SERUM CALPROTECTIN IN PHILADELPHIA NEGATIVE MYELOPROLIFERATIVE NEOPLASMS

Cilj istraživanja: Cilj ovog istraživanja bio je istražiti serumsku koncentraciju kalprotektina u bolesnika s Philadelphia negativnim mijeloproliferativnim neoplazmama (MPN) i procijeniti njegove kliničke korelacije. Ispitanici i metode: Koristeći ELISA test izmjerili smo razine serumskog kalprotektina u 43 bolesnika s MPN [13 sa esencijalnom trombocitemijom (ET), 16 s policitemijom verom (PV) i 14 s primarnom mijelofibrozom (PMF)] i u 17 zdravih kontrola. Rezultati: Sva tri entiteta unutar MPN spektra imala su više serumske koncentracije kalprotektina u usporedbi sa kontrolnom grupom (p1,11 μg/mL ima osjetljivost od 81,4% i specifičnost od 88,2% za detekciju bolesnika s MPN (AUC 0,867, STD±0,047, 95% CI 0,775-0,958, p<0,001). Više koncentracije serumskog kalprotektina povezane su sa starijom dobi (p=0,007), CRP-om (p<0,001), lošijim performansom statusom (p<0,001), konstitucijskim simptomima (p=0,006), potrebom za liječenjem hidroksiurejom (p=0,004), retikulinskom fibrozom koštane srži (p<0,001) i kardiovaskularnim rizičnim čimbenicima (p=0,005). Serumski kalprotektin nije korelirao sa spolom, mutacijskim statusom, brojem leukocita, granulocita i trombocita, hemoglobinom, hematokritom ili prisutnošću palpabilne splenomegalije. Zaključci: Povišene koncentracije serumskog kalprotektina u bolesnika s MPN vjerojatno odražavaju stanje kronične upale, ne nužno i stupanj mijeloproliferacije. Dodatna istraživanja na većem broju bolesnika s MPN su potrebna kako bi potpuno razjasnila ulogu kalprotektina u patogenezi MPN, ali i njegove prognostičke posljedice.Objectives: The aim of our study was to investigate serum calprotectin levels in Philadelphia negative myeloproliferative neoplasms (MPNs) and to assess its clinical correlations. Patients and Methods: Using ELISA test we measured serum calprotectin levels in 43 MPN patients [13 essential thrombocythemia (ET), 16 polycythemia vera (PV) and 14 primary myelofibrosis (PMF)] and in 17 healthy controls. Results: All three MPN disorders (ET, PV and PMF) had higher serum calprotectin levels when compared to controls (p1.11 μg/mL, serum calprotectin has a sensitivity of 81.4% and specificity of 88.2% for detection of patients with MPNs (AUC 0.867, STErr±0.047, 95% CI 0.775-0.958, p<0,001). Higher serum calprotectin levels were associated with older age (p=0.007), higher CRP (p<0.001), poor performance status (p<0.001), constitutional symptoms (p=0.006), the need for hydroxycarbamide therapy (p=0.004), reticulin fibrosis (p<0.001) and the presence of cardiovascular risk factors (p=0.005). Serum calprotectin did not correlate with sex, mutational status, leukocyte, granulocyte and platelet counts, hemoglobin and hematocrit levels, or the presence of palpable splenomegaly. Conclusions: Elevated serum calprotectin levels in patients with MPNs might primarily reflect the state of chronic inflammation, not necessarily the extent of myeloproliferation. Further studies are needed to elucidate the role of calprotectin in the pathogenesis of MPN's, as well as its prognostic implications

SERUM CALPROTECTIN IN PHILADELPHIA NEGATIVE MYELOPROLIFERATIVE NEOPLASMS

Cilj istraživanja: Cilj ovog istraživanja bio je istražiti serumsku koncentraciju kalprotektina u bolesnika s Philadelphia negativnim mijeloproliferativnim neoplazmama (MPN) i procijeniti njegove kliničke korelacije. Ispitanici i metode: Koristeći ELISA test izmjerili smo razine serumskog kalprotektina u 43 bolesnika s MPN [13 sa esencijalnom trombocitemijom (ET), 16 s policitemijom verom (PV) i 14 s primarnom mijelofibrozom (PMF)] i u 17 zdravih kontrola. Rezultati: Sva tri entiteta unutar MPN spektra imala su više serumske koncentracije kalprotektina u usporedbi sa kontrolnom grupom (p1,11 μg/mL ima osjetljivost od 81,4% i specifičnost od 88,2% za detekciju bolesnika s MPN (AUC 0,867, STD±0,047, 95% CI 0,775-0,958, p<0,001). Više koncentracije serumskog kalprotektina povezane su sa starijom dobi (p=0,007), CRP-om (p<0,001), lošijim performansom statusom (p<0,001), konstitucijskim simptomima (p=0,006), potrebom za liječenjem hidroksiurejom (p=0,004), retikulinskom fibrozom koštane srži (p<0,001) i kardiovaskularnim rizičnim čimbenicima (p=0,005). Serumski kalprotektin nije korelirao sa spolom, mutacijskim statusom, brojem leukocita, granulocita i trombocita, hemoglobinom, hematokritom ili prisutnošću palpabilne splenomegalije. Zaključci: Povišene koncentracije serumskog kalprotektina u bolesnika s MPN vjerojatno odražavaju stanje kronične upale, ne nužno i stupanj mijeloproliferacije. Dodatna istraživanja na većem broju bolesnika s MPN su potrebna kako bi potpuno razjasnila ulogu kalprotektina u patogenezi MPN, ali i njegove prognostičke posljedice.Objectives: The aim of our study was to investigate serum calprotectin levels in Philadelphia negative myeloproliferative neoplasms (MPNs) and to assess its clinical correlations. Patients and Methods: Using ELISA test we measured serum calprotectin levels in 43 MPN patients [13 essential thrombocythemia (ET), 16 polycythemia vera (PV) and 14 primary myelofibrosis (PMF)] and in 17 healthy controls. Results: All three MPN disorders (ET, PV and PMF) had higher serum calprotectin levels when compared to controls (p1.11 μg/mL, serum calprotectin has a sensitivity of 81.4% and specificity of 88.2% for detection of patients with MPNs (AUC 0.867, STErr±0.047, 95% CI 0.775-0.958, p<0,001). Higher serum calprotectin levels were associated with older age (p=0.007), higher CRP (p<0.001), poor performance status (p<0.001), constitutional symptoms (p=0.006), the need for hydroxycarbamide therapy (p=0.004), reticulin fibrosis (p<0.001) and the presence of cardiovascular risk factors (p=0.005). Serum calprotectin did not correlate with sex, mutational status, leukocyte, granulocyte and platelet counts, hemoglobin and hematocrit levels, or the presence of palpable splenomegaly. Conclusions: Elevated serum calprotectin levels in patients with MPNs might primarily reflect the state of chronic inflammation, not necessarily the extent of myeloproliferation. Further studies are needed to elucidate the role of calprotectin in the pathogenesis of MPN's, as well as its prognostic implications

Serum procalcitonin in Philadelphia-negative myeloproliferative neoplasms

Philadelphia-negative myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are rare clonal hematopoietic stem cell disorders accompanied by a strong inflammatory milieu, which is directly responsible for constitutional symptoms associated with the disease, such as fever, weight loss or night sweats. Non-hematologists sometimes (and often wrongly) consider the fever in MPN patients to be a symptom of an underlying disease, which may have devastating consequences. Serum procalcitonin (PCT) is a circulating biomarker commonly used to improve the diagnostic accuracy of bacterial infections and to guide antibiotic therapy. The aim of this study was to test whether PCT could aid the clinician in the early diagnosis of bacterial infections in MPNs. This study investigated PCT in 41 ambulatory MPN patients (13 ET, 13 PV and 15 MF) who had no signs of infection and compared it to 10 MPN patients with microbiologically and/or serologically documented bacterial infections. Median PCT in MPN patients was 0.02 ng/mL (range 0.01-0.09 ng/mL). No difference in PCT was found between ET, PV and MF patients (p = 0.993), whereas MPN patients with documented bacterial infections had significantly higher PCT (median PCT 2.45, range 0.90-5.40 ng/mL) when compared to MPN patients with (median PCT 0.03 ng/mL) or without constitutional symptoms (median PCT 0.02 ng/mL; p < 0.001 for both analyses). These results clearly show that PCT should not be considered as a disease biomarker in MPNs and careful clinical assessment for the signs of infection is needed when MPN patients present with fever and high PCT

Immune-mediated platelet transfusion refractoriness in a severely thrombocytopenic patient with myelodysplastic syndrome successfully treated with romiplostim

Immune-mediated platelet transfusion refractoriness due to anti-human leukocyte antigen (HLA) antibodies can occur in approximately 9% of patients with myelodysplastic syndromes (MDS) and can lead to an increased risk of clinically relevant bleeds and treatment delays. These patients are typically managed with frequent platelet transfusions; however, HLA-matched platelet transfusions are usually available only in large blood centers. For this reason, alloimunized thrombocytopenic MDS patients are notoriously difficult to manage. Here, we present a case of a MDS patient with an immune-mediated platelet transfusion refractoriness, severe thrombocytopenia and spontaneous subarachnoid hemorhage who we successfully treated with romiplostim, a thrombopoietin receptor agonist

Circulating YKL-40 in Philadelphia-negative myeloproliferative neoplasms

Objectives: Philadelphia-negative chronic myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF), are characterized by clonal myeloproliferation and a strong inflammatory atmosphere. YKL-40, expressed in granulocytes, macrophages, megakaryocytes and malignant cells, is an acute phase reactant with an important role in tissue remodeling and atherosclerotic inflammation. The aim of this study was to investigate serum YKL-40 levels in MPNs and to assess its clinical correlations. ----- Methods: ELISA test was used to measure serum YKL-40 levels in 111 MPN patients and in 32 healthy controls. ----- Results: Serum YKL-40 levels were higher in ET, post-ET MF, PV, post-PV MF and primary MF patients, when compared to healthy controls (p < 0.001). Higher serum YKL-40 levels were associated with parameters indicative of the increased inflammatory state (higher C-reactive protein, poor performance status, presence of constitutional symptoms and cardiovascular risk factors). Additionally, higher serum YKL-40 levels in MF patients were associated with blast phase disease, lower hemoglobin and higher Dynamic International Prognostic Scoring System score. In the multivariate Cox regression models, higher serum YKL-40 levels in ET and PV patients were independently associated with an increased risk of thrombosis (HR 4.64, p = 0.031) and impaired survival in MF patients (HR 4.31, p = 0.038). ----- Conclusion: These results indicate that higher circulating YKL-40 levels in MPNs might have a pathophysiological role in disease progression and thrombosis development. Assessing circulating YKL-40 could help in identification of ET and PV patients at a high risk of future cardiovascular events and has a good potential for improving prognostication of MF patients

Retrospektivna analiza učinkovitosti i podnošljivosti trifluridin/tipiracila u bolesnika s refraktornim metastatskim kolorektalnim karcinomom u općoj bolnici Šibensko-kninske županije

In randomized clinical trials, trifluridine / tipiracil (TT) demonstrated beneficial effects on progression-free survival (PFS) and overall survival (OS) in patients with refractory metastatic colorectal cancer (mCRC). The aim of this unicentric study was to evaluate the efficacy and safety of TT in patients with refractory mCRC in everyday clinical practice. Treatment outcomes of 20 patients were retrospectively analyzed. The median OS was 6.25 months (range 1-18) and the median PFS was 3 months (range 2–13). The most common (80%) side effect of TT was neutropenia and 35% of patients had neutropeniagrades 3 of 4; however, only two patients (10%) had neutropenic fever and no deaths wereattributable to neutropenia. In conclusion, treatment outcomes in this real-life study seem comparable to those from randomized clinical trials.U randomiziranim kliničkim studijama trifluridin/tipiracil (TT) je pokazao povoljan učinak na preživljenje bez progresije bolesti (PFS) i na ukupno preživljenje (OS) u bolesnika s refraktornim metastatskim kolorektalnim karcinomom (mKRK). Cilj ovog unicentričnog istraživanja bio je procijeniti učinkovitost i sigurnost primjene TT kod bolesnika s refraktornim mKRK u svakodnevnoj kliničkoj praksi. Retrospektivno su analizirani ishodi liječenja 20 bolesnika. Medijan OS bio je 6.25 mjeseci (raspon 1-18) a medijan PFS 3 mjeseca (raspon 2-13). Najčešća (80%) nuspojava TT bila je neutropenija, u 35% bolesnika gradusa 3 i 4. Ipak, u samo dva bolesnika (10%) zabilježena je neutropenična vrućica, a nijedan bolesnik nije preminuo zbog neutropenije. Zaključno, ishodi liječenja bolesnika s mKRK s TT u svakodnevnom kliničkom radu usporedivi su s onima iz randomiziranih kliničkih studija

Glycated hemoglobin (HbA1c) and thrombotic risk in polycythemia vera and essential thrombocythemia

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