[Retinoblastoma gene analysis in a patient with osteosarcoma following previous bilateral retinoblastoma].

In a native osteosarcoma specimen of a patient cured of a bilateral retinoblastoma eight years before we found a homozygous deletion of a 7.5 kb Hind III-fragment within the retinoblastoma gene and a hemizygous deletion of the same fragment in its constitutional cells. In a native osteosarcoma tissue of a lung metastasis of a patient with sporadic osteosarcoma the Rb-gene-analysis did not reveal any deletion within the gene.

Doxorubicin: effect of different schedules on toxicity and anti-tumor efficacy.

The risk of congestive heart failure restricts the clinical use of doxorubicin to cumulative doses of 450-550 mg/m2, when it is given using high-dose rapid intravenous application. As the high peak serum levels which follow rapid administration seem to be correlated with cardiotoxicity, application schedules leading to lower peak serum concentrations have been developed. This paper reviews the influence of those schedules on cardiotoxicity, non-cardiac toxicities, pharmacokinetic data and antineoplastic efficacy.

[Anthracycline transport in sensitive and resistant leukemia cells].

The in-vitro uptake of four anthracyclines into leukemic cells was investigated. The accumulation was found to be dependent on the extracellular anthracycline concentration in a linear fashion. The steady state intracellular drug level was reached very quickly and was found to be correlated to the extracellular pH-value in the range between 6.

Platinum disposition after intraarterial and intravenous infusion of cisplatin for osteosarcoma. Cooperative Osteosarcoma Study Group COSS.

Preoperative chemotherapy according to the COSS 86 protocol, including two courses of cisplatin, was used for high-risk osteosarcoma. Patients were randomised to receive either intraarterial (i.a.

Long term doxorubicin cardiotoxicity in childhood: non-invasive evaluation of the contractile state and diastolic filling.

Cardiac performance was evaluated at least two years after doxorubicin treatment in childhood in 55 patients without overt congestive cardiomyopathy. None of the patients had received mediastinal irradiation. Computer-assisted analysis of digitised echocardiograms showed impaired rapid diastolic filling and an increased change of dimension between minimal cavity dimension and mitral valve opening.

[Antineoplastic effectiveness and toxicity of idarubicin (4-demethoxy-daunorubicin) in recurrent acute leukemias in childhood].

11 patients with refractory acute leukemia of childhood were treated with idarubicin per os. Bone marrow toxicity which was observed at a dose level of 60 mg/m2 p.o.

Pharmacokinetics of doxorubicin in man: dose and schedule dependence.

Doxorubicin serum elimination kinetics were measured by HPLC in three different patient groups. A dose of (a) 30 mg/m2; (b) 50 mg/m2, and (c) 4 x 15 mg/m2 every 10 h was administered by bolus injection to (a) 10, (b) 6, and (c) 8 patients. The results obtained provided strong evidence for a nonlinear dependence of doxorubicin serum elimination on the dose and administration schedule used.

[Detection of neuroblastoma cells in bone marrow by Southern blot and in situ hybridization using a NMYC DNA probe].

Recently an amplification of NMYC oncogene was discovered in stage III and stage IV as well as in stage II neuroblastoma cells. The extent of NMYC amplification is of prognostic value. A high expression of NMYC on mRNA level is correlated to the NMYC gene-amplification.

Translocation (9;11)(p21;q23) in a child with acute monoblastic leukemia following 2 1/2 years after successful chemotherapy for neuroblastoma.

This is a case report of a 4 1/2-year-old boy who developed acute monoblastic leukemia 2 1/2 years after he had been treated successfully with combined chemotherapy for neuroblastoma. All analyzable bone marrow-derived metaphases had the karyotype 47,XY, + 8,t(9;11)(p21;q23). The rare occurrence of specific chromosomal translocations in leukemias following prior chemotherapy and/or radiotherapy and their possible clinical implications in such cases are discussed.

[The pharmacokinetics of doxorubicin].

Doxorubicin serum levels were measured with a highly specific reversed-phase HPLC-method in patients undergoing combination chemotherapy. Serum elimination kinetics of doxorubicin follow a bi- or triphasic first order pattern with a high interpatient variability. T 1/2 of the first distribution phase was 5.

A rapid chromatographic procedure for the determination of adriamycin, daunomycin and their 13-OH metabolites adriamycinol and daunomycinol.

A rapid chromatographic procedure for the quantitative determination of the anthracycline antibiotics adriamycin and daunorubicin and their chief metabolites adriamycinol and daunorubicinol in plasma and urine is described. The extraction is performed using SEP-PAK silica cartridges. After filtration the eluate is chromatographed on a reversed-phase column.

Determination of 7-hydroxymethotrexate in human plasma by reversed phase high-performance liquid chromatography.

A rapid and sensitive reversed phase HPLC method was developed for the detection of 7-hydroxymethotrexate (7-OHMTX) which is the main metabolite in human plasma after high-dose methotrexate (MTX) therapy. The simple clean-up procedure of plasma samples described allows the measurement of 7-OHMTX during clinical management of MTX infusions. Elimination kinetics of 7-OHMTX are given from 53 drug cycles of 6 patients.

Effect of oral cholestyramine on the elimination of high-dose methotrexate.

The anion exchange resin cholestyramine binds methotrexate (MTX) effectively in vitro. The binding capacity exceeds that of activated charcoal by a factor of 5.4.

Kinetics of 7-hydroxy-methotrexate after high-dose methotrexate therapy.

Kinetics of 7-hydroxy-methotrexate (7-OH-MTX) excretion after high-dose methotrexate (MTX) (12 g/m2) therapy were monitored in 93 consecutive drug cycles of 19 adolescent patients with osteosarcoma. A reversed-phase HPLC method was used. Serum elimination was found to be monophasic with a mean half-life of 5.

7-Hydroxy-methotrexate and clinical toxicity following high-dose methotrexate therapy.

7-Hydroxy-MTX production after consecutive high-dose MTX therapy (12 g/m2) was measured in 7 patients with osteosarcoma by HPLC. 7-Hydroxy-MTX serum values in the last cycle were found to be significantly lower compared with the first high-dose MTX treatment of the adjuvant chemotherapy protocol (COSS 80). Moreover, in another patient highly reduced 7-hydroxy-MTX production was correlated with severe clinical toxicity.

[Acyclovir therapy in varicella/zoster diseases in immunocompromised children with cancer].

21 patients, aged 1 to 15 years, who developed manifest varicella/zoster-virus infection while on chemotherapy for malignant disease were treated with acyclovir. Drug dosage was 10 mg/kg every eight hours for 5 days as a one hour infusion. The clinical course of the infection in all patients was mild.

[Intracranial metastasis in neuroblastoma].

Computed tomography is the most useful diagnostic method to demonstrate the pathophysiological consequences of secondary craniocerebral neuroblastoma. Hyperostotic metastases with subperiostal epidural tumour plaques as well as tumour deposits displacing and compressing adjacent venous sinuses show up well. Moreover, post-contrast computed tomography is a sensitive method for controlling patients under cytostatic or radiation therapy.

[Wiskott-Aldrich syndrome].

Current concepts of pathogenesis and therapy of Wiskott-Aldrich syndrome are discussed, along with demonstrating the case history of a patient with the clinical features of this rare disorder. In addition to the known symptoms there was an elevated blood monocyte count together with a decreased total number of lymphocytes. Immunological analysis of the mononuclear cell fraction revealed an imbalance between mature T-cells, "natural-killer"-cells and monocytes.

[COALL-80 therapy in the management of acute lymphoblastic leukemia in childhood--an interim report].

In order to reduce the toxicity of the otherwise very effective childhood ALL treatment protocol BFM 76/79 asparaginase was omitted from the 4-drug induction regimen and placed as single drug before the intensification phase. In addition the effect of 3-monthly intermediate dose methotrexate (ID-MTX) pulses versus conventional vincristine (VCR) pulses during maintenance therapy was studied. Of 145 evaluable patients 124 (85.

Pancreatic sonography in thalassemia major.

Four patients with thalassemia major and well documented transfusional anamnesis were investigated sonographically. Beside the fibrous reaction of iron overload in the liver the outstanding finding was the grossly increased echogenicity of the normal sized fibrotic pancreas in transfusional hemosiderosis. Upper abdominal sonography may be an useful - noninvasive - method for the assessment of iron load in regularly transfused patients.

[Therapy of acute lymphoblastic leukemia in childhood. Multicenter prospective therapy study COALL-80].

Since 1979 in a cooperative study (COALL-80) 110 children with acute lymphoblastic leukemia (ALL) and 13 children with high grade malignant non Hodgkin's lymphoma (NHL) have been treated with a less aggressive modification of the Westberlin Study Program BFM 76/79. Asparaginase has been delayed from the initial 4 drugs regimen and interposed in between induction therapy and treatment of central nervous system (CNS). Induction therapy that way was well tolerated and realized mostly on an outpatient basis.

Adjuvant chemotherapy in osteosarcoma - effects of cisplatinum, BCD, and fibroblast interferon in sequential combination with HD-MTX and adriamycin. Preliminary results of the COSS 80 study.

In a cooperative adjuvant chemotherapy study of osteosarcoma (COSS-80), 192 patients were registered from December 1979 to March 1982. Forty-one patients have been excluded from study because of their nonadjuvant situation, therapy-limiting clinical conditions, or inadequate diagnosis. One hundred and fifty-one patients have been randomized to receive either the drug combination bleomycin + cyclophosphamide + dactinomycin (BCD) or cisplatinum (CPL) within a course of sequential multidrug chemotherapy including adriamycin (ADR) and high dose methotrexate (HDMTX).