PubMed Health⌕ Search

Biomedical subjects

D Körholz

Publications and source records attributed to D Körholz.

At least 19 recordsLinked to original sources
PubMed2005

Prognostic value of T-1 cell numbers prior to allogeneic stem cell transplantation in patients with severe graft-versus-host disease.

Assessment of risk factors for acute graft-versus-host disease (aGvHD) might help in tailoring the intensity of prophylactic immunosuppression after allogeneic stem cell transplantation (SCT), thereby decreasing the relapse rate in leukaemia patients. In this study, we analysed whether the number of recipient blood T cells and plasma levels of different cytokines were correlated with the risk of aGvHD after allogeneic SCT. Analyses were performed in 23 patients receiving pSCT immediately before or during the first 2 days of the conditioning regimen. In all, 40 or more Tc-1 cells/microl pretransplant were associated with a significantly increased risk of aGvHD (10/10 patients with GvHD>/=II; 4/13 patients without aGvHD with a Tc-1 number >40/microl, P<0.002, Fisher's exact test). In addition, 40 or more Th-1 cells/microl pretransplant were also associated with a significantly increased risk of aGvHD (P<0.04, Fisher's exact test). Furthermore, the number of Th-2 cells was significantly higher in patients with severe aGvHD even though the median absolute cell counts were very low. However, all other investigated parameters did not reveal predictive value. In conclusion, determination of T-1 cells prior to SCT might determine patients with high/low risk of aGvHD and could thus be used to control immunosuppression after SCT.

Adult↗
PubMed2004

Regulation of interleukin-2 induced soluble Fas ligand release from human peripheral blood mononuclear cells.

Adjuvant interleukin (IL)-2 immunotherapy has been used in the treatment of different malignant dieseases. However, clinical results have been rather disappointing. Therefore, further investigations on IL-2-induced mediators of cytotoxicity seem to be necessary in order to possibly create cytokine cocktails which could enhance the IL-2-induced cytotoxicity. We therefore investigated the regulation of IL-2-induced release of soluble Fas Ligand (sFasL), since this factor is known to possess anti-tumor activities. In CD3-stimulated peripheral blood mononuclear cells IL-2 induced sFasL in a dose-dependent fashion. Maximum sFasL concentrations were obtained after stimulation of MNC for 120 hrs. Inhibition of endogenous IL-12 production significantly reduced IL-2-mediated sFasL release by about 25%. In contrast, addition of IL-12 enhanced the IL-2-induced sFasL about 1,5-fold. IL-10 and IL-4 reduced the IL-2-stimulated sFasL by about 30%. Interestingly, these suppressive effects could be antagonized by the addition of IL-12. Not only exogenous IL-10 but also endogenously produced IL-10 decreased the sFasL release to that extent which had been stimulated by IL-12. Since IL-12 and IL-10 only marginally influenced the IL-2-mediated cell proliferation as well as the IL-2-induced cell death, the IL-12- and IL-10-controlled sFasL release seems to be based on an enhanced production per cell. However, the increase in cell numbers as well as the decrease of viability during cell culture might additionally contribute to the IL-2-induced increase of sFasL release. This secondary effect might explain why IL-2-mediated sFasL production is only partially controlled by regulatory cytokines such as IL-4, IL-10 or IL-12. In conclusion, addition of IL-12 might increase the efficacy of IL-2 immunotherapy by inhibition of the IL-10-mediated negative feed-back loop on IL-2-mediated sFasL release.

CD3 Complex↗
PubMed2003

Patient stratification based on prednisolone-vincristine-asparaginase resistance profiles in children with acute lymphoblastic leukemia.

PURPOSE: To confirm the prognostic value of a drug resistance profile combining prednisolone, vincristine, and l-asparaginase (PVA) cytotoxicity in an independent group of children with acute lymphoblastic leukemia (ALL) treated with a different protocol and analyzed at longer follow-up compared with our previous study of patients treated according to the Dutch Childhood Leukemia Study Group (DCLSG) ALL VII/VIII protocol. PATIENTS AND METHODS: Drug resistance profiles were determined in 202 children (aged 1 to 18 years) with newly diagnosed ALL who were treated according to the German Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia (COALL)-92 protocol. RESULTS: At a median follow-up of 6.2 years (range, 4.1 to 9.3 years), the 5-year disease-free survival probability (pDFS) rate +/- SE was 69% +/- 7.0%, 83% +/- 4.4%, and 84% +/- 6.8% for patients with resistant (PVA score 7 to 9), intermediate-sensitive (PVA score 5 to 6), and sensitive (SPVA score 3 to 4) profiles, respectively (sensitive and intermediate-sensitive v resistant, P </=.05). Resistant patients were at increased risk of an early event (nonresponse or relapse within 2.5 years of diagnosis) compared with sensitive and intermediate-sensitive patients (P =.03). The profile did not identify patients at higher risk of late relapse, which was also observed for DCLSG ALL-VII/VIII patients now analyzed at a median of 7.5 years of follow-up (range, 4.4 to 10.8 years). Despite being nondiscriminative for late relapses, the resistant profile was still the strongest prognostic factor for COALL-92 patients in a multivariate analysis including known risk factors (P =.07). CONCLUSION: Drug resistance profiles identify patients at higher risk of early treatment failures and may, therefore, be used to improve risk-group stratification of children with ALL.

Adolescent↗
PubMed2003

Infantile malignant peripheral nerve sheath tumour of the ileum causing ileo-ileal intussusception in an infant.

Nerve sheath tumours are rare tumours. We report here for the first time a malignant peripheral nerve sheath tumour of the ileum in a child who presented with recurrent intussusceptions. The tumour was excised with wide margins and staging procedures did not show any metastatically suspicious lesions. Complete resection in non-metastatic tumours seems to be the therapy of choice.

Female↗
PubMed2003

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.

Adolescent↗
PubMed2002

Endogenous pro-inflammatory cytokines in children and adolescents during chemotherapy-induced neutropenia.

Monocyte-derived pro-inflammatory cytokines such as GM-CSF, IL-12, and IP-10 might protect patients with chemotherapy-induced neutropenia against infections. In settings with abundant neutrophils, G-CSF has been described as a suppressor of IL-12, but also as an inducer of GM-CSF. In 25 pediatric patients with chemotherapy-induced neutropenia the authors measured plasma levels of these four cytokines. GM-CSF was detectable in only a minority of patients (6/25). It was, however, positively correlated with high plasma levels of IL-12 and IP-10. G-CSF levels, however, were in no way correlated with the levels of any of these three cytokines.

Adolescent↗
PubMed2001

Infectious complications in children with acute lymphoblastic leukemia and T-cell lymphoma--a rationale for tailored supportive care.

Infections still remain a major cause of therapy-associated morbidity and death in patients with malignant diseases. To further lower the risk of serious and long-lasting infections by additional supportive measures, detailed information on the frequency and characteristic features of infections is needed. Therefore, patient data from 112 children with acute lymphoblastic leukemia and T-cell lymphoma who were treated according to the COALL-05-92 protocol in our department were analyzed for differences in the frequency and origin of febrile episodes in relation to age, immunological type of leukemia, treatment in group assessed as being at high or low risk of relapse, actual occurrence of relapse, and course of chemotherapy. At the time of diagnosis, low-risk patients more commonly presented with febrile episodes than high-risk patients. In total, patients developed a fever in 313 (24%) of 1,307 evaluated chemotherapy cycles. Febrile episodes were associated with microbiologically or clinically documented infections in 60% of all cases, while in 40% the fever was of unknown origin. Gram-positive pathogens had a markedly higher incidence than gram-negative or fungal ones. The incidence of febrile episodes during therapy appeared to be correlated with certain chemotherapeutic drug combinations. The highest rate was found after high-dose cytarabine and asparaginase causing a long period of leukopenia. However, after other chemotherapy courses with a similar duration of leukopenia the incidence of febrile episodes was significantly lower, suggesting that specific interactions of different chemotherapeutic agents with the immune response might be an important factor in development of infections. Individual factors might also account for an increased incidence of infections, since the number of high-risk patients with recurrent infections was significantly higher than expected on the basis of statistical evaluation. In conclusion, our findings suggest that the risk of infections during chemotherapy may not only be influenced by leukopenia, but that drug-specific effects of the various chemotherapeutic agents and individual factors may also be important contributory factors. These observations must be further expanded in prospective studies so that new tailored supportive care protocols can be elaborated.

Adolescent↗
PubMed2001

Glycosylated vs non-glycosylated granulocyte colony-stimulating factor (G-CSF)--results of a prospective randomised monocentre study.

The discovery of the haematopoietic growth factor granulocyte colony-stimulating factor (G-CSF) has reduced infection-related morbidity in cancer patients by alleviating post-chemotherapy neutropenia. Two formulations of recombinant human (rh) G-CSF, one glycosylated and one non-glycosylated, are available. The glycosylated form, lenograstim, possesses at least 25% greater bioactivity in vitro. Some comparative studies into the preparation's potential to mobilise haematopoietic stem cells suggest a similar advantage. In the light of the great clinical importance of G-CSF, we have performed the first prospective, randomised, crossover study on children with chemotherapy-induced neutropenia. G-CSF (250 microg/m(2)) was started 1 day after the chemotherapy block, and was administered until a WBC >1500/microl was achieved on 3 successive days. Thirty-three G-CSF cycles from 11 patients (16 lenograstim, 17 filgrastim) were studied. They were investigated for duration of very severe (WBC <500/microl, 9 vs 9.5 days, lenograstim vs filgrastim, median) and severe leukopenia (WBC <1000/microl, 11 vs 11 days), infections (CRP >5 mg/dl, 5 vs 5.5 days), infection-related hospital stay (11 vs 9 days) and antibiotic treatment (9 vs 9 days). Statistical evaluation by paired analysis could not detect any difference between treatment groups; the median difference for all end-points was zero. In summary, at least at 250 microg/m(2), in terms of their clinical effect on neutropenia, the two G-CSF preparations appear to have identical activity.

Adolescent↗
PubMed2001

Outcome of paratesticular involvement in infants with neuroblastoma.

The authors report on 3 infants suffering from disseminated neuroblastoma (NB) involving the testes or paratesticular structures. INSS stage 4 in 2 cases, and "biological" INSS stage 4S were considered, respectively. One patient with a stage 4 NB died of tumor progression; one patient is under therapy. The patient with NB 4S was cured with preservation of both testes after antineoplastic chemotherapy and reduction of the retroperitoneal primary. J Pediatr Surg 36:E23.

Antineoplastic Agents↗
PubMed2001

Co-operation of IL-1 and IL-2 on T-cell activation in mononuclear cell cultures.

In search of an optimized anti-cancer immunotherapy, the combination of IL-2 and IL-1 has been tried. In an in-vitro LAK model, this cytokine cocktail seemed to be quite promising. In our in-vitro model of IL-2 induced T-cell activation we have therefore investigated the co-operation of these two potent immunostimulators. Mononuclear cells were stimulated with CD3 activating antibody in the presence of different cytokines and blocking or neutralizing antibodies. Cytokine concentrations were detected in the supernatants with ELISA. Intracellular IFN-gamma and IL-4 in the different T-cell subsets was measured by flow cytometry. IL-1 and IL-1 receptor antagonist (IL-1Ra) were up-regulated by IL-2, this was achieved independently of IL-12 or CD40/CD40L interaction. As a negative feedback mechanism, IL-1beta induced its natural antagonist, IL-1Ra. Both endogenous and exogenous IL-10 suppressed IL-1beta and induced IL-1Ra, thus markedly decreased the amount of functional IL-1. The combination of IL-2 and IL-1beta lead to a mildly increased Interferon-gamma (IFN-gamma) secretion (+20%, p < 0.05), however, this appeared to be the result of an increased IFN-gamma production per secreting cell, rather than of an increased recruitment of non-secreting cells. Similarly, IL-6 was also induced in an additive fashion (+30%, p < 0.05). For both cytokines, this effect could be significantly augmented by neutralizing IL-1Ra. Concentrations of IL-2 induced IL-10 and soluble Fas ligand (sFasL) were not affected by IL-1beta. We were thus able to demonstrate that IL-1 relays its activity through different pathways than IL-2. Furthermore, we could show that the potentially synergistic action of IL-2 and IL-1 was hindered by the simultaneous induction of signficant amounts of IL-1Ra. From the latter findings we conclude that the combination of IL-2 and IL-1 for cytokine-induced anti-tumor activity may not, but a combination of IL-2 and anti-IL-1Ra might prove beneficial.

CD40 Ligand↗
PubMed2001

Efficacy and outcome of intensive care in pediatric oncologic patients.

OBJECTIVE: Because the long-term survival of children with cancer has dramatically improved because of multimodal treatment strategies, intensive care medicine has become more relevant for these patients. This study was performed to assess the efficacy of intensive care medicine in newly diagnosed pediatric oncologic patients and in patients under ongoing oncologic treatment. DESIGN: A retrospective analysis of children admitted to the pediatric intensive care unit (PICU) of the University Hospital Duesseldorf for life-threatening conditions between 1995 and 1999 was performed to identify those patients with an oncologic condition. SETTING: University hospital. PATIENTS: A total of 123 patients were identified. Children admitted for uncomplicated postoperative care and children admitted after bone marrow transplantation were excluded from this analysis. Forty-eight patients could be divided into two groups. Group A contained children admitted to the PICU at the time of cancer diagnosis and group B children receiving ongoing oncologic treatment. INTERVENTIONS: The evaluation included diagnosis, risk factors, complications leading to PICU admission, PICU therapy, and outcome. Statistical analysis included evaluation of Pediatric Risk of Mortality (PRISM) and Therapeutic Intervention Scoring System (TISS) scores. MEASUREMENTS AND MAIN RESULTS: Respiratory insufficiency was the leading diagnosis for PICU admission, whereas in the remaining children cardiovascular insufficiency, renal failure, neurologic impairment, ileus, and tumor-associated complications led to PICU admission. The number of organ failures was correlated to outcome. All children but one of group A could be discharged from the PICU, whereas 12 of 35 children in group B died, despite intensive care treatment attempts. The PRISM and TISS scores at admission to the PICU were significantly higher in children who did not survive the period of intensive care treatment in group B. However, all patients with a PRISM score of >20 died. CONCLUSIONS: Diagnosis of cancer does not exclude potential benefit from intensive care medicine in these children, although severe complications might affect the prognosis.

Adolescent↗
PubMed2000

Monocyte deactivation and its reversal in a patient with chemotherapy-induced leukopenia and severe systemic infection.

BACKGROUND: Serious infections constitute a major problem for patients with cancer, and new approaches must be found in dealing with these. The pathophysiology of neutropenic infection is not well understood, although there is some evidence that, as in sepsis in the primarily immunocompetent host, a pro- and an antiinflammatory phase can be discriminated. In the recent literature is described a series of nonneutropenic patients with sepsis in whom interferon-gamma was successfully administered during the immunoparalytic phase, a concept that might possibly be extended to immunocompromised hosts. PROCEDURE: A 14-year-old patient with RAEB-T/hypoplastic M2 and chemothera py-induced neutropenia developed a severe infection and continued to deteriorate clinically despite maximum supportive measures, including broad antibacterial and antifungal coverage. On the basis of monocyte de-activation this patient was considered to be in the immunoparalytic phase of sepsis and consequently treated with 60 microg/m(2) of interferon-gamma per day for 10 days. RESULTS: The patient made a rapid clinical recovery, and biochemical markers of infection improved promptly. At the same time, the fraction of activated monocytes normalized rapidly and stably. We hypothesize that treatment with interferon-gamma effected this rapid restoral of monocyte activation and that monocyte reactivation might have contributed to the patient's prompt recovery from his severe infection. Interferon-gamma treatment was well tolerated. CONCLUSIONS: Immunostimulation with interferon-gamma might prove to be a valuable adjuvant treatment for patients with chemotherapy-induced neutropenia during the rare scenario of infection with immunoparalysis.

Adolescent↗
PubMed2000

Anticipatory symptoms and anticipatory immune responses in pediatric cancer patients receiving chemotherapy: features of a classically conditioned response?

UNLABELLED: There is considerable evidence from studies in adult patients that classical conditioning contributes to anticipatory nausea and/or vomiting (ANV) in cancer chemotherapy: The stimuli predicting the infusion serve as conditioned stimuli (CS). When reexposed to the CS, some patients experience ANV prior to infusion onset. In adult patients, anticipatory immunomodulation (AIM) has also been observed. The present study examines whether ANV and AIM occur in pediatric cancer patients and whether they show features of a conditioned response. METHODS: Nineteen pediatric cancer patients (M = 10.1 years, > 2 previous chemotherapies) were studied over two consecutive cycles (A, B). In both cycles, self-reported symptoms, for example nausea and vomiting, were recorded from two days prior to the onset (Day -2), during infusion, and two days after the end of the infusion (Day +2). In Cycle B, blood was drawn at home at Day -2, and at Day 0 in the hospital prior to infusion onset, thus using a quasi-experimental variation of the CS content of the environment. Immune parameters valid for tumor defense and cytotoxic competence (natural killer cell activity [NKCA], plasma interleukin [IL]-1beta, IL-2, IL-10, interferon [IFN]-gamma, tumor necrosis factor [TNF]-alpha) and cortisol were measured. RESULTS: ANV was reported by 7 patients in at least one cycle. In Cycle A, ANV was positively associated with emetogenity of chemotherapy. Features of ANV-duration and occurrence-tended to be positively associated with those of posttreatment nausea and vomiting. AN increased as infusion onset time approached. NKCA and IFN-gamma increased from home to hospital, independent from cortisol level. The NKCA increase was predominantly observed in patients with ANV. CONCLUSIONS: ANV in pediatric patients showed features of a CR. Immune parameters were sensitive to the CS content of the environment, predominantly in patients with ANV. This is consistent with the manifestation of multiple CRs.

Adolescent↗
PubMed2000

Allogeneic and autologous stem-cell transplantation in advanced Ewing tumors. An update after long-term follow-up from two centers of the European Intergroup study EICESS. Stem-Cell Transplant Programs at Düsseldorf University Medical Center, Germany and St. Anna Kinderspital, Vienna, Austria.

BACKGROUND: An update of results from the High Risk Protocol of the Meta-EICESS Study, conducted at the Pediatric Stem-Cell Transplant Centers of Düsseldorf and Vienna. In order to evaluate a possible therapeutic benefit after allogeneic SCT in patients with advanced Ewing tumors (AET), we compared outcome after autologous and allogeneic stem-cell transplantation (SCT). PATIENTS AND METHODS: We analyzed 36 patients treated with the myeloablative Hyper-ME protocol (hyperfractionated total body irradiation, melphalan, etoposide +/- carboplatin) between November 1986 and December 1994. Minimal follow-up for all patients was five years. All patients underwent remission induction chemotherapy and local treatment before myeloablative therapy. Seventeen of thirty-six patients had multifocal primary Ewing's tumor, eighteen of thirty-six had early, multiple or multifocal relapse, one of thirty-six patients had unifocal late relapse. Twenty-six of thirty-six were treated with autologous and ten of thirty-six with allogeneic hematopoietic stem cells. We analyzed the following risk factors, that could possibly influence the event-free survival (EFS): number of involved bones, degree of remission at time of SCT, type of graft, indication for SCT, bone marrow infiltration, bone with concomitant lung disease, age at time of diagnosis, pelvic involvement, involved compartment radiation, histopathological diagnosis. RESULTS: EFS for the 36 patients was 0.24 (0.21) +/- 0.07. Eighteen of thirty-six patients suffered relapse or died of disease, nine of thirty-six died of treatment related toxicity (DOC). Nine of thirty-six patients are alive in CR. Age > or = 17 years at initial diagnosis (P < 0.005) significantly deteriorated outcome. According to the type of graft, EFS was 0.25 +/- 0.08 after autologous and 0.20 +/- 0.13 after allogeneic SCT. Incidence of DOC was more than twice as high after allogeneic (40%) compared to autologous (19%) SCT, even though the difference did not reach significance (P = 0.08, Fisher's exact test). CONCLUSIONS: Because of the rather short observation period. secondary malignant neoplasms (SMN) may complicate the future clinical course of some of our patients who are currently viewed as event-free survivors. EFS in AET is not improved by allogeneic SCT due to a higher complication rate. The patient group was to small to analyze for a possible graft-versus-tumor effect.

Adolescent↗
PubMed2000

Successful treatment of relapsed CML after cord blood transplantation with donor leukocyte infusion IL-2 and IFNalpha.

A 3-year-old girl with BCR/ABL-positive CML relapsed after related HLA-identical cord blood transplantation. She was treated with three cycles of donor lymphocyte (DLI) infusion from her 15-month-old brother. Interferon alpha was added after the second DLI, whereas a trial of IL-2 had to be discontinued because of increasing immature myeloid cells in the blood smear. No signs of GVHD were observed, but she developed myelosuppression and needed one platelet and one red blood cell transfusion. She achieved a molecular remission after 6 months with transient molecular relapse followed by sustained remission for 15 months. Thus, DLI with or without interferon alpha might prove to be a promising treatment option with tolerable side-effects in relapsed CML after cord blood transplantation. Bone Marrow Transplantation (2000) 25, 219-222.

Blood Component Transfusion↗
PubMed2000

In vivo cytokine responses to interleukin-2 immunotherapy after autologous stem cell transplantation in children with solid tumors.

The potent immunostimulatory cytokine interleukin-2 (IL-2) has been extensively investigated for its potential to induce anti-tumor immunity in a number of tumor models. Only recently the complex interplay of mutually suppressive or supportive cytokines of the IL-2-induced network of cytokines has been better characterized. The aim of this study was to assess which of these in vitro findings are reproducible in vivo in recipients of stem cell transplants (SCT), since in these patients long- lasting impairments in cytokine inducibility have been described. We have therefore studied the kinetics of putative modulators and mediators of IL-2-induced immune activation, namely IL-1beta, IL-4, IL-5, IL-10, IL-12, soluble Fas ligand (sFasL), and GM-CSF during IL-2 therapy. All patients were children or adolescents suffering from solid tumors with poor prognosis who received three 5-day courses of high-dose intravenous IL-2 as an adjuvant to their radio-chemotherapy and autologous SCT. While IL-1beta, IL-4 and IL-12 were not, and sFasL was only mildly affected by the IL-2 therapy, we observed a consistent and early rise of IL-10, IL-5, and GM-CSF. These increases were rapidly reversible after discontinuation of IL-2 therapy. The inducibility of IL-10, IL-5 and GM-CSF was more pronounced with increasing time from the SCT, and in the third cycle reached an order of magnitude as in high-dose IL-2 patients without SCT. Together with the abundant in vitro data, these findings may help devise a combination immunotherapy permitting stronger anti-tumor effects, but lesser adverse effects.

Adolescent↗