the international workshop on chronic lymphocytic leukemia ( iwcll ) changed the diagnosis of cll to require a peripheral blood b - cell count of 510/l and the presence of monoclonal b - cells that have the typical immunophenotype of cll cells ( cd19 + , cd5 + , cd23 + , and decreased expression of surface ig , cd20 , and cd79b ) . cd5 is characteristically only expressed in cll and mantle cell lymphoma ( mcl ) , thereby distinguishing these entities from other small chronic b - cell lymphoproliferative disorders . however , several recent studies of patients diagnosed with cll based on clinical presentation and morphologic features have identified a subset of cd5-negative clls [ 49 ] . cll generally runs an indolent clinical course , with most patients not requiring therapy for a long time . cd5-negative b - cll is often associated with an aggressive clinical course [ 1113 ] . on the other hand , information about biological differences , clinical differences , and the incidence of these two clinical entities classified according to cd5 expression is limited , and the data are contradictory . we report here a series of 19 cd5-negative b - cll cases and compare their clinical , biological , and prognostic characteristics with a control group of 105 cases of cd5-positive b - cll . the hematology department of the yuzuncu yil university , medical faculty , turkey , conducted this study retrospectively . the files and data in hospital record systems on 124 patients who were followed up with the diagnosis of cll between 2009 and 2015 in our clinic were examined retrospectively . the procedures followed were in accordance with the helsinki international ethical standards on human experimentation . the patients were classified into two groups , cd5-negative and cd5-positive b - cll , based on the data of 124 patients . in our study , lack of cd5 expression there were 19 patients in the cd5-negative b - cll group and 105 patients in the cd5-positive b - cll group , which was selected as a control group . routine hematological , biochemical , and immunological studies were performed for all patients , including hemogram , direct coombs test , serum protein electrophoresis , peripheral blood smears , serum ldh , and bilirubins . immunophenotyping of peripheral blood was performed in patients with b - cll by four - color multiparameter flow cytometry analysis using a panel of monoclonal antibodies . antibodies for cd5 , cd19 , cd23 , cd20 , cd10 , and sm igm were used for all cases . statistical analysis was performed using the spss 19.0 software package . for the studied clinical and hematological parameters , after this test , for the parameters that the normality assumption met , the independent samples t - test was performed for the differences between cd5-negative and cd5- positive b - cll patients . however , the mann - whitney u test , which is a non - parametric test , was also performed for the parameters that the normality assumption violated . survival was analyzed using the kaplan - meier method , and the log - rank test was used to compare survival curves . the hematology department of the yuzuncu yil university , medical faculty , turkey , conducted this study retrospectively . the files and data in hospital record systems on 124 patients who were followed up with the diagnosis of cll between 2009 and 2015 in our clinic were examined retrospectively . the procedures followed were in accordance with the helsinki international ethical standards on human experimentation . the patients were classified into two groups , cd5-negative and cd5-positive b - cll , based on the data of 124 patients . in our study , lack of cd5 expression there were 19 patients in the cd5-negative b - cll group and 105 patients in the cd5-positive b - cll group , which was selected as a control group . routine hematological , biochemical , and immunological studies were performed for all patients , including hemogram , direct coombs test , serum protein electrophoresis , peripheral blood smears , serum ldh , and bilirubins . immunophenotyping of peripheral blood was performed in patients with b - cll by four - color multiparameter flow cytometry analysis using a panel of monoclonal antibodies . antibodies for cd5 , cd19 , cd23 , cd20 , cd10 , and sm igm were used for all cases . statistical analysis was performed using the spss 19.0 software package . for the studied clinical and hematological parameters , after this test , for the parameters that the normality assumption met , the independent samples t - test was performed for the differences between cd5-negative and cd5- positive b - cll patients . however , the mann - whitney u test , which is a non - parametric test , was also performed for the parameters that the normality assumption violated . survival was analyzed using the kaplan - meier method , and the log - rank test was used to compare survival curves . a total of 124 patients ( 83 males and 41 females ) with a diagnosis of b - cll were included in this study . there were 105 patients in the cd5-positive b - cll group , which served as a control group . the mean ages of cd5-negative and cd5-positive patients were found to be similar ( p=0 . 339 ) cd5-negative and cd5-positive b - cll patients were evaluated according to the binet staging system . we did not find a statistically significant difference between the two groups in terms of stage a , b , and c ( p=0.118 , p=0.051 , and p=0.882 , respectively ) . we found a statistically significant difference between the two groups in terms of lymph node involvement ( p=0.029 ) . patients with cd5-positive b - cll more frequently had isolated lymphadenopathy at diagnosis ( p=0.005 ) . similarly , extensive lymph node involvement ( three or more regions ) was found more frequently in the cd5-positive b - cll group ( p=0.030 ) . patients with cd5-negative b - cll more frequently had both total and isolated splenomegaly ( p=0.029 and p=0.033 , respectively ) . there was no significant difference between the two groups in terms of association of splenomegaly and lymphadenopathy ( p=0.860 ) . the mean hemoglobin level and neutrophil count did not differ between the two groups ( p=0.180 and p=0.169 , respectively ) . autoimmune hemolytic anemia ( aiha ) and autoimmune thrombocytopenia ( aitp ) were observed similarly in both groups ( p=0.790 and p=0.526 , respectively ) . hematological parameters and autoimmune manifestations of patients are shown in table 2 . in five - year follow - up , 84.2% of cd5-negative patients and 90.5% of cd5-positive patients were alive ( table 3 ) . there was no statistical difference between the groups in terms of survival data at five - year follow - up ( p=0.393 ) ( figure 1 ) . the defining feature of the b - cll clone is the co - expression of cd19 , cd20 , cd5 , and cd23 . the levels of surface immunoglobulin , cd20 , and cd79 are characteristically low compared to those found on normal b cells . some patients diagnosed with cll according to clinical and morphological features have cd5-negative clonal b cells in the peripheral blood . the incidence of cd5-negative b - cll varies from 7% to 20% [ 1719 ] . contradictory results have been found in these studies due to disagreement mainly on the definition of cd5 negativity [ 12,17,1921 ] . efstathiou et al . defined cd5 negativity as the expression of cd5 by fewer than 5% of cells . cartron et al . used the same concept , studying a group of 42 cd5-negative b - cll patients . some authors accept a cut - off value of 20% to 30% for cd5 positivity . in our study , cd5 negativity was defined as a situation where fewer than 20% of cells expressed cd5 . similarly , we also found the incidence of splenomegaly to be higher in cd5-negative cll patients compared to the cd5-positive group . on the other hand , we found that isolated splenomegaly was also more common in the cd5-negative group , similar to total splenomegaly ( spleen + lymph node ) . similarly , cartron et al .   also found that isolated splenomegaly was more common in the cd5-negative group . isolated splenomegaly is seen more often in some types of non - hodgkin lymphoma ( nhl ) rather than cll . thus , these nhl types were taken into consideration in differential diagnosis , and these entities were eliminated with appropriate tests . lymphadenopathy was detected to be present less frequently in cd5-negative patients compared to cd5-positive patients in two previously conducted studies . we also found a higher rate of lymphadenopathy in cd5-positive patients compared to cd5-negative patients . some authors reported that cd5-negative b - cll patients had a more advanced stage of disease . similarly , it was pointed out in another study that cd5 negativity was associated with shorter survival and a more advanced stage of disease . unlike these studies , some other studies reported that cd5-negative patients had an earlier stage of disease compared to cd5-positive patients . there was no difference between the groups in terms of disease stages in our study . although there was an accumulation of stage b disease in the cd5-positive group , it was not significant cd5-negative patients were found to have less hemoglobin than cd5-positive patients in two previously conducted studies . on the other hand , frequency of anemia among cd5-positive patients was reported to be higher than that among cd5-negative patients in another study . unlike these studies , cartron et al .   found no difference between the groups in terms of hemoglobin , neutrophils , lymphocytes , and thrombocyte count . we found no difference between these two entities in terms of hemoglobin and neutrophil count . however , we detected a higher lymphocyte count and a lower thrombocyte count in the cd5-negative group . the most common complication is aiha ( about 7% ) , whereas the incidence of aitp , and particularly autoimmune neutropenia and pure red cell aplasia , is lower in most studies ( < 12% ) [ 2529 ] . in our study , the rate of autoimmune hemolytic anemia was 4% and the rate of immune thrombocytopenia was 2.4% in all cll patients . there have been a very limited number of studies investigating differences in autoimmune manifestations in cd5-negative and cd5-positive subgroups . therefore , it is difficult to make general conclusions . there was no difference between the groups in terms of autoimmune manifestations in our study . similar to our study , there was no difference between cd5-negative and cd5-positive groups in terms of autoimmune manifestations in another study . on the other hand , the incidence of hemolytic anemia was found to be significantly higher in cd5-positive patients , but there was no other immunological difference in the other study . there have been studies reporting that cd5-negative patients have better , worse , or similar survival ratios compared to cd5-positive patients . for instance , kurec et al .   found that 5-year survival was worse in the cd5-negative cll group . cd5-negative patients survived an average of 13 months longer compared to cd5-positive patients in another study . there was no difference between the groups in terms of survival considering 5-year follow - up data in our study . similarly , there was no survival difference between the two groups in two previously conducted studies . we found more isolated splenomegaly , less lymphadenopathy , a higher lymphocyte count , and a lower thrombocyte count in the cd5-negative group . there was no difference between the groups in terms of clinical stage , autoimmune phenomena , hemoglobin and neutrophil count , and survival . since there were fewer cd5-negative patients in our study and there have been different results in the literature , it is necessary to conduct an extensive prospective study in order to identify clinical and biological effects of cd5-negative cll .
backgroundchronic lymphocytic leukemia ( cll ) usually expresses cd5 antigen . 
 however , 720% of patients are cd5 negative . 
 we report here a series of 19 cd5-negative b - cll cases.material/methodswe reviewed 19 consecutive cd5-negative b - cll cases seen in our medical center from 2009 to 2015 and compared them with 105 cd5-positive b - cll cases . 
 the two groups were compared in terms of clinical parameters , laboratory parameters , and survival characteristics.resultslymphadenopathy was present in 31.5% of the cd5-negative group and 51.4% of the cd5-positive group ( p=0.029 ) . 
 splenomegaly was present in 42.1% of the cd5-negative group and 16.1% of the cd5-positive group ( p=0.029 ) . 
 there was no difference between the groups in terms of binet a , b , and c stages ( p=0.118 , p=0.051 , and p=0.882 , respectively ) . 
 the median thrombocyte count was 144109/l and 160109/l in the cd5-negative and cd5-positive groups , respectively ( p=0.044 ) . 
 there was no difference between the two groups in terms of median neutrophil count ( p=0.169 ) . 
 the mean lymphocyte count was 43.24.0109/l and 36.73.2109/l in the cd5-negative and cd5-positive groups , respectively ( p=0.001 ) . 
 there was no difference between the groups in terms of autoimmune hemolytic anemia and autoimmune thrombocytopenia . in five - year follow - up , 
 84.2% of cd5-negative patients and 90.5% of cd5-positive patients were alive ( p=0.393).conclusionswe found more isolated splenomegaly , less lymphadenopathy , a higher lymphocyte count , and a lower thrombocyte count in the cd5-negative group . 
 there was no difference between the groups in terms of clinical stage , autoimmune phenomena , hemoglobin and neutrophil count , and survival .