Biomedical subjects

J Kühl

Publications and source records attributed to J Kühl.

At least 19 recordsLinked to original sources

PubMed2004

Surgery and adjuvant dendritic cell-based tumour vaccination for patients with relapsed malignant glioma, a feasibility study.

Patients with relapsed malignant glioma have a poor prognosis. We developed a strategy of vaccination using autologous mature dendritic cells loaded with autologous tumour homogenate. In total, 12 patients with a median age of 36 years (range: 11-78) were treated. All had relapsing malignant glioma. After surgery, vaccines were given at weeks 1 and 3, and later every 4 weeks. A median of 5 (range: 2-7) vaccines was given. There were no serious adverse events except in one patient with gross residual tumour prior to vaccination, who repetitively developed vaccine-related peritumoral oedema. Minor toxicities were recorded in four out of 12 patients. In six patients with postoperative residual tumour, vaccination induced one stable disease during 8 weeks, and one partial response. Two of six patients with complete resection are in CCR for 3 years. Tumour vaccination for patients with relapsed malignant glioma is feasible and likely beneficial for patients with minimal residual tumour burden.

Adjuvants, Immunologic↗

PubMed2004

Subdural enhancement on postoperative spinal MRI after resection of posterior cranial fossa tumours.

In malignant brain tumours which may disseminate staging, usually by cranial and spinal MRI is necessary. If MRI is performed in the postoperative period pitfalls should be considered. Nonspecific subdural contrast enhancement on spinal staging MRI is rarely reported after resection of posterior fossa tumours, which may be mistaken for dissemination of malignancy. We investigated the frequency of spinal subdural enhancement after posterior cranial fossa neurosurgery in children. We reviewed 53 postoperative spinal MRI studies performed for staging of paediatric malignant brain tumours, mainly infratentorial primitive neuroectodermal tumours 2-40 days after surgery. There was contrast enhancement in the spinal subdural space in seven cases. This was not seen in any of eight patients who had been operated upon for a supratentorial tumour. After resection of 45 posterior cranial fossa tumours the frequency of subdural enhancement was 15.5%. MRI showing subdural enhancement was obtained up to 25 days postoperatively. No patient with subdural enhancement had cerebrospinal fluid (CSF) examinations positive for tumour cells or developed dissemination of disease in the CSF. Because the characteristic appearances of subdural contrast enhancement, appropriate interpretation is possible; diagnosis of neoplastic meningitis should rarely be impeded. Because of the striking similarity to that in patients with a low CSF-pressure syndrome and in view of the fact that only resection of tumours of the posterior cranial fossa, usually associated with obstructive hydrocephalus, was followed by this type of enhancement one might suggest that rapid changes in CSF pressure are implicated, rather the effects of blood introduced into the spinal canal at surgery.

Adolescent↗

PubMed2003

[Differential infratentorial brain tumor diagnosis in children].

With the exception of the first year of life, infratentorial brain tumors are more frequent in the first decade than tumors in the supratentorial compartment. In particular these are cerebellar low-grade astrocytomas, medulloblastomas, brainstem gliomas and ependymomas of the fourth ventricle. The morphology on MRI and CT and the mode of dissemination permit differential diagnosis in many cases. To allow correct stratification into different treatments in possibly disseminating malignant brain tumors, knowledge of the status of dissemination is essential, and therefore not only cranial but also spinal MRI is indispensable for staging. If the spinal MRI is performed in the immediate postoperative period, knowledge of the normal non-specific purely postoperative changes, often seen as enhancement in the subdural spinal spaces, is necessary in order to avoid misinterpretation as meningial seeding. The differential diagnosis of pediatric infratentorial brain tumors and the morphology of subdural enhancement are illustrated with typical images. The natural history of the most frequent tumors and its importance for treatment decisions is discussed in light of the literature.

Brain↗

PubMed2002

Short courses of intravenous empirical antibiotic treatment in selected febrile neutropenic children with cancer.

BACKGROUND: Since the optimal duration of antibiotic therapy in febrile neutropenic patients is not clear, we evaluated the safety and efficacy of short courses of intravenous antibiotic treatment in selected pediatric cancer patients admitted for fever and neutropenia. PATIENTS AND METHODS: We retrospectively analyzed the clinical course of children with chemotherapy-induced neutropenia and fever. All patients were treated with empirical intravenous antibiotics. In episodes of fever of unknown origin (FUO), treatment regimen allowed discontinuation of antibiotics and early hospital discharge regardless of absolute neutrophil count (ANC) or evidence of bone marrow recovery as long as patients were afebrile for at least 24 h and had been treated for a minimum of 72 h. RESULTS: 106 episodes of febrile neutropenia occurred in 56 patients. 84 episodes were classified as FUO and intravenous antibiotic therapy was discontinued regardless of ANC when patients met the criteria described above. No death or major complication occurred. None of the patients had to be rehospitalized for recurrent fever or infection. CONCLUSION: Discontinuation of intravenous antibiotics regardless of ANC or evidence of bone marrow recovery seems safe and effective in pediatric cancer patients with FUO when children are afebrile for at least 24 h and are treated for a minimum of 72 h.

Adolescent↗

PubMed2001

Population-based epidemiologic data on brain tumors in German children.

BACKGROUND: Brain tumors are the most common disease group of solid tumors in childhood, and children with brain tumors have a relatively poor survival rate. Epidemiologic data from a population-based cancer registry provide the necessary information to obtain a full picture of the frequency of this disease, which is a great challenge in pediatric oncology. METHODS: The German Childhood Cancer Registry (GCCR) is a population-based registry. The level of completeness of patient registration is 95%, but it is somewhat lower for patients with brain tumors. More than 300 children with newly diagnosed brain tumors are reported every year. Analyses of GCCR data are performed according to the International Classification of Childhood Cancer and the recently published World Health Organization classification of tumors of the nervous system. In addition, incidence rates of childhood brain tumors in Germany are compared with those of other countries, as published by the International Agency for Research on Cancer. RESULTS: In the years 1990-1999, a total of 3268 brain tumors were observed (excluding intracranial and intraspinal germ cell tumors). The respective incidence rate for children age < 15 years was 2.6 per 100,000 children and lies between the rates from other countries, which range between 1.7 and 4.1 per 100,000 children. The most common brain tumors were astrocytomas (41.7%), medulloblastomas (18.1%), ependymomas (10.4%), supratentorial primative neuroectodermal tumors (PNETs; 6.7%), and craniopharyngiomas (4.4%). They were located mainly in the cerebellum (27.9%) and the cerebrum (21.2%). The 5-year survival rate for all brain tumors was 64%, with the poorest prognosis for children with PNET. CONCLUSIONS: The large data base of the GCCR made it possible to present representative data on patients with childhood tumors of the central nervous system in Germany. The data quality was high, not least because of the strong cooperation with corresponding clinical trials. However, for children with central nervous system tumors, the ascertainment of newly diagnosed patients needs further improvement.

Adolescent↗

PubMed2001

Cytogenetic and histopathologic studies of congenital supratentorial primitive neuroectodermal tumors: a case report.

Primitive neuroectodermal tumors (PNET) represent about 25% of primary central nervous system tumors in childhood, but congenital PNETs are rare. Cytogenetic studies and studies on molecular pathology have identified several genetic alterations in medulloblastoma, but molecular investigations on supratentorial PNETs are infrequent. We present a male newborn with a large congenital PNET of the right cerebral hemisphere and the molecular analysis of the tumor. Tumor tissue was investigated by routine histology and immunohistochemistry. Fluorescence in-situ hybridization was carried out on native tumor tissue to investigate deletions on chromosome 17p and to analyze c-Myc or N-Myc amplifications. Histologic examination revealed a primitive neuroectodermal tumor with massive extension covering almost the entire right hemisphere. Genetic analysis of the native tumor tissue of our patient excluded a deletion of chromosome 17p. An amplification of the c-Myc or N-Myc oncogene was absent using fluorescence in-situ hybridization. Despite unremarkable genetic analysis in our case prognosis was poor, suggesting that there are additional, yet unknown constitutional genetic aberrations in the pathogenesis of congenital supratentorial PNET.

Biomarkers, Tumor↗

PubMed2001

[Current and future strategies in interdisciplinary treatment of medulloblastomas, supratentorial PNET (primitive neuroectodermal tumors) and intracranial germ cell tumors in childhood].

BACKGROUND: The chances for cure in medulloblastoma, supratentorial primitive neuroectodermal tumors (stPNET) and intracranial germ cell tumors have decisively improved within the last decades. Today long-term survival in the range between 60% and 80% and more than 90%, respectively, can be achieved. The low incidence of brain tumors in childhood and the necessity for optimal patient care has led to the fact that more than 90% of children are treated within national and international controlled studies today in order to assure a constant improvement of therapeutic outcome. Recent developments in neurosurgery achieved complete tumor resections in the majority of children at a low risk for morbidity and mortality. METHODS: Systemic irradiation of neuroaxis is an essential part in the management of medulloblastoma, stPNET and intracranial germ cell tumors. The introduction of quality assurance programs in radiooncology assures a precise radiotherapy of target volumes and is a prerequisite to improve survival. RESULTS: Hyperfractionated radiotherapy has the potential of increasing dose to tumor more safely without increasing the risk for late adverse effects. Pilot studies revealed excellent tumor control in medulloblastoma with acceptable acute toxicity and a long-term survival of up to 96%. In medulloblastoma stereotactic radiation techniques reveal an acceptable toxicity and promising results in tumor control in recurrent disease or as primary treatment. They are now part of future treatment protocols in case of persisting residual tumor. Radiotherapy alone in pure germinoma is continuously yielding high cure rates. In secreting germ cell tumors cisplatin containing chemotherapies in conjunction with radiotherapy achieve a long-term survival rate of 80% today. Especially in high risk medulloblastoma and secreting germ cell tumors chemotherapies are playing an increasingly important role in the interdisciplinary management. It can be expected that future developments of chemotherapeutic protocols and the introduction of new cytostatic substances will further improve the therapeutic outcome. CONCLUSIONS: The therapeutic endeavors of all those caring for children are aiming to study modifications of the therapeutic components in the interdisciplinary approach in order to optimize the therapeutic strategies. In future the affected children and young adolescents should be accrued for the forthcoming cooperative, prospective trial HIT 2000 and ongoing trial SIOP CNS GCT 96, respectively, in order to provide the body of data supporting the selection of novel and optimized approaches for future treatment strategies.

Adolescent↗

PubMed2001

Medulloblastoma displays distinct regional matrix metalloprotease expression.

Matrix metalloproteases (MMPs) play an important role in tissue remodeling and neoangiogenesis during tumor progression. Little is known about the presence and regional distribution of MMPs in medulloblastomas. Based on immunohistochemical, immunocytochemical and zymographical analysis is the present study illustrates the differential pattern of MMP expression for the medulloblastoma compared to that of glioma and ependymoma. In 10 examined medulloblastoma tumors gelatinase-A was strongly expressed by clusters of tumor cells. Gelatinase-B was, similar to glioma and ependymoma, predominantly found around endothelial cells. The DAB signal for macrophage metalloelastase was seen around macrophages and matrilysin was expressed by single tumor cells. Stromelysin-1 protein was detected in medulloblastoma but not in glioma or ependymoma. From the presented data it follows that each tumor entity might display its own characteristic MMP expression pattern.

Astrocytoma↗

PubMed2001

Idarubicin improves blast cell clearance during induction therapy in children with AML: results of study AML-BFM 93. AML-BFM Study Group.

In the randomized trial AML-BFM 93 we compared 60 mg/m2/day daunorubicin with 12 mg/m2/day idarubicin for 3 days each, combined with cytarabine and etoposide during induction. Results showed a significant better blast cell reduction in the bone marrow on day 15 in patients of the idarubicin arm (25 of 144 = 17% of patients with > or = 5% blasts compared to 46 of 149 = 31% of patients after daunorubicin, Pchi2 = 0.01). This was, however, mainly seen in high risk patients treated with idarubicin (19% vs 38%, Pchi2 = 0.007). Cardiotoxicity, WHO grade 1-3 shortening fraction reduction after induction occurred in 6% patients in both arms. Bone marrow toxicity differed slightly with a median recovery time of neutrophils >500/microl of 25 days (daunorubicin) compared to 27 days (idarubicin), P = 0.05. In the total group of patients probabilities of 5 years event-free survival and disease-free survival were similar for patients treated with daunorubicin or idarubicin (49% +/- 4% vs 55% +/- 4% and 57% +/- 4% vs 64% +/- 4%, P logrank 0.29 and 0.15, respectively). However, in patients presenting with more than 5% blasts on day 15 there was a trend for a better outcome after treatment with idarubicin (P logrank 0.06). Together with the early effect seen for high risk patients these results indicate a better efficacy of idarubicin than of daunorubicin during induction with a similar rate of toxicity.

Antibiotics, Antineoplastic↗

PubMed2000

Postoperative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of medulloblastoma in childhood: results of the German prospective randomized trial HIT '91.

PURPOSE: The German Society of Pediatric Hematology and Oncology (GPOH) conducted a randomized, prospective, multicenter trial (HIT '91) in order to improve the survival of children with medulloblastoma by using postoperative neoadjuvant chemotherapy before radiation therapy as opposed to maintenance chemotherapy after immediate postoperative radiotherapy. METHODS AND MATERIALS: Between 1991 and 1997, 158 patients were enrolled and 137 patients randomized. Seventy-two patients were allocated to receive neoadjuvant chemotherapy before radiotherapy (arm I, investigational). Chemotherapy consisted of ifosfamide, etoposide, intravenous high-dose methotrexate, cisplatin, and cytarabine given in two cycles. In arm II (standard arm), 65 patients were assigned to receive immediate postoperative radiotherapy, with concomitant vincristine followed by 8 cycles of maintenance chemotherapy consisting of cisplatin, CCNU, and vincristine ("Philadelphia protocol"). All patients received radiotherapy to the craniospinal axis (35.2 Gy total dose, 1.6 Gy fractionated dose / 5 times per week followed by a boost to posterior fossa with 20 Gy, 2.0 Gy fractionated dose). RESULTS: During chemotherapy Grade III/IV infections were predominant in arm I (40%). Peripheral neuropathy and ototoxicity were prevailing in arm II (37% and 34%, respectively). Dose modification was necessary in particular in arm II (63%). During radiotherapy acute toxicity was mild in the majority of patients and equally distributed in both arms. Myelosuppression led to a mean prolongation of treatment time of 11.5 days in arm I and 7.5 days in arm II, and interruptions in 35% of patients in arm I. Quality control of radiotherapy revealed correct treatment in more than 88% for dose prescription, more than 88% for coverage of target volume, and 98% for field matching. At a median follow-up of 30 months (range 1.4-62 months), the Kaplan-Meier estimates for relapse-free survival at 3 years for all randomized patients were 0.70+/-0.08; for patients with residual disease: 0.72+/-0.06; without residual disease: 0.68+/-0.09; M0: 0.72+/-0.04; M1: 0.65+/-0.12; and M2/3: 0.30+/-0.15. For all randomized patients without M2/3 disease: 0.65+/-0.05 (arm I) and 0.78+/-0.06 (arm II) (p < 0.03); patients between 3 and 5.9 years: 0.60+/-0.13 and 0.64+/-0.14, respectively, but patients between 6 and 18 years: 0.62+/-0.09 and 0.84+/-0.08, respectively (p < 0.03). In a univariate analysis the only negative prognostic factors were M2/3 disease (p < 0.002) and an age of less than 8 years (p < 0.03). CONCLUSIONS: Maintenance chemotherapy would seem to be more effective in low-risk medulloblastoma, especially in patients older than 6 years of age. Neoadjuvant chemotherapy was accompanied by increased myelotoxicity of the subsequent radiotherapy, causing a higher rate of interruptions and an extended overall treatment time. Delayed and/or protracted radiotherapy may therefore have a negative impact on outcome. M2/3 disease was associated with a poor survival in both arms, suggesting the need for a more intensive treatment. Young age and M2/3 stage were negative prognostic factors in medulloblastoma, but residual or M1 disease was not, suggesting a new stratification system for risk subgroups. High quality of radiotherapy may be a major contributing factor for the overall outcome.

Adolescent↗

PubMed2000

Combined postoperative irradiation and chemotherapy for anaplastic ependymomas in childhood: results of the German prospective trials HIT 88/89 and HIT 91.

PURPOSE: To evaluate the outcome in children with anaplastic ependymomas after surgery, irradiation, and chemotherapy; and to identify prognostic factors for survival. METHODS AND MATERIALS: Fifty-five children (n = 27 girls, 28 boys; median age at diagnosis, 6.2 years) with newly diagnosed anaplastic ependymomas were treated in the multicenter, prospective trials HIT 88/89 and HIT 91. Macroscopic complete resection was achieved in 28 patients; 27 patients underwent incomplete resection. All patients received chemotherapy before (n = 40) or after irradiation (n = 15). The irradiation volume encompassed either the neuraxis followed by a boost to the primary tumor site (n = 40) or the tumor region only (n = 13). No radiotherapy was administered in two patients. RESULTS: Median follow-up was 38 months. The overall survival rate at 3 years after surgery was 75.6%. Disease progression occurred in 25 children with local progression occurring in 20. The median time to disease progression was 45 months. The only significant prognostic factor was the extent of resection (estimated progression-free survival [EPFS] after 3 years was 83.3% after complete resection and 38.5% after incomplete resection) and the presence of metastases at the time of diagnosis (0% vs. 65.8% 3-year EPFS in localized tumors). Age, sex, tumor site, mode of chemotherapy, and irradiation volume did not influence survival. CONCLUSIONS: Treatment centers should be meticulous about surgery and diagnostic workup. Because the primary tumor region is the predominant site of failure it is important to intensify local treatment. Dose escalation by hyperfractionation or stereotactic radiotherapy might be a promising approach in macroscopically residual disease. The role of adjuvant chemotherapy requires further study.

Adolescent↗

PubMed2000

Rhabdoid tumors of the central nervous system.

Rhabdoid tumors of the central nervous system are rare malignancies with a still almost uniformly fatal outcome. There is still no proven curative therapy available. We report our experience with nine patients with central nervous system rhabdoid tumors. Gross complete surgical removal of the tumor was achieved in six patients. Seven patients received intensive chemotherapy. Four of these were treated in addition with both neuroaxis radiotherapy and a local boost directed to the tumor region, while two patients received local radiotherapy only. The therapy was reasonably well tolerated in most cases. Despite the aggressive therapy, eight of the nine patients died from progressive tumor disease, and one patient died from hemorrhagic brain stem lesions of unknown etiology. The mean survival time was 10 months after diagnosis. Conventional treatment, although aggressive, cannot change the fatal prognosis of central nervous system rhabdoid tumors. As these neoplasms are so rare, a coordinated register would probably be a good idea, offering a means of learning more about the tumor's biology and possible strategies of treatment.

Adolescent↗

PubMed2000

Non-Hodgkin's lymphoma in pediatric patients with chromosomal breakage syndromes (AT and NBS): experience from the BFM trials.

BACKGROUND: Lymphoma and leukemia are the commonest malignant diseases in patients with chromosomal breakage syndromes and immunodeficiency (Ataxia teleangiectasia (AT) and Nijmegen breakage syndrome (NBS)). With improved management of infections, malignant disease is more frequently diagnosed and has become one of the commonest causes of death in pediatric AT and NBS. PATIENTS AND METHODS: In three consecutive multicenter therapy trials for pediatric non-Hodgkin's lymphoma (NHL) (NHL-BFM), 1569 patients with newly diagnosed NHL have been registered between 1986 and 1997. Nine patients with AT (n = 5) and NBS (n = 4) were identified and analysed. RESULTS: Median age of patients with AT and NBS at diagnosis of NHL was nine years. NHL-entities differed from non-AT/NBS-patients: diffuse large B-cell lymphomas, n = 7 (78%); ALCL, n = 1; lymphoblastic T-cell lymphoma, n = 1. Cervical nodes, paranasal sinuses and epipharynx were the sites most frequently involved. Stages were: I and II in three patients, III in five and IV in one patient. All patients received polychemotherapy according to tumor-entity and stage, none received radiation. Dose reductions according to individual tolerance concerned mainly ethotrexate, alkylating agents and epipodophyllotoxines. One patient died of toxic complications, two patients relapsed and died, one patient suffered from second malignancy. Five of nine patients are in 1. CCR after a median follow-up of five years. CONCLUSIONS: Patients with AT and NBS suffer from rare entities of pediatric NHL. Curative treatment is possible and should be attempted. Intensity of therapy should be adjusted to individual risk factors and tolerance. Alkylating agents, epipodophyllotoxines should be omitted, dose of MTX should be limited to 1 g/m2. Further cooperative trials using standardized approaches are required.

Adolescent↗

PubMed1999

t(1;2)(q21;p23) and t(2;3)(p23;q21): two novel variant translocations of the t(2;5)(p23;q35) in anaplastic large cell lymphoma.

Cytogenetic investigations in two cases of anaplastic large cell lymphoma (ALCL) showed novel variants of the classical (2;5)(p23;q35) translocation, namely a t(1;2)(q21;p23) and a t(2;3)(p23;q21). The tumor cells in both cases gave positive immunohistochemical labeling for ALK protein (with both monoclonal and polyclonal antibodies), demonstrating that these translocations induce aberrant expression of this kinase and suggesting that genes other than NPM can activate the ALK gene in ALCL. These two cases were shown by an in vitro kinase assay to express ALK kinases (104 kD and 97 kD, respectively), which differed in size from the classical NPM-ALK fusion product (80 kD). Moreover, ALK expression was confined to the cytoplasm of the tumor cells in each case, supporting the hypothesis that the observed nuclear localization of NPM-ALK in classical ALCL is not the site of oncogenic activity of the ALK kinase.

Adolescent↗

PubMed1999

HIT '91 (prospective, co-operative study for the treatment of malignant brain tumors in childhood): accuracy and acute toxicity of the irradiation of the craniospinal axis. Results of the quality assurance program.

BACKGROUND: It was the aim of the quality control program of the randomized trial HIT '91 (intensive chemotherapy before irradiation versus maintenance chemotherapy after irradiation) to assess prospectively the quality of neuroaxis irradiation with respect to the protocol guidelines and to evaluate acute toxicity with respect to treatment arm. PATIENTS, MATERIALS AND METHODS: Data of 134 patients undergoing irradiation of the craniospinal axis were available. Positioning aids, shielding techniques, treatment machines, choice of energy, total dose and fractionation were evaluated. A total of 651 simulation and verification films were analyzed to assess the coverage of the clinical target volume (whole brain, posterior fossa, sacral nerve roots) and deviations of field alignment between simulation and verification of first treatment. Field matching between whole brain and adjacent cranial spinal fields was analyzed with respect to site and width of junction. Acute maximal side effects were evaluated according to a modified WHO score for neurotoxicity, infections, skin, mucosa and myelotoxicity. RESULTS: In 91.3% of patients contemporary positioning aids and individualized shielding techniques were used to assure a reproducible treatment. In 98 patients (73.1%) linear accelerators and in 36 patients (26.8%) Cobalt machines were used. Single and total dose were administered according to the protocol guidelines in more than 90% of patients. In 20.2% of patients the cribriform plate, in 1.4% the middle cranial fossa and in 21.1% the posterior fossa and in 4.5% the 2nd sacral segment were incompletely encompassed by the treatment portals. Ninety-five percent of deviations of field alignment were less than 13.0 mm (whole brain) and 12 mm (cranial spinal field) with a random error between 4.9 and 7.6 mm (whole brain) and 6.9 mm and 9.9 mm (spinal canal), respectively. In 77.5% of patients the junctions between whole brain and cranial spinal fields were placed without a gap. A gap between 5 and 10 mm was left in 15 patients (18.7%), exceeding 10 mm in 3 patients. Acute neurotoxicity and skin reactions were mild, the rate of infections was low in both treatment arms. However, myelotoxicity resulted in interruptions of radiotherapy in 31.9% after intensive chemotherapy as compared to 20.0% without preceding chemotherapy. CONCLUSIONS: In the HIT '91 trial a precise radiotherapy of craniospinal axis has been performed in the majority of patients. Our findings indicate that the high quality is possibly an important contributing factor for the therapeutic outcome. However, preceding intensive chemotherapy caused marked toxicity of subsequent irradiation leading to a high rate of interruptions. Our database is subject to a future analysis of recurrences.

Brain Neoplasms↗

PubMed1999

Chemotherapy of medulloblastoma.

Recent advances in neurosurgical techniques and diagnostic imaging capabilities have facilitated gross total resection and accurate staging of disease extent in a greater proportion of patients. The addition of chemotherapy to surgery and craniospinal radiation has improved the outcome of patients diagnosed with medulloblastoma. Long-term follow-up studies have documented the neuroendocrine and neuropsychological deficits seen in the survivors. This paper reviews key studies using all three modalities over the past two decades and presents on-going therapeutic strategies using a risk-adapted approach. Further areas of basic research and evolving data on studies in relapsed patients are also briefly discussed.

Antineoplastic Agents↗

PubMed1999

Assessment of measuring circulating levels of interleukin-6, interleukin-8, C-reactive protein, soluble Fc gamma receptor type III, and mannose-binding protein in febrile children with cancer and neutropenia.

Circulating levels of interleukin (IL)-6, IL-8, soluble Fc gamma receptor type III (sFc gammaRIII), mannose-binding protein (MBP), and C-reactive protein (CrP) were assessed among febrile children with cancer and neutropenia. Levels of IL-6, IL-8, sFc gammaRIII, MBP, and CrP were measured in serum from 56 pediatric cancer patients at the time of admission for 121 episodes of febrile neutropenia (88 febrile episodes without identifiable source, 5 clinically documented infections, 20 episodes of bacteremia due to gram-positive and 5 due to gram-negative organisms, and 3 fungal infections). IL-6 and IL-8 levels were higher in patients with either bacteremia due to gram-negative organisms or fungal infections than in patients with febrile episodes without an identifiable source (P < .00001 for each). IL-6 and IL-8 levels were higher in children with bacteremia due to gram-negative organisms than in those with bacteremia due to gram-positive organisms (P = .0011 and P = .0003, respectively). The measured levels of CrP, MBP, and sFc gammaRIII were not useful for identifying the type of infection. These preliminary results show the potential usefulness of IL-6 and IL-8 as early indicators for life-threatening infections in febrile cancer patients with neutropenia.

Adolescent↗

PubMed1998

Vertebral remodeling in eosinophilic granuloma of the spine. A long-term follow-up.

STUDY DESIGN: In this study, 14 conservatively treated patients were reviewed who had eosinophilic granuloma of the spine, which had been diagnosed on the basis of histologic study of the vertebral lesion or of specimens from other sites in patients with multiple involvement. The remodeling of the vertebral body was studied in an average follow-up of 5.6 years. OBJECTIVES: To analyze the remodeling process of the involved growing vertebral body in Langerhans Cell Histiocytosis after conservative treatment and to assess the sagittal and frontal profile of the spine at the end of growth. Fourteen patients, aged between 1.2 and 11.3 years, with spinal involvement of a Langerhans' cell histiocytosis were treated in the department of orthopedics between 1980 and 1990. All patients had immobilization of the affected region by a custom-made brace. Six patients with symptomatic lesions had radiotherapy and four patients with disseminated disease were treated with chemotherapy. Clinical and radiologic examinations were made at regular intervals to evaluate the development of the vertebrae during the remodeling process. SUMMARY OF BACKGROUND DATA: In the 14 patients, both sexes were affected equally. The disease was located in the cervical spine in two patients and in thoracic and lumbar vertebrae in seven patients each. Two patients had two vertebral lesions. METHODS: The radiologic evolution of the 16 vertebral lesions was evaluated using follow-up standardized lateral radiographs. The reconstitution of the vertebral height in the presence of vertebra plana was calculated by measuring the ventral distance between the superior and inferior margins of the vertebral body in relation to the adjacent uninvolved vertebra. RESULTS: The measurements showed a growth rate of 1.5-6 (average, 3) in vertebrae with vertebra plana and a growth rate of 1.1-2.7 (average, 1.4) in the unaffected vertebra. The reconstitution of the vertebral height was between 18.2% and 63.8% of the adjacent vertebrae before and between 72.2% and 97% after skeletal maturity. CONCLUSIONS: The results demonstrate that conservative orthopedic treatment with immobilization in a brace is sufficient to allow for optimal vertebral remodeling. Partial to nearly complete reconstitution of vertebral height was seen in all cases. Thus, operative treatment with curettage of the lesion and bone grafting including multisegmental fusion with instrumentation is not necessary. In instances with neurologic impairment, rarely seen in adults, surgical decompression and short fusion of the spine is necessary. Nevertheless, complete staging and biopsy are mandatory for an accurate diagnosis.

Bone Remodeling↗