It is generally known that the nucleus : cytoplasmic ratio is a very useful marker for the evalua... more It is generally known that the nucleus : cytoplasmic ratio is a very useful marker for the evaluation of the cell activity and identification. In contrary, the nucleolus : nucleus ratio was less studied. The present study was undertaken to provide more information on that ratio during the differentiation and maturation of human lymphocytes. The ratio of nucleolar bodies to the nuclear body indicated that the size of the nuclear space occupied by nucleolar bodies in B chronic lymphocytic leukemia (CLL) during the cell differentiation and maturation (terminal differentiation) decreased in both untreated and treated patients with the anti-leukemic therapy. However, the nuclear space occupied by nucleolar bodies was apparently characteristic for each differentiation and maturation step. A similar trend was apparent in non-leukemic T lymphocytes of blood donors using in vitro de-differentiated lymphocytes as progenitors. During the cell differentiation and maturation, the size reduction ...
CLL is considered to be incurable disease by standard therapeutic approaches. We have demonstrate... more CLL is considered to be incurable disease by standard therapeutic approaches. We have demonstrated high remission rate including PCR negativity after combined therapeutic modality (rituximab, fludarabine, cyclophosphamide followed by HDT - BEAM - with ASCT) (Blood 2002, 100:804a). We present here longer follow up of larger pts cohort. Twenty four pts with B-CLL (median age 57 years (32–62)) have been recruited. Pts were eligible for study if they failed previous therapy, progressed without previous tx or if they exhibit at least two adverse prognostic factors at dg (elevated LDH or beta2microglobulin, adverse cytogenetic, diffuse involvement of BM, CD38 pos, low albumin l, short doubling time <1year). The mutational status was examined since 2002. The treatment protocol consists of 4 cycles of R-Flu/Cy (rituximab 375 mg/m2, fludarabine 3x25 mg/m2, cyclophosphamide 3x300 mg/m2), followed by mobilization regimen ESHAP with harvest of progenitor cells and HDT (BEAM) with ASCT. Pts w...
3589 Elevated levels of microRNA miR-155 represent a candidate pathogenic factor in chronic B-lym... more 3589 Elevated levels of microRNA miR-155 represent a candidate pathogenic factor in chronic B-lymphocytic leukemia (B-CLL). In our study, B-CLL patients (N=71, F/M 31/40, median age 65) were subject to molecular analyses that found significant overexpression of MYB and miR-155 in B-CLL and physical association of MYB with the promoter of MIR155 host gene (MIR155HG, also known as B-cell integration cluster). In CD19+ B-cells derived from healthy control individuals (N=13), MYB and miR-155 expression was significantly lower. Next, we found that MYB positively regulates MIR155HG transcription in reporter assays. The endogenous chromatin structure of the MIR155HG promoter in B-CLL cells is characterized by spreading of active chromatin mark, histone H3K9 acetylation. Gene expression arrays on B-CLL patients (N=11) identified a set of predicted miR-155 target genes (N=94) that are downregulated. Their expression pattern displayed significant negative correlation with pri-miR-155 levels. ...
2681 Mantle-cell lymphoma (MCL) is a lymphoma subtype with poor prognosis. Recently, new drugs ta... more 2681 Mantle-cell lymphoma (MCL) is a lymphoma subtype with poor prognosis. Recently, new drugs targeting at least partially the angiogenesis cascade have been successfully tested in the therapy of relapsed MCL patients, including temsirolimus, enzastaurin and lenalidomide. To reveal molecular mechanisms that regulate MCL-induced angiogenesis (and that might represent potential new druggable targets), we established and analyzed two mouse models of human MCL. Immunodeficient mice were subcutaneously (s.c.) xenografted with MCL cell lines JEKO-1 and HBL-2, and when tumor diameters reached 3cm in any size, the mice were sacrificed, and the excized tumors subjected to immunohistochemical (IHC) analysis. Alternatively, ex vivo obtained MCL cells were magnetically sorted using CD45 microbeads, and subjected to gene expression and flow cytometry analyses compared to the in vitro growing controls. IHC analysis proved that the tumors were neovascularized. Gene expression profiling by TaqMan ...
4600 MicroRNA miR-155 represents a candidate pathogenic factor in chronic lymphocytic leukemia (C... more 4600 MicroRNA miR-155 represents a candidate pathogenic factor in chronic lymphocytic leukemia (CLL) and lymphomas (Eis PS, et al. 2005, Fulci V, et al. 2007, Calin GA, et al. 2005, Kluiver J, et al. 2005, Metzler M, et al. 2004, van den Berg A, et al. 2003., Vargova K. et al 2011). In diffuse large B-cell lymphoma (DLBCL) expression of miR-155 was associated with NFkB pathway (Rai et al., 2008). In addition, increased miR-155 levels were associated with more aggressive (Activated B-cell like) DLBCL (Eis et al. 2005). The targets of up-regulated miR-155 apparently include a key hematopoietic transcription factor PU.1. Down-regulation of PU.1 represents an important and critical step for both myeloid as well as lymphoid tumorigenesis. We herein found the increased levels of miR-155 coupled with downregulation of its target PU.1 are frequent events in B cells of a vast majority of CLL patients (N=169). To advance understanding of miR-155 and PU.1 in lymphoid malignancies we studied ly...
Background Chronic lymphocytic leukemia (CLL) in most patients is diagnosed with early stage dise... more Background Chronic lymphocytic leukemia (CLL) in most patients is diagnosed with early stage disease identified incidentally on blood counts obtained for unrelated purposes. Immunophenotyping of peripheral blood (PB) is required for the diagnosis of CLL. A scoring system that helps in the differential diagnosis between CLL and other mature B-cell neoplasms (MBN) has been described twenty years ago (Matutes et al., Leukemia 1994; modified by Moreau et al., Am J Clin Pathol 1997). CLL/SLL typically demonstrates low-intensity staining for surface immunoglobulin, low or absent expression of CD22, CD79b and FMC7 and moderate to strong expression of CD5 and CD23. However, this phenotype is not entirely specific and some overlap in immunophenotype exists between CLL and non-CLL MBN. In particular, leukemic phase of CD5 positive mantle cell lymphoma (MCL) can be misdiagnosed as CLL. Recently, it has been shown that CD200 expression may help in differential diagnosis between CLL and other MB...
Trisomy 12 was found to be the most frequent chromosomal aberration identified by conventional cy... more Trisomy 12 was found to be the most frequent chromosomal aberration identified by conventional cytogenetic studies of bone marrow cells and peripheral lymphocytes of patients with CLL. Molecular-cytogenetic techniques which enable examination of dividing and/or non-diving interphase nuclei (I-FISH), proved existence of other chromosomal abnormalities, mainly deletions, which could have in CLL patients relation to the origin, course and prognosis of the disease. During the last two years bone marrow chromosomes of all patients with CLL were examined by G-banding and by I-FISH. The numerical changes of chromosome 12 were followed by centromeric DNA probe in dividing and non-dividing cells. The small deletions were ascertained by locus specific probes for 13q14 (Rb gene), 17p13 (p53 protein) and 11q23 (MLL gene). These genes are responsible for cell division and their function is probably in connection with neoplastic process. It is of interest whether numerical and structural chromoso...
The transcription factor PU.1 and its inhibitory microRNA-155 (miR-155) are important regulators ... more The transcription factor PU.1 and its inhibitory microRNA-155 (miR-155) are important regulators of B-cell differentiation. PU.1 downregulation coupled with oncogenic miR-155 upregulation has been reported in lymphoid malignancies; however, these data have not been studied across different subtypes in relation to clinical outcomes. We studied expression of miR-155 and PU.1 in the six most prevalent human B-cell lymphomas (n = 131) including aggressive (DLBCL, HL, MCL) and indolent (B-CLL/SLL, MZL, FL) types. Levels of miR-155 and PU.1 inversely correlated in DLBCL, B-CLL/SLL, and FL tumor tissues. In HL tissues, an exceptionally high level of miR-155 was found in patients with unfavorable responses to first-line therapy and those who had shorter survival times. PU.1 downregulation was noted in B-CLL/SLL samples positive for the adverse prognostic markers CD38 and ZAP-70. Upregulation of miR-155 and downregulation of PU.1 expression are integral aspects of lymphoma biology that could mark aggressive behavior of some, but not all, lymphoma types.
Hypermethylation of CpG islands within gene promoters is one of various mechanisms of gene silenc... more Hypermethylation of CpG islands within gene promoters is one of various mechanisms of gene silencing involved in the pathogenesis of human cancer. By using methylation-specific polymerase chain reaction we explored aberrant promoter methylation of five tumour suppressor genes in 29 patients with chronic lymphocytic leukaemia. Aberrant methylation of DLC1, SHP1, p15 and p16 occurred, respectively, in 89.7 %, 70 %, 62.1 % and 31 % of patients at diagnosis. Lamin A/C was unmethylated in all the samples. Hypermethylation of at least one gene was detected in 96.6 % of patients. Concurrent methylation of two or more genes correlated with Rai stage at diagnosis.
We report a unique case of indolent lymphoma with an unusual VDJ rearrangement. Polymerase chain ... more We report a unique case of indolent lymphoma with an unusual VDJ rearrangement. Polymerase chain reaction (PCR) analysis of bone marrow at the time of diagnosis was positive for both BCL-2/JH and CDRIII rearrangements. After treatment, the patient achieved complete remission (CR) with slow disappearance of both rearrangements (CDRIII and then BCL-2/JH). Subsequently, two new CDRIII rearrangements were detected in bone marrow, peripheral blood, and lymph node tissue. After this conversion, fluorescent activated cell sorting (FACS) analysis demonstrated monoclonal disease, suggesting that both CDRIII rearrangements originated from one cell. Histological evidence of a B-cell small lymphocytic lymphoma (B-SLL) infiltrate in the bone marrow became evident approximately 1 year after the two CDRIII rearrangements appeared. Direct sequencing revealed that one of the CDRIII sequences consisted of a VDVDJ rearrangement. This is the first report of such a rearrangement in a case of indolent ly...
The B-chronic lymphocytic leukemia (B-CLL) has highly variable prognosis. Possibility of more rel... more The B-chronic lymphocytic leukemia (B-CLL) has highly variable prognosis. Possibility of more relevant prognosis has a great impact for the beginning and mode of therapy. One hundred patients diagnosed as having B-CLL were included into the study. Beside usual examinations necessary to establish the diagnosis, cytogenetic examination for the detection of deletion 13q14, 17p13, 11q23 and trisomy 12 and immunophenotyping was done. The mean age of the patients was 58.2 years, there were 62 men and 38 women. 91 evaluated patients were divided into two groups--those with the steady disease (55 pts) and those with progressive disease (36 pts). No relation between the number of cytogenetic abnormalities and the Rai stage of the disease was found. We identified a relation between the bone marrow infiltration pattern (diffuse) and the number of cytogenetic abnormalities and the del 13q14 (p.05). Using the immunophenotyping of the lymphocytes we found a relation between the expression of CD38...
A case story of a patient with renal biopsy (RB) proven infiltration with lymphoma is given. RB i... more A case story of a patient with renal biopsy (RB) proven infiltration with lymphoma is given. RB in patient with known malignancy and onset of renal failure was indicated with regard to an atypical picture of kidney involvement (non-enlarged kidneys, without any structural changes typical for tumour mass presence). Though spread of the primary tumour to the kidney is not uncommon, involvement severe enough to impair renal function is unusual and occurs primarily with rapidly growing haematologic malignancies; diagnosis is being established by renal biopsy only rarely.
B-chronic lymphocytic leukemia (B-CLL) is the most common adult leukemia in the Western countries... more B-chronic lymphocytic leukemia (B-CLL) is the most common adult leukemia in the Western countries. Any routinely used staging system does not distinguish exactly the probable course of the disease at the time of diagnosis. Therefore the new prognostic factors, which help to assess the optimal therapeutic plan of patients, are searched intensively. We evaluated 154 patients with the B-CLL at the time of diagnosis--133 of them were retrospectively divided into two groups--one with stable form and the other with progressive form of the disease. We compared these two groups of patients with some of the prognostic factors (absolute lymphocyte count, the level of C-reactive protein, lactatdehydrogenase, beta-2-microglobulin, tumour necrosis factor, the immunoglobulin levels, the expression of CD38, FMC7, surface immunoglobulins, the type of bone marrow infiltration, and the cytogenetic abnormalities (trisomy 12, del(13)(q14), del(17)(p13) a del(11)(q23)). We found higher absolute lymphocy...
A number of prognostic scoring systems for patients with myelodysplastic syndrome (MDS) have been... more A number of prognostic scoring systems for patients with myelodysplastic syndrome (MDS) have been introduced since FAB classification of the MDS in 1982. Recently, the International Prognostic Scoring System (IPSS), published in 1997 by Greenberg et al. [9] is based on the percentage of bone marrow (BM) blasts, cytogenetic abnormalities and number of cytopenias. We applied criteria of the IPSS on 205 patients (pts) with primary MDS (RA = 82, RARS = 49, RAEB = 42, RAEB-t = 8, CMML = 24 pts). IPSS discriminated within each of the FAB-subgroups: RA pts were present in low risk and intermediate (Int) I and II risk subgroups, RARS pts were separated into low and Int I, RAEB were distributed predominantly between Int I and Int II risk groups, RAEB-t in high-risk group, and CMML pts were distributed in all groups. In contrary to Greenberg's group of the MDS patients there are only three risk-groups in our study: low risk (score 0-0.5), intermediate (1-2) and high risk (> 2); the med...
It is generally known that the nucleus : cytoplasmic ratio is a very useful marker for the evalua... more It is generally known that the nucleus : cytoplasmic ratio is a very useful marker for the evaluation of the cell activity and identification. In contrary, the nucleolus : nucleus ratio was less studied. The present study was undertaken to provide more information on that ratio during the differentiation and maturation of human lymphocytes. The ratio of nucleolar bodies to the nuclear body indicated that the size of the nuclear space occupied by nucleolar bodies in B chronic lymphocytic leukemia (CLL) during the cell differentiation and maturation (terminal differentiation) decreased in both untreated and treated patients with the anti-leukemic therapy. However, the nuclear space occupied by nucleolar bodies was apparently characteristic for each differentiation and maturation step. A similar trend was apparent in non-leukemic T lymphocytes of blood donors using in vitro de-differentiated lymphocytes as progenitors. During the cell differentiation and maturation, the size reduction ...
CLL is considered to be incurable disease by standard therapeutic approaches. We have demonstrate... more CLL is considered to be incurable disease by standard therapeutic approaches. We have demonstrated high remission rate including PCR negativity after combined therapeutic modality (rituximab, fludarabine, cyclophosphamide followed by HDT - BEAM - with ASCT) (Blood 2002, 100:804a). We present here longer follow up of larger pts cohort. Twenty four pts with B-CLL (median age 57 years (32–62)) have been recruited. Pts were eligible for study if they failed previous therapy, progressed without previous tx or if they exhibit at least two adverse prognostic factors at dg (elevated LDH or beta2microglobulin, adverse cytogenetic, diffuse involvement of BM, CD38 pos, low albumin l, short doubling time <1year). The mutational status was examined since 2002. The treatment protocol consists of 4 cycles of R-Flu/Cy (rituximab 375 mg/m2, fludarabine 3x25 mg/m2, cyclophosphamide 3x300 mg/m2), followed by mobilization regimen ESHAP with harvest of progenitor cells and HDT (BEAM) with ASCT. Pts w...
3589 Elevated levels of microRNA miR-155 represent a candidate pathogenic factor in chronic B-lym... more 3589 Elevated levels of microRNA miR-155 represent a candidate pathogenic factor in chronic B-lymphocytic leukemia (B-CLL). In our study, B-CLL patients (N=71, F/M 31/40, median age 65) were subject to molecular analyses that found significant overexpression of MYB and miR-155 in B-CLL and physical association of MYB with the promoter of MIR155 host gene (MIR155HG, also known as B-cell integration cluster). In CD19+ B-cells derived from healthy control individuals (N=13), MYB and miR-155 expression was significantly lower. Next, we found that MYB positively regulates MIR155HG transcription in reporter assays. The endogenous chromatin structure of the MIR155HG promoter in B-CLL cells is characterized by spreading of active chromatin mark, histone H3K9 acetylation. Gene expression arrays on B-CLL patients (N=11) identified a set of predicted miR-155 target genes (N=94) that are downregulated. Their expression pattern displayed significant negative correlation with pri-miR-155 levels. ...
2681 Mantle-cell lymphoma (MCL) is a lymphoma subtype with poor prognosis. Recently, new drugs ta... more 2681 Mantle-cell lymphoma (MCL) is a lymphoma subtype with poor prognosis. Recently, new drugs targeting at least partially the angiogenesis cascade have been successfully tested in the therapy of relapsed MCL patients, including temsirolimus, enzastaurin and lenalidomide. To reveal molecular mechanisms that regulate MCL-induced angiogenesis (and that might represent potential new druggable targets), we established and analyzed two mouse models of human MCL. Immunodeficient mice were subcutaneously (s.c.) xenografted with MCL cell lines JEKO-1 and HBL-2, and when tumor diameters reached 3cm in any size, the mice were sacrificed, and the excized tumors subjected to immunohistochemical (IHC) analysis. Alternatively, ex vivo obtained MCL cells were magnetically sorted using CD45 microbeads, and subjected to gene expression and flow cytometry analyses compared to the in vitro growing controls. IHC analysis proved that the tumors were neovascularized. Gene expression profiling by TaqMan ...
4600 MicroRNA miR-155 represents a candidate pathogenic factor in chronic lymphocytic leukemia (C... more 4600 MicroRNA miR-155 represents a candidate pathogenic factor in chronic lymphocytic leukemia (CLL) and lymphomas (Eis PS, et al. 2005, Fulci V, et al. 2007, Calin GA, et al. 2005, Kluiver J, et al. 2005, Metzler M, et al. 2004, van den Berg A, et al. 2003., Vargova K. et al 2011). In diffuse large B-cell lymphoma (DLBCL) expression of miR-155 was associated with NFkB pathway (Rai et al., 2008). In addition, increased miR-155 levels were associated with more aggressive (Activated B-cell like) DLBCL (Eis et al. 2005). The targets of up-regulated miR-155 apparently include a key hematopoietic transcription factor PU.1. Down-regulation of PU.1 represents an important and critical step for both myeloid as well as lymphoid tumorigenesis. We herein found the increased levels of miR-155 coupled with downregulation of its target PU.1 are frequent events in B cells of a vast majority of CLL patients (N=169). To advance understanding of miR-155 and PU.1 in lymphoid malignancies we studied ly...
Background Chronic lymphocytic leukemia (CLL) in most patients is diagnosed with early stage dise... more Background Chronic lymphocytic leukemia (CLL) in most patients is diagnosed with early stage disease identified incidentally on blood counts obtained for unrelated purposes. Immunophenotyping of peripheral blood (PB) is required for the diagnosis of CLL. A scoring system that helps in the differential diagnosis between CLL and other mature B-cell neoplasms (MBN) has been described twenty years ago (Matutes et al., Leukemia 1994; modified by Moreau et al., Am J Clin Pathol 1997). CLL/SLL typically demonstrates low-intensity staining for surface immunoglobulin, low or absent expression of CD22, CD79b and FMC7 and moderate to strong expression of CD5 and CD23. However, this phenotype is not entirely specific and some overlap in immunophenotype exists between CLL and non-CLL MBN. In particular, leukemic phase of CD5 positive mantle cell lymphoma (MCL) can be misdiagnosed as CLL. Recently, it has been shown that CD200 expression may help in differential diagnosis between CLL and other MB...
Trisomy 12 was found to be the most frequent chromosomal aberration identified by conventional cy... more Trisomy 12 was found to be the most frequent chromosomal aberration identified by conventional cytogenetic studies of bone marrow cells and peripheral lymphocytes of patients with CLL. Molecular-cytogenetic techniques which enable examination of dividing and/or non-diving interphase nuclei (I-FISH), proved existence of other chromosomal abnormalities, mainly deletions, which could have in CLL patients relation to the origin, course and prognosis of the disease. During the last two years bone marrow chromosomes of all patients with CLL were examined by G-banding and by I-FISH. The numerical changes of chromosome 12 were followed by centromeric DNA probe in dividing and non-dividing cells. The small deletions were ascertained by locus specific probes for 13q14 (Rb gene), 17p13 (p53 protein) and 11q23 (MLL gene). These genes are responsible for cell division and their function is probably in connection with neoplastic process. It is of interest whether numerical and structural chromoso...
The transcription factor PU.1 and its inhibitory microRNA-155 (miR-155) are important regulators ... more The transcription factor PU.1 and its inhibitory microRNA-155 (miR-155) are important regulators of B-cell differentiation. PU.1 downregulation coupled with oncogenic miR-155 upregulation has been reported in lymphoid malignancies; however, these data have not been studied across different subtypes in relation to clinical outcomes. We studied expression of miR-155 and PU.1 in the six most prevalent human B-cell lymphomas (n = 131) including aggressive (DLBCL, HL, MCL) and indolent (B-CLL/SLL, MZL, FL) types. Levels of miR-155 and PU.1 inversely correlated in DLBCL, B-CLL/SLL, and FL tumor tissues. In HL tissues, an exceptionally high level of miR-155 was found in patients with unfavorable responses to first-line therapy and those who had shorter survival times. PU.1 downregulation was noted in B-CLL/SLL samples positive for the adverse prognostic markers CD38 and ZAP-70. Upregulation of miR-155 and downregulation of PU.1 expression are integral aspects of lymphoma biology that could mark aggressive behavior of some, but not all, lymphoma types.
Hypermethylation of CpG islands within gene promoters is one of various mechanisms of gene silenc... more Hypermethylation of CpG islands within gene promoters is one of various mechanisms of gene silencing involved in the pathogenesis of human cancer. By using methylation-specific polymerase chain reaction we explored aberrant promoter methylation of five tumour suppressor genes in 29 patients with chronic lymphocytic leukaemia. Aberrant methylation of DLC1, SHP1, p15 and p16 occurred, respectively, in 89.7 %, 70 %, 62.1 % and 31 % of patients at diagnosis. Lamin A/C was unmethylated in all the samples. Hypermethylation of at least one gene was detected in 96.6 % of patients. Concurrent methylation of two or more genes correlated with Rai stage at diagnosis.
We report a unique case of indolent lymphoma with an unusual VDJ rearrangement. Polymerase chain ... more We report a unique case of indolent lymphoma with an unusual VDJ rearrangement. Polymerase chain reaction (PCR) analysis of bone marrow at the time of diagnosis was positive for both BCL-2/JH and CDRIII rearrangements. After treatment, the patient achieved complete remission (CR) with slow disappearance of both rearrangements (CDRIII and then BCL-2/JH). Subsequently, two new CDRIII rearrangements were detected in bone marrow, peripheral blood, and lymph node tissue. After this conversion, fluorescent activated cell sorting (FACS) analysis demonstrated monoclonal disease, suggesting that both CDRIII rearrangements originated from one cell. Histological evidence of a B-cell small lymphocytic lymphoma (B-SLL) infiltrate in the bone marrow became evident approximately 1 year after the two CDRIII rearrangements appeared. Direct sequencing revealed that one of the CDRIII sequences consisted of a VDVDJ rearrangement. This is the first report of such a rearrangement in a case of indolent ly...
The B-chronic lymphocytic leukemia (B-CLL) has highly variable prognosis. Possibility of more rel... more The B-chronic lymphocytic leukemia (B-CLL) has highly variable prognosis. Possibility of more relevant prognosis has a great impact for the beginning and mode of therapy. One hundred patients diagnosed as having B-CLL were included into the study. Beside usual examinations necessary to establish the diagnosis, cytogenetic examination for the detection of deletion 13q14, 17p13, 11q23 and trisomy 12 and immunophenotyping was done. The mean age of the patients was 58.2 years, there were 62 men and 38 women. 91 evaluated patients were divided into two groups--those with the steady disease (55 pts) and those with progressive disease (36 pts). No relation between the number of cytogenetic abnormalities and the Rai stage of the disease was found. We identified a relation between the bone marrow infiltration pattern (diffuse) and the number of cytogenetic abnormalities and the del 13q14 (p.05). Using the immunophenotyping of the lymphocytes we found a relation between the expression of CD38...
A case story of a patient with renal biopsy (RB) proven infiltration with lymphoma is given. RB i... more A case story of a patient with renal biopsy (RB) proven infiltration with lymphoma is given. RB in patient with known malignancy and onset of renal failure was indicated with regard to an atypical picture of kidney involvement (non-enlarged kidneys, without any structural changes typical for tumour mass presence). Though spread of the primary tumour to the kidney is not uncommon, involvement severe enough to impair renal function is unusual and occurs primarily with rapidly growing haematologic malignancies; diagnosis is being established by renal biopsy only rarely.
B-chronic lymphocytic leukemia (B-CLL) is the most common adult leukemia in the Western countries... more B-chronic lymphocytic leukemia (B-CLL) is the most common adult leukemia in the Western countries. Any routinely used staging system does not distinguish exactly the probable course of the disease at the time of diagnosis. Therefore the new prognostic factors, which help to assess the optimal therapeutic plan of patients, are searched intensively. We evaluated 154 patients with the B-CLL at the time of diagnosis--133 of them were retrospectively divided into two groups--one with stable form and the other with progressive form of the disease. We compared these two groups of patients with some of the prognostic factors (absolute lymphocyte count, the level of C-reactive protein, lactatdehydrogenase, beta-2-microglobulin, tumour necrosis factor, the immunoglobulin levels, the expression of CD38, FMC7, surface immunoglobulins, the type of bone marrow infiltration, and the cytogenetic abnormalities (trisomy 12, del(13)(q14), del(17)(p13) a del(11)(q23)). We found higher absolute lymphocy...
A number of prognostic scoring systems for patients with myelodysplastic syndrome (MDS) have been... more A number of prognostic scoring systems for patients with myelodysplastic syndrome (MDS) have been introduced since FAB classification of the MDS in 1982. Recently, the International Prognostic Scoring System (IPSS), published in 1997 by Greenberg et al. [9] is based on the percentage of bone marrow (BM) blasts, cytogenetic abnormalities and number of cytopenias. We applied criteria of the IPSS on 205 patients (pts) with primary MDS (RA = 82, RARS = 49, RAEB = 42, RAEB-t = 8, CMML = 24 pts). IPSS discriminated within each of the FAB-subgroups: RA pts were present in low risk and intermediate (Int) I and II risk subgroups, RARS pts were separated into low and Int I, RAEB were distributed predominantly between Int I and Int II risk groups, RAEB-t in high-risk group, and CMML pts were distributed in all groups. In contrary to Greenberg's group of the MDS patients there are only three risk-groups in our study: low risk (score 0-0.5), intermediate (1-2) and high risk (> 2); the med...
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Papers by Josef Karban