SEARCH · PubMed Health

Results for “CLL”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30Linked to original sources

PubMedDate not supplied

Molecular cytogenetic analysis of B-CLL patients with aggressive disease.

We tested a set of commercially available probes to determine the feasibility and accuracy of FISH in the detection of abnormalities in 13 patients with Chronic Lymphocytic Leukemia (CLL) with a particular aggressive clinical disease. We utilized three different probes for the 13q12-14 region, one for the centromeric region of chromosome 12, one for the P53 gene at 17p13.1 and one for 3'-5' IGH at 14q32, covering the entire region of IGH, thus potentially allowing to detect more rearrangements. Conventional cytogenetic study showed a normal karyotype in 8/13 patients. FISH was able to detect chromosomal abnormalities in 10/13 pts (85%): +12 in 4 pts (38%); del 13q in 4 (38%); del 17p in 3 (35%); del of 5'-IGH in 1 (15%). In conclusion FISH confirmed its ability to improve the detection of cytogenetic abnormalities especially in patients with an aggressive disease.

Acute Disease↗

PubMed2002

Clinical efficacy of irradiation in CLL patients: predictive value of in vitro radio-induced apoptosis.

In order to identify CLL patients for whom irradiation could be beneficial, we investigated the relationship between in vitro radio-induced apoptosis of leukemic cells and response to low-dose splenic or lymph node radiotherapy. Fourteen patients were included in the in vitro study. Leukemic cells were analyzed by Hoechst staining immediately after collection or 24h of culture following in vitro irradiation of 0-10 Gy. The tumor response rate was 47% (one CR and six PR), with a mean duration of response of 3 months (range: 1-4). A high correlation between tumor response and in vitro tests was observed (p < 0.01) and the positive predictive value of the in vitro tests for tumor and hematological responses was 100% at 5 Gy. These results suggest that the sensitivity of leukemic cells to irradiation should be first evaluated in an in vitro assay to spare refractory patients from the useless toxicity radiotherapy.

Adult↗

PubMed2004

The prognostic value of CD38 expression and its quantification in B cell chronic lymphocytic leukemia (B-CLL).

A large number of prognostic factors are available to help predict the outcome of patients who present with B-cell chronic lymphocytic leukemia (B-CLL). These include clinical stage, leukemic cell morphology, lymphocyte doubling time, the pattern of infiltration in bone marrow trephine biopsies, cytogenetic abnormalities, p53 function and serum factors such as beta-2 microglobulin. Two recently described major prognostic factors are immunoglobulin heavy chain variable region (IgVH) mutation status and cell membrane expression of CD38. These are both highly significant independent prognostic factors, but are not closely correlated. Whereas IgVH mutational status is a time consuming and demanding technique, only available in a limited number of centres, CD38 expression by flow cytometry is relatively simple and rapidly obtained in most diagnostic laboratories. The predictive value of CD38 expression is enhanced by measurement of antigen density in terms of antibody binding capacity (ABC) rather than as the percentage of cells expressing the antigen. ABC correlates closely with relative median fluorescence (RMF), a parameter which is even more simply and cheaply obtained by flow cytometry. One of these methods of determining CD38 expression should be employed routinely. Recent work suggests that membrane ZAP-70 expression determined by flow cytometry will prove to be an accurate proxy for IgVH mutational status and this assay will be within the reach of any laboratory skilled in flow cytometry. The combination of ZAP-70 expression, CD38 antigen density, p53 function and the concentration of serum factors such as soluble CD23, is likely to provide extremely accurate prognostic information in future studies. This will assist in identifying Stage A patients who may benfit from early and/or more intensive treatment, as well as Stage B and C patients who may require alternative treatment strategies at the outset.

ADP-ribosyl Cyclase↗

PubMed2004

Remission induction using alemtuzumab can permit chemotherapy-refractory chronic lymphocytic leukemia (CLL) patients to undergo allogeneic stem cell transplantation.

The outcome of allogeneic stem cell transplantation depends upon the disease status before transplantation. Patients with refractory disease are at high risk for relapse. To improve the curative potential of the transplant procedure, we treated 3 chemotherapy-refractory CLL patients with alemtuzumab before allogeneic stem cell transplantation. Prior to therapy, all patients suffered from B-symptoms, and had massive adenopathy, splenomegaly, thrombocytopenia, and anemia; two patients had hepatomegaly. Alemtuzumab greatly reduced tumor mass in blood and bone marrow, B-symptoms resolved, and organomegaly improved. Two patients became blood product independent. All patients proceeded to transplantation after conditioning with TBI 2 Gy (n=1) or Treosulfan (n=2) in combination with Fludarabine either from an HLA-matched sibling (n=2) or from an HLA-matched unrelated donor (n=1). All patients engrafted, and are alive and well. Two patients reached complete remission (CR); one patient attained stable partial remission (PR). These heavily pre-treated refractory patients gained substantial clinical benefit from alemtuzumab, and received successful allografts.

Alemtuzumab↗

PubMed1977

The biosynthesis and characterization of unreleased IgM in a case of CLL.

Intracellular IgM k is described in a case of CLL. The intracellular immunoglobulin occurred as amorphous spherical globules enclosed by rough endoplastic reticulum in the cytoplasms of the neoplastic lymphocytes. No abnormal IgM paraprotein could be found in the serum nor was there any Bence Jones protein detectable in concentrated urine. Biosynthetic studies confirmed the cells were able to synthesize IgM k immunoglobulin. On sizing gel analysis the intracellular IgM occurred as 7S monomer. The biosynthesis studies did not indicate secretion of IgM and was consistent with the serological findings. However, cells in culture secreted k light chain into the supernatant medium. It appears in this case that the secretory block is operating against heavy chain and not against free light chain. Some explanations for these findings are discussed.

Aged↗

PubMed1987

Long survival in B-CLL correlates with surface IgM kappa phenotype.

200 patients with B-cell chronic lymphocytic leukaemia (B-CLL) presenting to a single centre over 13 years have been studied. In 72.2% the diagnosis was made on an incidental blood count, and 70.1% were stage A at presentation. Those patients whose cells expressed surface IgM kappa were significantly more likely to be stage A at presentation and significantly less likely to have a lymphocyte count greater than 50 X 10(9)/l, to have progressive disease or to require treatment than those with other classes of surface Ig. Patients whose cells express surface IgM kappa have a significantly longer actuarial survival than others and this is also so when only patients in Binet stage A or when only patients presenting below the age of 75 are studied. By studying all of the cases presenting in a single catchment area we have attempted to avoid the bias against trivial disease likely to be seen in specialist referral centres.

Adult↗

PubMed1991

Analysis of multidrug resistance (MDR-1) gene expression in chronic lymphocytic leukaemia (CLL).

Multidrug resistance (MDR) in cultured human cells is caused by the overexpression of the MDR-1 gene. This gene codes for P-glycoprotein, a proposed ATP-dependent drug efflux pump, which reduces the net intracellular accumulation of a large group of chemotherapeutic agents in resistant cells. We have measured the level of expression of the human MDR-1 gene in a series of patients with chronic lymphocytic leukaemia (CLL). Forty-eight patients included in the study were at different stages of disease and were either untreated or had been treated with alkylating agents or alkylating agents in combination with drugs of the MDR spectrum, and were tested over a period of 3 years. The level of MDR-1 expression was monitored by Northern blotting analysis using a specific cDNA hybridization probe and also after polymerase chain reaction (PCR) amplification of MDR-1 complementary DNA (cDNA). Four of 28 previously untreated patients showed intrinsically high levels of MDR-1 mRNA while 5/19 treated patients had elevated MDR-1 expression. Elevated MDR-1 expression in treated patients was unrelated to the type of chemotherapy and was independent of previous exposure to drugs of the MDR spectrum. Intrinsic MDR-1 gene expression in positive patients did not appear to influence their response to chemotherapy with non-MDR drugs such as alkylating agents.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1993

Reversing of chlorambucil resistance by ethacrynic acid in a B-CLL patient.

We evaluated the reversing activity of ethacrynic acid in a B-CLL patient resistant to chlorambucil. The glutathione S-transferase (GST) activity, measured in peripheral blood lymphocytes, resulted extremely elevated. Ethacrynic acid, at pharmacological concentrations, partially reversed chlorambucil resistance and this result appeared related to the increased GST levels.

Aged↗

PubMed1991

Human hybridomas derived from CD5+ B lymphocytes of patients with chronic lymphocytic leukemia (B-CLL) produce multi-specific natural IgM (kappa) antibodies.

Great numbers of CD5+ B lymphocytes were detected in the peripheral blood of patients with B-CLL. To study the antibody repertoire of this immune cell subpopulation on a monoclonal level, we fused the lymphocytes derived from five different donors to a highly efficient HAT-sensitive heteromyeloma line (CB-F7). A fusion frequency of up to 10(-5) allowed us to analyse hundreds of initial hybridoma lines per fusion. In all culture supernatants in three out of five fusions IgM lambda antibodies were detected, in two experiments only IgM kappa was measured, suggesting monoclonality of the primary hybridoma cell lines. The later fusions resulted in hybridomas producing multi-specific antibodies against both an autoantigen and an infectious agent: (i) dsDNA/influenza virus haemagglutinin; (ii) dsDNA/class V outer membrane protein type C from Neisseria meningitidis. However, no antibodies of the described specificity were detected in blood sera of patients, indicating a 'switch-on' of the immunoglobulin secretion capacity of malignant B cells during fusion to a myeloma partner. We discuss the results as further evidence for the natural multi-reactive antibody repertoire of CD5+ B cells.

Adult↗

PubMed1992

Predictors of infection in chronic lymphocytic leukaemia (CLL).

A group of patients with chronic lymphocytic leukaemia (CLL) were studied to determine whether particular clinical and laboratory parameters might help to identify those patients at risk of recurrent infection who would benefit from immunoglobulin replacement therapy. The case notes of 59 patients were reviewed with regard to stage and duration of disease, chemotherapy and frequency of infection over the preceding 2 years. Serum IgG levels and specific antibodies to tetanus, diphtheria and pneumococcal capsular polysaccharide were measured at the end of the 2-year period. A group of 56 healthy age-matched volunteers were used as controls. Eighteen patients had severe or multiple infections during the study period, 11 patients had recurrent infections and the remaining 30 patients had only minimal infections. Overall, serum IgG levels were low in 32 patients but in none of the control group (P = 8.8 x 10(-11). However, less than half of those patients with hypogammaglobulinaemia suffered from severe or multiple infections. Specific antibodies to pneumococcal capsular polysaccharide were low in 23 patients compared with six of the control group (P = 4.9 x 10(-4)). The majority of patients with severe or multiple infections (13/18) had low levels of both total IgG and specific antibodies to pneumococcal capsular polysaccharide. However, in the groups of patients with less frequent infections, a higher proportion had low serum IgG than low pneumococcal antibody levels. Low levels of pneumococcal antibodies were particularly associated with severe or multiple infections (P = less than 0.00001).

Aged↗

PubMed1987

Three kinds of tumour-unique surface molecules on a human T-cell chronic lymphocytic leukaemia (T-CLL) detected by monoclonal antibodies.

Mouse monoclonal antibodies recognizing cell surface molecules on tumour cells from a patient with a T-cell chronic lymphatic leukaemia (T-CLL) have been produced. Three different types of idiotype-like cell surface structures were identified. One molecule had a relative molecular weight (Mr) of 90,000 under non-reduced conditions and of 42,000 upon reduction, which corresponds well to the T-cell receptor for antigen (Ti). The two other molecules, which also behaved like unique tumour markers, have not previously been described, to our knowledge. One molecule was a monomer with an Mr of 74,000-80,000 when non-reduced and 80,000 upon reduction. The other idiotypic molecule was a dimer with a non-reduced Mr of 74,000-80,000, and 38,000 after reduction.

Antibodies, Monoclonal↗

PubMed1984

PHM 14: a novel monoclonal antibody that reacts with both normal and neoplastic human B cells but not B-CLL.

The reactivity of PHM 14, a monoclonal antibody to B cells produced in our laboratory was compared with Leu 10, a commercially produced antibody. Flow microfluorometric analysis showed that both PHM 14 and Leu 10 reacted with normal B cells, a variety of B cell lines and with B cell leukaemias and lymphomas, except in the case of B-CLL where PHM 14 reacted with a minority of cases, whereas Leu 10 reacted with a majority. PHM 14 and Leu 10 did not react with normal monocytes, granulocytes, T cells, T cell lines or with T cell leukaemias or lymphomas. Specificity of PHM 14 for B cells was further supported by the demonstration that PHM 14-positive blood cells, sorted from PHM 14-negative blood cells, reacted with polyclonal anti-immunoglobulins and with a panel of B cell markers but did not react with markers for T cells, monocytes, granulocytes or NK cells. Our results suggest that both PHM 14 and Leu 10 should be useful diagnostic reagents in the investigation of B cell-derived leukaemias and lymphomas.

Antibodies, Monoclonal↗

PubMed1988

Phenotypic heterogeneity of B- and T-cell differentiation antigens in B-CLL.

Peripheral blood from 38 B-CLL patients was studied by flow cytometry with 25 clustered or non-clustered monoclonal antibodies (moAbs) in order to characterize the cell surface phenotype of lymphoid cells. All moAbs chosen detected B or CD1-8 T-cell differentiation antigens or MHC class II antigens. The results showed a heterogeneity in the leukemic cell reactivity with the various moAbs and between patients. The restricted B-cell antigens recognized by BL14, Y2955 and anti-class II moAbs were constantly expressed in leukemic cells, while B-cell antigens reacting with FMC7 and BL13 moAbs were variably detected. In addition to CD5 antigens, other T-cell markers, including several epitopes of the CD1 group, were also found to be present on the leukemic cell surface in several cases. The relationship between the various clinical and/or biological features of the disease and the cell surface phenotype was studied. Our results indicated a correlation between the lymphoid cell reactivity with M241 (CD1) and BL13 (CD21) and the severity of the disease.

Antibodies, Monoclonal↗

PubMed2004

A narrow deletion of 7q is common to HCL, and SMZL, but not CLL.

To further characterise the genetic background of the two closely related B-lymphocytic malignancies hairy cell leukaemia (HCL), and splenic marginal zone lymphoma (SMZL) we have identified characteristic copy number imbalances by comparative genomic hybridisation (CGH). Based on these findings, areas of special interest were fine mapped, and relevant probes constructed for use in interphase-fluorescence in situ hybridisation (FISH) investigations. Thus, using the CGH data from 52 HCL and 61 SMZL patients, we identified the characteristic profiles of copy number imbalances for both diseases. These were a gain of 5q13-31 (19%) and loss of 7q22-q35 (6%) for HCL, and gain of 3q25 (28%), loss of 7q31 (16%), and gain of 12q15 (16%) for SMZL. A partial loss of 7q unusual for low-malignant B-cell diseases was found to be common to the two diseases. This loss was therefore fine mapped with BAC/PAC clones. Fine mapping revealed that in SMZL the minimal lost region covers 11.4 Mb spanning from 7q31.33 to 7q33 located between sequence tagged site (STS)-markers SHGC-3275 and D7S725. This area was distinct from the commonly deleted 7q region of myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML). A FISH probe specific for the 7q region was constructed. Using this probe in an interphase-FISH investigation we showed the minimal lost 7q-region of HCL and SMZL to be one and the same. In one HCL case, this investigation furthermore showed the extent of the deleted region to be below the detection limit of CGH, whereas interphase-FISH screening of 36 chronic lymphocytic leukaemia (CLL) cases showed no deletion of the 7q area. In conclusion, we have identified characteristic profiles of copy number imbalances in HCL and SMZL and fine mapped the minimal extent of a commonly lost 7q area of special interest. We hypothesise that this region may contain (a) gene(s) important for the pathology of HCL and SMZL.

Biopsy↗

PubMed1992

Immunoregulatory capability of murine CLL-like CD5+ B cells.

NZB mice spontaneously develop clones of hyperdiploid CD5+B cells, which are much like the malignant cells of CLL. We have found that these clonal CD5+B cells are immunoregulatory. The development of these cells is accompanied by the loss of detectable normal percentages of IgM+ B220(6B2)+ B cells secondary to hyperplasia of splenic non-B cells, which are positively regulated by the hyperdiploid B-cell clone.

Animals↗

PubMed1983

Relationship between immunoglobulin levels, lymphocyte subpopulations and Rai staging in patients with B-CLL.

27 patients with B-CLL were evaluated before treatment. All patients were staged according to the 'Rai' classification and the following cell populations were studied B cells, surface immunoglobulin characteristics, mouse red cell rosettes, T cells (E+) and T cell subsets (TG and TM). Serum immunoglobulins were measured in all patients. The relationship between the clinical stage and the above immunological parameters was studied and the possible role of splenic involvement in the finding of abnormal ratios of T cell subsets in the peripheral blood of patients with B-Cell is discussed.

Agammaglobulinemia↗

PubMed1991

Prognostic value of autoantibodies against erythrocytes and platelets in chronic lymphocytic leukemia (CLL).

Antiglobulin test (AT) and Dixon tests were performed in 100 patients with CLL. Thirty-five of them had Rai stages 0 or 1, 19 stage 2, 13 stage 3, and 33 stage 4. Twelve patients showed red blood cells autoantibodies (RBCAb) positivity; positivity at Dixon test (direct, indirect, or both) was observed in 74%. The presence of autoantibodies against erythrocytes and platelets did not influence survival curves, but anemia and thrombocytopenia are considered risk factors, independently of the presence of an autoimmune disorder. Nine RBCAb positive patients with positive Dixon test had the worst survival curves, 5 of these were anemic and 1 thrombocytopenic and anemic.

Aged↗

PubMed2006

Current and investigational therapies for patients with CLL.

Clinical and laboratory investigations are driving the rapid change in treatments for patients with chronic lymphocytic leukemia (CLL). Randomized trials have demonstrated superior activity for fludarabine combined with cyclophosphamide versus single-agent fludarabine or chlorambucil as initial treatment. Chemoimmunotherapy holds promise for further improvement and is being tested in randomized trials. New combinations and agents are being identified and tested. Eliminating minimal residual disease is a therapeutic endpoint that may prove to prolong survival and is also under investigation in prospective clinical trials. Work continues toward improving survival and potentially curing patients of this disease.

Antineoplastic Combined Chemotherapy Protocols↗