[Post-transplant lymphoproliferative disease in liver transplant recipients--Merkur University Hospital single center experience]. / Post-transplantacijska limfoproliferativna bolest u bolesnika s transplantacijom jetre - iskustvo KB Merkur.

Post-transplant lymphoproliferative disorder (PTLD) is an increasingly recognized condition as the number of solid organ and bone marrow transplant recipients increases. It can be a life threatening fulminant disorder and affects approximately 8% of solid organ transplant recipients. Epstein-Barr virus (EBV) is closely involved in the pathogenesis of PTLD and the majority of PTLD cases arise in response to primary infection with EBV or to re-activation of previously acquired EBV. The principal risk factors underlying the development of PTLD are the degree of overall immunosuppression and EBV serostatus of the recipient. The most commonly used pathologic classification of PTLD is the World Health Organization classification, which divides PTLD into three categories: early lesions, polymorphic PTLD, and monomorphic PTLD. Early lesions are characterized by reactive plasmacytic hyperplasia. Polymorphic PTLD may be either polyclonal or monoclonal and is characterized by destruction of the underlying lymphoid architecture, necrosis, and nuclear atypia. In monomorphic PTLD, the majority of cases (>80%) arise from B cells, similar to non-Hodgkin's lymphoma in immunocompetent hosts. The most common subtype is diffuse large B-cell lymphoma, but Burkitt's/Burkitt's-like lymphoma and plasma cell myeloma are also seen. Rarely T-cell variants occur, which include peripheral T-cell lymphomas and, rarely, other uncommon types, including gamma/delta T-cell lymphoma and T-natural killer (NK) cell varieties. Hodgkin's disease-like lymphoma is very unusual. An accurate diagnosis of PTLD requires a high index of suspicion, since the disorder may present subtly and/or extranodally. Radiologic evidence of a mass or the presence of elevated serum markers (such as increased LDH levels) are suggestive of PTLD, with positive finding on ultrasonography, computed tomography, magnetic resonance and/or positron emission tomography scanning (possibly indicating metabolically active areas) also favoring the diagnosis. The management of PTLD poses a major therapeutic challenge and although there is reasonable agreement about the overall principles of treatment, there is still considerable controversy about the optimal treatment of individual patients. EBV-related PTLDs are a significant cause of mortality in patients undergoing orthotopic liver transplantation with the observed mortality rate of up to 50%. This paper presents the experience acquired at Merkur University Hospital in the diagnosis and treatment of patients with liver transplantation and PTLD.

[Erythrocyte morphology in urine determined by light microscopy in patients with bladder cancer]. / Podrijetlo eritrocita u urinu odredivano svjetlosnim mikroskopom kod bolesnika s karcinomom mokracnog mjehura.

A finding of 80% or more of dysmorphic erythrocytes is assumed to point to kidney glomeruli, and of 80% or more of isomorphic erythrocytes to lower urinary tract as the origin of bleeding. In urine samples without significant origin of bleeding, there were 20%-80% of mixed results with both dysmorphic and isomorphic erythrocytes. The aim of the study was to show the origin of erythrocytes in malignant urine samples. Samples were fresh native urine sediment contrast stained with 0.1% safranin solution and analyzed under light microscope (X40). Out of 72 patients with malignant cells detected in urine, the origin of erythrocytes was identified in 25 patients (nine female and 16 male) through 90 samples (approximately 3-4 samples per patient); 26 (28.9%) samples did not have enough erythrocytes to define their origin, a mixed origin of erythrocytes was identified in 33 (36.7%) samples, dysmorphic erythrocytes were found in 25 (27.9%) samples, and isomorphic erythrocytes in 6 (6.3%) samples. In conclusion, there was no specific connection between malignant cell findings in urine and origin of erythrocytes. However, the high presence of mixed erythrocyte origin in malignant samples may suggest that the existence of a malignant process and renal disease should be taken in consideration.

[Acute plastic bronchitis--case report]. / Akutni odljevni bronhitis--prikaz bolesnika.

Plastic bronchitis is a rare disorder characterized by formation and sometimes dramatic expectoration of bronchial casts. It may occur at any age, but most published cases refer to pediatric population. We report a case of an 81-year-old man hospitalized at intensive care unit, who presented with the appearance of plastic bronchitis type I. He had profuse expectoration of several pieces, a few cm long and up to 1 cm wide, of wormlike reddish-brownish "tissue". Histologically, it was a slimy purulent secretion with abundant fibrin and blood and with cytopathic effect of herpes virus. The pathogenesis of plastic bronchitis is not clear.

[Isolated myeloid sarcoma involving the mediastinum]. / Izolirani mijeloidni sarkom medijastinuma.

Myeloid sarcoma is a rare extramedullary solid tumor consisting of immature myeloid cells and most commonly involving the bone, skin, lymph nodes, soft tissue, gastrointestinal tract and testis. Mediastinal myeloid sarcoma is very rare. There are two major types of myeloid sarcoma: granulocytic sarcoma and monoblastic sarcoma, according to immature cell type. Myeloid sarcoma is found in 2%-8% of patients with acute myeloid leukemia (AML). Myeloid sarcoma may develop before or concurrently with AML, or may be the initial manifestation of AML relapse in previously treated patients. Blast transformation of some form of myeloproliferative neoplasm or myelodysplastic syndrome may also manifest as myeloid sarcoma. A major differential diagnostic problem is isolated primary myeloid sarcoma without bone marrow and peripheral blood involvement, which may precede leukemic stage for months or years, and which is frequently misdiagnosed, mostly as malignant lymphoma. A case is presented of a 56-year-old female patient complaining of weakness, vertigo, dry cough and breathing difficulties. Clinical examination revealed enhanced vascular pattern on the right chest and right arm edema. Computed tomography (CT) of the thorax showed an expansive growth measuring 11 cm craniocaudally in the anterior mediastinum. Fine needle aspiration cytology of tumor mass yielded a scarcely cellular sample with individual atypical immature cells, fine chromatin structure and scarce cytoplasm with occasional granules and Auer rods. Considering the morphological, cytochemical and immunocytochemical characteristics of immature cells, the diagnosis of myeloid sarcoma was made and verified by histopathology of tumor biopsy sample. Immature cells were not found by analysis of bone marrow puncture sample, immunophenotyping of bone marrow cells and bone biopsy analysis. As immature cell proliferation was not detected in bone marrow and peripheral blood, while spread of the disease beyond the mediastinum was ruled out by imaging methods (CT, ultrasonography), it was decided to be a primary non-leukemic form of mediastinal myeloid sarcoma. Myeloid sarcoma should be taken in consideration on differential diagnosis of solid tumors because making an accurate diagnosis is necessary for timely initiation of appropriate therapy. Weakly expressed or lacking clear signs of myeloid differentiation may hamper morphological diagnosis. As isolated myeloid sarcoma is a very rare entity frequently resembling lymphoma in clinical presentation, it poses a major diagnostic challenge for both morphologists and clinicians.

[Acute renal failure as first manifestation of B-CLL]. / Akutno zatajenje bubrega kao prva manifestacija kronicne limfocitne leukemije.

In December 2005, the 55-year-old patient was hospitalized because of acute kidney failure and suspected hemorrhagic fever. The physical examination showed splenomegaly (spleen ultrasound-18 cm in large diameter, and 11 cm by palpation) with thrombocytopenia and anemia. He underwent kidney biopsy which described infiltration of small B cell lymphocytes with positive lambda chains. His bone marrow showed infiltration of atypical lymphocytes, and flow cytometry was typical of B-cell CLL. Patient started therapy with corticosteroids (methylprednisolone 80 mg iv) and continued treatment with prednisone (Decortin 20 mg tablets) and chlorambucil (Leukeran 16 mg tablets) through three days. An addition to therapy lead to an increase in platelet count, creatinine level decline and recovery of renal function was observed. He was treated with 6 cycles of therapy with prednisone and chlorambucil and achieved a satisfactory therapeutic effect with adequate hematologic parameters and less severe splenomegaly. Maintenance therapy was continued with prednison at daily dose of 10 mg. Our patient is one of the amongst previously reported as an example of a rare complication of CLL'with leukemic infiltrate causing acute renal insufficiency. Renal biopsy is necessary to confirm the diagnosis. This complication appears to respond well to a variety of treatments. Our patient achieved complete resolution of renal failure and partial hematological response with combination of chlorambucil and prednisone.

[Erythroblasts in the peripheral blood of adult patient as an adverse prognostic sign--a case report]. / Eritroblasti u perifernoj krvi odraslog bolesnika kao nepovoljan prognosticki predznak--prikaz bolesnika.

Red blood cells (RBC) normally lose their nuclei before appearing in peripheral blood. After having undergone differentiation in bone marrow, blood cells must cross the blood-marrow barrier to enter the bloodstream. Erythroblasts, or nucleated red blood cells (NRBC), do not distort easily, so they cannot escape this barrier. Therefore, with the exception of the neonatal period, the presence of NRBCs in peripheral blood is always a pathologic finding. NRBCs may be found in the course of severe diseases and are associated with poor prognosis and higher mortality. The underlying pathophysiology of NRBCs in peripheral blood is not fully understood. It is hypothesized that their appearance could be provoked by either increased erythropoiesis or bone marrow micro-architectural damage mostly caused by inflammation and/or decreased tissue oxygenation. In addition, it is known that the mortality is higher in NRBC-positive patients as compared with NRBC-negative patients. Hereby we present a patient admitted to the hospital with the symptoms of cardiac failure and decompensated liver cirrhosis. The patient was already known to have liver cirrhosis of ethylic etiology, cardiac decompensation caused by hypertensive heart disease with permanent atrial fibrillation, chronic obstructive pulmonary disease, diabetes mellitus type 2, and cholelithiasis. During hospital stay, the patient developed acute pancreatitis and, soon after that, a stroke with left hemiparesis followed by cardiopulmonary arrest. Then he was transferred to the intensive care unit. Despite appropriate therapy, intensive care treatment and cardiopulmonary support, the patient's general state worsened, he developed multiple organ failure and died on day 10 of intensive care unit stay. Three days earlier, NRBCs were detected in peripheral blood and their concentration increased during the next two days before death. NRBCs are known to appear 1-3 weeks before death, but their appearance does not seem to be related to one particular cause of death. Still, detection of NRBCs is an independent risk of poor outcome, where the mortality increases with the increasing NRBC concentration. Detection of NRBCs in blood is a relatively early phenomenon prior to death, so screening for NRBCs may aid in the early identification of patients at high risk, and in making duly decision for NRBC-positive patients to obtain ongoing intensive care treatment.

[Disseminated aspergillosis in a patient with simultaneous pancreas and kidney transplant]. / Diseminirana aspergiloza u bolesnice s transplantiranim bubregom i gusteracom.

A 31-year-old woman suffering from diabetes type1 and terminal kidney disease, with simultaneously transplanted kidney and pancreas, developed an episode of acute organ rejection caused by antibodies. The management of organ rejection was complicated by cytomegalovirus viremia, with accompanying leukopenia and neutropenia. The patient also developed invasive aspergillosis of the lungs, which progressed and disseminated hematogenously to the thyroid gland and the skin. Due to resistance to classical antimycotic therapy, the patient was treated with a combination of caspofungin and variconazole. In the beginning of treatment, the effects of this combined therapy were not evident due to strong immunosuppression caused by antimycotic immunoglobulin, which the patient had been administered on her previous hospital stay to treat acute kidney transplant rejection caused by antibodies, as well as due to immunosuppression caused by tacrolimus, mycophenolate mofetil and prednisone. On combined therapy with antimycotic drugs and supportive therapy, the patient was completely cured.

Flow cytometry immunophenotyping (FCI) of fine needle aspirates (FNAs) of lymph nodes.

Flow cytometry immunophenotyping (FCI) has an important role in the clinic work-up of fine needle aspirates (FNAs) of lymph nodes. Its standardization has been defined by proposed analytical protocols and procedures used to assure proper analytical results also in those non-routine samples. In Institute of Clinical Chemistry, "Merkur" University Hospital, FCI is accredited method according to laboratory accreditation standard ISO 15189. According to this laboratory accreditation standard, participation in external quality assessment (EQA) programs is a prerequisite for assuring integrity and quality of the entire laboratory process. A critical analysis of our institutional experience in the feasibility of FCI of the material obtained by FNA of lymph nodes with suspected lymphoma represented the purpose of the study. During an eight-year period in Institute of Clinical Chemistry, "Merkur" University Hospital, a total of 1295 FNA analysis was done, 245 of them with a possible diagnosis of B-cell Non-Hodgkin lymphomas (B-NHL) formed the basis of the study. Lymphocytes were isolated on density gradient according to Boyum et al. The average feasibility of FNAs for FCI analysis was 86% (ranged 78-93%). An acceptable total cell number in FNAs for FCI analysis (4257) was established. In total population of respondents statistical significances in expressions of cellular antigens CD3, CD5, CD22, CD23, CD19 and CD5 on B-cells (CD5+CD19+) between patient's with final diagnosis of benign, reactive lymphoid proliferations and patient's with diagnosis of B-NHL were found. EQA results analysis showed that all results were either inside target values (X +/- 1SD) or inside accepted values (X +/- 2SD). Compatibility of the restriction of immunoglobulins light chains determinated by FCI and cytomorphology diagnosis depends on the choice of criterion values of the light chains ratio which determine the monoclonality. According to the matrix of shares of all classified data of retained neural network, ranges of diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and prevalency of 82%, 72%, 93%, 48%, and 72% were produced. As a conclusion, FCI is a reliable methodology for phenotyping FNAs of lymph nodes with suspected B-NHLs detecting their clonality easily.

Role of fine needle aspiration cytology in management of hepatocellular carcinoma: a single centre experience.

Hepatocellular carcinoma (HCC) mostly occurs in chronic liver disease and cirrhosis. Liver resection and liver transplantation (LT) represent potentially curative treatments of choice and if not feasible, palliative strategies such as percutaneous interventional techniques (PITs) and chemotherapy (ChT) are considered. Elevated alfa-fetoprotein, typical imaging pattern, needle core biopsy (NCB) and fine needle aspiration cytology (FNAC) complement diagnostic assessment of HCC. We have retrospectively analyzed all patients with contraindications for NCB in which HCC was diagnosed by FNAC during consecutive 5 years in our hospital. Ultrasound guided FNAC provided a safe method of approach and, except for mild transitory discomfort at the site of puncture, no complications were documented. The diagnosis was established on May-Grünwald-Giemsa (MGG) stained aspirates and additional immunocytochemistry. Of our 62 patients, HCC developed in 61.3% cirrhotic and 38.7% non-cirrhotic livers. In the setting of cirrhosis 18.4% of patients underwent LT, 15.8% PITs, 26.3% ChT and 39.5% symptomatic therapy. In non-cirrhotic setting 46% of patients underwent liver resection, and PIT, ChT and symptomatic therapy were applied in 4%, 25%, 25% of cases, respectively. Pathohistology of resected and explanted livers (18 cases) confirmed the initial diagnosis made on FNAC. Since only early stage of HCC has a better prognosis, every effort should be made to establish prompt and accurate diagnosis. Our observations demonstrate that FNAC offers minimally invasive, rapid and uncomplicated diagnostic approach, with sensitivity from 67% to 93% and specificity from 96% to 100%. FNAC, is of utmost importance in the setting of abnormal coagulation tests and ascites commonly seen in advanced liver disease, facilitating diagnostic workup and treatment decisions.

Recurrent chromosomal abnormalities in lymphomas in fine needle aspirates of lymph node.

The detection of specific chromosomal abnormalities is important in the diagnostic workup of aggressive lymphomas, giving its impact on the treatment strategies and prognosis. This has been accomplished by using the fluorescent in situ hybridisation method (FISH) performed on fine needle aspiration (FNA) specimens what is attractive in the diagnosis of lymphoma in the comparation with other methods for collecting samples. The cytogenetic analyses were performed in series of 80 patients with lymphoma (43 women and 37 men, median age 48, range 3-90 years). In our series 89.0% (71) of the specimens yield sufficient numbers of analysable metaphases, comprising 63 non-Hodgkin lymphomas (NHL) and 8 examples of Hodgkin disease (HD). Among 71 successful karyotyped specimens 58 (82.0%) showed clonal karyotypic abnormalities. Numerical changes in 4, structural changes in 20 and both and numerical with structural changes in 30 of 54 NHL cases. Trisomies 3, 7, 8, 12, 18, X and monosomies 1 were most common numerical abnormalities. The NHL cases were typically characterised by structural rather than numerical aberrations with chromosome arms 1p/q, 3p/q, 6q, 11q, 17p and 14q most frequently involved. The expected translocation (14;18) (q32;q21) in 8 and t(8;14) (q24;q34) in 6 cases, both translocations at the same time in three cases, complex rearrangement with chromosome 8, 14, and 18, namely t(8;14;18) (q24;q32;q21) in one case, t(11;14) (q13;q32) in three and one case with translocation 14q32 with chromosome 3q27, 6q and 14q32 were found. In 28 of 54 (52%) NHL cases t(14;v) was present. Four abnormal clones detected in Hodgkin disease were typically consisted of a small percentage of metaphases. The use of FISH method enable the detection of loss or gain of genetic material and reveal rearrangements unsuspected by conventional cytogenetics in 34 (48.0%) cases.

Septic arthritis due to Streptococcus sanguis.

Septic arthritis may represent a direct invasion of joint space by various microorganisms, including bacteria, viruses and fungi. Although any infectious agent may cause bacterial arthritis, bacterial pathogens are the most significant because of their rapidly destructive nature. We present a case of septic arthritis in a 56-year old male patient due to Streptococcus viridans which is member of the viridans group streptococci. Patient was admitted to Our Hospital presented as fever of unknown origin, losing more than 30 kg of body weight during couple of months, and anemia of chronic disease as paraneoplastic process. He had long history of arterial hypertension and stroke. There was swelling and pain of the right sternoclavicular joint and precordial systolic murmur in physical status. A large diagnostic panel has been made, computerized tomography (CT) of right sternoclavicular joint showed widening of periarticular soft tissue and loss of clavicular corticalis. Cytologic analysis of synovial fluid showed more than 90% of polymorphonuclear leukocytes. There were no crystals on microscopic examination and Gram stain of fluid was negative. Blood cultures were positive for S. sanguis and there was a consideration about possible periodontal disease. Stomatologic examination verified periapical ostitis and extraction of potential cause of infection has been done. Therapy with benzilpenicilline was followed by the gradual improvement of clinical and laboratory parameters. Although viridans group streptococci and Streptococcus sanguis in particular are rare causes of septic arthritis in native joints, they should be considered in the differential diagnosis of periodontal disease.

Parvovirus B 19 (PVB19) induced pure red cell aplasia (PRCA) in immunocompromised patient after liver transplantation.

Presented here is a case of human parvovirus B19 (PVB19) induced pure red-cell aplasia (PRCA) in immunocompromised patient after orthotopic liver transplantation (OLT). PVB19 is a small, single-stranded DNA whose target cell is the erythroid progenitor in bone marrow. Manifestations of PVB19 infection vary with the immunologic status of the patient, ranging from asymptomatic to severe infections and PRCA. Post-transplant PRCA is induced either by immunosuppressive agents or PVB19. In the presented case, bone marrow aspiration characterized by the absence of mature erythroid precursors and detection of PVB19 DNA in blood led to treatment with high-dose intravenous human immunoglobulins (IVIG) and subsequent recovery of erythropoiesis. Due to insufficient antibody response in immunocompromised patients, suppression of the PVB19 infection is delayed and repetitive treatments may be administrated in attempt of reversing PRCA.

Morphometry of tumor cells in different grades and types of breast cancer.

The aim of the study was to compare morphometric characteristics of different types and grades of breast cancer. Morphometric analysis was performed using the SFORM software (Vamstec, Zagreb) on the May-Grünwald-Giemsa stained fine needle aspiration cytology (FNAC) breast tissue specimens. The study included 42 patients diagnosed with breast carcinoma by breast smear FNAC at Merkur University Hospital during the 2001-2005 period. Postoperative tumor histopathology and semi-quantitative tumor grading by the method of Elston and Ellis' showed invasive ductal carcinoma grade I in 10, invasive ductal carcinoma grade II in 9, invasive ductal carcinoma grade III in 13, and invasive lobular carcinoma in 13 patients, the latter also including a subtype of invasive tubulolobular carcinoma. The following parameters were assessed by use of Statistica 7.1 and chi2-test: tumor area, circumference, maximal radius, minimal radius, convexity, length, width, elongation, nucleus/cytoplasm ratio, and shape factor. Morphometric analysis yielded statistically significant differences among all study groups (p < 0.001). Morphometric parameters showed significant individual correlation with tumor type and grade, whereby the area, convexity and circumference were most significant at both nuclear and cellular level.

Cytogenetics of multiple myeloma.

Great studies of multiple myeloma (MM) strongly suggested that specific chromosomal changes are of prognostic significance in patients with MM1. We have performed cytogenetic analysis and recently fluorescent in situ hybridization (FISH) on 43 cases of MM. Clonal chromosomal changes were present in 24 (56%) cases. Hyperdiploid karyotype was found in 12 (50%) cases, hypodiploid in 8 (33%) cases, and 4 (17%) cases had a pseudodiploid karyotype. The most common numerical abnormalities were gains of whole chromosomes 15, 11, 3 and 6. Whole chromosome losses were also frequent involving chromosomes X, 13, 14, and 8. Most cases showed also structural rearrangements 71% (n = 17): del(1p), dup(1q), del(5q), del(13q), del(17p) and t(11;14)(q13;q32) (n = 4, 17%). Chromosome -13/13q deletion was found in 42% (n = 10) cases; complete loss of 13 was observed in 67% (n = 7) cases, whereas 33% (n = 3) had interstitial deletions. In the majority of the cases there was a mixture of abnormal and normal metaphases.

Epitheloid hemangioendothelioma in patient with liver transplantation.

Malignant hepatic epithelioid hemangioendothelioma (HEH) is a rare malignant tumor of vascular origin with unknown aetiology and a variable natural course. At the time of diagnosis, most patients present with multifocal tumours lesions that involve both liver lobes. From the therapeutic aspect, liver resection (LRx), liver transplantation (LTx), chemotherapy, radiotherapy, and/or immunotherapy have been used in the treatment of patients with HEH. However, because of the rarity of this tumor and its unpredictable natural history, it is impossible to assess the effectiveness of these respective therapies. In this report, our objective was to present clinical aspects, diagnostic options, therapeutic modalities, and the clinical outcome of single patient with LTx because of this rare tumor.

[Clinical and laboratory prognostic parameters for leukemic types of chronic lymphoproliferative diseases]. / Klinicki i laboratorijski prognosticki pokazatelji kronicnih leukemijskih limfoproliferativnih bolesti.

AIM: The aim of the study was to identify the clinical and laboratory (hematologic, biochemical and morphological) prognostic parameters of chronic leukemic lymphoproliferative diseases (CLLPD). METHODS: The study included 155 CLLPD patients. Analysis was performed in the overall CLLPD population and separately in a subgroup of patients with B chronic lymphocytic leukemia with variants (B-CLL+V) including typical B chronic lymphocytic leukemia (B-CLL), mixed chronic lymphocytic leukemia and prolymphocytic leukemia (CLL/PLL), and a variant of chronic lymphocytic leukemia with lymphoplasmocytoid differentiation (CLL/IMC). Kaplan-Meier method (Statistica 7.1) was used on survival analysis. RESULTS: Male patients older than 62 (p=0.03991), female patients (p=0.02871), patients not receiving antitumor therapy on study entry (p=0.01902) and patients not treated for CLLPB upon study entry (p=0.04076) showed better survival rate. Older patient predominated in the group requiring no antitumor therapy (p=0.019247). Analyis of sex distribution yielded an equal male to female ratio in the overall CLLPD population and B-CLL+V subgroup. Mann-Whitney U-test was used to assess the clinical significance of quantitative parameters related to patient age and sex. The level of bilirubin, the size of cervical lymph nodes and doubling of peripheral blood lymphocytosis (DTL) were lower in the group of older patients (>60 years). Men had higher levels of hemoglobin, bilirubin, SGOT and creatinine, and larger spleen and liver. Statistically significant survival differences were recorded for 16 of 20 clinical parameters. Patients older than 60, female patients and patients receiving no antitumor therapy showed better survival. Lower clinical stage according to Rai and Binet and total tumor mass (TTM) lower than 9 indicated better prognosis, whereas patients with spleen enlargement and multiple regions involved with lymph node enlargement showed poorer survival. B-CLL+V patients and patients free from doubling of total tumor (DTM) or of absolute lymphocyte count (DTL) within 12 months had better survival than the overall CLLPD patient population. A statistically significant survival difference was recorded for 5 of 15 bone marrow (BM) parameters tested: normal and less cellular BM puncture specimen, >70% of all lymphatic cells, >16% of atypical lymphatic cells, and >18% of granulocytes in myelogram indicated better prognosis. Poorer disease outcome was associated with interstitial and nodular infiltration found on bone biopsy. Ten of 20 hematologic parameters were found to be statistically significant. Poorer prognosis was associated with red blood cell count <2.5 x 10(12)/L, leukocyte count >100 x 10(9)/L, reticulocyte count >5/10(3) E, hemoglobin <100 g/L and iron <15 mol/L. Better survival was associated with absolute count of total lymphatic cells <100 x 10(9)/L and absolute count of atypical lymphatic cells <5 x 10(9)/L in peripheral blood; <10% of all atypical lymphatic cells, >5.1% monocytes and >10.1% granulocytes in differential blood count. Statistically significant survival differences were found for 10 of 20 biochemical parameters tested. Poorer survival was recorded in patients with LDH >300 U/L, SGOT >24 U/L, calcium <2.3 mmol/L, total protein <66.1 g/L, albumin <40 g/L, alpha2 globulin<5.9 g/L, beta globulin <7.3 g/L, y globulin <9 g/L and IgG <10 g/L. Better prognosis was only indicated by lower levels of IgM (<0.91 g/L). CONCLUSION: Careful clinical examination is an important step on assessing the extent and progression of the disease, and a major chain on tailoring individualized therapeutic approach, along with clinical stages according to Rai and Binet, CLLPD subtype and progression factors (DTM and DTL). Laboratory parameters (hematologic and biochemical) as objective quantitative parameters obtained by simple venipuncture, in contrast to the 'researcher-dependent' ones, increase the utilization of some of these parameters as risk factors in CLL.