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Biomedical subjects

G Henze

Publications and source records attributed to G Henze.

At least 163 records · Page 9Linked to original sources

[Implications of terminal deoxynucleotidyl transferase activity in various forms of childhood leukemia (author's transl)].

Terminal deoxynucleotidyl transferase (TdT) was examined in mononuclear peripheral blood cells (pB) and bone marrow (BM) specimens of 63 children with acute leukemia (AL). The enzyme activity in normal specimens (pB, BM) was below 0.2 U/10(8) cells; whereas, 49 of the 52 children with acute lymphoblastic leukemia (ALL) at diagnosis showed an activity in the range 1.2--60 U/10(8) cells. 2 of the remaining 3, devoid of TdT activity, were found to be B-cell leukemia. Patients with acute non-lymphoblastic leukemia (ANLL) were generally TdT-negative. Elevated level of TdT activity was detected in only one of 11 children with ANLL. In one patient with acute leukemia two distinct populations of cells with lymphoblastic (87%) and myeloblastic characteristics were evident. The clinical course and cell marker studies were consistent with the interpretation of a defect at the level of the common stem cell giving rise to a TdT-positive lymphoblastic cell population at diagnosis and, following the initial ALL-therapy (4 weeks), a predominant TdT-negative myeloblastic population. TdT as a marker for the modulation of chemotherapy was examined in the remission phase of the disease. Of the nine patients in the first 3 months of remission, one was found to have elevated level of TdT activity (2.5 U/10(8) cells). These data define the usefulness of TdT in the classification of acute leukemia.

Acute Disease↗

Thymic involvement and initial white blood count in childhood acute lymphoblastic leukemia.

From 1970 to 1977, two nonrandomized groups of children with acute lymphoblastic leukemia (ALL) were treated with two different induction regimens. A total of 168 patients (group DAL) received induction therapy closely adapted to St. Jude protocol VII. A total of 119 patients (group BFM) were treated with the West Berlin induction protocol. Evaluable for analysis were 138 patients of group DAL and 113 patients of group BFM. Thirty children had thymic involvement (Thy+), 15 in each group. In children without thymic involvement (Thy+), the median initial white blood count (WBC) was 8400/mm3 in group DAL and 8000/mm3 in group BFM. In contrast, the initial WBC was 42,000/mm3 and 79,200/mm3 in the corresponding group with thymic involvement (Thy+). The probability of continuous complete remission (CCR) at 9 years is 0.41 +/- 0.05 for patients without thymic involvement and 0.09 +/- 0.09 for patients with thymic involvement in group DAL, and 0.65 +/- 0.05 for those without thymic involvement and 0.52 +/- 0.13 for those who had thymic involvement in group BFM. After adjustment for initial WBC (regression analysis) the presence of thymic involvement was still a predictor of poor outcome in group DAL (p less than 0.001), whereas it was not a predictor of poor response in group BFM. In view of comparable patient composition in both treatment groups, the favorable prognosis in BFM patients has to be related to the mode of induction therapy.

Adolescent↗

[ALL therapy study 1971-1974 of the German working group for leukemia research and therapy in childhood: prognostic significance of initial features and different therapeutic modalities (author's transl)].

495 children and adolescents with acute lymphoblastic leukemia entered a non-randomized therapy study between January 1st, 1971, and December 31st, 1974. They were treated at 40 pediatric clinics in the Federal Republic of Germany according to the protocol of the Deutsche Arbeitsgemeinschaft für Leukämieforschung und -Behandlung im Kindesalter, which was closely adapted to the Memphis protocol VII. These patients were analyzed retrospectively, data of evaluation was July 31st, 1978. 7 patients (1.4%) did not achieve remission, 14 patients (2.8%) died during the induction period, and another 37 patients (7.5%) died in continuous complete remission (CCR). For purposes of comparison only the remaining 437 patients were evaluated (remission group). The 7 1/2 years' probability of CCR is 0.33 +/- 0.02 for the total group (495 patients) and 0.37 +/- 0.03 for the remission group. The probability of survival for these groups is 0.40 +/- 0.03 and 0.45 +/- 0.03, respectively. After relapse the 5 years' probability of survival is 0.03 +/- 0.02. Patients with testicular relapse have a markedly better prognosis compared to those with bone-marrow or central nervous system relapses. The most important prognostic factor was found to be the white blood count at diagnosis. There is a negative correlation between the initial white blood count and the probability of CCR. Girls fared significantly better than boys (0.46 +/- 0.04 vs 0.31 +/- 0.03 in CCR, p less than 0.01). There is convincing evidence that the impaired prognosis in boys is at least partly due to the incidence of testicular relapses (36 of 268 relapses were found to be testicular, isolated in 20 patients and combined with bone-marrow relapse in 16 patients). Patients with thymic involvement and/or positive reaction of the acid phosphatase in their blast cell did significantly worse (0.12 +/- 0.05 in CCR). Irradiation of the skull was performed in two different doses (1800 and 2400 rads). Concerning the incidence of relapses primarily located in the central nervous system patients with low-dose irradiation had no worse prognosis than those with high-dose irradiation but the incidence of bone-marrow relapses was found to be higher in the 2400 rad group (50.5% vs. 41.7% in the 1800 rad group), possibly due to the higher initial white blood count (median 8900/mul vs. 6500/mul). The addition of vincristine/prednisone reinduction courses during the first year of continuation therapy showed no significant advantage.

Child↗

[Nitrogen balance and plasma amino acids in premature and newborn infants with partial parenteral feeding during the first 3 days of life].

Eight pre-terms, five with postnatal asphyxia, two hypotrophic newborns and one term infant with severe postnatal asphyxia (mean birth weight 2317 g) were fed in addition to oral nutrition partialy parenterally with glucose solution and a mother-milk adapted amino-acid solution during their first three days of life. At increasing protein supplies with a parenteral share of more than 50% during the three days, the N balances resulted positive on all days although the calories supplied were far below the postulated optimum. On days two and three N retention was about 60% of the supply. Every four hours after discontinuation of the total 16 hours' amino-acid infusion the amino acid levels in plasma were controlled by means of column chromatography. The resulting mean values did not show any imbalances of the amino-acid homeostasis. The maximum mean loss in weight of the present group was 4% of their birth weight during the first ten days of life and thus equalled the loss in weight of normal, healthy pre-terms. Clinical and chemical paramters did not reveal any disadvantageous side effects of parenteral nutrition.

Amino Acids↗

[Improved treatment results in children with AML: Results of study AML-BFM 93].

BACKGROUND: In the multicenter trial AML-BFM 93 daunorubicin or idarubicin was randomly applied in all patients during induction in combination with cytarabine and etoposide. After induction all patients were stratified to the standard or high risk group. To improve outcome in high risk patients high dose cytarabine and mitoxantrone (HAM) was introduced. The placing of HAM as either the 2nd or 3rd therapy block was randomized to evaluate the efficacy and toxicity accordingly. PATIENTS AND METHODS: 471 children with de novo AML entered the trial AML-BFM 93 (161 standard risk, 310 high risk). RESULTS: Overall, 387 of 471 (82 %) patients achieved remission, 5-year survival, event free survival (EFS), and disease free survival were 60 % SE 3 %, 51 % SE 2 % and 62 % SE 3 %, respectively. Idarubicin-based induction resulted in a significantly better blast cell reduction in the bone marrow on day 15 (25 of 144=17 % patients with > 5 % blasts compared to 46 of 149=31 % patients after daunorubicin, pchi(2)=0.01). This was, however, mainly seen in high risk patients treated with idarubicin (19 % vs. 38 %, pchi(2)=0.007). Cardiotoxicity, WHO grade 1 - 3 shortening fraction reduction after induction occurred in 6 % patients in both arms. In the total group of patients probabilities of five years event-free survival and disease-free survival were similar for patients treated with daunorubicin or idarubicin. However, in patients presenting with more than 5 % blasts on day 15 there was a trend for a better outcome after treatment with idarubicin (p logrank 0.06). Outcome in high risk patients was superior in study 93 compared to study 87 (remission rate and 5-year pEFS in study AML-BFM 93 vs. study 87: 78 % vs. 68 %, p=0.007, and 44 % vs. 31 %, p logrank=0.01). The placing of HAM as the 2nd or 3rd therapy block was of minor importance. However, patients who received the daunorubicin treatment during induction benefited from early HAM. CONCLUSION: Compared to study AML-BFM 87 treatment results in study AML 93 improved significantly in high risk patients. This can partly be contributed to the better response on day 15 after idarubicin induction but is mainly due to the introduction of HAM.

Acute Disease↗

[Quality management within the competence network of paediatric oncology and haematology].

The competence network paediatric oncology and haematology aims at improving the structure of paediatric oncology and haematology as a whole focussing in particular on the quality of clinical trials and study centres. This implicates the following measures: (1) Employment of research and trial assistants in order to improve the quality of documentation and study management in the participating hospitals. (2) Building up of an Internet portal to provide medical information for non-professionals, for patients and their families as well as for health professionals. (3) The project "Study Assistance" supports study centers during the process of writing and examining new treatment protocols so that they are in compliance with the Good Clinical Practice criteria, formal criteria and statutory provisions. It presently works on a structural standardisation of study protocols and case record forms in order to improve their usability. In addition, the working group "Quality Assurance in GPOH Study Centres" is engaged in developing a quality management system for study centers.

Clinical Trials as Topic↗

[The VIP-secreting tumor as a differential diagnosis of protracted diarrhea in pediatrics].

BACKGROUND: Vasoactive intestinal peptide (VIP) can be produced by mature neurogenic tumors. Pathologically elevated VIP plasma levels cause secretory diarrhea with excessive loss of water and electrolytes. Despite the clinical severity diagnosis of a VIP-secreting tumor is often delayed and subsequently its extirpation as the mainstay of therapy. PATIENTS: We report on two patients with ganglioneuroblastoma and secretory diarrhea. We contrast the case of a 13-month-old boy with advanced symptoms of secretory diarrhea, high VIP plasma levels, and late diagnosis to the case of a 14-month-old boy with mild secretory diarrhea and normal VIP plasma levels but positive proof of VIP in tumor tissue. Reviewing the literature we found 57 cases of pediatric VIP-secreting tumors. RESULTS: The clinical situation is characterized by the typical symptoms of secretory diarrhea with hypokalemia and metabolic acidosis. Histopathology predominantly reveals ganglioneuroblastoma or ganglioneuroma. The symptoms mostly stop after complete resection of the tumor whereas lack of resection is associated with elevated mortality rates. CONCLUSIONS: In case of prolonged therapy-resistant secretory diarrhea the existence of a VIP-secreting tumor should be considered. Diagnostic work-up should include the assessment of VIP plasma levels, catecholamines in urine, and appropriate imaging techniques in order to rule out or confirm the possibility of a VIP producing tumor.

Diagnosis, Differential↗

[Concepts of the Society of Paediatric Oncology and Haematology (GPOH) and the German Competence Network in Paediatric Oncology and Haematology for the quality controlled development in paediatric oncology].

For more than 30 years Paediatric Oncology has striven to achieve an optimum of care for children with cancer everywhere. The consistency of diagnostic procedures and treatment within successive therapy studies has yielded high cure rates. Meanwhile the focus has moved to placing the quality control of diagnostics and treatment into the hands of experts in the field, accommodating new requirements of the health care system. We report on the already realised and the future concepts and methods employed in improving the quality in institutions and studies with the support of the German Competence Network in Paediatric Oncology and Haematology (Kompetenznetz Padiatrische Onkologie und Hamatologie, KPOH). The issue of per-patient flat rate funding is raised, and structural requirements to be fulfilled by Centers of Paediatric Oncology are presented and discussed.

Adolescent↗

FDG-PET in 10 children with non-Hodgkin's lymphoma: initial experience in staging and follow-up.

BACKGROUND: The use of FDG-PET was evaluated for initial staging and therapy efficacy in paediatric patients with non-Hodgkin's lymphoma (NHL) and compared to the established conventional imaging modalities (CIM). The results of this retrospective analysis are presented in conjunction with a critical review of the current literature. PATIENTS AND METHODS: Ten paediatric patients with NHL were examined using whole-body FDG-PET initially (n = 6), during therapy (n = 5) and after completion of therapy (n = 5), respectively. FDG-PET findings were compared to CIM performed according to the protocol of the German NHL-BFM 95 study. The results were evaluated for their impact on disease classification and therapy decision (St. Jude, REAL) in correspondence to a clinical follow-up of at least 24 months. RESULTS: Concerning initial staging, all lymphoma manifestations detected by conventional imaging were also detected by FDG-PET (15 nodal, 2 extranodal). Furthermore, an additional nodal lesion was detected by FDG-PET in three patients. This resulted in an upstaging followed by an intensified poly-chemotherapy in one patient. In five patients showing unclear residual masses on conventional imaging during therapy, FDG-PET indicated viable residual tumours in one case. This patient showed a relapse during follow-up while the four FDG-PET negative patients did not. After completion of initial therapy, FDG-PET revealed in one out of five patients persistent tumour metabolism in the primary lesions and also detected new manifestations. The patient died shortly after restaging due to disease progression. CONCLUSIONS: These first results on the use of FDG-PET in paediatric non-Hodgkin lymphoma indicate a high potential to improve the therapeutic management.

Adolescent↗

[Effect of cranial irradiation on rate of recurrence in children with acute myeloid leukemia. Initial results of the AML-BFM-87 study. The AML-BFM Study Group].

Study AML-BFM-87 compared prospectively if cranial irradiation could be abandoned by adding two blocks of intensification with high dose ARA-C and VP-16 after consolidation and furthermore, improve prognosis compared to study -83. 210 children were enrolled in study AML-BFM-87 until March 31, 1991. 164 (78%) achieved complete remission. Probabilities for event-free survival (EFS) and event-free interval (EFI) of 5 years were: .45 (SD .04) and .57 (SD .05). In the first 2.5 years of the study irradiation was randomized (n = 31), selected or refused (n = 24). However, during this period irradiation was mandatory in patients with leukocyte count greater than 70,000/mm3, and also in children with initial CNS involvement. Since July 1989 prophylactic cranial irradiation was abandoned. Patients of the group with mandatory irradiation (n = 39) presented with more unfavourable risk parameters than the group of non-irradiated children, who were enrolled in the study after randomisation had been stopped. Nevertheless, results showed in randomized and selected patient groups as well as in the total cohort a longer relapse-free interval (RFI) in irradiated (n = 66) compared to non-irradiated (n = 94) patients (RFI of 5 years: .70, SD .04 vs. .51, SD .07, p less than .05). Relapses in non-irradiated children occurred mainly in the bone marrow and less often in the CNS. The increase in relapse rate was seen especially in non-irradiated patients of the low risk group as defined in study AML-BFM-83 (RFI: .40, SD .14 vs. .79, SD .09 with irradiation, p less than .01). In the high risk group, however, the differences were not significant. Our results suggest that cranial irradiation is an important part of therapy in childhood AML, and that the good prognosis of the low risk group in study AML-BFM-83 was probably based on the combination of intensive chemotherapy and cranial irradiation.

Antineoplastic Combined Chemotherapy Protocols↗

[Long-term study of anthracycline-induced cardiomyopathy in children and adolescents].

In order to detect changes in cardiac function, electrocardiographic, echocardiographic and radiologic studies were performed in 71 patients (age 1-26 yrs) who had been treated at the University Children's Hospital Berlin because of malignant diseases according to protocols of the DAL/GPO and had received anthracyclines (doxorubicin or daunorubicin) at cumulative doses up to 480 mg/m2 (median 280 mg/m2). Clinically overt cardiomyopathy was observed in one girl and required transient administration of digoxin. In 2 patients echocardiographic changes led to a reduction of the scheduled anthracycline doses. No patient died from congestive heart failure. During treatment, an increase in the cardiothoracic index was observed in 14 children, and in 16 the ECG showed pathological findings. A decrease in contractility to 25% or less as detected by ultrasound was seen in 15 patients. More than 50% of patients developed echocardiographical signs indicating an impairment of myocardial function. However, persistent changes were only found in 1 patient after discontinuation of treatment. Long-term echocardiographic follow-up studies for 4-48 months (median 14 months) after completion of anthracycline therapy were performed in 18 patients and the findings compared to matched-pair controls. The observed M-mode parameters were completely normal, and the ejection fractions calculated from the two-dimensional ultrasound investigations were in the normal range but slightly diminished compared to controls. Cardiac ultrasound is a non-invasive, reproducible and tolerable procedure for early detection of an anthracycline cardiomyopathy. In our patients, time of occurrence and the extent of pathological changes were not associated with the cumulative applied anthracycline doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Clinical applications of the study of immunoglobulin and T-cell receptor gene rearrangements in acute leukemia and non-Hodgkin's lymphoma in children].

In addition to conventional morphological, histological and immunological marker studies, cells from 150 children with leukemia or non Hodgkin's lymphoma were analysed using the Southern blot hybridization technique to examine immunoglobulin- (Ig) and T-cell receptor (TCR) gene rearrangements. Patients with B-lineage leukemia or NHL demonstrated in 90% an Ig heavy chain gene rearrangement, 6% with an additional light chain kappa gene rearrangement. Combined Ig- with TCR-beta-gene rearrangements were mainly found in patients with common ALL: 19% at first presentation, and 33% in relapse. Moreover, 6 c-ALL patients showed rearrangements in all 3 gene loci (JH-, Ck- and TCR). Based on the developmental hierarchy of Ig- and TCR gene rearrangements it was possible to further subclassify c-ALL into different stages of B cell development. No correlation could be established between the different constellations of gene rearrangements, the number of rearranged fragments and the course of illness. All patients with T-lineage leukemia or NHL demonstrated TCR rearrangements of the beta-, g- and delta-gene loci, two with an additional Ig gene rearrangement. These data confirm recent reports indicating that immunoglobulin heavy chain gene rearrangements are not restricted to B-lineage neoplasms. Furthermore, non-germline configuration was found in tumor cells of every patient with AUL, O-ALL and AHL, permitting a classification to B- or T-cell lineage. Noteworthy is that every AML patient with Ig- and/or TCR gene rearrangements showed a poor or non-response towards therapy. Specimens of individual patients with differently involved tissues at diagnosis always showed an identical rearrangement. The intensity depended on the number of infiltrating blast cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Transplantation↗

[Effect of 7S immunoglobulin substitution on the incidence and course of infection in cytostatic drug treated patients].

This retrospective analysis evaluates the effect of intravenously administered immunoglobulin against infections occurring during bone marrow depression after cancer chemotherapy in 85 children with leukemia and lymphoma. There was no statistical difference between patients with and without immunoglobulin administration neither when immunoglobulins were used prophylactically nor therapeutically in addition to antibodies during episodes of infection. Duration of fever, duration of antibiotic therapy, maximum of temperature, white blood cell counts, and kind of infections were comparable in 84 fever episodes in patients who had received immunoglobulin therapeutically and 69 fever episodes in patients who had not. This study supports the aspect that immunoglobulin administration does not have preventive or therapeutic efficacy on infections during cancer chemotherapy in children.

Adolescent↗