fast is fast enough for clinical laboratory turnaround time? Measurement of the interval between result entry and inquiries for reports.

We measured the time interval from result entry by the clinical laboratory to inquiry for reports by clinicians as a proxy for the actual turnaround time required to meet current patient care needs and to determine whether different patterns of report inquiry occur among clinical departments. The study included 4,004 complete blood cell (CBC) count reports that were sought by the clinical services using the hospital information system. The median time to report inquiry was 90 minutes for routine inpatient tests, 35 minutes for stat inpatient tests, and 30 minutes for the stat outpatient CBC counts. Most reports (range, 86%-94%) from these three subgroups were requested within 4 hours from entry of the results in the hospital information system. Of the routine outpatient test reports, 14%, 23%, and 31% were requested within the first 2 hours, 4 hours, and 8 hours, respectively. Although the interdepartmental variations in the median time for report inquiry were statistically significant for routine inpatient tests, stat inpatient tests, and stat outpatient tests, inquiries for the preponderance of reports for all three groups were within the first 1.5 to 3 hours from entry of the results in the hospital information system. We conclude that the majority of CBC counts and other tests with effects on immediate patient care management must be performed very rapidly on site and cannot be moved off site without compromising current standards of medical practice.

Blood Cell Count↗
PubMed1997

NB87 induction protocol for stage 4 neuroblastoma in children over 1 year of age: a report from the French Society of Pediatric Oncology.

PURPOSE: NB87 was designed to test the efficacy of a short, non cross-resistant, induction protocol for unselected patients over 1 year of age with stage 4 neuroblastoma. A secondary objective was to compare in a randomized study the toxicity of two modalities of cisplatin administration. PATIENTS AND METHODS: A total of 183 patients received two cycles of alternating sequences: cyclophosphamide 300 mg/m2/d on days 1 to 5, vincristine 1.5 mg/m2/d on days 1 and 5, and doxorubicin 60 mg/m2/d on day 5 (CADO); and cisplatin 40 mg/m2/d and etoposide 100 mg/m2/d on days 1 to 5 (CVP), followed by surgery of the primary tumor (126 patients). Ninety-one were randomized to receive cisplatin either as bolus (BO; n = 48) or continuous infusion (CI; n = 43). International Neuroblastoma Staging System (INSS) and Response Criteria (INRC) were used with emphasis on skeletal evaluation by meta-iodobenzylguanidine (MIBG). RESULTS: Hematotoxicity was predominant, with a higher incidence of neutropenia (P = .01) for CADO and of thrombocytopenia for CVP (P < .001). Severe infections, as well as nonhematologic toxicities, occurred more often after the first sequence. Gastrointestinal complications were predominant during both courses of CVP. The toxic death rate, including surgery, was 3%. Complete remissions (CRs) were less frequent on MIBG (45%) compared with marrow (66%) or other metastases (61%). Combining all metastatic sites resulted in a 39% CR rate. After surgery, the final CR rate was 42%. Nephrotoxicity was minimal in both arms (92% normal clearance for CI v 82% for BO). Hearing loss greater than 40 dB at 6,000 to 8,000 Hz was reported equally in both arms (n = 6 for CI v n = 5 for BO). CONCLUSION: Intensified chemotherapy using CADO/CVP increases CR rates despite a shorter induction duration. However, the rate of MIBG normalization remains unsatisfactory and could be raised through the dose-intensive use of agents such as cyclophosphamide.

Adolescent↗
PubMed1997

Systemic effect of intrathecal methotrexate during the initial phase of treatment of childhood acute lymphoblastic leukemia. The European Organization for Research and Treatment of Cancer Children's Leukemia Cooperative Group.

PURPOSE: The in vivo response to prephase corticosteroid therapy for 1 week has been described as a major prognostic factor in childhood acute lymphoblastic leukemia (ALL). Patients with less than 1,000 blasts/microL at day 8 are considered responders and have a better prognosis. This prephase therapy is usually considered as an evaluation of glucocorticoid sensitivity. In fact, it also includes one intrathecal (IT) injection of methotrexate (MTX). In this study, we try to clarify the influence of this injection of IT MTX on the response to the prephase therapy. PATIENTS AND METHODS: This retrospective study analyzed the response to prephase therapy in 1,044 children with ALL entered onto the European Organization for Research and Treatment of Cancer (EORTC) trial 58881 of the Children's Leukemia Cooperative Group (CLCG). Analysis was restricted to 732 cases with an initial blast count greater than 1,000/microL. The following variables were tested to analyze response to prephase therapy: age, sex, evaluated risk factor (RF), blast count on day 0, actual dose of prednisolone administered, immunophenotype (T v non-T), and day of IT MTX. For statistical analysis, the variable day of IT MTX (D) was stratified into three groups: group 1 if D less than 2, group 2 if D > or = 2 but < or = 6, and group 3 if D greater than 6. RESULTS: All variables tested had a significant influence on response to the prephase therapy. This was especially true for IT MTX: 90.4% responders in group 1, 76.9% in group 2, and 70% in group 3 (P < .001). Immunophenotype was also a major predictor of response to the prephase: 88% responders in B-lineage ALL versus 56.2% in T-lineage ALL. IT MTX had a significant influence in B-lineage ALL (96% responders in group 1, 90% in group 2, and 79% in group 3; P < .001), whereas the influence could not be detected in T-lineage ALL. CONCLUSION: These results clearly demonstrate a therapeutic systemic effect of low doses of IT MTX in childhood ALL, and response to prephase therapy should not be considered as an in vivo test for cortico-sensitivity only. Earlier use of IT MTX leads to a higher percentage of responders.

Antimetabolites, Antineoplastic↗
PubMed1997

Cutaneous involvement in children with acute lymphoblastic leukemia or lymphoblastic lymphoma. The Children's Leukemia Cooperative Group of the European Organization of Research and Treatment of Cancer (EORTC).

OBJECTIVE: Skin involvement in children with acute monocytic leukemia or CD30-positive anaplastic large-cell lymphoma is well-known. In contrast, very little is known about the malignant cutaneous infiltrates in children with acute lymphoblatic leukemia (ALL) or lymphoblastic lymphoma (LBL). This study was designed to determine the frequency of these specific lesions in childhood ALL or LBL and the characteristics of such patients. DESIGN: We studied the clinical and biological findings of children with cutaneous involvement at initial diagnosis of ALL or LBL enrolled between August 1989 and March 1995 in the multicentric trial 58881 of the Children's Leukemia Cooperative Group of the European Organization of Research and Treatment of Cancer (EORTC). RESULTS: Among the 1359 children enrolled in the multicenter trial EORTC 58881, 24 presented with skin involvement at diagnosis. ALL was diagnosed in 15 patients and LBL in 9. In 15 cases, skin lesions were observed within a median time of 6 weeks (range, a few days to 8 months) before the diagnosis of the hematologic disease. Twenty-one children had at least one skin lesion located on the head. Diffuse cutaneous lesions were observed in 7 infants with high-risk ALL. Seventeen of the 24 children remain in the first complete remission (median follow-up of 3 years; range 2 months to 5 years) and 3 are in the second remission with a follow-up of 14 to 24 months. CONCLUSION: The present study demonstrates that cutaneous involvement can be an early manifestation of ALL or LBL. Cutaneous leukemic infiltrates can be observed in children with standard risk as well as in high-risk ALL. Cutaneous involvement in children with LBL is mainly associated with a B-cell precursor immunophenotype of the lymphomatous cells. The most frequent location of skin lesions in children with ALL or LBL is on the head. Further studies are needed to evaluate the prognosis of children with such involvement at diagnosis.

Age Factors↗
PubMed1996

Mitoxantrone-containing regimen for treatment of childhood acute leukemia (AML) and analysis of prognostic factors: results of the EORTC Children Leukemia Cooperative Study 58872.

The objective of this study was to evaluate the feasibility, the toxicity and the efficiency of a BFM-like treatment protocol for acute nonlymphoblastic leukemia (ANLL) of children in which mitoxantrone was substituted for conventional anthracycline. The chemotherapy called for induction (mitoxantrone, cytosine arabinoside, etoposide), consolidation (mitoxantrone, cytosine arabinoside, 6 thioguanine), followed by two intensification courses with cytosine arabinoside plus, respectively, mitoxantrone during the first and etoposide during the second courses. Maintenance therapy consisted of daily 6 thioguanine, four-weekly courses of cytosine arabinoside (s.c. daily during 4 days) and eight-weekly courses of mitoxantrone. The latter drug was pursued up to a total cumulative dose of 150 mg/sqm. Maintenance therapy was stopped at 2 years of diagnosis. Out of 108 patients, 84 (77%) achieved a complete remission, 10 died during induction of hemorrhage, sepsis or pulmonary infiltration by leukemic cells. A total of 32 relapses occurred. The median follow-up was 3.5 years. Actuarial event-free survival, disease-free survival and overall survival at 3 years as 41%, 52%, 56%, respectively. These results compare favorably with most reported data, and cytogenetic findings appear to be the most important prognostic factor.

Adolescent↗
PubMed1996

Dobutamine stress echocardiography in the evaluation of late anthracycline cardiotoxicity in childhood cancer survivors.

Late anthracycline cardiotoxicity has been of increasing concern to pediatric oncologists. An increasing number of patients with cardiac dysfunction has been reported without a good correlation between cardiac function or symptoms and routine echocardiographic follow-up. We studied dobutamine stress echocardiography in patients who had received moderate doses of anthracyclines years before. Twenty-three patients (14 male, 9 female; 7-25 y) who completed chemotherapy with moderate doses of anthracyclines (180-380 mg/m2) more than 2 y previously underwent dobutamine stress echocardiography and were compared with a control group of 26 healthy young people (15 male, 11 female; 6-26 y) matched for age and weight. Dobutamine was administered in three periods up to a rate of 5 micro g/kg/min. Eighty-five percent of the patients showed an abnormal response to dobutamine. Both systolic and diastolic functions were affected. The systolic dysfunction was not related to diminished contractility but to an elevated systolic wall stress due to inadequate cardiac muscle thickening. The diminished wall thickening was related to the length of follow-up. Dobutamine proved to be a very sensitive method to detect clinical and subclinical cardiac dysfunction in patients post anthracycline chemotherapy and questions the concept of a safe dose.

Adolescent↗
PubMed1996

Juvenile myelomonocytic leukemia: analyses of treatment results in the EORTC Children's Leukemia Cooperative Group (CLCG).

Forty-six children with juvenile myelomonocytic leukemia (JMML) diagnosed between 1978 and 1993 in 12 centers were retrospectively studied. There is no evidence that any conventional treatment influences the long-term evolution of JMML. Among 28 patients treated without bone marrow transplantation (BMT), 26 died (median survival: 17 months), two are alive, one in complete remission (CR) after intensive chemotherapy. Allogenic BMT is the best treatment: 18 patients underwent BMT, 11 are in CR (at 9, 15, 22, 25, 41, 45, 49, 53, 66, 90 and 108 months). Conditioning regimens using chemotherapy alone may cure some patients (3/6) occasionally despite autologous reconstitution (1/3); if relapse occurs, a second BMT may be curative (2/3). Among the 12 patients conditioned immediately with TBI, six are in CR, one is in relapse, five died (one of them in durable autologus CR from Schwannoma). It is our opinion that splenectomy is of therapeutic value and seems not to have influenced the incidence of infections complications. We found no argument in favor of intensive chemotherapy before conditioning. Results with HLA-matched unrelated donors are satisfactory. One patient relapsed at 4 months after an unrelated BMT and entered a new CR after discontinuation of cyclosporine.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Control of nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis among healthcare workers and HIV-infected patients.

From 1988 to 1990, an outbreak of multidrug-resistant tuberculosis (MDR-TB) among patients, and an increased number of tuberculin-skin-test conversions among healthcare workers, occurred on the HIV ward of Jackson Memorial Hospital, Miami, Florida, USA. Measures similar to those subsequently recommended in the 1990 Centers for Disease Control and Prevention guidelines were implemented on the HIV ward by June, 1990, and in September, 1992, we evaluated the efficacy of these control measures. Among MDR-TB patients and healthcare workers with tuberculin-skin-test conversions on the HIV ward, we looked for evidence of exposure to HIV ward MDR-TB patients positive for acid-fast bacilli in sputum during initial (January-May, 1990) and follow-up (June, 1990-June, 1992) periods. Exposure before implementation of control measures to an infectious MDR-TB patient on the HIV ward was recorded in 12 of 15 (80%) MDR-TB patients during the initial period and 5 of 11 (45%) MDR-TB patients during follow-up. After implementation of control measures, no episodes of MDR-TB could be traced to contact with infectious MDR-TB patients on the HIV ward. Skin-test conversions among workers on the HIV ward declined from 7 of 25 (28%) during the initial period to 3 of 17 (18%) in the early (June, 1990-February, 1991) and 0 of 23 in the late (March, 1991-June, 1992) follow-up periods (p < 0.01). Skin-test conversions among healthcare workers were not associated with increased exposure to MDR-TB patients, and were not significantly higher among workers on the HIV ward than on a control ward without tuberculosis patients (3/27 vs 0/16). These data demonstrate that implementation of measures similar to the Centers for Disease Control and Prevention 1990 tuberculosis-control guidelines were effective in halting transmission of MDR-TB to healthcare workers and HIV-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed1995

Tropisetron in the prevention of nausea and vomiting in 131 children receiving cytotoxic chemotherapy.

Tropisetron (Navoban, Sandoz Pharma Ltd., Basel, Switzerland), a selective antagonist of the serotonin receptor (5-HT3) dosed once-daily at 0.2 mg/kg (with a maximum of 5 mg daily), was evaluated in the prevention of chemotherapy-induced nausea and vomiting in 131 children with a median age of 5 years (age 10 weeks to 21 years). Acute lymphocytic leukemia was the most common malignancy (49%). Most children (82%) had received cytotoxic chemotherapy before enrollment. Patients received tropisetron during one or more courses of chemotherapy (455 courses in total). Tropisetron was administered slowly intravenously as a single dose before the start of chemotherapy on day 1 and intravenously or by mouth the subsequent days as a single daily dose (median treatment duration: 5 days). Response to tropisetron per 24 hour period on the first 5 days of each chemotherapy course was graded as complete (absence of both nausea and vomiting), partial (one to four vomits and/or less than 5 hours of nausea), or failure. Overall complete response on day 1 was observed in 305 out of 455 chemotherapy courses (67%). The patients receiving intravenous chemotherapy (N = 92) had a 70% complete response rate and a 26% partial response rate on day 1, both for course 1 and course 2. The percentage of complete responders increased the subsequent days of the course. Emesis after day 1 was observed primarily during courses with the most emetogenic chemotherapy. No side-effects of tropisetron other than a single case of diarrhoea were documented in this study.

Adolescent↗