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Biomedical subjects

N Graf

Publications and source records attributed to N Graf.

120 records · Page 7Linked to original sources
PubMedDate not supplied

[Neoadjuvant therapy for localized osteosarcoma of extremities. Results from the Cooperative osteosarcoma study group COSS of 925 patients].

BACKGROUND: Owing to twenty years of multicentric interdisciplinary cooperation, the COSS group has been able to collect data on a large group of osteosarcoma patients treated by neoadjuvant therapy. This paper reviews results achieved in patients with localized extremity tumors. PATIENTS AND METHODS INCLUSION CRITERIA: Registration into a completed neoadjuvant COSS-Study. Histologically confirmed, primary, localized, high-grade, central osteosarcoma of an extremity; age < 40 years; no pretreatment; interval diagnosis to chemotherapy < or = 3 weeks; no severe comorbidity. Chemotherapy: HD-methotrexate +/- doxorubicin +/- cisplatin +/- ifosfamide +/- BCD. Scheduled local therapy: Surgery. RESULTS: 925 evaluable patients from 101 institutions. Median age 15 years, m:f 1.4:1. Primary site: femur 510, tibia 251, humerus 100, fibula 51, other 13. Tumor-size < 1/3 of the involved bone 616, > or = 1/3 304. Definitive surgery in 903/925 cases, 443 limb salvage procedures. Good response (> 90% necrosis) in 469/806 (58.2%) evaluated tumors. Median follow-up for surviving patients: 5.42 years. Actuarial survival after 5 and 10 years: 72.5% (95%-CI 69.3-75.7) and 66.3% (62.5-70.0), relapse-free 62.1% (58.7-65.4) and 59.4% (55.8-63.0). 683/925 alive (601 first remission), 242 deceased (212 tumor progression, 30 other causes). 66.2% (97.3%) of all relapses within 2 (5) years. Prognosis correlates with tumor-size (< vs. > or = 1/3: 69.9% vs. 58.3% at 10 years) and -site (tibia: 74.2%, humerus: 54.5%) and -response (good vs. poor: 78.2% vs. 52.5%) (all p < 0.01). Actuarial 10-year survival by response grading I-VI according to Salzer-Kuntschik 80.9%, 82.8%, 71.1%, 60.7%, 47.7%, 27.3%. COSS-studies with preoperative 4-drug therapy more efficacious than less aggressive protocols. No impact of doxorubicin scheduling (sequential: rapid vs. 48 h-continuous infusion) or cisplatin scheduling (randomized: 5 h vs. 72 h-infusion) on prognosis detected. CONCLUSIONS: Intensive multiagent chemotherapy and delayed surgery for localized extremity osteosarcoma led to excellent oncologic results in the COSS-studies. Tumor-size, -site, and -response as well as the intensity of upfront chemotherapy correlated with outcome. Giving doxorubicin and cisplatin by continuous infusions did not result in discernible prognostic disadvantages.

Adolescent↗
PubMedDate not supplied

[Churg-Strauss syndrome in a 15-year old boy].

A 15 year-old boy was admitted in our hospital with the clinical signs of cardiopulmonary deterioration. His history showed bronchial asthma since 3 years. Furthermore he revealed signs of polyneuropathy, exanthema and a transitory pulmonary infiltration. Elevation of eosinophilic granulocytes and IgE confirmed the diagnosis of a Churg-Strauss syndrome. A rapid improvement of the symptoms was achieved by high-dose steroids and symptomatic therapy. The impaired systolic and diastolic myocardial function improved, but a cardiomyopathy with a shortening fraction below 25% persisted. The Churg-Strauss syndrome is a rare disease in childhood and is classified as a systemic granulomatosis of the vessels. The marked perimyocarditis with consecutive restrictive cardiomyopathy is a rare manifestation in childhood and adolescence. The prognosis of this disease is mainly influenced by the cardiac involvement.

Adolescent↗
PubMedDate not supplied

Preradiation chemotherapy of children and young adults with malignant brain tumors: results of the German pilot trial HIT'88/'89.

BACKGROUND: Preradiation chemotherapy could be beneficial in malignant brain tumors, because the blood-brain tumor-barrier is disrupted after surgery, bone marrow recovery--essential for intense chemotherapy--is still intact, and CNS toxicity and ototoxicity of active drugs are lower before irradiation of a child's brain. PATIENTS AND METHODS: A neoadjuvant phase 2 and a single arm pilot trial were initiated to investigate the efficacy and toxicity of an intense multidrug regimen before radiotherapy in 147 patients aged between 3 and 29; 9 years with medulloblastoma (94), malignant glioma (22), ependymoma (21), and stPNET (10). They were treated with one or two cycles consisting of procarbazine, ifosfamide/mesna with etoposide, high dose methotrexate/CF, and cisplatin with cytarabine. RESULTS: Radiation therapy was delayed for 17-30 weeks (median 23 weeks) in 112 patients who received two cycles. Chemotherapy was well tolerated. Serious infections were observed in 20 patients, with one fatal fungal septicemia. In 69 high risk patients with a residual tumor and/or solid CNS metastases an objective response (CR plus PR) was achieved in 67% medulloblastoma, 57% stPNET, 55% anaplastic ependymoma and 25% malignant glioma. Progression-free survival (PFS) at 5 years was 57% in 14 high risk patients with medulloblastoma, who achieved a complete response (CR). After a less than CR the PFS was 20% (p = 0.01). Overall survival at 5 years was 57% in medulloblastoma, 62% in ependymoma, 36% in malignant glioma and 30% in stPNET. CONCLUSION: The HIT'88/'89 regimen was well tolerated and efficacious in regard to response rates and early PSF particularly in medulloblastoma and anaplastic ependymoma. Based on these results the prospectively randomized trial HIT'91 was designed to investigate the optimal timing of chemotherapy. Preradiation chemotherapy according to the HIT'88/'89 regimen was compared with the standard regimen using CCNU, cisplatin, and vincristine after radiation therapy. Additionally, strict quality control of the three treatment modalities was instituted to help improve the survival rates in both trial arms.

Adolescent↗
PubMedDate not supplied

[Skeletal changes in thalassemia].

Display of this hereditary blood disease (haemoglobinopathy) which is endemic in the Mediterranean area and rarely appearing in our area, characterized by early blood cell destruction and increasing transfusion siderosis of internal and endocrine organs, secondary osteoporosis, epiphyseal growth disturbances and spontaneous fractures by means of two typical cases.

Adolescent↗
PubMedDate not supplied

High dose consolidation with autologous stem cell rescue (ASCR) for nephroblastoma initially treated according to the SIOP 9/GPOH trial and study.

UNLABELLED: Patients with nephroblastoma have a high risk of relapse if they present with stage IV and anaplastic histology or with extraregional lymph node involvement; at time of relapse, bad prognosis is heralded by recurrence in an irradiated region, second or subsequent relapse, early first relapse (6 months after nephrectomy), relapse with adverse histology, relapse in two or more organ systems and lymph node or bone metastases at relapse. For such patients, an attempt to increase survival by high-dose chemotherapy seems to be justified. In 8 children aged 7.3 years (3.8-14.7) treated within the German Nephroblastoma Study SIOP9/GPOH, high dose chemotherapy with autologous hematopoietic rescue was instituted for the following reasons: stage IV with anaplastic histology and extra-regional lymph nodes (1), second or subsequent pulmonary relapse (3), early relapse with diffuse pleural (1) or skeletal (1) dissemination, recurrence in irradiated area (1) and lung metastases after early local relapse (1). At megatherapy, the patients were in first (1), second (2), third (2) and fourth complete (2) or in partial remission (1). The high dose regimen consisted of carboplatin, etoposide and melphalan. Treatment related toxicity, all non-lethal, included acute but reversible renal failure (1), esophagitis with need of parenteral nutrition for 6 months (1), cardiomyopathy (3; chronic in 1). After a follow-up of 2.1 years (0.5-3.7), 6/8 patients survive in complete remission; for 5 of them who are in remission since > 18 months a recurrence is unlikely. Both children with local relapse died after a further recurrence 3 and 8 months after high dose treatment. CONCLUSION: High dose consolidation with ASCR seems to effectively ameliorate the prognosis of patients with high risk nephroblastoma.

Adolescent↗
PubMedDate not supplied

[IDA-FLAG (idarubicin, fludarabine, high dosage cytarabine and G-CSF)--an effective therapy regimen in treatment of recurrent acute myelocytic leukemia in children and adolescents. Initial results of a pilot study].

Intensive chemotherapy has improved the prognosis of patients with AML. The success rate of relapse treatment correlates with the length of first remission. Thus early relapses and primarily refractory diseases have a grave prognosis. New chemotherapeutic regimens could be useful for those patients. Patients treated for newly diagnosed or relapsed AML with polychemotherapy regimen of the AML-BFM-studies containing induction, consolidation and high-dose cytarabine combined with mitoxantrone (HAM) and relapsed within 2 up to 31 months after the first CR entered a pilot trial, the so called IDA-FLAG regimen. This regimen includes G-CSF (day 0 up to ANC > 1000/microliter, 400 micrograms/m2.d), fludarabine (day 1-4, 30 mg/m2.d), high-dose cytarabine (day 1-4, 2000 mg/m2.d) and idarubicin (day 2-4, 12 mg/m2.d). 10 patients aged 1,8 to 28,1 years (mean = 9,6 years) having the first (n = 8) or second relapse (n = 1) of AML or an acute blastcrisis of myelodysplastic syndrome (n = 1) (FAB classification: M1/M2 = 3, M4/M5 = 5, M7 = 1, CMML = 1) received 14 courses. Overall, 7 patients achieved CR with a mean duration of 8,9 months (1-22 months), one patient showed a partial remission and two were nonresponders. 4 patients are in continuous CR for 7,5 to 22 months (mean = 13,2 months). 3 patients got a bone marrow transplantation (allogenic = 2, autologous = 1) in CR following this treatment. Toxicity was considerable, mainly bone marrow aplasia with leucopenia < 1000/microliter for 15 to 40 days (mean = 26,1 days), neutropenia < 500/microliter for 14 to 39 days (mean = 26,0 days) and thrombocytopenia < 30,000/microliter for 14 to 90 days (mean = 36,5 days). Further important side effects were fever, mucositis and pneumonia. One patient died from an fulminant aspergillus sepsis during long-term neutropenia. The sequential administration of G-CSF, fludarabine, cytarabine and idarubicin is effective in treatment of relapsed AML in childhood and an advisable option prior to allogenic or autologous bone marrow transplantation. With regard to the unfavorable prognosis of relapsed or refractory AML the toxicity of this regimen seems acceptable.

Adolescent↗
PubMedDate not supplied

Retinoids in the treatment of acute promyelocytic leukemia. Review of the literature.

Retinoids are derivates of vitamin A. They play an important role in embryogenesis and differentiation of normal cells. All-trans retinoic acid (ATRA, Tretinoin) and 13-cis retinoid acid (cRA, Isotretinoin) are the most important isomers. The first treatment with retinoids in a patient with an acute promyelocytic leukemia (APL) is reported in 1983. Since 1988 studies are done investigating the effect of retinoids in APL. These studies demonstrate, that retinoids can achieve a high remission rate in patients with APL but without curing patients. A combination with chemotherapy is always necessary. The main advantage of using retinoids in this disease is a rapid improvement of the hemostatic disorder and the absence of an aplastic phase. Side effects of retinoids are those of the hypervitaminosis A syndrome and have to be considered in every patient treated with this drug. The addition of alpha-Tocopherol seems to ameliorate the toxicity of retinoic acid (RA). The theoretical background of the treatment with retinoids in APL as well as the clinical studies done so far are explained in detail.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

[NHL-BFM 90 therapy study in treatment of malignant non-Hodgkin's lymphomas in children and adolescents. Part 2: An intermediate term analysis of the non-B-NHL therapy group. BFM Study group].

The goals of study NHL-BFM 90 for the therapy group Non-B NHL are to prospectively evaluate the dynamic of tumor regression and the persistence of a residual mass after induction therapy for its prognostic impact. Patients (pts) of stages I and II receive induction composed of prednisone, vincristine (VCR), daunorubicin, L-asparaginase (L-ASP), cyclophosphamide (CP), cytarabine (ARA-C), 6-mercaptopurine (6-MP) and intrathecally (i.th.) methotrexate (MTX), followed by consolidation (6-MP,MTX 5 g/m2 x 4, MTX i.th.), and maintenance up to 24 months. Pts of stages III and IV receive additionally reinduction (Dexamethasone, VCR, doxorubicin, L-ASP, CP, ARA-C, 6-thioguanine, MTX i.th.) and cranial irradiation. Pts with < 70% tumor regression at day 33 of induction receive an intensified chemotherapy. Pts with > 70% tumor regression at day 33 but a persistent mass at the end of induction have a surgical resection. Pts with a completely necrotic residual mass continue with consolidation therapy. Pts with active residual lymphoma receive an intensified chemotherapy. No local radiotherapy is given. From 4/1990 to 12/1992, 80 pts were registered; 71 pts are evaluable for response. The distribution of stages is as follows: 6, 1, 47, 17 pts of stage I, II, III, IV, respectively. The probability of event free survival at 3 years is 87 +/- 4% for the whole group (median observation time 21 months). 66 pts are evaluable for the dynamic of response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Hemofiltration and plasmapheresis in newborns using a small blood pump system.

Extracorporeal detoxification methods in newborns and premature infants are unavailable and contraindicated because of technical problems. The authors' experiences with a blood pump unit that was miniaturized for hemodialysis, hemofiltration, and plasmapheresis in newborns are reported. In 28 newborns and premature infants, 32 hemofiltrations, 3 hemodialyses, and 57 plasmaphereses were carried out for different diseases. Thirteen of 28 patients died despite hemofiltration and/or plasmapheresis as a result of their primary disease and/or immaturity, and 15 patients improved.

Acute Kidney Injury↗
PubMedDate not supplied

Cerebroretinal vasculopathy and leukoencephalopathy mimicking a brain tumor. Report of two early-onset cases with Fanconi's anemia-like phenotypes suggesting an autosomal-recessive inheritance pattern.

We report two sisters affected with a unique disorder characterized by recurrent space-occupying brain lesions and retinal vasculopathy since their early twenties. Affection status was associated with abnormalities characteristic of Fanconi's anemia, i.e. aplastic anemia, microcephaly, short stature, an unusual face and pigmentation abnormalities of skin. In cytogenetic analyses performed in childhood signs of chromosome fragility or any chromosomal aberration were lacking. Histopathological examination of brain biopsy samples in both cases demonstrated identical histomorphological features of an unusual occlusive vasculopathy with multilayered basement membranes and coagulation necroses which were confined to the white matter. A veno-occlusive retinopathy with neovascularization attributed to progressive visual loss. One of the sisters died at an age of just 24 years, the other is now 27 years old. Unlike any other published cases of hereditary cerebroretinal vasculopathy, the sisters' complex early-onset vaso-occlusive CNS-/eye-disease seems to be genetically associated with their Fanconi's anemia-like phenotypes and is suggested to constitute an autosomal-recessive variant. Patchy white matter calcifications, an incidental finding in either of the affected sisters, may represent preclinical manifestation of disease onset in childhood.

Adult↗