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Biomedical subjects

G Henze

Publications and source records attributed to G Henze.

197 records · Page 11Linked to original sources

[Late sequelae of CNS recurrence of acute lymphoblastic leukemia in childhood].

Study objective was to evaluate retrospectively central nervous system (CNS) morbidity of children with acute lymphoblastic leukemia treated with intensive chemotherapy and cranial radiotherapy for a first isolated or combined CNS relapse. Neurological (Touwen), neuropsychological (CFT 20, Wechsler scales, d2 attention test) and neuromorphological (CT, MRI) assessments were performed in 17 children (9 girls, 8 boys) aged between 7 and 14 years. Patients were off therapy for median 4 years; cranial radiotherapy for CNS relapse (12-24 Gy) was given to all patients 2 to 9 years ago (median 5.5 years). Ten patients had received preventive cranial radiotherapy during front-line treatment, previously. In this group, the cumulative radiation dose ranged between 30 and 39 Gy. Patients received 12 to 30 intrathecal methotrexate doses (median 22). Compared with normative levels for age (100 points) performance IQ (89.9) and full scale IQ (92.0), Culture Fair IQ (88.3) and attention and concentration (90.9) were significantly impaired. Verbal IQ (95.5) was not significantly different from normal expectations. Neurological investigations of 16 patients showed mild signs in 7 (44%) of them, mostly of fine-motor skills and coordination, but no major motor disability. In MRI and CT, white matter changes or ventricular enlargement were noted in 10 of 16 patients (63%). Parent-completed questionnaires indicated problem behaviors in 5 children. Cumulative doses of methotrexate correlated significantly with neuropsychological test results. Children irradiated twice as well as girls had poorer cognitive functions, not being statistically significant. Despite pathological test results, all children attended a normal school and did not exhibit obvious impairment in daily life. In conclusion, CNS relapse and attendant therapy, mostly consisting of a second course of cranial radiotherapy, caused measurable intellectual deficits and CNS morbidity, which did not result in severely impaired performance. Periodic psychological und clinical examinations are recommended for recognition of delayed morbiditiy and early intervention.

Adolescent↗

[Multi-national therapy study for Hodgkin's disease in children and adolescents GPOH-DH 95. Interim report after 2 1/2 years].

Based on concepts of the successful German-Austrian pediatric Hodgkin studies DAL-HD 78 until-90, a new trial was initiated addressing the question whether radiotherapy can be further reduced or can be omitted in case of complete remission after initial chemotherapy, aiming at reduction of sequelae after radiotherapy, especially radiogenic second malignancies. In respect to CHEMOTHERAPY patients are stratified into 3 therapy groups (TG) according to stage and gender: 2 courses of OPPA (girls) or OEPA (boys) in TG1 (stage IA/B, IIA), and in addition 2 (TG2: stage IEA/B, IIEA, IIB, IIIA) or 4 (TG3: stage IIEB, IIIEA/B, IIIB, IVA/B) COPP courses. Boys with stage IIIB and IIIEB receive OPPA instead of OEPA. RADIOTHERAPY is administered according to response to chemotherapy independent of stage: patients with complete remission or minimal residues do not receive irradiation; patients with more than 75% tumor regression are irradiated to involved fields at a dose of 20 Gy. Doses of 30 or 35 Gy are given to regions with tumor regression below 75% or residual bulky tumor of > 50 ml, respectively. INTERIM RESULTS: From 8/95 till 1/98 we registered 385 patients under the age of 18 years from Germany, Austria, Switzerland, Sweden and the Netherlands. Therapy has been completed in 334 patients. Three patients with solitary nodular paragranuloma were treated with surgery only. Out of 331 patients 89 (26.9%) achieved a complete remission with chemotherapy. Tumor regression of more than 75% was seen in 193 (58.3%) patients and below 75% in 39 (11.8%) patients. Tumor progression during chemotherapy occurred in 1 (0.3%) patient. Response after chemotherapy was not evaluable for 9 (2.7%) patients. Radiotherapy was omitted in 91 (27.1%) patients: in TG1 50 of 142 (34%) patients, TG2 24 of 98 (24.5%) patients and TG3 18 of 94 (19.2%) patients. Initially involved regions were irradiated at a dose of 20 Gy in 164 of 334 (49.1%) patients. Doses up to 30 Gy or 35 Gy were given to 19 (5.7%) or 57 (17.1%) patients respectively. Events (tumor progression, relapse or death) occurred in 23 of 334 patients until now. The event-free survival rate is 0.91 at 2 1/2 years for all study patients and 0.89 for patients without radiotherapy. Six relapses occurred in 91 patients without radiotherapy. No relapse occurred in TG1 (n = 49), but in 5 of 24 TG2-patients, and in 1 of 18 TG3 patients without radiotherapy. As yet, the results are not significantly inferior compared with trial DAL-HD 82. Therefore this trial aiming at omitting radiation therapy in patients with complete remission after a short lasting chemotherapy will be continued. Longer follow up is necessary for final evaluations and conclusions.

Adolescent↗

Preliminary results of primary chemotherapy in retinoblastoma.

BACKGROUND: Eye retention rates after external beam therapy for advanced retinoblastoma are close to 90% with very few ocular side effects like radiation retinopathy or radiation induced optic neuropathy. Late complications, however, comprise a sixfold increase of secondary non-ocular cancers like soft tissue sarcomas demanding alternative treatment options in the management of advanced retinoblastoma. PURPOSE: A phase I study on primary chemotherapy using vincristine, cyclophosphamide, etoposide and carboplatin in advanced bilateral retinoblastoma was undertaken to evaluate the potential of a treatment regimen not including external beam therapy. PATIENTS AND METHODS: 12 eyes with 17 tumors in 9 children were treated with primary chemotherapy as first treatment option with a mean follow-up of 16.7 months. Planned enucleation of a tumor containing eye was performed in 2 eyes. In one of these enucleated eyes no viable tumor cells were visible on histopathological examination while in the other eye marked tumor regression was detectable. Of the remaining 10 eyes clinical regression of the intraocular tumors was present in all eyes; on average the tumor size was reduced by 50% within 3-6 weeks. Most of the tumors showed a type I (cottage cheese) regression indistinguishable from regression patterns found after external beam radiotherapy. Ancillary treatments including laser photocoagulation, beta-ray brachytherapy, external beam radiotherapy and cryotherapy were performed in 15 out of the 17 tumors. CONCLUSION: Based on the results of this study and on the results published by others primary chemotherapy may result in the same eye retention rate as conventional external beam therapy avoiding the unacceptable high rate of secondary non-ocular cancers in the latter. A prospective study to be undertaken by the GPOH (Gesellschaft für Pädiatrische Onkologie und Hämatologie) and the RG (Retinologische Gesellschaft) is planned to further evaluate this new and promising approach.

Antineoplastic Combined Chemotherapy Protocols↗

[Long-term infusion of L-asparaginase--an alternative to intramuscular injection?].

Nine children of the ALL-REZ BFM 87 and 90 trial received L-Asparginase (L-ASP) as a continuous infusion for 48-72 hs (i.e. 25 therapy cycles). Seven patients had had an allergic reaction towards an i.m. application (i.m., 29 therapy cycles). Two further patients got L-ASP initially as continuous infusion. The i.m. applications were carried out 19 times with Erwinia and 10 times with E. coli-Asparaginase, the continuous infusions 15 times with Erwinia and 10 times with E. coli-Asparaginase. In case of four patients continuous infusions of the same L-ASP type (E. coli or Erwinia) was well tolerated, after there had been an allergic reaction after i.m. application. Allergic reactions after i.m. application occurred during 10 courses as local painful erythema, during five courses as urticaria, during four courses as a general exanthema during one course as difficult breathing and during a further course as drop in blood pressure. After continuous infusion of L-ASP urticaria and difficult breathing occurred once and a transient exanthema two times. There was no anaphylactic reaction in any case. These data show that i.m. application of L-ASP causes no life-threatening side effects but allergic reactions (local pain and swelling) which clearly impaired general condition. Continuous infusion is a pharmacologically equivalent alternative with less impairment of the patients' general condition.

Adolescent↗

[Imported visceral leishmaniasis (kala azar) in a German infant].

We here report the case of a 1 4/12 year old girl with visceral leishmaniasis. Returning from a trip to Mallorca she presented with pancytopenia, splenomegaly and fever and was admitted to hospital with suspected malignancy. Diagnosis was established microscopically from bone marrow smear and confirmed by PCR-assisted amplification of leishmania-specific DNA from peripheral blood. Treatment was conducted with stibogluconate for 25 days. Defervescence and improvement of clinical symptoms was seen after 4 days of treatment. Infection due to Leishmania donovani can be acquired throughout the entire mediterranean area and should therefore be included in the differential diagnosis of suspected malignancies in patients with a history of travel to mediterranean countries. PCR proved to be a sensitive tool for establishing the diagnosis of visceral leishmaniasis.

Antimony Sodium Gluconate↗

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↗

[Severe renal impairment of methotrexate elimination after high dose therapy].

Even in patients with normal renal function, high-dose methotrexate therapy (HDMTX) may be followed by extremely prolonged MTX elimination through alkaline diuresis is performed correctly. By inquiry in Germany, Austria and Switzerland for HDMTX infusions with MTX plasma concentration 42 h after start of exposure (MTX-42) higher than 5 mumol/l (microM), we analyzed data from 21 patients in whom impairment of renal methotrexate elimination had received 5 g/m2.24h, 3 had received 12 g/m2.4h. They presented with MTX-48 serum level between 1.7 and 1404 microM. There was no recognizable causative factor. As early signs for impaired elimination, we identified enhanced vomiting during MTX infusion in 8/21, elevated steady-state-MTX in 11/15, and a rise of serum creatinine greater than 50% in 14/16 patients in whom respective data were available. Creatinine rose to a maximum of 1.0-4.9 mg/dl within 1-4 days in 19/21 patients (accompanied by diuresis problems in only 5 patients) and normalized within 3-17 days in all but two patients. Creatinine maximum correlated weakly with MTX-48 (r = 0.34) and with extrarenal toxicity. 8 patients had normal (WHO 0-II degree), 8 other had intensified (III-IV degrees) but not critical extrarenal MTX toxicity with calcium folinate (CF) doses of 0.2-1.6 mg/kg.microM MTX q 6 h started 28-54 h after beginning of MTX exposure. 5 patients had unusual toxicity. 2 patients suffered from severe but reversible encephalopathies with CF doses of 0.05 and 1 mg/kg.microM MTX q 6 h started after 51 and 36 h, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

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↗

Neurofibromatosis 1 associated with embryonal rhabdomyosarcoma of the urinary bladder.

A 10-month-old boy presented with a 6-week history of abdominal pain. The pain was due to a large, stage IV embryonal rhabdomyosarcoma of the urinary bladder. The rhabdomyosarcoma was found in association with neurofibromatosis 1 (NF1) manifesting multiple café au lait spots and bowing of the right calf. The diagnosis of NF1 had not been made before presentation. This case report is intended to heighten the awareness of the manifestations of NF1 and the possibility of developing a nonneuroectodermal tumor as a concomitant of NF1, and to emphasize the importance of timely diagnosis and treatment of such an NF1-associated malignancy. Reports of the epidemiologic evidence for rhabdomyosarcoma in children with NF1 are reviewed.

Humans↗

The stomach and pulmonary interlobular space as unusual sites of osteosarcoma.

The authors report a girl with high-grade intraosseous osteosarcoma of the left femur who lost one eye during early infancy for an unknown reason. Nine months after treatment, osteosarcoma in the stomach was detected and completely excised when the girl underwent endoscopy for Helicobacter pylori infection. Three years later osteosarcoma in the pulmonary interlobular space was noticed and completely removed. The girl is doing well and free of disease 26 months after the last resection.

Child↗

Intermediate dose methotrexate is as effective as high dose methotrexate in preventing isolated testicular relapse in childhood acute lymphoblastic leukemia.

PURPOSE: We evaluated the influence of three different dosages of methotrexate (MTX) during consolidation on the incidence of testicular relapse in children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: One thousand one hundred forty-four boys with newly diagnosed ALL, enrolled in three consecutive trials of the Berlin-Frankfurt-Münster group (ALL-BFM 81, 83, 86), were retrospectively evaluated for the influence of MTX on testicular relapse-free interval. The basic treatment design was similar in all trials. No intravenous MTX was used in trial ALL-BFM 81 in the group who received cranial irradiation (CRT) except for a part of standard risk patients. Four courses of intermediate dose MTX (IDM) (0.5 g/m2) were introduced for all patients in trial ALL-BFM 83 (IDM group), which were replaced by high dose MTX (HDM) (5 g/m2) in trial ALL-BFM 86 (HDM group). The media observation time was > 9 years. RESULTS: The cumulative incidence of isolated testicular relapses was significantly higher in the CRT group as compared to the IDM and HDM groups (6.7% versus 2.5% and 2.3%, p = 0.02 and 0.01). HDM decreased neither the incidence nor the rate of isolated testicular relapses any further. Event-free survival (EFS) for boys was similar between trial ALL-BFM 81 and 86 (64% versus 69%, p = 0.35), but differed significantly between trials ALL-BFM 83 and 86 (61% versus 69%, p = 0.0078). CONCLUSION: The introduction of IDM reduced the incidence of isolated testicular relapses significantly by a factor two, but had no significant influence on overall survival. HDM did not result in a more effective prevention of testicular relapses, but resulted in better systemic control and hence better survival than IDM.

Antimetabolites, Antineoplastic↗

Partial parenteral nutrition in preterm and newborn infants during the first three days of life.

Eight preterm infants, five with postnatal asphyxia, as well as two hypotrophic neonates and one term infant with severe postnatal asphyxia (mean birth weight 2300 g) were fed, in addition to oral nutrition, partially parenterally with glucose solution and mother's-milk-adapted amino acid solution during their first three days of life. By increasing protein supplies with a parenteral share of more than 50% during the three days, the nitrogen balances were positive on all days, although the calories supplied were far below the postulated optimum. On days 2 and 3, nitrogen retention was about 60% of the supply. Every 4 hrs after discontinuation of the 16 hr amino acid infusion, the amino acid levels in the plasma were examined by column chromatography. The resulting mean values did not show any imbalances of amino acid homeostasis. The maximum mean loss in weight of the present groups was 4% of the birth weight during the first 10 days of life and thus equalled the loss in weight of normal healthy preterms. Clinical and chemical parameters did not reveal any disadvantageous side effects of partial parenteral nutrition.

Amino Acids↗

Fosfomycin does not reduce cytostatic activity of cis-platinum against human osteosarcoma cell lines in vitro.

Fosfomycin has been shown to ameliorate the dose-limiting ototoxicity and nephrotoxicity associated with the antineoplastic agent cis-platinum. Clinical use of fosfomycin in cis-platinum-treated tumor patients critically depends on retaining therapeutic efficacy of cis-platinum while designing modalities to reduce side effects. This study uses two independent assay systems for cell viability and proliferation; we demonstrate that cytocidal activity of cis-platinum against human osteosarcoma cell lines is not affected by various concentrations of fosfomycin up to 0.1 mg/ml in vitro. This suggests that in these cells there is no direct pharmacodynamic interaction of cis-platinum and fosfomycin with respect to mechanisms crucial for tumor kill.

Antineoplastic Combined Chemotherapy Protocols↗

Pharmacokinetics of the 5HT3 receptor antagonist tropisetron in children.

A pharmacokinetic study in children was performed to assess whether the pharmacokinetic profile of tropisetron in pediatric patients in similar to that in adults. In three pediatric centers, three dosages were tested in two age groups during chemotherapy (Group A, 3-6 years, 2, 5, or 20 mg/m2; group B, 7-15 years, 2, 5, or 20 mg). Children received tropisetron intravenously (course 1) or orally (course 2) before the start of chemotherapy. Blood samples were drawn over 24 hours. Tropisetron treatment continued for up to 6 days at the same daily dose, administered orally. Data were available for 45 patients after intravenous and for 38 patients after oral administration. 82% of course 1 patients and 72% of course 2 patients had no emesis on day 1. Headache occurred in eight patients and abdominal symptoms in three patients. Terminal half-life (5.3-6.6 hours), tmax (1.4-1.5 hours), and absolute bioavailability (41-42%) were identical in both age groups and comparable to those in adults. Because of a smaller volume of distribution, group A children showed a higher Cmax/dose (P < .001) and a higher area under curve (AUC) dose (P < .05) than adults. All parameters were independent of the dose administered. In conclusion, the elimination and absolute bioavailability of tropisetron in children are similar to those in adults. Because of its age-dependent volume of distribution, tropisetron should be administered once a day according to the body surface area in children below 10 years of age.

Administration, Oral↗