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Biomedical subjects

F Lampert

Publications and source records attributed to F Lampert.

At least 91 records · Page 5Linked to original sources
PubMed1993

Clinical and immunological aspects of hepatitis B virus infection in children receiving multidrug cancer chemotherapy.

For two reasons hepatitis B virus infection is an important problem in patients with cancer. First, multidrug cancer chemotherapy may reactivate or worsen a previously benign chronic HBV infection. Second, patients undergoing cancer chemotherapy are at an increased risk of acquiring and spreading HBV which may result in an endemic infection. HBV reactivation may precipitate into a severe acute disease including fulminant hepatitis. In contrast, the acquisition of HBV during cancer chemotherapy commonly takes a mild clinical course but frequently leads to persistently high viremia. This state of immunotolerance to viral antigens allows viral replication without any sign of liver cell destruction. Withdrawal of chemotherapy does not cause significant changes if infection occurred during cytotoxic chemotherapy. Infection with HBV during cancer chemotherapy, therefore, may be considered as a model of an induced antigen-specific immunotolerance. In agreement with this hypothesis, vaccination against HBV during cancer chemotherapy does not prevent spread of HBV in oncology wards as it does not produce significant anti-HBs titers. Furthermore, vaccination even suppresses the immune response to later booster doses after chemotherapy has been withdrawn.

Antineoplastic Agents↗
PubMed1993

BCR-ABL rearrangement in a child with acute myelogenous leukaemia without a Philadelphia chromosome.

We describe a BCR/ABL rearrangement positive but Philadelphia chromosome negative status in a 9-year-old boy suffering from an acute myelogenous leukaemia (AML). This case was detected in a prospective PCR screening procedure including 21 children with newly diagnosed AML and 150 children with acute lymphoblastic leukaemia (ALL). We found a 5.4% incidence of BCR/ABL rearrangement positive cases in pre-B and c-ALL in childhood.

Child↗
PubMed1993

Quantification of leukaemic cells based on heteroduplex formation of tal-1 gene sequences after PCR coamplification.

Based on the high sensitivity of the polymerase chain reaction (PCR) several assays have already been described which can be applied to monitor minimal residual disease in patients with leukaemia. However, most of these approaches are only qualitative or semiquantitative at best. Moreover, the semiquantitative assays require rather large-scale procedures such as oligonucleotide hybridization or sampling of aliquots during the exponential phase of PCR amplification, which is time consuming and may be error prone. Using the deletion in the tal-1 gene as a clonal marker of malignant cells, which can be found in about 10-25% of T-cell acute lymphoblastic leukaemia, we have developed a rapid and simple PCR assay for the quantification of residual leukaemic cells. The assay is based on heteroduplex formation between standard and template DNA sequences after coamplification of both DNA sequences in the same PCR reaction. The sensitivity of this PCR approach allows the detection of neoplastic cells at frequency of at least 10(-4). Application of such an assay needs not to be restricted to patients harbouring a tal-1 gene deletion. It may easily be adapted to other clonal DNA markers of blast cells and therefore facilitate monitoring of minimal residual disease in many different kinds of leukaemia.

Base Sequence↗
PubMed1993

Genotyping by multiplex polymerase chain reaction for detection of endemic hepatitis B virus transmission.

A nested polymerase chain reaction (PCR) protocol was developed for rapid genotyping of hepatitis B virus (HBV). During the first PCR round, a universal HBV primer pair was used to amplify the entire pre-S region of the HBV genome. Within the pre-S region, many nucleotide exchanges are observed. These are partly correlated to the serological hepatitis B surface antigen subtypes. Five additional subtype-specific primers were selected from that region which, together with two universal non-group-specific primers, generated specific combinations of two to four DNA fragments of defined sizes. By this approach, 55 hepatitis B surface antigen-positive patients from a pediatric oncology unit in Germany were analyzed. Fifty-four patients who had been infected within 2 years had an identical pattern in the multiplex PCR, suggesting a common source of infection and person-to-person transmission within the unit. One child who was infected 5 years later had a different PCR pattern and, therefore, must have been infected from a different source. Furthermore, 109 serum samples taken from pregnant Cameroonian women and 25 serum samples from their babies taken 6 months after birth were analyzed. In one case, mother-to-infant transmission of the virus was demonstrated. Apart from its role in epidemiological studies on HBV, multiplex PCR may also be a useful tool for rapid genetic analysis in other fields if there is a moderate degree of sequence variation which enables the design of specific primers.

Base Sequence↗
PubMed1993

[Risk of hepatitis B virus transmission by highly viremic chronic carriers in schools].

To determine the frequency of hepatitis B virus (HBV) transmission by hepatitis B surface antigen (HBsAg) carriers in school classes 44 highly viremic children were examined over an average period of 5 years. All these HBsAg carriers had been infected with the virus in a hospital endemia during treatment for childhood malignancies. They have been continuously positive for HBeAg with very high HBV-DNA titers of more than 10(8) viral genomes/ml serum. Due to data protection reasons no serologic tests could be done in these school classes. Therefore, the patients and their parents were asked to fill in a questionnaire about any cases of hepatitis in the school classes during the study period. These results were compared with the hepatitis B registrations in the records of the public health offices. No differences were found between the two sources of data. In the school classes of the HBsAg carriers the incidence of hepatitis cases was 0.3 per 1000 pupils per year, which is not different from the hepatitis B morbidity within the general population. Therefore, there is no reason to impose any restrictions on HBsAg carriers in school. In contrast, several cases of HBV transmissions occurred to non-vaccinated family members of the HBV carriers.

Adolescent↗
PubMed1992

Favorable outcome of B-cell acute lymphoblastic leukemia in childhood: a report of three consecutive studies of the BFM group.

In 1981 the BFM group introduced a new treatment strategy for B-cell acute lymphoblastic leukemia (B-ALL). A cytoreductive prephase (prednisone/cyclophosphamide) was followed by eight 5-day courses of chemotherapy. Fractionated cyclophosphamide, methotrexate (MTX) 0.5 g/m2 (24-hour infusion), and MTX intrathecally were administered at each course and cytosine arabinoside (ARA-C)/teniposide (VM-26) was given alternately with doxorubicin. In study ALL-BFM-83, central nervous system (CNS) chemotherapy was intensified by adding dexamethasone, while MTX/ARA-C was administered intraventricularly. Therapy duration was reduced to six courses. In study ALL-BFM-86, MTX 0.5 g/m2 was replaced by high-dose (HD) MTX, 5 g/m2 (24-hour infusion), and MTX/ARA-C/prednisolone intrathecal therapy was introduced. Doses of ARA-C and VM-26 were increased and fractionated, cyclophosphamide was partially replaced by ifosfamide, and vincristine was added. CNS irradiation was 24 Gy for prevention and 30 Gy for overt disease in studies ALL-BFM-81 and -83, but was omitted in ALL-BFM-86. In all, 87 patients were enrolled, 22 (8 CNS-positive) in study All-BFM-81, 24 (7 CNS-positive) in study ALL-BFM-83, and 41 (0 CNS-positive) in study ALL-BFM-86. The estimated 5-year duration of event-free survival (EFS) was 43% in study ALL-BFM 81, 50% in study ALL-BFM-83, and 78% in study ALL-BFM-86 (minimal follow-up, 25 months). Nineteen of 24 relapses occurred while on therapy or shortly thereafter. In study ALL-BFM 81, the CNS was the most frequent site of failure. In ALL-BFM-83, there were no isolated CNS relapses, but more bone marrow (BM) relapses occurred. In ALL-BFM-86, localized manifestations were the predominant site of failure, no isolated BM relapses occurred, and only one CNS relapse was diagnosed. No single parameter exerted a consistent influence on outcome with one exception. The presence of residual disease after the first two courses was correlated with an increased risk of therapy failure. We conclude that an intensive, short-pulse therapy delivered within a 4-month period is highly effective in the treatment of B-ALL. In addition to fractionated cyclophosphamide/ifosfamide, a 24-hour infusion of HD MTX 5 g/m2 in conjunction with an i.th. therapy is an important component for prevention of both systemic and CNS relapses. CNS irradiation is not needed for CNS-negative patients.

Adolescent↗
PubMed1992

Clinical impact of chromosome 1 aberrations in neuroblastoma: a metaphase and interphase cytogenetic study.

Neuroblastoma tumors are characterized by aberrations of chromosome 1. Rapid detection of these chromosomal aberrations at diagnosis could give important clues to outcome and therapy. We attempted to detect numerical and structural aberrations of chromosome 1 not only by classical metaphase cytogenetics but also by interphase cytogenetics in order to overcome difficulties of karyotyping due to diminished metaphase quality and quantity in primary neuroblastoma samples. Karyotypic changes of chromosome 1 in 53 primary neuroblastomas were evaluated. In addition, we successfully performed interphase cytogenetics using single and double in situ hybridization procedures with chromosome 1-specific repetitive DNA probes on nuclei preparations obtained from 46 and 20 tumors, respectively. Polysomies of structurally normal chromosomes 1 were predominantly seen in tumors with good prognosis, whereas deletions of 1p material were nearly exclusively confined to progressive tumors. Numerical and structural chromosome 1 aberrations as studied by metaphase and interphase cytogenetics are thus valuable prognostic markers in neuroblastoma.

Chromosome Deletion↗
PubMed1992

Detection of transcriptionally active hepatitis B virus DNA in peripheral mononuclear blood cells after infection during immunosuppressive chemotherapy using the polymerase chain reaction.

Using PCR we have studied mononuclear peripheral blood leucocytes (PMBLs) from HBV-infected immunosuppressed patients in order to detect the presence of HBV genomes. Our results indicate that non-transient PMBL infection is common in immunotolerant carriers. In addition, the presence of pregenomic mRNA sequences suggests that virus replication may take place in PMBLs, possibly implicating the latter as a source of virus after replication has ceased in the liver.

Adolescent↗
PubMed1992

Frequency and DNA sequence of tal-1 rearrangement in children with T-cell acute lymphoblastic leukemia.

Using nested polymerase chain reaction (PCR) a gene rearrangement named tal-1 deletion was found in five of 56 leukemic bone marrow samples from children with T-cell acute lymphoblastic leukemia (ALL). The DNA sequences of the PCR fragments consisted of the known conserved germline sequences in addition to short DNA insertions at the breakpoint region, which were different in each patient. Moreover, one patient was examined at diagnosis and at relapse 11 months later, revealing identical DNA sequences at the rearrangement site. The recombination site of the tal rearrangement therefore may be used as a genetic marker for detecting minimal residual disease in about 10% of T-cell ALL in childhood.

Base Sequence↗
PubMed1992

Translocation (5;22) in an Askin's tumor.

A boy with a brain metastasis of an Askin's tumor was investigated. Cytogenetic studies revealed a near-diploid karyotype with monosomies of chromosomes 5 and 22 in the presence of a derivative chromosome der(5)t(5;22)(q35;q11). In particular, no involvement of chromosome 11 was seen.

Brain Neoplasms↗
PubMed1992

Cytogenetic findings in acute leukaemias of infants.

Of 706 children, 528 with acute lymphoblastic leukaemia (ALL) and 178 with acute myelocytic leukaemia (AML), whose leukaemia karyotypes could be successfully analysed, 48 were infants less than 1 year of age, 28 with ALL (5% of ALL patients) and 20 with AML (11% of AML patients). In contrast to older children. ALL-leukaemocytogenetics in infants was characterised by lack of hyperdiploidy with over 50 chromosomes and higher incidence of pseudodiploidy. Thirteen (= 46%) infants had an 11q23 aberration, and 11 of them had t(4;11). In AML, nine (= 45%) infants also had an 11q23 abnormality, e.g. t(9;11). Thus, the 11q23 aberration was present in almost 50% of all leukaemia karyotypes of infants. In ALL of infants, the CALLA negative, pre-pre-B immunophenotype prevailed. In AML of infants, the monocytic subtype dominated. A biphenotypic morphology (lymphoid-monocytic) with the expression of lymphoid and myeloid antigens was seen in several ALL and AML cases. In conclusion, leukaemogenesis in infants is a rare event, arising in stem cells of very early hematopoietic differentiation (probably due to gene rearrangement errors, most frequently at FRA11B), and differs from leukaemogenesis in older age groups by unique clinical and cellular features.

Bone Marrow↗
PubMed1991

HOX11, a homeobox-containing T-cell oncogene on human chromosome 10q24.

A common chromosomal abnormality in childhood T-cell acute leukemia is a translocation, t(10;14) (q24;q11), that together with the variant t(7;10)(q35;q24) is present in up to 7% of this tumor type. The gene adjacent to the 10q24 region is transcriptionally activated after translocation to either TCRD (14q11) or TCRB (7q35). It encodes a homeobox gene closely related to the developmentally regulated homeotic genes of flies and mammals. The coding capacity of this activated gene, designated HOX11, is undisturbed in a T-cell line carrying the translocation t(7;10)(q35;q24). Therefore, the HOX11 homeobox gene seems to be involved in T-cell tumorigenesis.

Amino Acid Sequence↗