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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Hematology and cell therapy 39 (1997), S. S31 
    ISSN: 1279-8509
    Keywords: CLL treatment ; Chlorambucil ; Purine analogues
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three main question were addressed during this session: 1) Is early treatment better than deferring treatment until necessary for early stage patients?; 2) Is there still a place for chlorambucil (CB) in the treatment of CLL? and 3) Should we consider purine analogues for first line of therapy in CLL? The first question was discussed by Ph. Travade, who presented the long term results from two trials of the French Cooperative Group in previously untreated stage A CLL patients and by Sue Richards who submitted to meta-analysis the data from the American, British, French, and Spanish groups. Consensus was reached to accept that the different randomized trials and the meta-analysis results clearly demonstrate that conventional CB schedules do not prolong survival in these patients. Since deferring therapy until it is required by disease progression to stages B or C does not compromise survival of these patients, therapy should be deferred until progression is observed. It is widely admitted that CB treatment provides relief from symptoms for a large proportion of patients. However, results from different trials presented indicate that at least at conventional schedules, CB is unlikely to prolong survival in CLL. However, Jaksic presented favorable results with high dose (i.e., 10-15 mg/day) continuous CB schedule. The role of purine analogues was discussed by M. Keating and A. Saven, who presented long term results in non-randomized studies with fludarabine (FDB) and 2-chloro-deoxyadenosine (CDA), respectively. In addition the results from two randomized American and French Trials were presented by K. Rai and M. Leporrier. Long term results indicate that purine analogues are active agents in CLL. Both drugs obtain important overall response rates (〉 75%) and about 25% complete remissions. Long term results from MD Anderson series indicate that the median progression free interval is 30 months and that, in previously untreated patients, FDB is well tolerated. However, opportunistic infections and autoimmune complications are frequently observed in previously treated patients. Results from the American and French trials confirm that FDB is probably the best single agent in terms of response, since it appears to induce higher response rates than CB and anthracycline containing regimens. No important toxicities were observed in these series including exclusively previously untreated patients. The long term results from MD Anderson show a median survival of 5 years for CLL patients receiving FDB, which is not different to the historical results with other treatment modalities and is confirmed by the present results of the the American and French trials showing no improvement of the overall survival. These results suggest that purine analogues should be included in the list of drugs with proven efficacy in the initial treatment of patients with CLL. Although these drugsproduce better responses, they do not cure CLL. For young patients with poor prognosis CLL, future attempts shouldbe made to improve complete remissions at molecular level, which may lead towards significantly increasing the overall survival. Combination of purine analogues with other drugs, autologous transplantation and/or biological response modifiers like monoclonal antibodies or anti-idiotypic vaccines deserve investigation.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Hematology and cell therapy 39 (1997), S. S1 
    ISSN: 1279-8509
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Hematology and cell therapy 39 (1997), S. S1 
    ISSN: 1279-8509
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1279-8509
    Keywords: CLL MRD ; IgH genes rearrangement ; PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the absence of specific chromosomal translocations the best method for detecting minimal residual disease (MRD) in B cell malignancies is based on the uniqueness of immunoglobulin (Ig) genes rearrangement. We here report a very sensitive method for assessing MRD in complete hematological remission (CHR) chronic lymphocytic leukemia (CLL) patients as defined by the international workshop on CLL (IWCLL). Patients: Twelve CLL patients in CHR and complete phenotypic remission (CPR) were included in the study. Eight of them received Fludarabine (FDR), one was treated by Chop regimen, and the remaining 3 were rescued by polychemotherapy followed by autologous bone marrow transplantation (ABMT). Methods: DNA extracted from peripheral blood lymphocytes (PBL) of each patient was amplified with VH family specific and framework 3 primers in 5′ and a consensus JH primer in 3′, before treatment and sequentially after the CPR completion. When no clonal rearrangement could be detected by this assay, the CDR3 sequence specific probe of the clone was used as the 3′ primer, associated to the VH family specific primer in 5′. PCR products were analyzed by classical procedures in agarose and/or acrylamide gels. Results: Mixtures of leukemic cells and normal PBL showed detection of a single leukemic cell among more than 105 normal cells. Four out of the 12 patients achieved molecular remission (MR) when employing CDR3 amplifification. All 3 autografted patients were in MR, whereas only one out of the 9 patients treated by chemotherapy alone achieved MR. When using a clone specific probe, a clonal signal was observed in all cases but one (ABMT). Results presented here confirm that MR may be achieved in a few cases of B-CLL. Further studies are needed to determine the exact relationship between MRD and clinical outcome.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Hematology and cell therapy 39 (1997), S. S31 
    ISSN: 1279-8509
    Keywords: CLL treatment ; Chlorambucil ; Purine analogues
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three main question were addressed during this session: 1) Is early treatment better than deferring treatment until necessary for early stage patients?; 2) Is there still a place for chlorambucil (CB) in the treatment of CLL? and 3) Should we consider purine analogues for first line of therapy in CLL? The first question was discussed by Ph. Travade, who presented the long term results from two trials of the French Cooperative Group in previously untreated stage A CLL patients and by Sue Richards who submitted to meta-analysis the data from the American, British, French, and Spanish groups. Consensus was reached to accept that the different randomized trials and the meta-analysis results clearly demonstrate that conventional CB schedules do not prolong survival in these patients. Since deferring therapy until it is required by disease progression to stages B or C does not compromise survival of these patients, therapy should be deferred until progression is observed. It is widely admitted that CB treatment provides relief from symptoms for a large proportion of patients. However, results from different trials presented indicate that at least at conventional schedules, CB is unlikely to prolong survival in CLL. However, Jaksic presented favorable results with high dose (i.e., 10-15 mg/day) continuous CB schedule. The role of purine analogues was discussed by M. Keating and A. Saven, who presented long term results in non-randomized studies with fludarabine (FDB) and 2-chloro-deoxyadenosine (CDA), respectively. In addition the results from two randomized American and French Trials were presented by K. Rai and M. Leporrier. Long term results indicate that purine analogues are active agents in CLL. Both drugs obtain important overall response rates (〉 75%) and about 25% complete remissions. Long term results from MD Anderson series indicate that the median progression free interval is 30 months and that, in previously untreated patients, FDB is well tolerated. However, opportunistic infections and autoimmune complications are frequently observed in previously treated patients. Results from the American and French trials confirm that FDB is probably the best single agent in terms of response, since it appears to induce higher response rates than CB and anthracycline containing regimens. No important toxicities were observed in these series including exclusively previously untreated patients. The long term results from MD Anderson show a median survival of 5 years for CLL patients receiving FDB, which is not different to the historical results with other treatment modalities and is confirmed by the present results of the the American and French trials showing no improvement of the overall survival. These results suggest that purine analogues should be included in the list of drugs with proven efficacy in the initial treatment of patients with CLL. Although these drugsproduce better responses, they do not cure CLL. For young patients with poor prognosis CLL, future attempts shouldbe made to improve complete remissions at molecular level, which may lead towards significantly increasing the overall survival. Combination of purine analogues with other drugs, autologous transplantation and/or biological response modifiers like monoclonal antibodies or anti-idiotypic vaccines deserve investigation.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1279-8509
    Keywords: MRD ; B-cell malignancies ; IgH genes ; PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In B-cell malignancies, the uniqueness of the immunoglobulin heavy chain locus (IgH) clonal rearrangement provides a useful marker for the detection of minimal residual disease (MRD) after treatment. During the last decade, several techniques have been proposed and used for detecting MRD. In this review, we report the current PCR based techniques dealing with amplification of the VDJ segment since the CDR3 region is unique to each IgH rearrangement. The sensitivity of these techniques varies considerably with a detection level of one tumoral cell in 10−2 to 10−6 normal cells. Accurate and sensitive assessment of MRD may have profound impact in the clinical management of patients with hematologic malignancies. Although, a majority of studies have shown a good correlation between the rapidity or extent of the reduction in the number of tumoral cells and the subsequent relapse, other studies demonstrated substained positivity of PCR in patients in long term remission. Thus, current clinical studies of MRD should establish whether MRD predicts relapse uniformly and, therefore, justifies intensification of therapy in positive cases, or whether it simply detects leukemic cell populations whose proliferative potential has been altered by chemotherapy.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Hematology and cell therapy 42 (2000), S. 27-30 
    ISSN: 1279-8509
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A preliminary experiment showed that the supernatants of in vitro cultured peritoneal cells (rich in Ly-1 B cell subset shown to secrete most IgM autoantibodies against bromelain-treated mouse red blood cells (BrMRBC) and DNA) from different mouse strains did not contain any significant antibody activity against DNA and cytoskeleton proteins, although the presence of anti-BrMRBC antibodies was clearly evident. Therefore, we investigated comparative natural antibody (NAb) specificities against an antigen panel (DNA, cytoskeleton proteins, IgG. bovine serum albumin (BSA), BrMRBC, trinitrophenyl (TNP), and trimethylammonium (TMA) haptens) among Ig-secreting hybridoma collections from the splenic (158) and peritoneal (230) immune compartments of autoimmune New Zealand black (NZB) and lipopolysaccharide (LPS)-stimulated BALB/c mice. The data showed: (i) isotypic restriction (μ and γ3 only), predominance of TMA ion-reactive (including BrMRBC) but negligible anti-DNA-reactive antibody specificities, and lack of simultaneous polyspecific widespread reactivity (i.e. at least four or more antigens) against DNA and cytoskeleton proteins in the peritoneal cavity; (ii) predominance of simultaneous widespread polyspecific reactivity against DNA and cytoskeleton proteins but negligible or no TMA hapten-reactive antibody specificities in the spleen. These observations reflect certain differences in the B cell repertoire of peritoneal cavity (rich in Ly-1 B cells) compared with spleen. The NAb against BrMRBC and those reactive with DNA and cytoskeleton proteins, which have been suggested to be secreted by the Ly-1 B cell subset, are distinguishable on the basis of the presence of separate recurrent idiotypes and preferential localization of B lymphocytes directed against these autoantigens.
    Type of Medium: Electronic Resource
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  • 10
    Publication Date: 2018-06-22
    Description: The previous edition of the consensus guidelines of the International Workshop on Chronic Lymphocytic Leukemia (iwCLL), published in 2008, has found broad acceptance by physicians and investigators caring for patients with CLL. Recent advances including the discovery of the genomic landscape of the disease, the development of genetic tests with prognostic relevance, and the detection of minimal residual disease (MRD), coupled with the increased availability of novel targeted agents with impressive efficacy, prompted an international panel to provide updated evidence- and expert opinion–based recommendations. These recommendations include a revised version of the iwCLL response criteria, an update on the use of MRD status for clinical evaluation, and recommendations regarding the assessment and prophylaxis of viral diseases during management of CLL.
    Keywords: Special Reports, Free Research Articles, Lymphoid Neoplasia, Clinical Trials and Observations
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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