• Ika Kardum-Skelin, Ana Planinc-Peraica, Ostojić Kolonić Slobodanka S, Delfa Radić-Kristo, Marina Milas, Radovan Vrhovac, Dunja Sustercić, Hrvoje Minigo, and Branimir Jaksić.
• Klinicka bolnica Merkur, Zagreb, Hrvatska. ikardum@hi.t-com.hr
• Acta Med Croatica. 2008 Oct 1; 62 (4): 351-64.

AimThe aim of the study was to identify the clinical and laboratory (hematologic, biochemical and morphological) prognostic parameters of chronic leukemic lymphoproliferative diseases (CLLPD).MethodsThe 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.ResultsMale 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).ConclusionCareful 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.

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