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W Schwinger

Publications and source records attributed to W Schwinger.

At least 19 recordsLinked to original sources
PubMed2005

Feasibility of high-dose interleukin-2 in heavily pretreated pediatric cancer patients.

BACKGROUND: The administration of high-dose interleukin-2 (IL-2) seems to be a therapeutic option for children with refractory and metastatic solid malignancies. METHODS: We prospectively studied treatment-related toxicities, quality of life and laboratory parameters in 10 children with progressive or metastatic solid tumors (metastatic osteosarcoma, n=4; neuroblastoma stage IV, n=3; metastatic Ewing's sarcoma, n=2; metastatic Wilms' tumor, n=1) during IL-2 therapy. Patients were scheduled to receive five cycles of high-dose IL-2 by continuous infusion for 5 days every 3 weeks. RESULTS: All patients developed fever >39 degrees C and influenza-like symptoms, with a significant decrease in Karnofsky score. In two patients treatment had to be stopped after three cycles because of severe side-effects. During IL-2 therapy a statistical significant increase in white blood cells (WBC), creatinine, gamma-glutamyltransferase, C-reactive protein, glucose and body weight was observed. In contrast, red blood cells, platelets, protein, albumin and cholinesterase significantly decreased. When results from day 1 of the first and of the fifth cycle were compared, an increase of WBC and a decrease of alkaline phosphatase was shown. No constant quantitative changes in total lymphocytes and subsets were observed during IL-2 therapy. CONCLUSIONS: IL-2 treatment in children with refractory and relapsed solid malignancies is associated with severe, but reversible, side-effects. However, five of the 10 patients with diseases of worst prognosis could be rescued by this treatment.

Adolescent↗
PubMed2005

Procalcitonin--a marker of invasive fungal infection?

Procalcitonin (PCT) has been described as a marker of bacterial sepsis. However, little is known of its diagnostic value in fungal infections. We calculated the sensitivity of PCT for detection of invasive fungal infections (IFI) by analyzing 55 episodes of proven or probable IFI (three in our series, 52 reported in the recent literature). In the early phase of IFI, PCT was elevated in fewer than half of invasive candidiasis episodes and in only one patient (5.3%) with invasive aspergillosis. Due to low sensitivity and specificity, PCT adds little to the diagnosis of IFI.

Adolescent↗
PubMed2005

Non-radiotherapy conditioning with stem cell transplantation from alternative donors in children with refractory severe aplastic anemia.

Conditioning including total body/lymphoid irradiation is widely used to prevent graft rejection in patients with refractory severe aplastic anemia (SAA) undergoing hemopoietic cell transplantation (HCT) from alternative donors and or after graft manipulation. To reduce regimen-related toxicity we transplanted three children with refractory SAA after conditioning with radiotherapy-free regimens. Conditioning included fludarabine 175-180 mg/m2 in all patients. In addition, patient 1 (failing two previous grafts) received thiotepa 10 mg/kg and Campath-1H 60 mg/m2; patient 2 cyclophosphamide 120 mg/kg, thiotepa 15 mg/kg and OKT-3 0.1 mg/kg/day for 4 weeks; and patient 3 cyclophosphamide 120 and ATG 90 mg/kg. Stem cell source was unmanipulated marrow from the same unrelated donor as for the two previous transplantations in patient 1 and CD34+-purified peripheral blood stem cells from an HLA-matched unrelated donor and from the haploidentical mother in patients 2 and 3. Only patient 1 received graft-versus-host disease (GVHD) prophylaxis with cyclosporine A and mycophenolate mofetil. Follow-up is now 30, 51, and 15 months. None of the patients developed GVHD. All patients have normal counts with complete donor chimerism. Fludarabine-based conditioning is powerfully immunosuppressive and may be used for children with refractory SAA undergoing HCT from alternative donors even after rejection following previous HCT.

Anemia, Aplastic↗
PubMed2003

Procalcitonin and C-reactive protein do not discriminate between febrile reaction to anti-T-lymphocyte antibodies and Gram-negative sepsis.

Treatment with antibodies against T-lymphocytes usually triggers a febrile response potentially mimicking or masking infection. Procalcitonin (PCT) is considered a sensitive and specific marker of systemic bacterial and fungal infection. It was the aim of this study to investigate the characteristics of PCT and C-reactive protein (CRP) during treatment with polyclonal or monoclonal anti-T-cell antibodies, in order to examine the ability of these parameters to distinguish between systemic bacterial infection and reaction to antibody treatment. Thus, 15 consecutive febrile episodes after T-cell antibody infusion without clinical signs of infection were compared with nine episodes of Gram-negative sepsis. After T-cell antibody infusion PCT and CRP serum levels increased to a similar extent as in Gram-negative sepsis. Therefore, during T-cell antibody treatment neither PCT nor CRP are adequate for differentiating between fever due to infection or to unspecific cytokine release.

Adolescent↗
PubMed2002

Organ tolerance following cadaveric liver transplantation for chronic graft-versus-host disease after allogeneic bone marrow transplantation.

A paediatric patient was treated with orthotopic liver transplantation after he developed cirrhosis of the liver due to chronic graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation. His pre-existing chronic GVHD of the skin disappeared and immunosuppressive therapy could be gradually tapered and finally withdrawn 71 months after liver transplantation. Two and a half years after discontinuation of all immunosuppressive therapy, the patient is in excellent condition with neither signs of chronic GVHD nor rejection of the liver graft.

Anemia, Sideroblastic↗
PubMed2001

Amplitude coded-colour Doppler sonography in paediatric renal disease.

The aim of our study was to assess the ability of amplitude coded-colour Doppler sonography (ACDS) to depict altered perfusion in paediatric renal disease in a prospective study. Colour Doppler sonography (CDS) and ACDS examinations were performed in 180 renal units (90 patients; age range newborn to 16 years) with unilateral or bilateral renal disease (e.g. reflux nephropathy, renal scars, end-stage renal disease, ureteropelvic junction obstruction, urinary tract infection, renal failure, haemolytic uraemic syndrome, nephrotic syndrome, systemic lupus erythematosus (LE), renal biopsy, congenital dysplasia, tumour/infiltration). The ACDS results were compared with scintigraphy or CT as well as to clinical findings. Amplitude colour-coded Doppler sonography accurately demonstrated normal vasculature in 49 of 51 healthy kidneys (= 96%); 3 healthy kidneys could not be evaluated due to motion/artefacts. In 39 of 43 kidneys with focally altered perfusion ACDS could be performed and correctly depicted focally impaired vasculature/perfusion in 35 kidneys (= 89.7%). Seventy-three of 83 kidneys with diffusely impaired perfusion could be evaluated by ACDS and altered pattern was correctly depicted in 58 kidneys (= 79.4%), with an overall percentage of agreement of 87.1%. Amplitude CDS appears to be useful in infants and children. Compared with CDS it improves visualisation of especially focally impaired vasculature/perfusion and should be considered a valuable adjunct to conventional investigations.

Adolescent↗
PubMed2001

Outcome and long-term side effects after synchronous radiochemotherapy for childhood brain stem gliomas.

Between 1993 and 1999, 11 children with histologically confirmed diffuse and exophytic brain stem glioma (BSG) were treated with intensive induction chemotherapy and simultaneous external beam irradiation. Chemotherapy was performed according to the German/Austrian Pediatric Brain Tumor Study HIT '91 and included two cycles of ifosfamide (days 1-3), etoposide (days 4-6), methotrexate (days 15 and 22), cisplatin (days 29-31) and cytarabine (days 29-31), separated by a 3-week interval. Maintenance chemotherapy with carmustine, carboplatin and vincristine (8 cycles over a 1-year period) was given in those patients who responded clinically or radiographically to induction chemotherapy. Six of 11 patients showed an objective reduction in tumor size on magnetic resonance imaging and 4 of 11 are alive in good general condition >22, >22, >90 and >92 months, respectively, after diagnosis without radiographic evidence of tumor progression (1 complete remission, 2 partial remissions, 1 stable disease), but suffer from moderate to severe long-term side effects. Three patients died due to disease progression after having achieved a partial remission which lasted 5, 6 and 18 months, respectively, whereas only short-term stabilization was observed in 4 patients who died within 1 year after diagnosis. Acute hematologic toxicity was severe but manageable. This intensive combined modality treatment was toxic but yielded objective responses in more than 50% and long-term survivors in one third of childhood BSG patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Tunneled femoral central venous catheters in children with cancer.

OBJECTIVE: We discuss the feasibility of long-term femoral venous access by means of a cuffed subcutaneously tunneled central venous catheter (Broviac catheter) in selected pediatric cancer and stem cell transplant patients in whom access via the veins of the upper part of the torso is difficult or contraindicated and in whom alternative routes must be used. PATIENTS AND METHODS: We report on our experience with 9 patients (3 of whom underwent stem cell transplantation) who received femoral Broviac catheters between December 1990 and November 1999. Results. Time in place ranged from 4 to 155 days with a median of 58 days (mean: 71.2 days). Three catheters had to be removed: 1 because of infection of the subcutaneous tunnel and 2 because of catheter obstruction. The remaining 6 catheters functioned well without problems as long as they were needed; 1 of them got accidentally dislodged while the patient was off treatment. No episodes of catheter-related septicemia, thrombosis, kinking, or drug extravasation were noted; there were no catheter-related infectious complications in the transplant patients. CONCLUSIONS: Our experience indicates that in those instances in which customary access to the superior vena cava is precluded, long-term venous access by way of the femoral vein is a feasible and safe alternative in children, even in the setting of stem cell transplantation.

Adolescent↗
PubMed2000

Prospective evaluation of late effects after childhood cancer therapy with a follow-up over 9 years.

UNLABELLED: Intensive multimodality treatment has led to a remarkable improvement of prognosis in paediatric cancer patients, however, a great number of long-term survivors suffer from considerable tumour- or treatment-related late effects. Between January 1990 and December 1998, 223 consecutive survivors of childhood malignancies entered a prospective follow-up study designed to evaluate the frequency and severity of tumour- and/or therapy-related long-term sequelae. After cessation of therapy and subsequently once a year, all patients underwent a detailed examination programme including physical examination, laboratory tests, abdominal sonography, echocardiography, electrocardiography, electroencephalography, spirometry, audiometry, ophthalmological examination and endocrine stimulation tests. Median follow-up was 5 years (range 0.4 to 9.6 years). A total of 167 patients (75%) had at least one chronic medical problem of whom 80 needed permanent medical support. The organ systems most frequently affected were the nervous system in 39%, the endocrine system in 32%, the ears/eyes in 22%, the kidneys in 17%, and the liver in 12% of the patients. Some late effects (endocrine deficits, hearing loss, tubulopathy) were primarily diagnosed only several years after the end of oncological therapy. CONCLUSION: The results of this study indicate that a considerable number of former paediatric cancer patients suffer from remarkable long-term side-effects. Since life quality is an important parameter of cancer survival, careful follow-up of long-term survivors is mandatory with the aim to reduce or even abrogate possible side-effects at the earliest time.

Adolescent↗
PubMed2000

Unrelated peripheral blood stem cell transplantation with 'megadoses' of purified CD34+ cells in three children with refractory severe aplastic anemia.

Three children with refractory severe aplastic anemia were transfused with high numbers of unrelated matched (n = 2) or C-locus haploidentical mismatched (n = 1) CD34-selected peripheral blood stem cells in the absence of an HLA-identical family donor. Two leukaphereses of the donors yielded a median number of 10.1 x 10(10) nucleated cells (range 9.7-15.4) with a median number of 9.89 x 10(8) CD34+ cells (range 7.46-26.1) and a median percentage of CD34+cells of 0.98% (range 0.77-1.7). After positive selection by magnetic cell sorting the patients received a median of 14.3 x 10(6) CD34+ cells/kg (range 11.7-24.3) and of 1.3 x 10(4) CD3+ cells/kg (range 0.57-5.8). Median time to ANC >/=0.5 x 10(9)/l was 7 days (range 7-12) and to platelets >/=20 x 10(9)/l 13 days (range 13-27). Chimerism analysis of peripheral blood after transplantation revealed permanent 100% donor hematopoiesis in all patients. The patient with the C-locus haploidentical mismatch presented with acute GVHD (grade III-IV) of the skin, liver and lower gastrointestinal tract (onset day +40) and died despite intensive immunosuppressive treatment on day +238. The two survivors developed lymphopoietic recovery of B and T lymphocytes within 3 months after transplantation. To our knowledge this experience represents the first report of transplantation with unrelated CD34+ enriched peripheral blood stem cell in children with refractory severe aplastic anemia. Bone Marrow Transplantation (2000) 25, 513-517.

Adolescent↗
PubMed2000

Unrelated partially matched peripheral blood stem cell transplantation with highly purified CD34+ cells in a child with Wiskott-Aldrich syndrome.

Stem cell transplantation is the only curative approach to the treatment of Wiskott-Aldrich syndrome. However, using grafts from partially matched unrelated donors is associated with increased risk of graft rejection and graft-versus-host disease. In an attempt to prevent these problems, a 6-year-old boy with Wiskott-Aldrich syndrome lacking a suitable family donor, was transplanted with large numbers of unrelated highly purified CD34+ peripheral blood stem cells mismatched at one C locus. Conditioning consisted of busulfan 16 mg/kg body weight, cyclophosphamide 200 mg/kg body weight and antithymocyte globulin 20 mg/kg body weight x 3 days. The boy had a rapid hematopoietic engraftment and showed immunologic reconstitution by day +92. Although he did not receive prophylactic immunosuppression he did not develop any graft-versus-host disease and is well and alive up to now, 25 months after transplantation.

Antigens, CD34↗
PubMed2000

Interferon-alpha and ribavirin in treating children and young adults with chronic hepatitis C after malignancy.

OBJECTIVE: Chronic hepatitis C is a major long-term problem for children who survive cancer. Interferon (IFN)-alpha has been shown to be effective in treating patients with chronic hepatitis C; however, the rate of sustained response is low. Combining IFN-alpha and ribavirin (RBV) has been shown to significantly improve the response in adult patients with chronic hepatitis C. The aim of this pilot study was to evaluate the efficacy and safety of a combined virostatic treatment with IFN-alpha and RBV in a small cohort of children and adolescents with chronic hepatitis C and previous malignancy. METHODS: Twelve patients with a history of a hematooncologic disease (median follow-up: 13.5 years; range: 7-14.7 years) and chronic hepatitis C were treated with recombinant IFN-alpha-2a (6 megaunits/m(2) body surface area, 3 times a week, subcutaneously) combined with RBV (15 mg/kg body weight/day, orally) for 12 months. They were tested monthly for blood counts and liver function, and for serum virus concentrations (hepatitis C virus RNA by polymerase chain reaction) every 3 months. RESULTS: At the end of the treatment, hepatitis C virus RNA could not be detected in the serum of 8 of the 12 patients; 2 of these patients relapsed soon after therapy withdrawal, whereas 6 patients maintained in sustained virologic and biochemical remission (follow-up: 12 months). Treatment-induced toxicity was moderate and reversible with influenza-like symptoms and a decrease in blood counts in all 12 patients, alopecia in 5 of the 12, hemolysis in 4 of the 12, and weight loss of >10% in 2 of the 12. CONCLUSIONS: As demonstrated in adults with chronic hepatitis C, treatment with IFN-alpha and RBV also seems to be an effective and safe therapeutic option for children and adolescents with chronic hepatitis C after malignancy.

Adolescent↗
PubMed2000

Allogeneic transplantation of G-CSF mobilized peripheral blood stem cells from unrelated donors: a retrospective analysis.

BACKGROUND AND OBJECTIVES: Allogeneic peripheral blood stem cell transplantation (PBSCT) from matched siblings has lead to clinical results comparable to those of standard bone marrow transplantation (BMT). We report the outcome of 79 patients transplanted with PBSC from unrelated donors. DESIGN AND METHODS: In 61 cases PBSC were used for primary transplantation whereas 18 patients were treated for relapse or graft-failure. In 35 patients receiving primary transplants, T-cell depletion (TCD) using CD34 positive selection of PBSC with or without additional T-cell depletion had been performed to reduce the risk of graft-versus-host-disease (GvHD). RESULTS: The rate of primary graft-failure was higher (20%) in the TCD group than in that receiving unmanipulated grafts (UM) (5%, p=0.007). Patients with standard risk (n=34) receiving first transplants had a significantly better overall (60.4% vs. 24%, p=0.02) and disease-free survival (57.2% vs. 22.3%, p=0.006) compared to a high risk group of patients (n=21). There were no differences in the speed of neutrophil and platelet engraftment between TCD and UM transplants. As expected, the cumulative risk for acute GvHD grade II.-IV was significantly higher in the patients who had received UM grafts (71.8% vs. 38.1%, p=0.005). Although a trend towards a better survival rate was observed after TCD transplantation (52.2%) compared to the UM group (38.1%), this difference was not statistically significant. The probability of relapse was significantly higher in patients after UM transplants (38.8% vs. 8. 4%). This apparent paradox is explained by the higher number of high-risk patients in this group (p=0.03). Multivariable analysis of disease-free survival revealed risk category (p=0.02) and use of ATG (p=0.03) to be of significant impact. All patients (n=6) with non-malignant diseases are alive with full donor chimerism. INTERPRETATION AND CONCLUSIONS: These data show that PBSC from unrelated donors can be transplanted either unmanipulated or CD34 selected. Prospective studies comparing BMT with PBSCT from unrelated donors are needed in defined disease categories.

Adolescent↗
PubMed1999

Transplantation of related and unrelated umbilical cord blood stem cells in Austria. Austrian Working Party for Stem Cell Transplantation. Austrian Society of Hematology and Oncology.

Allogeneic bone marrow transplantation is limited by the availability of suitable HLA-matched donors and the risk of graft versus host disease (GvHD). In an attempt to overcome these limitations umbilical cord blood (UCB), has become a further alternative. UCB transplantations in Austria were started in 1991. As of September 31, 1998, six patients have been transplanted. Diagnoses were severe aplastic anaemia (SAA) (n = 2), acute lymphoblastic leukaemia (ALL) (n = 1), familial hemophagocytic syndrome (FHL) (n = 2) and chronic myelomonocytic leukaemia (CMML) (n = 1). Three patients received UCB grafts from HLA-identical siblings and three patients from unrelated donors, of whom two were disparate at two HLA loci (A/B) and one mismatched at one locus (C). Five patients were engrafted with complete donor hematopoiesis, with a median time of 26.5 days (range 14 to 39 days) to an ANC count of > or = 0.5 x 10(9)/L and a median time of 42.5 days (range 24 to 67 days) to a platelet count of > or = 20 x 10(9)/L. One patient with FHL had partial engraftment and died due to reactivation of cytomegalovirus (CMV) infection and CMV pneumonia on day +25. Of the five patients surviving the post-transplant period, one with CMML had a relapse on day +128 and died after a HLA-matched bone marrow transplantation from the same sibling donor in the second relapse. Another patient with ALL relapsed on day +200 but is still alive under palliative treatment; one patient with SAA showed graft rejection and autologous hematopoietic reconstitution and later had a successful CD34(+)-selected allogeneic peripheral stem cell transplant from a C-locus mismatched unrelated donor. Two patients (one with SAA and one with FHL) are alive with complete remission of the underlying disease. This report reflects the experience and results of UCB transplantation in Austria and discusses the position of UCB transplantation in the context of the other stem cell alternatives available today.

Anemia, Aplastic↗
PubMed1999

Comparison of different methods for separation and ex vivo expansion of cord blood progenitor cells.

Umbilical cord blood is capable of hematopoietic stem cell reconstitution in children. However, the major limitation of cord blood is a relatively low content of pluripotent progenitor cells. Thus, safe engraftment for adolescents and for adults is still not predictable and a technology for ex vivo expansion of umbilical cord blood cells is desirable. In a first step, four different methods of red cell depletion followed by magnetic cell sorting of CD34+ cells were evaluated in this study in order to assess the efficacy and safety of optimal stem cell recovery. A modified two-step Ficoll gradient separation and a hydroxyethyl starch separation tended to produce a better WBC/MNC recovery (median 94.2+/-2.44% vs. 90.2+/-5. 8%) as compared with standard Ficoll gradient separation and a gelatin-based procedure (median 78.35+/-7.1% vs. 67.2+/-5.5%). However, the recovery of CD34+ cells after magnetic cell sorting did not reach a statistically significant difference after the four different methods of red cell depletion, indicating that the recovery of WBC/MNC is not predictably correlated with the recovery of stem cells within these fractions. In a second step, we established three different cytokine combinations by adding the megakaryocyte growth and development factor +/- erythropoietin and granulocyte colony-stimulating factor to a fetal calf serum containing medium with Flt 3, stem cell factor, and interleukin-3. Net expansion of total colony-forming cells 20- to 50-fold and expansion of colony-forming cells after 5 weeks of culture 1.5- to 3-fold were obtained over a period of 7-14 days. These results demonstrate that cord blood stem cells can be expanded substantially in this short-term culture system.

Antigens, CD34↗