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Usporedba efikasnosti mobilizacije perifernih krvotvornih matičnih stanica Neupogenom i biosličnim lijekom Nivestimom u jednom centru

Procjena aktivnosti bolesti metodom kvantificiranja monoklonskog izotipa teških/lakih lanaca u serumu kod oboljelih od multiplog mijeloma.

Pedesettrogodišnja bolesnica hospitalizirana je u Zavodu za hematologiju KBC Zagreb u kolovozu 2013 godine s B simptomima te nespecifičnim intraabdominalnim tegobama koje traju otprilike mjesec dana. Obradom je verificiran difuzni B- velikostanični limfomom (GC podtipa) inicijalno zahvaćenih svih regija limfnih čvorova, sa splenomegalijom te infiltracijom bubrega, a bez infiltracije koštane srži ; kliničkog stadija IVB. Imunohistokemijski je CD20+ CD10+ Bcl6+ MUM1- CD3- i bez ostataka folikularne dendritičke mreže dokazivog bojenjem na CD21. Istovremeno je verificiran i multicentrični ekspanzivni proces u lijevoj dojci, mamografski stelatna sjena spikuliranih rubova veličine 2.3 x 2 cm uz dodatne dvije promjene u GLK lijevo 1.9 cm i 0.9 cm, otvorene

A retrospective analysis was performed in patients stratified according to GCSF used for mobilisation (Neupogen vs Nivestim) and the hematological malignancy they were treated for (Acute myeloid leukemia, Multiple myeloma, non- Hodgkin`s lymphoma, Hodgkin`s lymphoma) patients who were administered 10 mcg/kg of GCSF were analysed. The following parameters of stem cell mobilisation were surveyed: number of days GCSF was administered, total number of CD34 positive cells per kilogram collected, total number of colony forming units of the granulocyte macrophage order per kilogram collected. A matched pairs analysis was performed on a subset of patients treated for multiple myeloma.

Analiza aktivnosti timidin kinaze kod bolesnika s multiplim mijelomom i povezanost sa stanjm bolesti, te utjecaj na preživljenje - iskustvo jednog centra

Extramedullary plasmacytomas are plasma cell tumors that arise outside of the bone marrow. They account for approximately 3% of plasma cell neoplasms and are most frequently located in the head and neck region. Five months after undergoing cholecystectomy, a 69-year-old patient presented with the pain under the right costal margin and a 12 kg weight loss. Computed tomography of the abdomen demonstrated irregular, vascular mass in the gallbladder fossa that dents towards the duodenum and the pylorus and lowers caudally to the hepatic flexure. His laboratory tests indicated normocytic anemia and showed elevated sedimentation rate. During operative procedure, a tumorous mass in the gallbladder fossa was found, inseparable of the peritoneum of the hepatoduodenal ligament and the IVb liver segment. Histopathological examination and immunohistochemical staining determined the diagnosis of the plasmacytoma. Total resection of the tumor was achieved and after 24-month follow-up patient showed no signs of local recurrence or dissemination of the disease.

BACKGROUND: Therapy of multiple myeloma (MM) has been greatly advanced by introduction of autologous hematopoietic stem cell transplantation (AHSCT) in 90’s, and appearance of new potent drugs thalidomide, bortezomib and lenalidomide in the last decade. AIMS: to assess the efficacy of new treatment modalities on survival of MM patients treated at the University Hospital Center, Zagreb. PATIENTS AND METHODS: From 1985 till 2010, 560 consecutive MM patients (pts) were analyzed. Median age at diagnosis was 60 (range 28-89) years. Pts were divided into three groups according to time period of available treatment modalities: Group one treated from 1985-1995, period prior AHSCT (n=158, median age 63 [range: 31-87]) ; group two treated from 1996- 2001, period with AHSCT (n=139, median age 58 [range: 29-87]) ; and group three treated from 2002-2010, period with AHSCT+bortezomib+thalidomide (n=263, median age 60 [range: 28-89]). Each group was subdivided in two subgroups according to age at diagnosis indicating eligibility for AHSCT (

Uvod: Inhibitori tirozin kinaze (TKI) uvelike su promijenili prognozu kronične mijeloične Ph+ leukemije i zbog velike djelotvornosti a male toksičnosti potisnuli alogeničnu transplantaciju koštane srži kao prvu liniju liječenja. U prvoj polovici 2002. godine, ubrzo nakon što je registriran FDA za liječenje Ph+ KML, imatinib mesilat počeo se primjenjivati u Hrvatskoj, dok su 2 bolesnika započela liječenje ranije, od 2000. g, uključivanjem u studiju u inozemnoj ustanovi. 2007. godine započinje primjena nilotiniba i dasatiniba u slučaju rezistencije na imatinib ili njegovog nepodnošenja. U ovom radu smo retrospektivno analizirali podatke o bolesnicima s Ph+ KML liječenih s inhibitorima tirozin kinaze u KBC Zagreb. Metode i bolesnici: Studija je obuhvatila 120 bolesnika s Ph+ KML pozitivnom leukemijom dijagnosticiranom od 1984-2011. godine i liječenih inhibitorima tirozin kinaze od 2000. godine. Iz medicinske dokumentacije prikupljeni su podaci o datumu dijagnoze, fazi bolesti pri dijagnozi, vrsti terapije, datumu zadnje kontrole ili datumu smrti. Rezultati: Od 120 bolesnika liječenih s TKI bilo je 79 (66%) muškaraca i 41 (34%) žena. Medijan dobi pri dijagnozi bio je 44 godine (raspon 14-80). Imatinib kao 1. liniju primalo je 79 bolesnika, a još 29 bolesnika primalo je prije imatiniba interferon-α+/-ara-C. Dvoje bolesnika primalo je imatinib prvi puta za relaps nakon alogene transplantacije koštane srži, tri bolesnika primili su nilotinib kao prvu liniju, a 7 bolesnika je liječeno imatinibom u drugoj ustanovi te su nakon progresije upućeni u KBC Zagreb radi primjene 2. linije TKI, nilotiniba ili dasatiniba. Od 79 bolenika u 1. liniji 4 su bila u ubrzanoj fazi, 1 u blastičnoj transformaciji a 74 u KF. Drugi TKI primalo je 16 bolesnika (20%). Alogenom transplantacijom koštane srži liječeno je 5 bolesnika (4 srodnog, 1 nesrodnog davatelja). Kod jedne bolesnice nakon relapsa iza transplantacije s uspjehom je pronovno primjenjen imatinib. Od 29 bolesnika koji su primali interferon-α prije imatiniba troje je bilo u AF ili BT. Zbog citogenetske progresije 8 bolesnika je primalo dasatinib, a 4 nilotinib od kojih je jedna bolesnica primala nakon nilotiniba i dasatinib. Ukupno je umrlo 19 bolesnika, 12 povezano s progresijom i liječenjem KML a 7 zbog drugih razloga. Medijan praćenja pacijenata iznosi 72 (1-254) mjeseca. Medijan preživljenja inosi 254 mjeseca. Kumulativno 5- i 10- godišnje preživljenje iznosi redom 88% i 77%. Razlika u preživljenju među pacijentima liječenima imatinibom (IM), odnosno kombinacijom IM+ interferona alfa (IFA) nije statistički značajna. Zaključak: Naši rezultati liječenja kronične mijeloične leukemije potvrđuju efikasnost liječenja kronične mijeloične leukemije inhibitorima tirozin kinaze.

Određivanje teških lanaca imunoglobulin, novi test u dijagnostici i praćenju bolesnika s multiplim mijelomom

U radu je prikazan slučaj limfoblastnog limfoma s fenotipom T i B limfocita i klonalnim IgH, porijekla iz timusa. Iako se s sigurnošću nee može odrediti stanično porijeklo ovog tumora, najvjerojatnije se radi o T-LBL kod kojeg je aberantna ekspresija Pax-5 gena pokrenula program diferencijacij limfocita b na fenotipskoj i genotipskoj razini.

Prognostički značaj imunohistokemijskih algoritama kod difuznog B-velikostaničnog limfoma

Background: Imatinib is frontline therapy for chronic phase Philadelphia positive chronic myeloid leukemia (Ph+ CML). In about 70% of patients optimal treatment response could be achieved and sustained for more than 7 years of therapy. We present the experience of the imatinib frontline treatment for CML in University Hospital Center Zagreb, Department of Hematology. Patients and methods: A total of sixty seven patients with Ph+ CML were treated with first line imatinib, from February 2003. Here we evaluated fifty eight of them, who were eligible for twelve months follow up. Median follow up time was fifty two months (range 12-103 months). There were males and females, with a median age of forty nine years (range 14-74, years). Patients were treated with 400 mg/day. They were regularly checked for treatment response every 3 months with cytogenetic methods (G-banding and FISH) and quantitative RT-PCR. Results: In forty one patients (70%) complete cytogenetic response (CCR) was documented. Out of those forty one patients, twelve patients (20%) achieved complete molecular response (CMR). Twenty three patients (40%) achieved a major molecular response (MMR). Two patients (3.4%) were resistant to first line treatment and were subsequently treated with nilotinib. Another two patients (3.4%) progressed to acute lymphoblastic leukemia, both after 2.5 months of the therapy with imatinib. One of them had a T315I mutation, and was subsequently treated with MUD allogeneic stem cell transplantation. One patient progressed to acute myeloid leukemia. Another patient had a progression of the disease during the chronic phase, with a verified T315I mutation. He was treated with allogeneic stem cell transplantation. Eight patients (13%) died during the course of the treatment of the disease. In four patients imatinib dose was increased to 600 mg or 800 mg. Subsequent optimal response was documented in all four patients. Two patients (3%) had serious side effects to the treatment and were therefore switched to nilotinib. Conclusion: Optimal response with imatinib is reported in 41 patients. Progression of the disease to accelerated/blastic phase was found in 3 patients. Eight patients died. Four because of CML. Our experience has proved also that imatinib is an effective frontline therapy for Ph+CML.

High-dose chemotherapy followed by autologous hematopoetic stem cell transplantation is well established first line therapy for multiple myeloma. It has been previously shown that tandem transplantation carries survival benefit when compared to a single transplantation. We have conducted a trial of two successive high-dose chemotherapy followed by peripheral blood stem cell rescue for patients with advanced stage multiple myeloma. Aim Aim was to evaluate feasibility, efficacy and toxicity of tandem transplantation. Patients and Methods We included 107 patients, median age 54 years (32-66), 49 were female, and 58 male patients. Most of the patients had IgG monoclonal protein (54.2%), 17.7% patients had IgA monoclonal protein, 17.7% had light chain myeloma, while 9.3% had non-secretory myeloma, and one patient had IgD monoclonal protein. Patients were evaluated on a intention to treat basis, and from 107 included patients, 83 (77.5%) received tandem transplantation ; 4 patients did not collect adequate number of cells for two transplantations, 10 patients had low performance score, 7 were not transplanted due to physician decision, 1 patient refused second transplantation, 1 patient relapsed and for 1 patient the reason is unknown. Results Progression free survival (PFS) and overall survival (OS) were evaluated. Median time of progression free survival for the entire group was 77 months, while median time of overall survival was 138 months. Prior to first transplantation 8.6% of patients were in complete remission or very good partial remission (CR/VGPR), 78% were in partial remission (PR) and 11.4% had minimal response, while 1.9% had progressive disease. After the first transplantation 42.3% achieved CR/VGPR and 50% of patients were in PR, while after the second transplantation 71.8% of patients were in CR/VGPR and 26.2% were in PR. We conducted analysis of PFS and OS according to disease status prior to second transplantion and found no significant difference between patients that achieved CR or VGPR and the patients that did not do so. However, when the same analysis was done according to disease status 6 months after the second transplantation, a significant difference in both PFS and OS was found between patients that achieved CR/VGPR and the patients that did not achieve CR/VGPR (p=0.0179 and p=0.0056 respectively). Conclusion Tandem transplantation as first line treatment for multiple myeloma is an effective therapy offering patients long term progression free survival and overall survival. We found no significant difference in long term PFS and OS between patients that achieved CR/VGPR prior to second transplantation and those that did not, indicating important therapy efficacy of second transplantation. Also, patients achieving CR/VGPR after second transplantation have statistically better PFS and OS than patients failing to do so, which emphasizes importance of achieving CR as a final outcome.

Rad prikazuje naša iskustva u liječenju Hodgkinovog limfoma eBEACOPPom

Rad prikazuje naša iskustva sa CCEP kemoterapijom.

Fine-needle aspiration (FNA) biopsy has become a well established technique in the diagnosis, staging, and follow-up of patients with head and neck lesions. As in lymphoma diagnostics, FNA serves as a screening method in evaluating potentially affected lymph node for open or core biopsy. According to the World Health Organization classification of lymphoid neoplasms, today it is important to recognize cell morphology and reveal its phenotype, then combine it with different genotypic information and clinical data to provide appropriate therapy. The aim of this study was to assess the efficacy of FNA and immunocytochemistry based lymphoma diagnostic in head and neck region. We conducted a retrospective study during a period of three years where cases with either FNA diagnosis or clinical suspicion of newly recognized or relapsing lymphoma were reviewed. In the study were included patients that were referred to our laboratory from hematology department, in whom head and neck lymphadenopathia was found and lymph node FNA preceded other procedures. Two hundred eighty-five aspirations from 248 patients fulfilled study criteria. Adequate specimens were diagnosed as lymphoma in 100 cases (36%), in 65 male and 35 female patients, 76 in patients with newly discovered disease and 24 in patients with prior lymphoma diagnosis. Overall sensitivity of FNA specimens in the diagnosis of head and neck lymphomas was 90%, specificity 88%, predictive value of a positive result 97%, and predictive value of negative result 61%. Based on our results FNA corroborated with immunophenotyping by immunocytochemistry can be method of choice in primary lymphoma diagnosis as a method complementary to histopathology in lymphoma diagnostics.

Tekst u Biltenu broj 2 prikazuje definiciju nozoloških cjelina koje obuhvaća rad pododbora te evoluciju od tradicionalnih prema suvremenim klasifikacijama KLL.

Background. Myeloid sarcoma (MS) is a solid tumor found at any site other than the bone marrow, composed of myeloid blasts that may show different degrees of maturation. Infiltrates of myeloid cells found in any site in the patient with leukemia are not classified as MS. Case. We present the case of a 75-year old man with a nodular tumor on his right calf. The tumor was grayish, measuring 1, 8 cm in its largest diameter. Histologically, the dermis was diffusely infiltrated by large tumor cells. Immunohistochemistry showed that the tumor cells were positive for myeloperoxidase and myeloblasts were positive for CD34. The cells were mostly myeloblasts but there were also myeloid cells in different stages of maturation. The patient’s medical history revealed that he has been previously treated for a chronic myeloid leukemia (CML) and then for transition between accelerated phase and blast phase. So this case represents a disease progression of CML presented with myeloid sarcoma. Conclusion. Clinical presentation of acute leukemia and myeloproliferative disease as myeloid sarcoma of the skin is not rare, but always represents a diagnostic challenge. The differential diagnoses of MS include lymphoma and histiocytic sarcoma, both of which are excluded by the use of immunohistochemistry. To differentiate MS from AML or CML infiltrates the clinical data must be provided because morphology and immunohistochemistry are not sufficient.

Residual masses are frequently observed in patients with Hodgkin disease (HD) after therapy and discrimination between active tumor tissue and fibrotic residues remains a clinical challenge. In the large percentage of patients (> 60%) conventional imaging methods show remaining tumor masses at the end of therapy, although only a small percentage of these patients still have active disease and eventually will relapse. AIM: The aim of this study was to asses the value of the F-18-FDG PET in detecting residual disease in patients with residual masses after completed therapy, in comparison to the tumor masses volume changes according to the CT after therapy. METHODS: 66 patients with HD and residual masses (size1.2-5.2 cm in diameter) after completed initial or second line therapy were retrospectively included in our study (29 male ; 37 female), median age 29.5 (range 13-80 years). All lesions have been confirmed by histological examinations before treatment and patients staged according to Ann Arbor classification. They were assigned for FDG PET at least 3 weeks after chemotherapy and 12 weeks after radiotherapy. Using computed tomography patients were divided in four groups according to the changes in volume of tumor mass after the therapy (I- tumor reduction < 30% ; II- tumor reduction 30-50% ; III- tumor reduction > 50-70% ; IV- tumor reduction > 70%). RESULTS: PET negative residual mass were observed in 42 patients (64%) and positive findings were observed in residual masses of 19 patients (29%). Five patients had equivocal findings (7%). Although the percentage of PET positive findings were the highest in the first two groups with lowest regression, in comparison with the other groups in which higher percentage of tumor volume reduction was noticed (I – 32% positive ; II – 61% positive ; III 12, 5% positive and IV- 17% positive findings). CONCLUSIONS: Changes in volume of tumor mass, as documented with computed tomography, are neither sensitive nor specific enough for accurate evaluation of residual disease. FDG PET is superior to conventional imaging for detection of residual active disease at the end of treatment what has great influence on further management. In our study, 17% of patients with almost complete regression of tumor masses had residual disease after therapy and should be further treated. Contrary, even 58% patients with minimal tumor shrinkage had not active disease and should not be additionally treated.

70-yr-old women was referred to our department because of osteoporosis. She was previously followed by a hematologist for 1 year because of unexplained erythrocytosis with normal platelt and leukocyte count. Endocrinological evaluation showed preserved circadian rhythm of cortisol secretion, and the reverse rhythm of ACTH, with slightly elevated 24-h urinary free cortisol level. The overnight dexamethason suppression test showed inadequate cortisol suppression. MR disclosed a pituitary tumor. Transsphenoid tumor ablation was carried out. Pathohistology and immunohystochemistry revealed corticotropinoma. Six month after operation patient had erythrocytes count within normal limits.

Leukemija vlasatih stanica (triholeukemija) je kronična B-limfocitna leukemija karakterizirana klonalnom proliferacijom vlasastih stanica. Terapija izbora su purinski analozi, u prvom redu kladribin. Liječili smo trideset bolesnika kontinuiranom infuzijom kladribina kroz 7 dana u dozi od 0.1mg/kg dnevno ili dvosatnom infuzijom kroz 5 uzastopnih dana u dnevnoj dozi od 0.14mg/kg. Remisiju je postiglo 90% bolesnika. Nakon medijana praćenja od 44 mjeseca preživljavanje je 93%, a prosječno trajanje odgovora preko 6 godina. Dva bolesnika nisu reagirala na terapiju, a jedna bolesnica je umrla od infekcije kratko nakon terapije. Nuspojave su najčešće bile posljedica hematološke toksičnosti, neutropenični febrilitet zabilježen je kod 23% bolesnika, dok je 20% bolesnika je zahtijevalo transfuzije eritrocita i trombocita. Naši rezultati pokazuju da je kladribin siguran i učinkovit u liječenju leukemije vlasastih stanica. Nije bilo značajnijih razlika u toksičnosti i djelotvornosti između sedmodnevne kontinuirane i petodnevne intermitentne primjene lijeka.

Myeloproliferative disorders share clinical and biological similarities that may be influenced by presence of recently discovered point mutation in JAK2 gene (JAK2 V617F). The aim of this study was to determine the correlation between JAK2 V617F mutation and the clinical features of patients with polycythemia vera (PV) and essential thrombocythemia (ET). The study included 36 patients with PV (PV group) and 38 patients with ET (ET group). The diagnosis was established according to the Polycythemia Vera Study Group criteria. The detection of JAK2 V617F was performed by allele specific PCR (Baxter et al., Lancet 2005) on DNA isolated from bone marrow cells or peripheral blood cells. JAK2 V617F positive and negative members of PV and ET groups were analyzed for peripheral blood counts and bone marrow aspiration. JAK2 V617F positive PV patients exhibited statistically significantly higher number of red blood cells, white blood cells and platelets when compared to PV patients negative for JAK2 V617F. No statistically significant difference was found in hemoglobin concentration and hematocrit value. In contrast, JAK2 V617F positive subjects of the ET group had statistically significantly increased number of red blood cells, hemoglobin concentration and hematocrit value, and no significant difference in platelet or white blood cell count. Bone marrow evaluation revealed that JAK2 V617F positive patients of the PV group had myeloid hyperplasia with the excess of eosinophils and platelet clumps, which is consistent with the findings of the peripheral blood analysis. On the contrary, bone marrow evaluation of the ET group did not reveal any significant differences between JAK2 V617F positive and negative patients. Overall our data suggest that JAK2 V617F mutation status could serve as a criterion to categorize both PV and ET patients into distinct subgroups. Further studies are needed to determine whether JAK2 V617F mutation status in myeloproliferative disorders should be used as a criterion for therapy approach.

Molecular basis of myelodysplastic syndrome (MDS) is characterized by a number of frequently occurring abnormalities. Cytogenetic abnormalities in MDS are among the most important routine parts of diagnosis and prognosis, but mutations like internal tandem duplication (ITD) in FLT3 gene and point mutation V617F in JAK2 gene may provide supplementary information. Since some forms of MDS show a significant overlap with chronic myeloproliferative disease (MDS classified as MDS/MPD-U) or acute myeloid leukemia (AML transformed from MDS), this prompted us to determine the prevalence of FLT3 ITD and JAK2 V617F mutations in patients with MDS. The study included a total number od 50 MDS patients classified according to the World Health Organization classification: 4 patients with refractory anemia (RA), 13 patients with myelodysplastic/myeloproliferative disease-unclassifiable (MDS/MPD-U), 4 patients with chronic myelomonocytic leukemia (CMMoL), 8 patients with RA with excess of blasts (RAEB) and 21 patients with secondary AML (AML transformed from MDS, but not therapy-related MDS). Analysis of bone marrow was done by conventional cytogenetic and fluorescence in situ hybridization (FISH) for del(5q), del(7q) and rearrangement of MLL gene. DNA and RNA were isolated from bone marrow cells or peripheral blood cells. The detection of JAK2 V617F was performed by allele specific PCR (Baxter et al, Lancet 2005) and FLT3 ITD by RT-PCR (Nakao et al, Leukemia 1996). Structural and numerical cytogenetic abnormalities were frequent in patients with secondary AML and RAEB as expected. There were no patients with isolated del(5q) or del(7q). Patients with CMMoL did not have any karyotypic abnormalities with exception of one patient with del(20q) and izo(17q). The presence of JAK2 V617F was detected in one of four patients with RA and one out of thirteen patients with MDS/MPD-U. There was no mutation detected in patients with RAEB, CMMoL or secondary AML. On the contrary, the only two positive FLT3 ITD patients were those with secondary AML. In conclusion, there is a need to analyze the mutational status of JAK2 and FLT3 gene in order to properly differentiate MDS/MPD-U and to predict possible transformation of MDS toward AML.

Mijeloproliferativne bolesti obuhvaćaju skupinu poremećaja karakteriziranih sličnim kliničkim slikama te klonalnom proliferacijom jedne ili više staničnih loza, što je posljedica transformacije na razini pluripotentne matične stanice. Toj skupini pripadaju i policitemija vera (PV), esencijalna trombocitemija (ET) i idiopatska mijelofibroza (IM) za koje je tek odnedavno poznata molekularna podloga bolesti. Točkasta mutacija gvanina u timin u genu za Janus kinazu 2 (JAK2) koja kodira zamjenu valina fenilalaninom na poziciji 617 (V617F) javlja se u značajnom postotku kod bolesnika s dijagnozom PV, ET i IM. Mutacija V617F smještena je u domeni JH2 gena za JAK2, a uključena je u autoinhibiciju vlastite tirozin kinazne aktivnosti. Mutirani protein se neprekidno iznova fosforilira aktivirajući signalne putove, a stanice postaju neovisne ili preosjetljive na citokine te pojačano proliferiraju. Cilj ovog istraživanja bio je odrediti učestalost mutacije V617F u genu za JAK2 kod bolesnika s dijagnozom PV, ET ili IM. Obrađeno je ukupno 47 bolesnika od kojih 17 s uputnom dijagnozom PV (skupina PV), 20 s dijagnozom ET (skupina ET) te 10 s uputnom dijagnozom IM (skupina IM). Iz stanica periferne krvi ili koštane srži izolirana je DNA. Za dokazivanje točkaste mutacije V617F u genu za JAK2 korištena je metoda alel-specifičnog PCR-a (prema Baxter i sur., Lancet 2005.). Svim bolesnicima napravljena je i analiza PCR na fuzijski gen BCR/ABL. U skupini PV dokazana je učestalost mutacije V617F u genu za JAK2 od 59%, u skupini ET 70%, a u skupini IM 30%. Prisutnost fuzijskog gena BCR/ABL nije dokazana niti u jednom analiziranom uzorku. Nadalje, skupine PV i ET podijeljene su svaka na dvije podskupine s obzirom na prisutnost mutacije V617F u genu za JAK2 te su u svakoj podskupini analizirani parametri krvne slike. Utvrđeno je da ne postoji statistički značajna razlika u prosječnom povišenju broja eritrocita i hematokrita u skupini PV s obzirom na prisutnost mutacije. U skupini ET nema statistički značajne razlike u povišenju broja trombocita kod bolesnika s dokazanom mutacijom V617F, ali je dokazana statistički značajna razlika u povišenju broja leukocita (p=0.007) i hematokrita (p