Evaluation of Absolute Neutrophil, Lymphocyte and Platelet Count and Their Ratios as Predictors of Thrombotic Risk in Patients with Prefibrotic and Overt Myelofibrosis.

AIM: To investigate the prognostic contribution of absolute neutrophil (ANC), lymphocyte (ALC), platelet count and their ratios, neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), to thrombotic risk in patients with prefibrotic and overt fibrotic myelofibrosis (MF). METHODS: We retrospectively analyzed a cohort of 256 patients with prefibrotic (85 patients) and overt fibrotic MF (171 patients) treated in six Croatian hematological centers. RESULTS: Prefibrotic compared to overt fibrotic MF patients presented with significantly higher ALC, platelet count and PLR, and experienced longer time to thrombosis (TTT). Among prefibrotic patients, ANC > 8.33 × 109/L (HR 13.08, p = 0.036), ALC > 2.58 × 109/L (HR 20.63, p = 0.049) and platelet count > 752 × 109/L (HR 10.5, p = 0.043) remained independently associated with shorter TTT. Among overt fibrotic patients, ANC > 8.8 × 109/L (HR 4.49, p = 0.004), ALC ≤ 1.43 × 109/L (HR 4.15, p = 0.003), platelet count ≤ 385 × 109/L (HR 4.68, p = 0.004) and chronic kidney disease (HR 9.07, p < 0.001) remained independently associated with shorter TTT. CONCLUSIONS: Prognostic properties of ANC, ALC and platelet count are mutually independent and exceed those of NLR and PLR regarding thrombotic risk stratification. ALC and platelet count associate in opposite directions with thrombotic risk in prefibrotic and overt fibrotic MF patients.

Reduced Corticosteroid Exposure Is Safe and Does Not Reduce Disease Control among Hodgkin Lymphoma Patients Treated with Escalated BEACOPP (eBEACOPP).

Background and Objectives: eBEACOPP is the most effective chemotherapy regimen for younger patients with early unfavorable (EU) and advanced-stage (AS) Hodgkin lymphoma (HL), albeit with significant toxicities. The 14-day/cycle prednisone course contributes to side effects, including osteoarticular events like avascular bone necrosis (AVN). Our center has been using eBEACOPP since 2009 for AS and 2014 for EU patients. In 2016, we reduced prednisone treatment to 7-10 days to lessen AVN risk. We analyzed the effects of this approach. Materials and Methods: We retrospectively collected data on patients who received at least two cycles of eBEACOPP for first-line HL treatment. Results: A total of 162 patients (33 EU, 129 AS) were included. Their median age was 31 (range 19-59 years), and 88 were males. A total of 94 patients received full corticosteroid courses, and 68 received reduced corticosteroid courses. The overall response rate (ORR) was 98%. Different corticosteroid dosings had no significant effect on ORR, febrile neutropenia episodes, or hospital admissions. After a median follow-up (mFU) of 58 months, the 5yPFS for the entire cohort was 98% vs. 95% for the standard course vs. the short corticosteroids course, respectively (p = 0.37), while the 5yOS was 98% vs. 99% for the standard course vs. short corticosteroids course, respectively (p = 0.87). In AS patients intended to be treated with six eBEACOPP cycles, 5yPFS and 5yOS were 100% vs. 97% and 100% vs. 99% for standard vs. short corticosteroid courses, respectively (p = 0.56 and p = 0.17). In EU patients, 5yPFS was 97% (standard) vs. 95% (short) (p = 0.98) and 5yOS 100% vs. 93.3% (p = 0.87). Osteoarticular events were numerically lower in patients receiving the shorter prednisone course, both in the whole cohort and in the subgroup of patients treated with six cycles of eBEACOPP, but this difference failed to reach statistical significance. Conclusions: eBEACOPP provides excellent and durable first-line disease control. Shortening the corticosteroid course does not compromise efficacy, potentially reducing toxicity. However, longer follow-ups and larger studies are needed for confirmation.

Treatment-Related Risk Factors for Adverse Outcomes of COVID-19 in Patients Treated for Lymphoid Malignancies in the Pre-Omicron Era-A Study of KroHem, the Croatian Group for Hematologic Diseases.

Patients with lymphoid malignancies are at increased risk of death or prolonged infection due to COVID-19. Data on the influence of different antineoplastic treatment modalities on outcomes are conflicting. Anti-CD20 monoclonal antibodies increase the risk of prolonged infection. It is unclear whether this risk is affected by the choice of the antibody (rituximab vs. obinutuzumab). To elucidate the role of antineoplastic therapy on COVID-19 outcomes, KroHem collected data on patients with lymphoid malignancies diagnosed with COVID-19 between October 2020 and April 2021. A total of 314 patients were identified, 75 untreated, 61 off treatment and 178 on treatment. The mortality rate in untreated and off-treatment patients was 15% and 16%; 9% and 10% had prolonged infection. In the on-treatment group, 3% were still prolonged positive at time of data collection, 62% recovered and 35% died; 42% had prolonged infection. Disease type, use of anti-CD20 monoclonal antibodies, prior autologous stem-cell transplantation (ASCT) and line of treatment did not significantly affect mortality. Mortality was higher in older patients (p = 0.0078) and those treated with purine analogues (p = 0.012). Prolonged COVID-19 was significantly more frequent in patients treated with anti-CD20 monoclonal antibodies (p = 0.012), especially obinutuzumab, and purine analogues (p = 0.012). Age, prior ASCT and treatment line did not significantly affect risk of prolonged infection. These data suggest that increased age and use of purine analogues are main risk factors for increased mortality of COVID-19 in patients with lymphoid malignancies. Obinutuzumab further increases the risk of prolonged disease, but not of death, in comparison to rituximab. Epidemiological considerations should be taken into account when choosing the appropriate antineoplastic therapy for patients with lymphoid malignancies.

CHRONIC MEDICAL CONDITIONS IN CROATIAN WAR VETERANS COMPARED TO THE GENERAL POPULATION: 25 YEARS AFTER THE WAR.

Many published reports have documented an increased prevalence of chronic medical conditions among veterans, but there were only a few studies that compared these increases with the general population. The aim of this study was to determine differences in chronic medical conditions between Croatian war veterans and the general population. This study included two groups of subjects, i.e. 1453 participants who are Croatian war veterans and 1429 participants from the general population. Medical history, physical examination, laboratory tests and specific diagnostic procedures were taken during systematic physical examination in both groups. The prevalence of hypertension, diabetes, hyperlipidemia, hypothyroidism and hyperthyroidism, chronic obstructive pulmonary disease, coronary heart disease, malignancy, psychiatric diseases, cholelithiasis, nephrolithiasis, smoking and alcohol consumption was analyzed. Croatian war veterans were found to be more likely to develop hypertension than individuals in the general population (29.5% vs. 24.3%), as well as diabetes (7.3% vs. 3.8%), hyperlipidemia (56.4% vs. 27.3%), hyperthyroidism (3.1% vs. 0.8%), coronary heart disease (4.3% vs. 1%), malignancy (4.1% vs. 2.2%), psychiatric diseases (15.4% vs. 1.1%), and alcohol consumption (53% vs. 29%). Significant difference was found in favor of the general population for hypothyroidism (14.3% vs. 8%). There were no differences in the prevalence of chronic obstructive pulmonary disease, cholelithiasis, nephrolithiasis, and smoking. Our findings confirmed the hypothesis of a higher prevalence of cardiovascular diseases, malignancy and psychiatric diseases among Croatian war veterans and emphasized the need of better control of their medical conditions.

High platelet-to-lymphocyte ratio may differentiate polycythemia vera from secondary polycythemia.

Discriminating polycythemia vera (PV) from secondary polycythemia (SP) is crucial due to the inherent risk of thrombosis in PV and different treatment approaches. The majority of PV patients have subnormal serum erythropoietin levels and harbor Janus kinase 2 (JAK2) mutations; however, serum erythropoietin levels may be normal in approximately one third of PV patients and mutational analysis is costly and requires access to specialized laboratories. Recently, neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte ratios (PLR) emerged as rapidly available biomarkers to identify PV patients under an increased risk of thrombosis and death. This multicenter retrospective study investigated whether these two biomarkers may also be used to differentiate PV from SP. A total of 207 subjects were included (103 PV and 104 SP) with both baseline NLR (median 4.33 vs. 1.89) and PLR (median 259.12 vs. 81.11) being significantly higher in PV than in SP (p < 0.001 for both analyses). According to the receiver operating curve analysis, PLR (area under the curve, AUC 0.936, the optimal cut-off value of > 138.1 had 82.5% sensitivity and 91.67% specificity for the detection of PV) outperformed other tested variables (NLR, total leukocytes, neutrophils, lymphocytes and platelets) and its cut-off values with 100% specificity and sensitivity were able to confirm (PLR > 224.56; 31% patients) and to exclude (PLR < 68.8; 13% patients) the highest proportions of PV patients. Therefore, PLR may represent a cheap and a rapidly available biomarker with valuable diagnostic and prognostic properties. This information may be particularly useful in resource-limited settings; however, our results need validation on larger datasets.

Hematocrit to hemoglobin ratio as a prognostic marker in polycythemia vera.

BACKGROUND: The hematocrit to hemoglobin ratio (HHR) is frequently used in everyday practice to measure hemoconcentration; however, clinical associations of HHR in the context of polycythemia vera (PV) have not been investigated so far. PATIENTS AND METHODS: We retrospectively assessed HHR at the time of diagnosis in 107 PV and 40 secondary polycythemia (SP) patients from three community hospitals. RESULTS: Median HHR was higher in PV than in SP patients (3.131 vs. 2.975, p = 0.041). Among PV patients, higher HHR correlated with splenomegaly, higher total leukocyte and absolute granulocyte counts, higher red blood cell counts, lower hemoglobin, higher red blood cell distribution width, lower mean corpuscular hemoglobin and lower ferritin levels, whereas in SP patients higher HHR correlated with older age, female sex and lower hemoglobin (p < 0.050 for all analyses). Using the receiver operating curve analysis-defined cut-off points, higher HHR in PV was associated with a shorter time to thrombosis (hazard ratio-HR 5.20, p = 0.022) independently of high-risk disease status (HR 4.48, p = 0.034) and shorter overall survival (HR 6.69, p = 0.009) independently of leukocytosis (HR 4.48, P = 0.034) and the absence of aspirin use (HR 15.53, p < 0.001). CONCLUSION: Higher HHR may represent iron deficiency and a stronger clonal myeloproliferation in PV and could provide additional prognostic information to the classical risk assessment.

Higher serum uric acid is associated with higher risks of thrombosis and death in patients with primary myelofibrosis.

BACKGROUND: Serum uric acid (SUA) can promote inflammation and is associated with increased cardiovascular morbidity. Primary (PMF) and secondary myelofibrosis (SMF) are myeloproliferative neoplasms characterized by high cellular turnover and substantial risk of thrombosis and death. METHODS: We have retrospectively investigated SUA in 173 patients with myelofibrosis (125 PMF; 48 SMF) and 30 controls. RESULTS: The PMF patients had significantly higher SUA in comparison to SMF and controls. In both PMF and SMF higher SUA was significantly associated with arterial hypertension and decreased renal function. Among PMF patients, higher SUA was significantly associated with older age, larger spleen, higher white blood cell counts, higher lactate dehydrogenase, lower immunoglobulin G levels, allopurinol use and non-smoking. Among SMF patients, higher SUA was associated with male sex (P < 0.05 for all analyses). In PMF higher SUA was univariately associated with inferior survival (> 427 µmol/L hazard ratio (HR) = 2.22; P = 0.006) and shorter time to thrombosis (> 444 µmol/L HR = 5.05; P = 0.006), which could be shown separately for arterial (> 380 µmol/L; HR = 4.9; P = 0.013) and venous thromboses (> 530 µmol/L; HR = 17.9; P < 0.001). In multivariate analyses, SUA remained significantly associated with inferior survival independent of the Dynamic International Prognostic Staging System and with shorter time to thrombosis independent of age in PMF patients; however, the prognostic significance of SUA was diminished after including serum creatinine in the models. SUA was not prognostic in SMF patients. CONCLUSION: The PMF patients present with higher SUA levels, which are associated with features of more advanced disease and higher risks of arterial and venous thrombosis and death.