Up-front centralized data review and individualized treatment proposals in a multicenter pediatric Hodgkin's disease trial with 71 participating hospitals: the experience of the German-Austrian pediatric multicenter trial DAL-HD-90.

BACKGROUND AND PURPOSE: A systematic procedure for up-front centralized data review and the set-up of individualized treatment proposals was integrated prospectively into the German-Austrian multicenter trial DAL-HD-90 for pediatric Hodgkin's disease (HD) in order to introduce local radiotherapy according to the individual patient's spread of disease within a combined-modality treatment. This paper investigates the feasibility of such a procedure and its impact on the final definition of the extent and stage of disease as well as on the choice of treatment. PATIENTS AND METHODS: Between October 1990 and July 1995, 578 children and adolescents <18 years (259 girls, 319 boys, median age 12.9 years) with HD were enrolled into the HD-90 trial. After clinical and pathological staging (66.4/33.6%), patients were allocated to treatment groups (TG) 1 'early stage', TG2 'intermediate stage', or TG3 'advanced stage'. All groups underwent two cycles of OPPA (vincristine, prednisone, procarbazine, doxorubicin) (girls) or OEPA (E, etoposide) (boys) for induction chemotherapy. TG2 and TG3 continued on as two or four cycles, respectively, of COPP (C, cyclophosphamide). Low-dose local radiotherapy was given to the initially involved sites, with radiation doses of 25 Gy in TG1/TG2, and 20 Gy in TG3. All documentation forms, radiographs, and chest and abdominal computed tomography (CT) scans were centrally reviewed, addressing in particular the individual patient's extent and stage of disease. This review and the set-up of individualized treatment proposals were in the hands of the study coordinator, one additional pediatrician and two radiation oncologists and radiologists at the study center. During a time slot of at least 8 weeks (two cycles of standard chemotherapy in all three TGs) the individualized treatment proposals were to be sent to the participating hospital. RESULTS: Complete sets of documentation from 564/578 patients (97.6%) were submitted sufficiently early to the study center. A total of 285 out of 574 chest radiographs, 468 out of 553 chest CT scans and 421 out of 548 abdominal CT scans were available from 71 hospitals. A total of 564 individualized treatment proposals were worked out by the review group and sent to the hospitals before radiotherapy began. Re-analysis of images and documentation forms, including laboratory and clinical data, resulted in a revision of stage in 115/571 patients (20.1%) and of TG in 76/571 patients (13.3%). A total of 67/76 patients were shifted into a higher TG, 60 patients on account of additionally detected extralymphatic involvement, five patients because of additionally detected lymph node involvement and two patients due to clinical data which had to be classified as B-symptoms. A total of 9/76 patients were shifted into a lower TG; in three patients extranodal disease and in six patents local lymph node involvement could not be confirmed. CONCLUSIONS: The up-front centralized review of patient data and consecutive set-up and delivery of individualized treatment proposals for almost every patient are feasible within a large multicenter trial. Sufficient time and manpower at the study center are needed for the review process and the set-up of individualized treatment proposals. Such a procedure has a significant impact on the homogeneity of stage definition, allocation to TG, and individualized treatment proposals.

Congenital dyserythropoietic anemia type I (CDA I): molecular genetics, clinical appearance, and prognosis based on long-term observation.

Congenital dyserythropoietic anemia type I (CDA I) is a rare autosomal recessive disorder with ineffective erythropoiesis and iron overloading. More than 100 cases have been described, but with the exception of a report on a large Bedouin tribe, these reports include only small numbers of cases, and no data on the lifetime evolution of the disease are available. Since 1967, we have been able to follow 21 cases from 19 families for up to 37 years. Twenty-one patients with a confirmed diagnosis of CDA I exhibited chronic macrocytic anemia of variable severity, requiring regular red cell transfusions only in 2 individuals. Four developed gallstones before the age of 30 years. Fifteen of 16 cases alive at the time of analysis showed mutations of at least one allele from exons 6 to 28 within CDAN1. Iron overloading is to be expected in all patients. In 9 patients, iron depletion was started between the ages of 7 and 36 years. Splenectomy, which was performed in 7 patients, did not result in improvement of hemoglobin values. Five patients were treated with interferon alpha-2a, and all responded with a rise in hemoglobin concentration of between 25 and 35 g/L (2.5 and 3.5 g/dL) starting within 4 weeks.