New parameters of diploid histogram of image DNA cytometry and newly characterized types of nucleolar organizer region structures in defining the proliferative-kinetic index in chronic leukemic lymphoproliferative disorders.

OBJECTIVE: To introduce new parameters of diploid histogram of image DNA cytometry and new types of silver-stained nucleolar organizer regions (AgNORs) and to validate resulting proliferative-kinetic index (PKI) in a prognostic study of patients with chronic leukemic lymphoproliferative disorders (CLLPD). STUDY DESIGN: A total of 413 smears of from various tumor mass compartments-bone marrow, peripheral blood and lymph node-were analyzed in CLLPD as a whole, as well as separately in the B-chronic lymphocytic leukemia with variants (B-CLL+V). The analysis of the diploid histogram included percentage of cells at the peak of the DNA histogram and percentage of cells with lower and higher contents of DNA than cells at the peak. The new types of AgNORs were described as homogeneous, inhomogeneous and annular. RESULTS: The newly introduced parameters of DNA and AgNOR are significant predictors of survival. Based on the most representative AgNOR and DNA characteristics related to survival, the PKI score was calculated. The CLLPD and B-CLL+V patients had a statistically significantly better prognosis when PKI was < 4. CONCLUSION: PKIs have confirmed the hypothesis that different prognostic subgroups could be identified within the homogeneous groups of neoplasms with relatively low malignancy (CLLPD and B-CLL+V).

[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.