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Biomedical subjects

F Lampert

Publications and source records attributed to F Lampert.

At least 19 recordsLinked to original sources
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↗
PubMed1990

Multiple methylation-free islands flank a small breakpoint cluster region on 11p13 in the t(11;14)(p13;q11) translocation.

The t(11;14)(p13;q11) translocation is one of the most frequent chromosomal abnormalities in T-cell acute lymphoblastic leukemia (ALL). Ten different leukemias carrying this translocation have been analysed and all 10 breakpoints fall within a region of less than 25 kb on chromosome band 11p13. We have used PFGE and cosmid cloning to assess the presence of potential genes by analysing methylation-free islands in the vicinity. Four methylation-free islands, within 270 kb, flank the t(11;14)-associated breakpoint cluster region (T-ALLbcr), one occurring about 25 kb on the telomeric side and one about 100 kb on the centromeric side of the T-ALLbcr. Evidence for eight further methylation-free islands on both sides of the T-ALLbcr region is also presented. Thus multiple methylation-free islands exist on 11p13 flanking the t(11;14)(p13;q11) translocation-associated breakpoint cluster region, representing multiple potential transcription units whose chromosomal environment is altered by chromosome translocation.

Chromosomes, Human, Pair 11↗
PubMed1990

Neuroblastoma: inverse relationship between expression of N-myc and NGF-r.

12 primary neuroblastomas (NB) of different maturation stages, 2 ganglioneuromas (GN), and 2 neuroblastoma cell lines were analysed for RNA expression of the protooncogene N-myc and the gene encoding the nerve growth factor receptor (NGF-r) by Northern-blots, RNA-dot-blots and for receptor presence by immunohistological procedures. In 4 tumors with strongly elevated RNA expression of N-myc the NGF-r RNA expression was weak or absent. In all 8 tumors with highly increased NGF-r transcription no N-myc expression was detectable. These results, indicating an inverse relationship between N-myc and NGF-r expression, could help in establishing markers for differentiation, and thus prognosis, in neuroblastoma.

Blotting, Southern↗