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Biomedical subjects

H Gadner

Publications and source records attributed to H Gadner.

At least 343 records · Page 19Linked to original sources
PubMedDate not supplied

[Clinical applications of cytokines in pediatrics].

Cytokines are decisive for the regulation of the immune system as well as the renewal and maturation of the haematopoietic cells. The most important groups of substances, several of which are already produced by gentechnology, are the interferons, the interleukins and the haematopoietic growth factors. The main indications for the application of alpha-(less often beta-)Interferon in children are the juvenile larynx papillomatosis, chronic hepatitis B, viral encephalitis, and also chronic myeloic leukemia, extended haemangiomas, recurrent Langerhans cell histiocytosis and nasopharynx carcinomas. gamma-Interferon is administered successfully for chronic granulomatous disease and has recorded positive effects in therapy resistant rheumatoid arthritis, in kidney cell carcinoma and in osteopetrosis. G-CSF, GM-CSF and Interleukin 3 are the most effective haematopoietic growth factors currently in use. Through G-CSF congenital agranulocytosis (Kostmann syndrome) has become a treatable disease. Other proven applications are in the reduction of aplastic phases after chemotherapy and in critical situations of primary bone marrow failure as well as myelodysplastic syndromes, for prevention of transplant rejections after bone marrow transplantation and for mobilisation of stem cells into peripheral blood before apheresis. Erythropoietin is established in the treatment of chronic renal anaemia and is currently used in the treatment of anaemia in preterm infants. Finally, Interleukin 2 is also used for adoptive immunotherapy in children with minimal residual tumors. The future will show us, whether the spectrum of indications will expand and whether a definite benefit for sick children will result from a wider application of these substances. As long as the cost/benefit ratio for certain indications is not clear, the use of these drugs should be tested in prospective studies.

Adolescent↗
PubMedDate not supplied

Influence of fractionated total body irradiation on mucosal toxicity in intensified conditioning regimens for autologous bone marrow transplantation in pediatric cancer patients.

From April 1988 to March 1991 28 children with generalized solid tumors (N = 15) or hematologic malignancies (N = 13) received intensified myelotoxic regimens followed by autologous stem cell rescue (ABMT). These intensified regimens consisted of 12 Gy fractionated total body irradiation (FTBI) and 2 (or 3) cytotoxic drugs (group A, n = 19) or a combination of 3 cytotoxic drugs (group B, n = 9). FTBI-containing regimens produced more severe mucositis > = WHO grade 3 (p = 0.01) and a longer duration of severe mucositis. The mucositis had a median duration of 8 days (range 0-28) in group A compared with median 0 days (range 0-7) in group B (p < 0.01). Acute renal and liver toxicity were not different. The probability of overall survival at day +100 was 89% in all patients. In terms of long-term survival FTBI containing regimen did not prove superior: 5 out of 19 patients in group A and 6 out of 9 patients in group B have been survivors for a minimum of 3 years. In conclusion, severe gastrointestinal toxicity of such intensive regimens is avoidable if FTBI is omitted.

Adolescent↗
PubMedDate not supplied

[Venous thrombosis of cranial sinuses in asparaginase therapy. A case report].

Changes in the coagulation system due to steroids and asparaginase during treatment for acute lymphoblastic leukemia (ALL) are well known side effects and may cause bleeding or thrombosis. We report the case history of a 7-year old girl who developed thrombosis of the sinus sagittalis superior during ALL-treatment. Diagnosis was made by computed tomography and magnetic resonance imaging after the child became symptomatic with seizure. Until this event the girl had been treated already for two weeks with prednisone and E. coli-asparaginase (4 infusions). This medication caused distinct hypofibrinogenemia (Fibrinogen 53 mg/dl), prothrombin time expressed as percent of normal values of 58% was also pathological, activated partial thromboplastin time of 35 sec, antithrombin III 120% and thrombocyte count 178 G/l were in normal range. We were not successful in the attempt to adjust the imbalance in the coagulation system by transfusion of fresh frozen plasma (FFP)--seizure happened during FFP-infusion, fibrinogen blood level could be elevated only slightly. Our patient stayed consequently asymptomatic, the clinical recovery was confirmed radiologically.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Enteroviral meningoencephalitis in immunocompromised children after matched unrelated donor-bone marrow transplantation.

Two children are described who presented with fever and generalized seizures, days 50 and 200, respectively, after matched unrelated donor-bone marrow transplantation. Upon antiepileptic treatment the seizures vanished but somnolence and fever remained. Magnetic resonance imaging (MRI) of the brain was performed and revealed transient asymmetric multifocal hyperintense lesions. Seizures were considered related to infection, and the cyclosporin A (CsA) treatment was not interrupted. Enterovirus was detected by reverse transcriptase-polymerase chain reaction in the spinal fluid of one patient and in the sputum of the other. Both children recovered completely within the next weeks without neurological sequel. This report shows that enteroviral meningoencephalitis can present with seizures during the post-transplant period. It highlights the importance of MRI for neuroimaging and of viral infections as differential diagnosis to CsA neurotoxicity.

Adolescent↗
PubMedDate not supplied

Occurrence of acute nonlymphoblastic leukemia in two girls after treatment of recurrent, disseminated Langerhans cell histiocytosis.

The occurrence of Langerhans cell histiocytosis (LCH) and acute leukemia in one individual has rarely been observed. Despite few exceptions, two distinct patterns of association appear evident: acute lymphoblastic leukemia preceding LCH and LCH preceding acute nonlymphoblastic leukemia (ANLL). The latency of ANLL after the diagnosis of LCH is suggestive of a therapy-related process. This report describes two new cases in whom ANLL was diagnosed 7 years 8 months and 5 years 8 months after the start of initial treatment of disseminated recurrent LCH. Morphology showed blasts from FAB-type M4/M5 in the first patient, who died due to progression of leukemia. The second patient showed myelodysplastic syndrome (refractory anemia with excess of blasts in transformation; RAEB-t) and is now in remission from leukemia 3 years 11 months after allogeneic bone marrow transplantation. The review of a total of 26 patients with ANLL after LCH suggests that the disease has a poor prognosis and allogeneic BMT seems to be the treatment of choice.

Bone Marrow Transplantation↗
PubMedDate not supplied

Manifestations of graft-versus-host disease following allogenic bone marrow transplantation.

Sixty-seven patients undergoing allogenic bone marrow transplantation (BMT) were examined before and at regular intervals for up to 87 months (1-87 months, mean 18) after transplantation. Within a period of 1-39 months, 14 of these patients died (11 male, 3 female; age at BMT 16-46y). Five of these patients died within the first 100 days. They showed no eye involvement; three patients had intraretinal hemorrhage, in one case of squamous blepharitis and filiform keratitis developed during chronic graft-versus-host disease (GVHD). In contrast, 22 of 53 (41.5%) surviving patients (30 male, 23 female; age at BMT 1-47y) were found to have ocular involvement. Before BMT only two cases of retinal hemorrhage and central chorioretinal scars each were detected. During the stage of acute GVHD (up to day 100), nine patients were free of ocular manifestations. However, 16 of the 20 patients with chronic GVHD showed ocular involvement; 14 (70%) had reduced tearflow, ten had severe keratoconjunctivitis sicca, four suffered from sterile corneal ulcerations. Bilateral cataracts were detected in 11 patients, nine of whom only had minimal posterior subcapsular opacification, possibly resulting from highdose steroid medication. One additional case presented with bilateral multifocal recurrent chorioretinitis and panuveitis. The fundus lesions appeared some months after BMT (before cyclosporin-A treatment started) and recurred during systemic treatment. All patients undergoing allogenic BMT, especially when treated for severe chronic GVHD, require regular ocular observation to avoid complications such as keratoconjunctivitis sicca at an early stage, as late complications are often severe and hardly amenable to conservative or surgical treatment.

Acute Disease↗
PubMedDate not supplied

High-dose melphalan, etoposide +/- carboplatin (MEC) combined with 12-gray fractionated total-body irradiation in children with generalized solid tumors.

Long-term disease-free survival is poor in patients with primary generalized or relapsed solid tumors. High-dose chemoradiotherapy with stem cell rescue improved survival, but more effective protocols are needed. From January 1988 to November 1988, we treated 7 patients (median age, 9 years; range, 3-23 years) with an intensified treatment program. They received 12-Gy fractionated, total-body irradiation (FTBI). High-dose chemotherapy (MEC) consisted of melphalan (120-140 mg/m2 Mel) and etoposide (40-60 mg/kg VP-16) with or without carboplatin (1.5 g/m2 CBDCA). Although we combined 12-Gy FTBI with Mel, VP-16, +/- CBDCA in doses used previously for high-dose single-agent chemotherapy, the extramedullary toxicity of FTBI with ME(C) was tolerable. Two of the four patients who were grafted without delay after good initial chemotherapy response are still alive in continued complete remission 30 and 33 months, respectively, after initial diagnosis. Early application of FTBI and ME(C) during first chemotherapy response might improve outcome in patients with primarily generalized solid tumors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Limited tolerance of intensified conditioning regimens in children receiving methotrexate/cyclosporin A for graft-versus-host disease prophylaxis.

Twenty-one patients with a median age of 9 years (0.5-19) underwent intensified myeloblative therapy: 1800 mg/m2 etoposide (VP) was added to 120 mg/kg cyclophosphamide (CY) and 12 Gy fractionated total body irradiation (FTBI) or 12-16 mg/kg busulfan (BU) for treatment of acute lymphoblastic leukemia (11 patients), acute myeloid leukemia (8 patients), non-Hodgkin's lymphoma (1 patient), or myelodysplastic syndrome (1 patient). Severe liver toxicity occurred in 5 of 7 children (71%) receiving short-term methotrexate (MTX) and additional cyclosporin A (CSA) for prophylaxis of graft-versus-host disease (GVHD). Three of them died of subsequent acute renal failure on days 8, 13, and 34. In contrast, acute severe organ toxicity occurred in only 1 of 14 children (7%) receiving the same intensified regimens who were autografted (7 pts) or received MTX alone for GVHD prophylaxis (7 pts). These observations suggest that GVHD prophylaxis with MTX and CSA may adversely influence the tolerance of intensified antileukemic regimens in children.

Adolescent↗
PubMedDate not supplied

Conventional vs. liposomal amphotericin B in immunosuppressed children.

Invasive fungal infections, mostly caused by Candida and Aspergillus species, are a major cause of early morbidity and mortality in immunocompromised children. The treatment of choice for systemic fungal infections is still the early intravenous administration of amphotericin B. However, conventional AMB therapy is often limited by severe side effects such as fever, chills, bronchospasm, and nephrotoxicity. In recent reports liposomal AMB (AmBisome) was shown to be effective in the treatment of severe systemic fungal infections. So far, clinical experience with AmBisome in children is still anecdotal and no comparative study is yet available. In the following we report on 11 immunosuppressed children who were treated with conventional or liposomal AMB for longer than 3 weeks.

Adolescent↗
PubMedDate not supplied

High-dose cyclophosphamide, adriamycin, and vincristine (HD-CAV) in children with recurrent solid tumor.

A dose-intensive regimen of cyclophosphamide (140 mg/kg over 2 days), doxorubicin (Adriamycin, 75 mg/m2 over 3 days), and vincristine (1 mg/m2 on days 1, 2, and 3 and 1.5 mg/m2 on day 9) was tested in 18 children and adolescents with poor-prognosis recurrent or refractory solid tumors. Nine were affected by neuroblastoma, 3 by Ewing's tumors, 2 by rhabdomyosarcoma, 2 by synovial sarcoma, 1 by hepatocellular carcinoma, and 1 by osteogenic sarcoma. All enrolled patients were heavily pretreated, including 2 patients after bone marrow transplantation. Forty courses were applied (median, 2). The overall response rate was 33% (2 complete remissions and 4 partial remissions). Responses were obtained in children with neuroblastoma, Ewing's tumors, and hepatocellular carcinoma. Myelosuppression [World Health Organization (WHO) grade IV after all courses] and cardiac toxicity (3 WHO grade I, 5 WHO grade III, and 3 WHO grade IV) were the main side effects. Nephrotoxicity and hepatoxicity were not observed. With further therapy consisting of surgery, radiotherapy, and high-dose chemotherapy [cisplatin, carboplatin/etoposide (VP16), or ifosfamide/VP16 with or without autologous stem cell reinfusion after conditioning with melphalan/VP16/carboplatin], 3 complete remissions and 5 very good partial remissions were obtained. Ten of 18 patients are alive after a median follow-up of 16 months.

Adolescent↗
PubMedDate not supplied

Successful carboxypeptidase G2 rescue in delayed methotrexate elimination due to renal failure.

We report on an 18.5-year-old woman with osteosarcoma and delayed methotrexate (MTX) elimination due to renal failure after high-dose MTX, in whom rescue with high doses of folinic acid caused intolerable side effects. In this life-threatening clinical situation, the patients was rescued by the administration of recombinant carboxypeptidase G2, a bacterial enzyme that rapidly hydrolyzes MTX into inactive metabolites. This is the first report on the successful clinical use of this alternative catabolic route for the elimination of MTX.

Adolescent↗
PubMedDate not supplied

Partial nephrectomy in well-responding stage I Wilms' tumors: report of three cases.

We report on 3 of 21 stage I Wilms' tumor patients with tumor volumes of 190, 890, and 1300 mL, respectively, who responded dramatically to preoperative chemotherapy according to the Austrian/Hungarian Wilms' Tumor Study 89 by tumor volume reductions to 20%, 23%, and 13%, respectively. Radical resection of the tumors with renal preservation was achieved in all patients. Postoperative studies did not show any functional deficit in the preserved kidney. The patients have been in complete remission for 26, 33, and 60 months, respectively. Our preliminary results indicate that tumor resection should be feasible in patients with good responding stage I Wilms' tumors.

Antineoplastic Combined Chemotherapy Protocols↗