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W D Ludwig

Publications and source records attributed to W D Ludwig.

At least 181 records · Page 10Linked to original sources
PubMed1991

TTG-2, a new gene encoding a cysteine-rich protein with the LIM motif, is overexpressed in acute T-cell leukaemia with the t(11;14)(p13;q11).

We have cloned 70 kb of DNA from chromosome 11p13 at the site of a recurrent translocation in T-cell leukaemia (T-ALL): t(11;14)(p13;q11). The translocation involves the TCR-delta gene on 14q11 and a new site on 11p13. Two new and 10 previously identified translocations all mapped within 25 kb on 11p13, the 11p13 T-cell translocation cluster (11p13 ttc). A search for expressed sequences surrounding the breakpoint cluster region on 11p13 identified a gene telomeric of all breakpoints which is overexpressed in three T-ALL samples with a t(11;14). The gene T-cell translocation gene (TTG-2) encodes a small cysteine-rich protein. Forty-eight per cent of the amino acids are identical with another translocation-deregulated gene, TTG-1 (T-cell translocation gene 1 or rhombotin) in 11p15. There are two copies of a cysteine-rich motif in both proteins. Two tandem copies of the same cysteine-rich motif are also present in the recently described lin-11, isl-1 and mec-3 gene products, and one motif is found in the CRIP protein. Therefore the proteins encoded by these two translocation-deregulated genes belong to this new class of cysteine-rich proteins with the 'LIM' motif, which are important in normal development.

Amino Acid Sequence↗
PubMed1990

Recombinant human granulocyte-macrophage colony-stimulating factor after chemotherapy for acute leukemias at higher age or after relapse.

Chemotherapy (CT) induced critical cytopenia remains as the major dose limiting problem in the treatment of acute leukemias. This is especially true in patients at high risk of early death due to high intensity chemotherapy for relapse or to higher age. In an attempt to reduce the phase of risk we administered human recombinant GM-CSF to 23 patients at a median age of 65 (range 17-84) years including 8 acute myelogenous (AML) and 5 lymphoblastic (ALL) leukemias after early or second relapses and 10 patients of 65 years and older in primary induction treatment for AML. 3 patients with AML had prior bone marrow transplantation. 4 AML's were secondary to tumor chemotherapy (2) or myelodysplastic syndrome (2). The study was part of chemotherapeutic phase II and III studies using TAD9 for primary induction chemotherapy and S-HAM for relapses. Starting on day 4 after the end of intensive CT GM-CSF 250 micrograms/m2/day was given by continuous i.v. infusion and after recovery of neutrophils was deescalated in two 4 day steps and discontinued. 12/23 patients achieved a complete remission (CR) and median age of responders is 61 (range 17-84) years. In the group of the non-transplanted patients the median recovery time of neutrophils is reduced by one week when compared to controls receiving the same chemotherapy (p = 0.002). We observed a leukemic regrowth in 3 patients of 61, 70, and 78 years, 2 of whom having secondary AML. After discontinuation of GM-CSF the regrowth of blasts was reversible in 1 patient and continued unaffectedly in its kinetics in 2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1990

Possibilities and limitations of immunological marker analyses for the detection of minimal residual disease in childhood acute lymphoblastic leukemia.

Specific application of immunological markers in acute lymphoblastic leukemia (ALL) for detection of inadequate blast cell reduction after induction therapy or early recognition of a relapse requires a precise characterization of the immunophenotype at the time of diagnosis and an understanding of the biology of the disease. Therefore, the ALL-BFM 83 study is first used to demonstrate the incidence, antigen expression and dynamics of relapse occurrence of immunological subtypes in childhood ALL. This is then followed by a discussion of the different immunological features hitherto applied for identification of residual leukemia cells in ALL (terminal deoxynucleotidyl transferase--TdT; common acute lymphoblastic leukemia-associated antigen--CALLA, CD10; various T-cell differentiation antigens; kappa/lambda labelling); these are, however, not leukemia-specific and are expressed to varying degrees by normal lymphoid progenitor cells. The sensitivity of these analyses is therefore largely determined by the markers applied and the type of investigational material. Finally, suitable markers are presented for detecting residual leukemia cells in the different immunological subtypes of ALL. Their clinical relevance still remains to be evaluated in prospective therapy studies.

Antibodies, Monoclonal↗
PubMed1990

Recombinant human GM-CSF following chemotherapy in high-risk AML.

Chemotherapy (CT) induced critical neutropenia remains a major dose limiting problem in acute leukemias. In order to reduce the phase of risk we gave recombinant human GM-CSF to 30 patients at high risk of early death with acute myeloid leukemia (AML). 19 patients with untreated AML and 1 patient with AML late relapse were 65+ years of age and were treated for CT by the TAD9 regimen. 10 patients at all ages had AML early or second relapse and received S-HAM CT. Starting on day 4 after CT GM-CSF 250 micrograms/m2/d was given by continuous i.v. infusion until neutrophils recovered. GM-CSF reduced the median recovery time of neutrophils by 4 days in the TAD9 and 9 days in the S-HAM CT group when compared to controls. After the CT induced aplasia 3 patients with AML showed a regrowth of their blasts which after the stop of GM-CSF was reversible in 1 patient and unaffectedly continued in 2 patients. 57% of patients attained a complete remission, and the median age of the responders was 65 (34-84) years. Remission duration was not found to be reduced. Thus, GM-CSF reduces CT toxicity with a low risk of promoting the disease and may allow more effective antileukemic treatment.

Adult↗
PubMed1989

Immunosuppressive effects of recombinant interferon-alpha during long-term treatment of cancer patients.

Interferons (IFN) are known to modulate immune responses in an either stimulatory or inhibitory manner. Most of the knowledge about immunomodulatory activities of IFN comes from investigations of IFN effects on cells in vitro. This study examines the influence which long-term treatment with recombinant interferon-alpha 2 exerts on immune functions in cancer patients. Serial in vitro immune function studies of peripheral blood mononuclear cells were done to determine parameters of B-cell and T-cell functions as well as natural killer (NK)-cell activity. The authors detected profound suppression of in vitro immunoglobulin synthesis and lymphocyte proliferation as well as depression of NK-cell activity during IFN treatment. All suppressed immune functions normalized on discontinuation of IFN therapy. The authors conclude from these observations that, apart from their beneficial effects, IFN produce substantial immunosuppression.

Drug Administration Schedule↗
PubMed1989

Induction of lymphokine-activated killer cell against human leukemia cells in vitro.

The induction of lymphokine-activated killer (LAK) cells against fresh human leukemia cells was investigated. Two thirds of the 62 leukemias examined were susceptible to the lytic effect of allogeneic IL-2 induced LAK cells in vitro. No substantial differences could be detected between myeloid or lymphoid leukemias or with regard to the FAB subtype or the immunophenotype. Culturing mononuclear cells from peripheral blood or bone marrow of leukemia patients with IL-2 resulted in an expansion of residual large granular lymphocytes and development of cytotoxic activity. The combination of IL-2 with IFN-gamma or the presence of tumor cells during the activation process led to an enhancement of LAK cell cytotoxicity. These results suggest that LAK cells may be useful in the treatment of leukemia.

Cytotoxicity, Immunologic↗
PubMed1989

Calla-positive acute leukaemia with t(5q;14q) translocation and hypereosinophilia--a unique entity?

A patient with common acute lymphoblastic leukaemia (ALL), hypereosinophilic syndrome and t(5;14) (q31.1;q32.3) translocation is described. Even with intensive treatment only short periods of complete remission were achieved. Recurrence of the leukaemia was always accompanied by the appearance of eosinophilic granulocytes in the blood and in the bone marrow. Although there is no experimental proof we assume that the hypereosinophilic syndrome is causally related to the chromosome aberration. Translocation of the GM-CSF gene from chromosome No. 5 to chromosome No. 14, might have led to the deregulation of the gene by enhancer sequences of the immunoglobulin heavy-chain region on chromosome No. 14, with the consequence of an overproduction of neutrophilic and particularly eosinophilic granulocytes. Furthermore, stimulation of the leukaemic cell clone may have occurred by this translocation. The similarity of the clinical course with cases described in the literature suggests that this condition is a unique entity of ALL.

Child↗