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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.
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Enfermedad de Hodgkin , Masculino , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Femenino , Enfermedad de Hodgkin/tratamiento farmacológico , Prednisona/efectos adversos , Estudios Retrospectivos , Ciclofosfamida/efectos adversos , Vincristina/efectos adversos , Bleomicina/efectos adversos , Doxorrubicina/efectos adversos , Corticoesteroides/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Resultado del TratamientoRESUMEN
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.
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Colelitiasis , Enfermedad Coronaria , Diabetes Mellitus , Hiperlipidemias , Hipertensión , Hipertiroidismo , Hipotiroidismo , Neoplasias , Nefrolitiasis , Enfermedad Pulmonar Obstructiva Crónica , Trastornos por Estrés Postraumático , Veteranos , Humanos , Veteranos/psicología , Croacia/epidemiología , Enfermedad Crónica , Hiperlipidemias/epidemiología , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/psicologíaRESUMEN
We retrospectively investigated a cohort of 176 myelofibrosis patients (128 primary-PMF; 48 secondary-SMF) from five hematology centers. The presence of chronic kidney disease (CKD) was determined in addition to other clinical characteristics. CKD was present in 26.1% of MF patients and was significantly associated with older age (P < 0.001), higher WBC (P = 0.015), and its subsets (neutrophil, monocyte, and basophil counts), higher platelets (P = 0.001), lower albumin (P = 0.018), higher serum uric acid (P = 0.001), higher LDH (P = 0.022), and the presence of CV risk factors (P = 0.011). There was no significant association with driver mutations, degree of bone marrow fibrosis, PMF/SMF, or DIPSS risk categories (P > 0.05 for all analyses). The presence of CKD was significantly associated with shorter time to arterial (HR = 3.49; P = 0.041) and venous thrombosis (HR = 7.08; P = 0.030) as well as with shorter overall survival (HR 2.08; P = 0.009). In multivariate analyses, CKD (HR = 1.8; P = 0.014) was associated with shorter survival independently of the DIPSS (HR = 2.7; P < 0.001); its effect being more pronounced in lower (HR = 3.56; P = 0.036) than higher DIPSS categories (HR = 2.07; P = 0.023). MF patients with CKD should be candidates for active management aimed at the improvement of renal function. Prospective studies defining the optimal therapeutic approach are highly needed.
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Riñón/fisiología , Mielofibrosis Primaria/mortalidad , Insuficiencia Renal Crónica/mortalidad , Trombosis/mortalidad , Anciano , Estudios de Cohortes , Femenino , Tasa de Filtración Glomerular/fisiología , Humanos , Masculino , Persona de Mediana Edad , Mielofibrosis Primaria/diagnóstico , Mielofibrosis Primaria/fisiopatología , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Trombosis/diagnóstico , Trombosis/fisiopatologíaAsunto(s)
Neutrófilos , Mielofibrosis Primaria , Humanos , Mielofibrosis Primaria/sangre , Mielofibrosis Primaria/patología , Mielofibrosis Primaria/diagnóstico , Neutrófilos/patología , Recuento de Linfocitos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Recuento de Leucocitos , Pronóstico , Factores de Edad , Anciano de 80 o más Años , AdultoAsunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Flebotomía/métodos , Policitemia Vera/diagnóstico , Policitemia Vera/terapia , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
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.
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Background: This study aimed to evaluate the clinical and prognostic associations of the systemic inflammatory index (SII) in polycythemia vera (PV) patients. SII integrates information on absolute neutrophil (ANC), lymphocyte (ALC), and platelet counts into one index (calculated as ANCxALC/platelet count) and was previously shown to predict thrombotic and mortality risks in the general population. Methods: A total of 279 PV patients treated in several hematologic centers in Croatia and Serbia was retrospectively evaluated. Results: The median SII for the overall cohort was 1960. Higher SII stratified at the specific cut-off points was significantly associated with shorter time to thrombosis (TTT; p = 0.004) driven by arterial thrombotic events, and shorter overall survival (OS; p < 0.001). Higher SII was able to refine the European Leukemia Net-defined high-risk patient subgroup for both thrombotic and survival risks, especially in individuals over 60 years of age. SII and all other evaluated CBC components and indices (leukocytes, ANC, ALC, platelets, neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR)) demonstrated low-to-modest prognostic properties, whereas SII outperformed other parameters with respect to TTT and OS prognostications. Discussion: The presented results complement prior studies evaluating the prognostic performance of different CBC components for thrombotic and survival risk predictions and offer more options to personalize PV treatments.
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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.
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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 (pâ¯< 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 >â¯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 (PLRâ¯> 224.56; 31% patients) and to exclude (PLRâ¯< 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.
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Eritropoyetina , Policitemia Vera , Policitemia , Trombosis , Biomarcadores , Plaquetas , Humanos , Linfocitos , Neutrófilos , Recuento de Plaquetas , Policitemia Vera/diagnóstico , Pronóstico , Estudios RetrospectivosRESUMEN
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, pâ¯= 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 (pâ¯< 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, pâ¯= 0.022) independently of high-risk disease status (HR 4.48, pâ¯= 0.034) and shorter overall survival (HR 6.69, pâ¯= 0.009) independently of leukocytosis (HR 4.48, Pâ¯= 0.034) and the absence of aspirin use (HR 15.53, pâ¯< 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.
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Policitemia Vera , Femenino , Hematócrito , Hemoglobinas , Humanos , Masculino , Policitemia Vera/diagnóstico , Pronóstico , Estudios RetrospectivosRESUMEN
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 (Pâ¯<â¯0.05 for all analyses). In PMF higher SUA was univariately associated with inferior survival (>â¯427⯵mol/L hazard ratio (HR)â¯= 2.22; Pâ¯= 0.006) and shorter time to thrombosis (>â¯444⯵mol/L HRâ¯= 5.05; Pâ¯= 0.006), which could be shown separately for arterial (>â¯380⯵mol/L; HRâ¯= 4.9; Pâ¯= 0.013) and venous thromboses (>â¯530⯵mol/L; HRâ¯= 17.9; Pâ¯<â¯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.
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Mielofibrosis Primaria , Trombosis , Humanos , Masculino , Mielofibrosis Primaria/diagnóstico , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Ácido ÚricoRESUMEN
BACKGROUND: Reduced kidney function has been associated with worse clinical outcomes in patients with myeloproliferative neoplasms (MPN). Statins and angiotensin-converting enzyme inhibitors (ACE-i) have renoprotective properties and their pleiotropic effects might also affect the malignant MPN clone; however, whether concomitant use of statins and ACEi has a positive effect on estimated glomerular filtration rate (eGFR) in polycythemia vera (PV) patients is currently unknown. METHODS: This multicenter retrospective study investigated effects of statins and ACEi on 12-month eGFR dynamics in 75 PV patients. RESULTS: Of the patients 25 (33.3%) had a 10% or more increase in eGFR at 12 months. Univariately, statins (55.5% vs. 16.3%; pâ¯= 0.022), ACEi (61% vs. 24.6%; pâ¯= 0.004), male sex (54.3%, vs. 15%; pâ¯<â¯0.001) and the absence of chronic kidney disease (CKD, 45.5% vs. 16.1%; pâ¯= 0.008) were statistically significantly associated with an improvement in eGFR. ACEi (pâ¯= 0.008), CKD (pâ¯<â¯0.001), male sex (pâ¯= 0.004) and higher baseline eGFR (pâ¯= 0.007) remained statistically significantly associated with an improvement in eGFR in the multivariate logistic regression model also including statins, hydroxyurea, high-risk disease, cardiovascular risk factors, chronic heart failure and baseline hematocrit. CONCLUSION: The ACEi might have renoprotective properties in PV. Further studies are needed to elucidate whether the use of these drugs could also affect other MPN-related outcomes.
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Inhibidores de la Enzima Convertidora de Angiotensina , Policitemia Vera , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Tasa de Filtración Glomerular , Humanos , Riñón , Masculino , Policitemia Vera/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
We retrospectively investigated C reactive protein to albumin ratio (CAR) in a cohort of 142 patients with myelofibrosis [101 primary (PMF); 41 secondary (SMF)] and compared it to hematological and clinical parameters. Among other associations, higher CAR was significantly associated with higher grade of bone marrow fibrosis, lower frequency of Calreticulin (CALR) mutations, presence of constitutional symptoms, massive splenomegaly, transfusion dependency, blast phase disease, lower hemoglobin, lower platelets, higher ferritin and higher lactate dehydrogenase (LDH) (p < .05 for all analyses). Higher CAR was able to predict inferior survival in PMF independently of DIPSS [hazard ratio (HR)=2.17; p = .015 for high CAR and HR = 2.05; p < .001 for DIPSS] and in SMF independently of Mysec-PM (HR = 6.48; p = .022 for high CAR and HR = 2.63; p = .013 for Mysec-PM) demonstrating its good prognostic potential. CAR seems to be an independent and prognostically relevant parameter, both in PMF and SMF, and might aid in timely recognition of most vulnerable patients.