35 research outputs found
Izražaj cirkulirajuÄih mikronaRNA (miR-125a, miR-125b, miR-126, miR-99b, miR-let7a) u bolesnika s mijelodisplastiÄnim sindromom [Expression of circulating microRNA (miR-125a, miR-125b, miR-126, miR-99b, miR-let7a) in myelodysplastic syndrome patients]
Myelodysplastic syndrome (MDS) is a group of heterogeneous clonal hematologic
disorders of hematopoietic stem cells, followed by ineffective hematopoiesis of
one or more cell lines with the onset of consequent cytopenia with an increased risk
of progression to acute myeloid leukemia. According to the World Health Organization
classification, the diagnosis of MDS is based on morphological, clinical, cytogenetic,
immunophenotypic and biological criteria.
In everyday clinical practice, the diagnosis of MDS is based on invasive cytomorphological
analysis of peripheral blood and bone marrow cells, determination of
blast percent, type and degree of dysplasia, presence of ring sideroblasts, and cytogenetic
analysis of bone marrow cells.
Micro Messenger Ribonucleic Acids (miRNAs) are short, non-coding molecules
of 18 to 25 nucleotides in length that play an important role in regulating cell
development and metabolism, their differentiation and proliferation, regulation of the
cell cycle and cell death. Tumor cells release miRNAs into the circulation (plasma,
serum) where they remain relatively stable. Although their discovery allowed linking
of disease and miRNA gene expression, a precondition for their clinical application
was the determination of gene expression by real-time quantitative polymerase chain
reaction with satisfactory efficacy and specificity. In the literature, gene expression of
miRNAs has been linked to the diagnosis, classification and progression of various
diseases.
Many studies have been conducted so far about the molecular mechanisms
and epigenetic pathways in MDS and their prognostic and therapeutic significance,
but few studies have analyzed the importance of miRNAs in MDS.
The aim of this study was to examine the level of change of gene expression
of specific mRNAs (miR-125a, miR-99b, miR-126, miR-125b, miR-let-7a) in plasma of
healthy volunteers and subjects diagnosed with MDS.
Gene expression of these specific mRNAs was determined in plasma samples
from healthy volunteers (18) and subjects with MDS (41). This paper describes for the
first time the expression of a selected miRNA cluster (125a, 125b, 99b, let-7a) in the
plasma of untreated MDS patients.
A significant difference was found between the study group and healthy control
in miR-99b level, where at normalized values relative to miR-126, an increased level
in subjects compared to control was observed 4,521 times (P = 0.004).
Diagnostic and prognostic significance of miR-125a was observed and correlated
negatively with erythrocyte count and hemoglobin level in the diagnosis of
MDS.The results of the study suggest that gene expression of miRNA (125a, 125b,
99b, let7a) could be regulated by the same mechanism and may be clinically relevant
in subjects with MDS
WOUNDS IN HEMATOLOGY PATIENTS
Kod hematoloÅ”kog bolesnika rane mogu biti dio kliniÄke slike u trenutku postavljanja dijagnoze, posljedica infekcije, nuspojave terapije ili napredovanja tumorske bolesti s kožnim infiltratima. lijeÄenje rana kod hematoloÅ”kih bolesnika zahtijeva multidisciplinaran pristup hematologa, kirurga, dermatologa, mikrobiologa i ostalog medicinskog osoblja koje je ukljuÄeno u svakodnevnu brigu o bolesniku. Kako se radi o onkoloÅ”kim imunosuprimiranim bolesnicima, iznimno je važno pridržavati se mjera asepse te sprijeÄiti infekcije rana zbog kojih bi se zakomplicirao ionako dugotrajan oporavak i zalijeÄenje. Važno je na vrijeme prepoznati ranu s malignom infiltracijom jer je pravodobna kemoterapija u takvom sluÄaju kurativna mjera.Hematology patients can have wounds as part of the initial presentation of the disease, as a result of infection or therapy. Wound therapy is very important and requires multidisciplinary approach of the hematologist, surgeon, dermatologist, and all other medical staff involved in the patientās care. It is very important to provide aseptic care and prevent infections that could complicate the patientās recovery and cure. It is very important to recognize the wound with malignant infiltration because an appropriate chemotherapy can be curative
LIJEÄENJE ANEMIJE KRONIÄNE BUBREŽNE BOLESTI U PREDIJALIZNOJ FAZI
Erythropoiesis-stimulating agents (ESAs) administered either subcutaneously (sc.) or intravenously (iv.), along with iv. or oral iron therapy, are currently the cornerstones for treating anemia in patients with chronic kidney disease (CKD). Multiple factors are involved in the pathogenesis of anemia in CKD: iron deficiency, inadequate production of erythropoietin (Epo), hepcidin and hypoxia-inducible factors (HIFs). Patients with CKD are prone to iron deficiency (absolute and functional). In this study, we compared the efficacy and safety profile of oral and intravenous iron with erythropoietin beta (subcutaneously in a dose of 4000-6000 IU every week) for the treatment of iron deficiency anemia in 43 non dialysis patients (ND-CKD) with the confirmed diagnosis of iron deficiency anemia (A) at Merkur University Hospital. Exclusion criteria were patients on dialysis or transplantation, with heart failure, secondary hyperparathyroidism, malignancy, thromboembolism, gastrointestinal bleeding, hsCRP >5 mg/L, patients taking medicines that suppress Epo production, and uncontrolled resistant hypertension. Patients were divided into groups on intravenous iron in doses of 1000 mg every month and oral daily intake of iron (ferrous fumarate 350 mg). Iron supplementation was administrated in order to achieve serum ferritin 200-500 mg/L. Hemoglobin (Hb) was checked at the beginning and after 12 months in both groups. Paired sample t-test was applied for comparison of results. The mean level of iron at the beginning in M/F was 9.7/7.9Ā±0.28/0.31 and after 12 months 10.7/8.94Ā±0.27/0.43 Ī¼mol/L. In the treatment groups, the mean Hb level was 9.19Ā±0.84 g/dL (A) and 9.72Ā±0.95 g/ dL (B). The mean increase in Hb was 10.65Ā±0.97 g/dL (A) and 10.42Ā±1.22 g/dL (B) at 12 months (p20%. Srednja razina vrijednosti željeza na poÄetku iznosila je u M/F 9,7/7,9Ā±0,28/0,31, dok je na kraju studije bila 10,7/8,94Ā±0,27/0,43 Ī¼mol/L. Razina hemoglobina (Hb) je na poÄetku iznosila 9,19Ā±0,84 g/dL (skupina A) i 9,72Ā±0,95 g/dL (skupina B). Na kraju praÄenja doÅ”lo je u obje skupine do porasta razine Hb u odnosu na poÄetne vrijednosti: 10,65Ā±0,97 g/dL (skupina A) i 10,42Ā±1,22 g/ dL (skupina B) (p<0,001), no izmeÄu skupina A i B nije utvrÄena statistiÄki znaÄajna razlika. Rezultati studije pokazuju da je lijeÄenje anemije KBB postojeÄim dostupnim lijekovima uÄinkovito u sluÄaju iskljuÄenja Äimbenika koji mogu doprinijeti rezistenciji na lijeÄenje. Kako najveÄi broj bolesnika s KBB ima postojeÄe Äimbenike koji doprinose rezistenciji lijeÄenja anemije KBB-a, u buduÄnosti najviÅ”e obeÄava primjena stabilizatora HIF-a
Patient with myelodysplastic syndrome in emergency department
MijelodisplastiÄni sindrom (MDS) grupa je klonskih mijeloidnih poremeÄaja s heterogenom kliniÄkom slikom, a najveÄi broj komplikacija posljedica je citopenija koje su karakteristiÄno obilježje. Etiologija nije dovoljno poznata. Internacionalni bodovni sustav (engl. The International Prognostic Scoring System ā IPSS) služi kao prognostiÄki Äimbenik za nelijeÄene bolesnike s MDS-om. Nedjelotvorna hematopoeza, pa tako i eritropoeza, dovode do anemije, Å”to je najÄeÅ”Äi uzrok dolaska bolesnika s MDS-om u hitnu službu. Vrlo Äesto bolesnici imaju brojna pridružena stanja poput kroniÄne bubrežne bolesti i hipertenzije, a mogu imati i kliniÄku sliku akutnoga koronarnog sindroma. Prikazujemo 83-godiÅ”nju bolesnicu s MDS-om dijagnosticiranim 2014. godine i koja dosad nije lijeÄena specifiÄnom hematoloÅ”kom terapijom. Zbrinjavanje starijih hematoloÅ”kih bolesnika u hitnoj službi nalaže sveobuhvatni pristup zbog Äesto prisutnih pridruženih stanja koja se dodatno mogu pogorÅ”ati uz MDS.Myelodysplastic syndromes (MDS) are a group of clonal disorders arising from hematopoietic stem cells and are generally characterized by inefficient hematopoiesis and dysplasia. The International Prognostic
Scoring Sytem (IPSS) is an important standard for assessing prognosis of primary untreated adult patients with myelodysplastic syndromes (MDS). Ineffective hematopoiesis leading to anemia is the most common cause of the arrival of patients with MDS in the emergency room . Patients with MDS have a number of associated conditions
such as chronic kidney disease and hypertension, and may be present as acute coronary syndrome. We report a case of a 83-year-old female with MDS that was diagnosed in 2014 and had no specific treatment. She presented to the emergency department at the beginning of 2016 because of epigastric and chest pain that began in the morning. Diagnosis of subacute STEMI with a scar formed on front wall and elevated high-sensitivity troponin (hsTnI) which amounted to 1,369 ng / L (reference value < 15.6 ng / L) was made , and the patient was
hospitalized in the Coronary Care Unit . The care for this population of patients, mainly elderly, in the emergency department requires a comprehensive approach due to the presence of associated conditions such as hypertension, chronic kidney disease and ischemic heart disease. Cardiovascular diseases (CVD) are the leading cause of
death in all countries worldwide
Dasatinib-induced nephrotic syndrome: a case of phenoconversion?
We present the case of a 33-year-old chronic myeloid leukemia
(CML) female patient, in whom the occurrence of
nephrotic syndrome, during the treatment with tyrosine
kinase activity inhibitors (TKIs), was potentially influenced
by transient phenoconversion. Seven years after the CML
diagnosis in 2004 and complete response, the patient experienced
pain in the mandible and extremities. After this,
imatinib was replaced by nilotinib, but generalized maculopapular
rash was presented and successfully treated with
antihistamines. The therapy was then discontinued due to
planned pregnancy, and the patient experienced a relapse
of CML with BCR-ABL/ABL1 transcripts of 18.9%. Dasatinib
was introduced, and CML was in remission. Two years later,
urine protein levels (6.19 g/L) and erythrocyte sedimentation
rate were elevated (ESR = 90 mm/3.6 ks). The patient
was diagnosed with nephrotic syndrome. With dasatinib
dose reduction, urine protein level returned to the reference
range. In order to determine the best genotype-guided
therapy, the patient underwent pharmacogenomic
testing, showing a homozygous CYP3A4 genotype *1/*1,
associated with extensive metabolizer (EM) enzyme phenotype,
typical for normal rates of drug metabolism for TKIs.
However, this was inconsistent with nephrotic syndrome
occurrence. A possible explanation would be CYP3A4 EM
genotype coding a poor metabolizer enzyme phenotype,
leading to the drug accumulation in the patientās blood.
This transient phenoconversion can be explained by inflammation
with elevated ESR during nephrotic syndrome.
This case shows that a broader approach that recognizes
genetic, clinical, and epigenomic factors is required for a
quality decision on the personalized therapy regimen
ARE WE ENTERING CHEMO-FREE ERA IN CHRONIC LYMPHOCYTIC LEUKEMIA? THE ROLE OF IBRUTINIB AND VENETOCLAX AND LESSONS LEARNT FROM IDELALISIB
Glavni cilj ovog preglednog rada je predstaviti novu klasu lijekova u kroniÄnoj limfocitnoj leukemiji (KLL), najÄeÅ”Äoj leukemiji odrasle dobi, inhibitore staniÄnog signaliziranja B receptora (BCR). KLL se klasiÄno lijeÄila imunokemoterapijom, no pojedini bolesnici (poodmakla životna dob, nepovoljni bioloÅ”ki faktori) imali su loÅ”u prognozu. S boljim razumijevanjem patogeneze unutarstaniÄnih putova pojavila se moguÄnost selektivne inhibicije i ciljane terapije u KLL. Prvi lijek u svojoj klasi ibrutinib, inhibitor bruton kinaze, pokazao se superiornim u fazama III kliniÄkih pokusa te je eliminirao negativne prognostiÄke faktore u lijeÄenju KLL, pogotovo del (17p), s adekvatnim profi lom toksiÄnosti Å”to su prepoznale regulatorne agencije. Drugi BCR inhibitori idelalisib i venetoklaks su iznimno aktivni u relapsnom okruženju, no idelalisib se pokazao neprihvatljivo toksiÄnim u prvoj liniji lijeÄenja Å”to nam može poslužiti kao lekcija u dizajnu kliniÄkih pokusa s ovim lijekovima. Usprkos uÄinkovitosti, potreban je dodatni napredak u ovom podruÄju koji se nalazi u kombinacijama s imunoterapijom ili imunokemoterapijom, te moguÄoj meÄusobnoj kombinaciji kako bismo dodatno poboljÅ”ali ishode. No, najveÄa zapreka BCR inhibitorima da uÄu u Å”iroku praksu je njihova cijena i utjecaj na zdravstveni sustav Å”to nažalost ograniÄuje naÅ”u moguÄnost da lijeÄimo bolesnike s KLL u eri bez kemoterapije.The main aim of this review is to present a novel class of agents, the inhibitors of B cell receptor (BCR) signaling pathway, used in the treatment of chronic lymphocytic leukemia (CLL) as the most common leukemia in the Western world. Traditionally, CLL was treated with immunochemotherapy, but certain subpupulations (elderly, biological prognostic factors) had poor outcome. With advances in our understanding the pathogenesis of intracellular pathways, the possibility of selective inhibition and targeted therapy in CLL has arisen. The fi rst agent in the class of BCR inhibitors, ibrutinib, a Bruton kinase inhibitor, has been shown superior in phase III clinical trials eliminating negative prognostic factors such as del(17p), with adequate toxicity profi le, which was recognized by the respective regulatory agencies. Other BCR inhibitors idelalisib and venetoclax are extremely active in relapsed setting, but unfortunately, idelalisib combinations in fi rst line clinical trials resulted in unacceptable toxicity, which is a cautionary tale on designing trials. Despite their effi cacy, we are only at the beginning to improve them by combination with monoclonal antibodies, immunochemotherapy, or between each other to improve outcomes of CLL treatment even further. However, the main obstacle to chemo-free era in CLL is their price resulting in limited access to these agents and inequity in the modern treatment of CLL
ARE WE ENTERING CHEMO-FREE ERA IN CHRONIC LYMPHOCYTIC LEUKEMIA? THE ROLE OF IBRUTINIB AND VENETOCLAX AND LESSONS LEARNT FROM IDELALISIB
Glavni cilj ovog preglednog rada je predstaviti novu klasu lijekova u kroniÄnoj limfocitnoj leukemiji (KLL), najÄeÅ”Äoj leukemiji odrasle dobi, inhibitore staniÄnog signaliziranja B receptora (BCR). KLL se klasiÄno lijeÄila imunokemoterapijom, no pojedini bolesnici (poodmakla životna dob, nepovoljni bioloÅ”ki faktori) imali su loÅ”u prognozu. S boljim razumijevanjem patogeneze unutarstaniÄnih putova pojavila se moguÄnost selektivne inhibicije i ciljane terapije u KLL. Prvi lijek u svojoj klasi ibrutinib, inhibitor bruton kinaze, pokazao se superiornim u fazama III kliniÄkih pokusa te je eliminirao negativne prognostiÄke faktore u lijeÄenju KLL, pogotovo del (17p), s adekvatnim profi lom toksiÄnosti Å”to su prepoznale regulatorne agencije. Drugi BCR inhibitori idelalisib i venetoklaks su iznimno aktivni u relapsnom okruženju, no idelalisib se pokazao neprihvatljivo toksiÄnim u prvoj liniji lijeÄenja Å”to nam može poslužiti kao lekcija u dizajnu kliniÄkih pokusa s ovim lijekovima. Usprkos uÄinkovitosti, potreban je dodatni napredak u ovom podruÄju koji se nalazi u kombinacijama s imunoterapijom ili imunokemoterapijom, te moguÄoj meÄusobnoj kombinaciji kako bismo dodatno poboljÅ”ali ishode. No, najveÄa zapreka BCR inhibitorima da uÄu u Å”iroku praksu je njihova cijena i utjecaj na zdravstveni sustav Å”to nažalost ograniÄuje naÅ”u moguÄnost da lijeÄimo bolesnike s KLL u eri bez kemoterapije.The main aim of this review is to present a novel class of agents, the inhibitors of B cell receptor (BCR) signaling pathway, used in the treatment of chronic lymphocytic leukemia (CLL) as the most common leukemia in the Western world. Traditionally, CLL was treated with immunochemotherapy, but certain subpupulations (elderly, biological prognostic factors) had poor outcome. With advances in our understanding the pathogenesis of intracellular pathways, the possibility of selective inhibition and targeted therapy in CLL has arisen. The fi rst agent in the class of BCR inhibitors, ibrutinib, a Bruton kinase inhibitor, has been shown superior in phase III clinical trials eliminating negative prognostic factors such as del(17p), with adequate toxicity profi le, which was recognized by the respective regulatory agencies. Other BCR inhibitors idelalisib and venetoclax are extremely active in relapsed setting, but unfortunately, idelalisib combinations in fi rst line clinical trials resulted in unacceptable toxicity, which is a cautionary tale on designing trials. Despite their effi cacy, we are only at the beginning to improve them by combination with monoclonal antibodies, immunochemotherapy, or between each other to improve outcomes of CLL treatment even further. However, the main obstacle to chemo-free era in CLL is their price resulting in limited access to these agents and inequity in the modern treatment of CLL
Suvremeni pristup ne-Hodgkinovu limfomu plaŔtene zone: pregled literature [Current approach to non-Hodgkin mantle cell lymphoma: literature review]
Mantle cell lymphoma (MCL) represents the fourth most common type of non-Hodgkin lymphomas. It is characterized by aggressive course and frequent relapses. The main aim of this review is to evaluate current treatment approach towards this type of lymphoma. In younger patients the chemotherapy including high doses of cytarabine is the gold standard. In case of complete or partial remission, the consolidation with autologous stem cell transplantation is indicated as consolidation approach. In older patients CHOP-R regimen is not the treatment of choice. These patients should be treated with bendamustine in combination with rituximab. In case of complete or partial remission, further therapy with rituximab maintenance as consolidation represents an option. The vast majority of patients with MCL will ultimately relapse which poses a challenge in treatment approach. The approach in relapsed MCL can be divided in two types: chemotherapy or biologic therapy. In young fit patients chemotherapy based on bendamustine and cytarabine is a reasonable option. In patients with comorbidities or poor performance status biologic agents are reasonable options. Ibrutinib, Bruton kinase inhibitor, is characterized by highest overall response rate and the longest duration of response and should be offered to these patients. With the development of novel potent inhibitor of B cell receptor signaling pathway, these agents may become the gold standard in future and introduce the treatment of MCL in āchemo-freeāera
SKIN SIDE - EFFECTS OF HYDROXYUREA THERAPY
Kod hematoloÅ”kog bolesnika, kožne promjene mogu biti dio kliniÄke slike u trenutku postavljanja dijagnoze ili napredovanja bolesti koji se oÄituju kožnim iniltratima, posljedica infekcije ili nuspojave terapije. hidroksiureja je peroralni citostatik uz kojeg se mogu pojavljivati dermatoloÅ”ke nuspojave Äak i i nekoliko godina od poÄetka lijeÄenja. Prikazujemo bolesnicu s ulkusima potkoljenica nastalima u tijeku terapije hidroksiurejom. Važno je na vrijeme prepoznati kožne promjene vezane uz hidroksiureju jer je ukidanje navedenog citostatika u takvom sluÄaju kurativno.Hematology patients can have wounds as part of the initial presentation of the disease, as a result of infection, side effects of therapy, or disease progression with skin iniltration. hydroxyurea is an oral cytotoxic drug with known cutaneous side effects that can appear years after treatment initiation. here we present a case of a female patient who developed crural ulcerations during hydroxyurea treatment. It is very important to recognize the wound related to hydroxyurea treatment because drug discontinuation is usually curative