Late Effects Following Treatment of Hodgkin Lymphoma During Childhood and Adolescence. Results of the Hodgkin Lymphoma Late Effects Research Project.

Survival rates have been excellent in patients treated for Hodgkin lymphoma (HL) during childhood and adolescence. Unfortunately, severe treatment related late effects have been observed. It was therefore an important aim of the cooperative pediatric HL therapy studies in Germany to reduce the number of late effects without jeopardizing the excellent treatment results. Progress and relapses of HL were analyzed to obtain important information for the future salvage therapy. All late effects were documented and their etiologies analyzed. Information obtained from bacterial infections and late deaths following splenectomy were used to inform patients at risk and their local physicians about necessary preventive measurements. Procarbazine was recognized as major gonadotoxic agent in boys and eliminated successively from the treatment regimens. Parenthood was normal in female patients when compared to the German female population documenting normal ovarian function except in patients with pelvic radiation. Radiation was the most important risk factor for thyroid diseases, cardiac late effects and subsequent malignant neoplasms, especially thyroid and breast cancer. A special screening program was initiated for women with chest radiotherapy, since they had a high risk of breast cancer already at a young age. The results of the HL Late Effects Research Project are important for the aftercare of patients and for the design of future HL treatment regimens.

Pediatric Nodular Lymphocyte-predominant Hodgkin Lymphoma: Treatment Recommendations of the GPOH-HD Study Group.

Nodular lymphocyte-predominant Hodgkin lymphoma (nLPHL) is a very rare disease in childhood and adolescence. In Germany, about 15 newly diagnosed patients present with this disease annually; this number comprises less than 10% of all pediatric Hodgkin lymphoma cases. Since the EuroNet-PHL-LP1 trial for early stage nLPHL patients stopped recruiting in Germany in October 2014, the GPOH-HD writing committee reviewed the literature and decided to deliver treatment recommendations for childhood and adolescent nLPHL patients. These guidelines shall be applicable to young nLPHL patients in European countries that will no longer be able to participate in nLPHL trials for young patients. Therefore, the EuroNet-PHL-nLPHL-registry will be installed to provide quality assured central review of staging and response assessment for registered patients by the Central Review Board of EuroNet-PHL in Halle/Leipzig, Germany.

The concept of the GPOH-HD 2003 therapy study for pediatric Hodgkin's disease: evolution in the tradition of the DAL/GPOH studies.

Today it is possible to cure more than 90 % of children and adolescents with Hodgkin's disease with a combination of radiotherapy and chemotherapy. Since the DAL-HD 82 study, the main scientific focus has been on avoiding late effects such as the OPSI syndrome, late complications involving the heart, lungs, thyroid and/or gonads particularly sterility in men and premature onset of menopause in women, and the prevention of secondary malignancies. The GPOH-HD 2003 study will introduce FDG-PET to the initial diagnostic program and the assessment of response to therapy in order to evaluate further possibilities for reducing therapy. In this context, the central review of all clinical and radiological findings, systematically done since the DAL-HD 90 study, will be increasingly relevant in maintaining standardised stage classification and therapy group assignment which was established by the preceding studies. Continuing in the direction of the earlier studies, the indications for radiotherapy will be restricted even further. In the early stages (treatment group 1) patients with CR or a negative FDG-PET at the end of chemotherapy will receive no radiotherapy in order to reduce the risk of a secondary malignancy. In a randomized comparison, procarbazine will be replaced by dacarbazine in the COPP cycles to determine whether sterility in men and premature onset of menopause in women can be avoided by elimination of procarbazine while retaining the same clinical efficacy. Finally, relapse therapy is to be tailored according to the time of relapse, the initial therapy group, and the patient's response to the relapse therapy with more patients receiving autologous transplantation in order to further improve the results of relapse treatment.

Immunodeficiency and Hodgkin's disease: treatment and outcome in the DAL HD78-90 and GPOH HD95 studies.

BACKGROUND: Excellent treatment results have been obtained for children with Hodgkin's disease (HD). Children with immunodeficiencies who present with HD do not have such a favourable prognosis. PATIENTS AND METHODS: A systematic literature search using MEDLINE and a search for immunodeficiencies in the database of the trials DAL HD78-HD90 and GPOH HD95 (n = 2263) were carried out. Age, sex, type of immunodeficiency, disease stage, treatment and outcome of all HD cases with known immunodeficiency were recorded. RESULTS: 28 published cases and 13 children in the DAL/GPOH trials were identified. 19/28 and 6/13 patients have immunodeficiencies with increased DNA breakage (24/25 ataxia teleangiectasia, 1/25 Nijmegen breakage syndrome) who present largely with stage III - IV HD. Among the published cases with increased DNA breakage there is only one child who is surviving 16 months after diagnosis, while there are 6/9 survivors in the group of immunodeficiencies without increased DNA breakage. Similarly, only 1/6 children survives in the group of children reported to the DAL/GPOH trials suffering from HD and immunodeficiency with increased DNA breakage, while the outcome in children suffering from immunodeficiency without increased DNA breakage is much better with 5/7 survivors. CONCLUSIONS: The literature review and data analysis of the DAL/GPOH studies show that treatment outcome is almost invariably fatal in children with HD and immunodeficiency with increased DNA breakage. Thus we propose to treat children with or without increased DNA breakage differently to improve the outcome of Hodgkin's disease in the subgroup of children with immunodeficiency.

Importance of F18-fluorodeoxy-D-2-glucose positron emission tomography (FDG-PET) for staging and therapy control of Hodgkin's lymphoma in childhood and adolescence - consequences for the GPOH-HD 2003 protocol.

The prognosis for children and adolescents with Hodgkin's lymphoma is excellent. However, many patients will show secondary malignancies 15-30 years after the initial diagnosis, which appears to be connected with the intensity of treatment during primary disease. In the GPOH-HD 95 trial, the indication for radiotherapy was limited to patients who did not show a complete remission after chemotherapy, as determined radiographically. In the future protocol, the indication for radiotherapy in patients with early-stage Hodgkin's lymphoma should be further refined by using FDG-PET for evaluating the response to chemotherapy. Furthermore, in patients at an advanced stage of the disease, it should be determined if sequential FDG-PET research during chemotherapy can separate patients into subgroups with an excellent or a poor prognosis. This article gives a review of the current literature on FDG-PET in patients with Hodgkin's lymphoma and outlines the consequences for future protocols.

[Laser-based endoscopic measurement of airway dimensions]. / Lasergestützte endoskopische Vermessung der grossen Atemwege.

Bronchoscopy is the technique of choice for the evaluation of a stenosis in the large airways. However, no system has been successfully employed for the bronchoscopic measurement of airway stenosis. The purpose of these study was the development and validation of a method for measuring the cross-sectional areas in the large airways. Furthermore, this application should be used for the 3D-reconstruction and visualisation of airway stenosis. A laser probe inserted into the operating channel of the bronchoscope enabled assessment of the distance between the images and the tip of the bronchoscope by means of projecting a ring of light on to the endoluminal wall. Image distortion due to the wide-angle lens was corrected by a computer program developed by us. Plastic tubes with known diameters were used for validation. Additionally, distortion-corrected bronchoscopic images were compared with distortion-free videoscopic image analysis of tracheal slices taken from pigs. When plastic tubes were used, the correlation coefficient (r) was slightly higher (r = 0,99, p < 0,01) than the correlation of cross-sectional areas between bronchoscopic and videoscopic images of tracheal slices (r = 0,88, p < 0,01). Furthermore the system could be used in a few patients for 2D and 3D measurement and visualisation of airway stenosis. Application of the present method offer quantitative assessment of airway stenosis located in the large airways.

Preliminary results of the multicenter trial GPOH-HD 95 for the treatment of Hodgkin's disease in children and adolescents: analysis and outlook.

BACKGROUND: In 5 consecutive pediatric and adolescent Hodgkin's disease trials DAL-HD since 1978 the invasive diagnostic procedures and the radiotherapy have gradually been reduced and chemotherapy modified to minimize toxicity and the risk of late effects. Since 1982 the overall survival increased up to 95%. In this trial the possibility of reducing local radiation doses to 20 Gy in patients with good response to chemotherapy and omitting radiotherapy totally for patients with complete remission after chemotherapy was tested. PATIENTS AND METHODS: Over a period of 6 years, from August 1995 to July 2001, 1018 children and adolescents with Hodgkin's disease from Germany, Austria,Switzerland, the Netherlands, Sweden, Norway and Denmark were enrolled in this trial. The chemotherapy was equivalent to previous trial DAL-HD 90. The treatment group (TG) 1 (stages I and IIA) received 2 cycles OPPA for girls and 2 cycles OEPA for boys, TG2 (stages IIEA, IIB, IIIA) and TG3 (stages IIEB, IIIEA, IIIB, IV) received additional 2 or 4 cycles COPP respectively. In contrast to trial DAL-HD 90 boys in stage IIIB and IIIEB received OPPA instead of OEPA. The initial staging as well as the restaging for evaluating tumor volume reduction after chemotherapy was reviewed by the study center. Radiotherapy was planned accordingly: patients with complete remission after chemotherapy were not irradiated (21.9%); all other patients received local radiotherapy to the initially involved sites, depending on the tu-mor response. Patients with a partial remission of> 75 tumor regression were irradiated with 20 Gy (50AX), partial remission of< 75% with 30 Gy (4.1 %), and residual masses of > 50 ml were boosted up to 35 Gy (20.2 %). RESULTS: 36 tumor progressions and 49 relapses occurred over a period of 7 1/2 years (median followup 3 years, data deadline 12/19/02). Kaplan-Meier-analysis after 5 years showed a probability for event-free survival (pEFS) for all patients of 0.88 and for overall survival (pOS) of 0.97. For the total group the pDFS (disease free survival) was lower in 222 non irradiated patients than in the 758 irradiated patients (0.88 vs. 0.92,p - 0.049). But there was a difference between the individual treatment groups. In TG 1 there was no difference between nonirradiated and irradiated patients (0.97 vs. 0.94) and the non-ir-radiated patients showed a better trend. In TG 2, and in TG 2 and TG 3 combined, the pDFS was significantly worse for non irradiated patients in comparison with the irradiated patients (TG2:0.78 vs. 0.92; TG 2 +3:0.79 vs. 0.91). Compared to former DAL-HD trials the pOS stayed stable despite therapy reduction. CONCLUSIONS: A reduction of radiotherapy to 20 Gy for patients in all stages with good response to chemotherapy is possible without deterioration of the results. The omission of radiotherapy for patients in complete remission after chemotherapy is recommended only for patients in early stages (TG1). In future trials the possibility of a wider selection for chemotherapy alone for this group needs to be evaluated. In intermediate (TG2) and advanced (TG3) stages omission of radiotherapy for patients incomplete remission results in a lower pEFS, but the pOS is not significantly reduced. Only with knowledge of the long term effects of today's therapy we can give a satisfactory answer to the question whether in future trials the primary aim should be pEFS as high as possible due to front-line-therapy or reduction of late effects.

[18-FDG-PET-findings in children and adolescents with Hodgkin's disease: retrospective evaluation of the correlation to other imaging procedures in initial staging and to the predictive value of follow up examinations]. / 18-FDG-PET-Befunde bei Kindern und Jugendlichen mit Morbus Hodgkin: Retrospektive Auswertung zur Korrelation mit anderen bildgebenden Verfahren bei der initialen Stagingdiagnostik und zum prädiktiven Wert bei Verlaufsuntersuchungen.

Today no evidence based medicine analyses exist about the value of positron emission tomography (PET) in children and adolescents with Morbus Hodgkin. The increasing number of registered PET-examinations within the scope of the GPOH-HD 95 trial motivated to analyse the validity of 18-FDG-PET-examination findings in comparison to the conventional diagnostic methods (CT/MRI/ultrasound) and to the patients follow up. 67 PET-primary staging findings and 48 PET-follow up findings of altogether 106 patients from 27 PET-centres were analysed. Concerning the primary staging findings a concordance of 92% of the PET-findings and the findings of the CT/MRI/ultrasound-examinations per localisation was found, but in more than 50% of the patients a discrepancy occurred in at least one of the 9 investigated localisations. The analysis of the PET follow up findings showed a negative predictive value of 94% in regularly examinations (without previous suspicion of relapse), but only a positive predictive value of 25%. In case of relapse suspicion there was a negative predictive value of 83% and a positive predictive value of 76% in PET. A good prognosis is possible to predict from negative PET follow up findings (relapse risk in regularly controls 7%, at relapse suspicion 17%), whereas the probability for a true relapse in positive PET follow up findings is only markedly increased in case of former relapse suspicion (relapse risk in regularly controls 25%, at relapse suspicion 82%). A prospective multicenter PET study should be realized to analyse systematically the value of PET diagnostics in staging and restaging examinations of children and adolescents with Hodgkin's disease, especially to validate the PET diagnostics in exclusion of vital tumor residuals.

Response-adapted radiotherapy in the treatment of pediatric Hodgkin's disease: an interim report at 5 years of the German GPOH-HD 95 trial.

PURPOSE: A multinational trial on pediatric Hodgkin's disease (HD) with the aim to reduce the risk of long-term toxicity of combined modality treatment by restricting dose and volume of radiation therapy (RT) while maintaining the excellent treatment results of previous German multicenter trials (DAL-HD82-90). METHODS AND MATERIALS: Patients were treated according to stage of disease (CS) and defined risk factors in three treatment groups (TG) with 2, 4, or 6 cycles of combination chemotherapy. When a complete remission (CR) had been achieved, treatment was terminated without RT independent of initial stage or tumor bulk. Patients with a partial remission (PR) of >75% tumor regression were irradiated with 20 Gy using modified involved fields; in the case of PR <75% RT dose was 30 Gy, residual masses >50 mL received 35 Gy. RESULTS: From August 1995 to July 2000 a total of 956 patients have been registered, 830 as trial patients, 39% in TG1, 27% in TG2, 34% in TG3. 827 patients were evaluable by June 2001 with a median follow-up of 38 months. Chemotherapy (CTx) resulted in CR in 22%, PR >75% in 62%, PR <75% in 12%. Event-free survival (EFS) for the entire group is 90% (SD 0.01), for TG1 94%, TG2 91%, and TG3 84%; the overall survival is 97% in Kaplan-Meier-analysis. Relapse-free survival (RFS) is superior for patients with RT after PR (93%) than for those without RT after CR (89%); the difference is significant (p = 0.01) for advanced stages, however not in TG1. Seventy-two events were observed by June 2001: 28 progressions during the initial therapy or within the first 3 months, 38 relapses, 3 second malignancies, three fatal accidents or infections; 18 patients have died. CONCLUSION: Treatment results of the GPOH-HD 95 trial are excellent thus far. The reduction of RT dose and volume in PR has not caused a significant impairment of overall and event-free survival in comparison to the previous German trials; however, failure rates are higher in advanced stages when RT is omitted after achieving a CR. It is too early to tell whether the HD 95 protocol will be successful in reducing late toxicity.

Pharmacokinetics of native Escherichia coli asparaginase (Asparaginase medac) and hypersensitivity reactions in ALL-BFM 95 reinduction treatment.

Repeated asparaginase treatment has been associated with hypersensitivity reactions against the bacterial macromolecule in a considerable number of patients. Immunological reactions may range from anaphylaxis without impairment of serum asparaginase activity to a very fast decline in enzyme activity without any clinical symptoms. Previous investigations on a limited number of patients have shown high interindividual variability of asparaginase activity time courses and hypersensitivity reactions in about 30% of patients during reinduction treatment. Therefore, monitoring of reinduction treatment was performed prospectively in 76 children with newly diagnosed acute lymphoblastic leukaemia (ALL). According to the ALL-Berlin-Frankfurt-Münster (BFM) 95 protocol, 10 000 U/m2 body surface area of native Escherichia coli asparaginase (Asparaginase medac) was given on d 8, 11, 15 and 18. In 45/76 children, trough and peak activities were determined with every dose, and also on d 4 and d 11 after the last administration. Data on asparaginase activity were not available from the remaining 31 patients, but information with regard to hypersensitivity reactions only was given. Eighteen out of 76 patients (24%) suffered a clinical hypersensitivity reaction; however, no silent inactivation was observed. Activity in the therapeutic range of greater than 100 U/l for at least 14 d was determined in 43 of the 45 patients who were analysed for enzyme activity.

[Improved results in the treatment of acute myeloid leukemia - Results of study AML-BFM-93 in East Germany with comparisons to the preceding studies AML-I-82 and AML-II-87]. / Verbesserte Ergebnisse in der Therapie der akuten myeloischen Leukämie - Ergebnisse der Therapiestudie AML-BFM-93 in den neuen Bundesländern im Vergleich mit den Vorgängerstudien AML-I/82 und AML-II/87 der DDR.

BACKGROUND: Three multicenter studies were conducted in East Germany on the treatment of acute myeloid leukaemia in children. The latest of the three studies (AML-BFM-93-OST) was part of the common German study AML-BFM-93. PATIENTS AND METHODS: The total number of registered patients was 262. The number and dosage of administered chemotherapeutic agents was elevated with each new study. RESULTS: Both the remission rate (85 %) and the likelihood of an event free survival (52 % after 5 years) could be improved significantly in study AML-BFM-93-OST. The results of the common German study AML-BFM-93 were identical to those of the East German part AML-BFM-93-OST. Compared with international studies it was one of the most successful treatment strategies in children with AML. Patients who showed toxic side effects to heart, liver, kidneys, skin or nervous system during the chemotherapy had a significantly lower risk of relapse, once they overcame the intensive therapy. During the five years of study AML-BFM-93-OST, treatment results could be improved despite an unchanged therapy strategy. This may partly be due to the modernisations and restorations that were carried out in many East German hospitals in this time. CONCLUSIONS: The therapy regimen of study AML-BFM-93 allowed a substantial improvement in the treatment of children with AML. Further intensification of chemotherapy should only be undertaken in accordance to the individual sensitivity of each patient.

Relapse of TEL-AML1--positive acute lymphoblastic leukemia in childhood: a matched-pair analysis.

PURPOSE: The aim of this study was to investigate whether, in relapsed childhood acute lymphoblastic leukemia (ALL), the frequent genetic feature of TEL-AML1 fusion resulting from the cryptic chromosomal translocation t(12;21)(p13;q22) is an independent risk factor. PATIENTS AND METHODS: A matched-pair analysis was performed within a homogeneous group of children with first relapse of BCR-ABL-negative B-cell precursor (BPC) ALL treated according to relapse trials ALL-Rezidiv (REZ) of the Berlin-Frankfurt-Münster Study Group. A total of 249 patients were eligible for this study: 53 (21%) were positive for TEL-AML1, and 196 (79%) were negative. Positive patients were matched for established most-significant prognostic determinants at relapse, time point, and site of relapse, as well as age and peripheral blast cell count at relapse. RESULTS: Fifty pairs matching the aforementioned criteria could be determined. The probabilities with SE of event-free survival and survival at 5 years for matched TEL-AML1 positives and negatives are 0.63 +/- 0.10 versus 0.38 +/- 0.10 (P =.09) and 0.82 +/- 0.09 versus 0.42 +/- 0.19 (P =.10), respectively. These results were confirmed by multivariate analysis, revealing an independent prognostic significance of time point and site of relapse (both P <.001) but not of TEL-AML1 expression (P =.09). CONCLUSION: TEL-AML1 expression does not constitute an independent risk factor in relapsed childhood BCP-ALL after matching for relevant prognostic parameters. It undoubtedly characterizes genetically an ALL entity associated with established favorable prognostic parameters. High-risk therapeutic procedures such as allogeneic SCT should be considered restrictively.

Short-pulse B-non-Hodgkin lymphoma-type chemotherapy is efficacious treatment for pediatric anaplastic large cell lymphoma: a report of the Berlin-Frankfurt-Münster Group Trial NHL-BFM 90.

Anaplastic large-cell lymphoma (ALCL) accounts for approximately 10% of pediatric non-Hodgkin lymphoma (NHL). Previous experience from NHL-Berlin-Frankfurt-Münster (BFM) trials indicated that the short-pulse B-NHL-type treatment strategy may also be efficacious for ALCL. The purpose of this study was to test the efficacy of this protocol for treatment of childhood ALCL in a large prospective multicenter trial and to define risk factors. From April 1990 to March 1995, 89 patients younger than 18 years of age with newly diagnosed ALCL were enrolled in trial NHL-BFM 90. Immunophenotype was T-cell in 40 patients, B-cell in 5, null in 31, and not determined in 13. Stages were as follows: I, n = 8; II, n = 20; III, n = 55; IV, n = 6. Extranodal manifestations were as follows: mediastinum, n = 28; lung, n = 13; skin, n = 16; soft tissue, n = 13; bone, n = 14; central nervous system, n = 1; bone marrow, n = 5. After a cytoreductive prephase, treatment was stratified into 3 branches: patients in K1 (stage I and II resected) received three 5-day courses (methotrexate [MTX] 0.5 g/m(2), dexamethasone, oxazaphorins, etoposide, cytarabine, doxorubicin, and intrathecal therapy); patients in K2 (stage II nonresected and stage III) received 6 courses; patients in K3 (stage IV or multifocal bone disease) received 6 intensified courses including MTX 5 g/m(2), high-dose cytarabine/etoposide. The Kaplan-Meier estimate for a 5-year event-free survival was 76% +/- 5% (median follow-up, 5.6 years) for all patients and 100%, 73% +/- 6%, and 79% +/- 11% for K1, K2, and K3, respectively. Events were as follows: progression during therapy, n = 2; progression or relapse after therapy, n = 20; second malignancy, n = 1. It was concluded that short-pulse chemotherapy, stratified according to stage, is effective treatment for pediatric ALCL. B symptoms were associated with increased risk of failure. (Blood. 2001;97:3699-3706)

[Endotracheal silicon stents in therapy management of benign tracheal stenoses]. / Endotracheale Silikonstents im Therapiemanagement benigner Trachealstenosen. Ergebnisse nach 5-jähriger Anwendung.

BACKGROUND: Advances in endoscopic technique and the development of new materials have made stenting an interesting alternative to surgical treatment for extended tracheal stenoses. This 5 years' retrospective study describes long term results of silicon stents in patients with benign chronic tracheal stenoses. PATIENTS AND METHODS: 45 adult patients (mean age: 45 years) had endotracheal Dumon (Endoxane) stent placement as surgical therapy was not indicated. Fiberoptic controls were performed every 3-6 months. RESULTS: In 42 patients therapy proved successful with improved ventilation and high level of tolerance. Acut stent-removal was necessary in 2 patients because of edema of the vocal cords, in 1 patient because of stent independent paralysis of both recurrents nerves. Further complications included migration (16.6%), granuloma formation (33.3%) and airway obstruction due to heavy secretion (2.3%). CONCLUSIONS: Long term results have shown that this technique is associated with high efficiency and infrequent complications which are not life-threatening. Advantages consist in a minor-invasive technique with small expenditure of time.

[Secondary malignant neoplasms in patients with breast cancer]. / Sekundäre maligne Neoplasien bei Patientinnen mit Mammakarzinom.

OBJECTIVE: This report analyzes the occurrence of secondary malignancies among patients with breast cancer. MATERIAL AND METHODS: We evaluated all women diagnosed with breast cancer who were reported to the National Cancer Institute of the former GDR in 1976. There was a follow up of 5,485 patients from 1976 to 1988 (38,231 person-years at risk). Cancer incidence rates of the whole female population specific for age and calendar year were used for calculation of the standardized incidence ratio (SIR). RESULTS: Significantly increased risks were observed for neoplasms of the bilateral breast (SIR 2.44; 95% CI 2.04-2.93), colon (SIR 1.53; 95% CI 1.06-2.12), rectum (SIR 1.65; 95% CI 1.10-2.40), endometrium (SIR 1.55; 95% CI 1.02-2.27), and ovary (SIR 1.71; 95% CI 1.09-2.57). Neoplasms of the lung (SIR 1.65; 95% CI 0.93-2.73), kidney (SIR 1.51; 95% CI 0.69-2.87), bladder (SIR 1.32; 95% CI 0.48-2.87), connective tissue (SIR 3.54; 95% CI 0.73-10.34), and multiple myeloma (SIR 1.98; 95% CI 0.54-5.06) were also increased, not reaching statistical significance. Risk reduction was observed for malignant tumors of the gallbladder (SIR 0.36; 95% CI 0.12-0.83). CONCLUSION: In proposing recommendations for the follow-up and management of women with breast cancer, it is important to recognize their long-term predisposition to an array of secondary cancers.

Immunoadsorption in dilated cardiomyopathy.

The prognosis for patients suffering from advanced stages of dilated cardiomyopathy (DCM) is poor. Recent studies have shown that immunoadsorption (IA) may represent an effective alternative therapeutic approach for other kinds of autoimmune diseases with circulating autoantibodies. The objective of this pilot study was to ascertain the short-term hemodynamic effects of IA in patients with idiopathic DCM and circulating autoantibodies. Our study included 9 patients with circulating beta1-adrenoreceptor antibodies who suffered from idiopathic DCM as well as severe heart failure (left ventricular ejection fraction <30%). Immunoadsorption was performed on 5 consecutive days using an adsorber against immunoglobulins (Ig Therasorb, Baxter, Unterschleissheim, Germany). Substitution of 0.5 g/kg of polyclonal immunoglobulin took place after the final IA session. During IA, the cardiac index and stroke volume index increased from 2.0+/-0.42 to 2.9+/-0.79 L/min(-1)/m(-2), p < 0.01, and from 24.0+/-7.4 to 35.9+/-10.3 ml/m2, p < 0.05, respectively. In addition to drug therapy, IA may represent a promising alternative therapeutic possibility for hemodynamic stabilization of patients with severe idiopathic DCM.

Hemodynamic effects of immunoadsorption and subsequent immunoglobulin substitution in dilated cardiomyopathy: three-month results from a randomized study.

OBJECTIVES: The objective of our study was to assess the hemodynamic effects of immunoadsorption (IA) and subsequent immunoglobulin G (IgG) substitution in comparison with the effects of conventional medical treatment in patients with dilated cardiomyopathy (DCM). BACKGROUND: Various circulating cardiac autoantibodies have been detected among patients suffering from DCM. These antibodies are extractable by IA. METHODS: Patients with DCM (n = 18, New York Heart Association III-IV, left ventricular ejection fraction <30%) and who were on stable medication participated in the study. Hemodynamic measurements were performed using a Swan-Ganz thermodilution catheter. The patients were randomly assigned either to the treatment group with IA and subsequent IgG substitution (IA/IgG group, n = 9) or to the control group without IA/IgG (n = 9). In the IA/IgG group, the patients were initially treated in one IA session daily on three consecutive days. After the final IA session, 0.5 g/kg of polyclonal IgG was substituted. At one-month intervals, IA was then repeated for three further courses with one IA session daily on two consecutive days, until the third month. RESULTS: After the first IA course and IgG substitution, cardiac index (CI) increased from 2.1 (+/-0.1) to 2.8 (+/-0.1) L/min/m2 (p < 0.01) and stroke volume index (SVI) increased from 27.8 (+/-2.3) to 36.2 (+/-2.5) ml/m2 (p < 0.01). Systemic vascular resistance (SVR) decreased from 1,428 (+/-74) to 997 (+/-55) dyne x s x cm(-5) (p < 0.01). The improvement in CI, SVI and SVR persisted after three months. In contrast, hemodynamics did not change throughout the three months in the control group. CONCLUSIONS: Immunoadsorption and subsequent IgG substitution improves cardiovascular function in DCM.

[C-reactive protein, Il-6 and procalcitonin as infection parameters in children with oncologic diseases]. / CRP, IL-6 und PCT als Infektionsparameter bei onkologisch kranken Kindern.

BACKGROUND: Due to anti-neoplastic therapy, there is a high incidence of infections and fever in pediatric patients with malignant disease. We have searched for parameters that may be of value in the early diagnosis of infection, in discriminating between bacterial and non-bacterial causes and for monitoring the response to antimicrobiotic therapy. PATIENTS: 46 febrile episodes in 33 children with malignant diseases under anti-neoplastic therapy, aged 0.5 to 17 years, were included. Each patient was supplied with a central venous catheter (Hickman catheter). METHODS: Blood was taken for the evaluation of C-reactive-protein (CRP), Interleukin-6 (IL-6) and Procalcitonin (PCT). Laboratory data included WBC, blood cultures, as well as microbiologic and serologic tests for important infectious agents. Patients were grouped as follows: 1. Patients with febrile diseases and positive blood cultures, 2. Patients with localized bacterial or mycotic infections and negative blood cultures, 3. Patients with fever of unknown origin, 4. Patients with viral infections, 5. Control group. RESULTS: CRP and IL-6 were more sensitive than PCT in detecting bacterial and mycotic diseases in leukopenic children, because of low PCT-levels in patients with localized infections. IL-6 values were high shortly after onset of fever and decreased under sufficient antimicrobiotic therapy until day three. CONCLUSIONS: Because of the quick response, IL-6 may be helpful in monitoring antimicrobiotic therapy. Using Procalcitonin-levels, we were not able to distinguish between localized bacterial and viral infection in leukocytopenic patients.

A new bronchoscopic method to measure airway size.

Bronchoscopic evaluation of stenosis is limited due to radial distortion of bronchoscopic images and the unknown distance between the endoscope and the stenotic area. The purpose of this study was the development and validation of a method for measuring cross-sectional areas in large airways. Distance measurements were performed using a laser probe inserted into the working channel of a bronchoscope. The laser probe was positioned to the locus of interest in the airway, a ring of light (helium/neon) projected on to the luminal wall and the images acquired using an electronic bronchoscope. The images taken were distortion-corrected by means of a computer program. The method was validated by simulating airways using tubes of known diameter. Additionally, distortion-corrected bronchoscopic images were compared with distortion-free videoscopic image analysis of tracheal slices taken from pigs. In the case of the plastic tubes, Pearson's correlation coefficient (r) as well as the intraclass correlation coefficient (ICC) were slightly higher (r=0.99, p<0.01, ICC=0.97) than the correlation of cross-sectional areas between bronchoscopic and videoscopic images of tracheal slices (r=0.88, p<0.01, ICC=0.87). This concept allows accurate and reproducible determination of cross-sectional areas in large airways.

High cure rates and reduced long-term toxicity in pediatric Hodgkin's disease: the German-Austrian multicenter trial DAL-HD-90. The German-Austrian Pediatric Hodgkin's Disease Study Group.

PURPOSE: To further reduce therapy-related late effects in patients with pediatric Hodgkin's disease (HD) while maintaining the high cure rates achieved with vincristine, prednisone, procarbazine, and doxorubicin (OPPA) or OPPA/cyclophosphamide, vincristine, prednisone, and procarbazine (COPP) chemotherapy and involved-field radiotherapy. The risk of testicular dysfunction was addressed by substituting etoposide for procarbazine (OEPA) in the induction therapy for boys. Radiation doses and fields were further reduced. PATIENTS AND METHODS: Three hundred nineteen boys and 259 girls younger than 18 years with previously untreated HD, enrolled onto the study between 1990 and 1995, were allocated to treatment group (TG)1 (early stages), TG2 (intermediate stages), or TG3 (advanced stages). All groups underwent two cycles of OEPA (boys) or OPPA (girls) for induction chemotherapy. TG2 and TG3 continued on additional two or four cycles, respectively, of COPP. Low-dose radiotherapy was given to the initially involved sites, ie, reduced involved fields. RESULTS: Initial response to OPPA or OEPA induction was virtually identical. Eight of 578 patients experienced early progression of HD. Thirty-seven relapses, three secondary tumors, and no secondary leukemias have been recorded, with a median follow-up duration of 5.1 years (maximum, 8.1 years). Thirteen of 578 patients died. The probability of 5-year event-free survival/overall survival is 91%/98% in the total group, 94%/97% with OPPA, and 89%/98% with OEPA induction therapy. Risk factor analysis showed two significant prognostic factors: histologic subtype NS2 and "B" symptoms. OEPA induction therapy, large mediastinal tumor, and age were not significant. Preliminary studies of testicular function indicate a lower risk of germ cell damage than previously documented with OPPA. CONCLUSION: OEPA is a satisfactory alternative to OPPA. Radiotherapy can be confined to involved sites when combined with appropriate chemotherapy. The DAL-HD-90 regimen represents a comprehensive treatment program for all stages of pediatric HD and offers a favorable benefit/risk ratio, combining excellent disease control, moderate acute toxicity, and reduced long-term toxicity.