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The optimal conditioning for patients with acute myeloid leukemia in first complete remission treated with allogeneic hematopoietic cell transplantation (allo-HCT) has not been defined so far. In this retrospective study, we compared two "reduced-toxicity" regimens: intravenous busulfan at a total dose of 9.6 mg/kg (3 days) + fludarabine (Bu3/Flu) and total body irradiation at a dose of 8 Gy + fludarabine (TBI8Gy/Flu). In the entire study cohort (n = 518), the probabilities of overall survival (OS), leukemia-free survival (LFS), relapse and non-relapse mortality (NRM) at 2 years for Bu3/Flu and TBI8Gy/Flu were 62% vs. 72.5% (p = 0.051), 59.5% vs. 65% (p = 0.15), 30% vs. 20% (p = 0.01), and 10% vs. 14% (p = 0.18), respectively. In multivariate model for patients

Studija razina von Willebrandova faktora i faktora 8 u bolesnika sa kroničnim GVHD-om.

Kronična bolest presatka protiv primatelja (eng.Chronic Graft versus Host Disease - cGVHD) najvažnija je kasna komplikacija nakon transplantacije alogeničnih krvotvornih matičnih stanica (aloTKMS) i vodeći uzrok morbiditeta i mortaliteta koji nije povezan s relapsom osnovne bolesti u osoba nakon aloTKMS- a. U ovom izdanju opisuju se rezultati i aktivnosti multidisciplinarnog tima za cGVHD osnovanog 2013. godine na KBC Zagreb.

Introduction: Colonization with Candida sp has significant role in occurrence and pathogenesis of acute Graft-versus-Host Disease (aGVHD) via induction of mucosal innate immunity (Th 17/IL 23 responses). However, data about prevalence and role of Candida sp in chronic Graft-versus- Host Disease (cGVHD) are scarce. The aim of this study was to determine prevalence of oral colonization with different Candida sp in patients with cGVHD and possible association with cGVHD characteristics. Materials (or patients) and methods: This study enrolled cGVHD patients who are part of a larger multidisciplinary cGHVD project at the University Hospital Center Zagreb, Croatia. Patients were evaluated for clinical and cGVHD characteristics ; severity of cGVHD and oral involvement were determined by using established NIH Consensus criteria. Swabs from oral cavity were collected from all patients. Specimens were analyzed by standard cultivation methods (Sabouraud and blood agar, identification by automated biochemical test). Molecular detection was performed by real-time in house PCR designed to distinguish 12 Candida species. Candida isolates were analyzed at proteomic level by Mass Spectrometry (MS/MS). Data were evaluated descriptively. Fisher’s exact test or Wilcoxon test were used to calculate statistical significance. Results: Twenty-one patient was enrolled, median age was 42 years 38% were male. In 15 patients (71%) underlying disease was AML, ALL or MDS, 3 patients had CML or MPN, 1 patient had severe aplastic anemia and 2 patients had lymphoma. Nine patients (43%) underwent myeloablative conditioning. Majority (71%) received PSBC as stem source. Sixteen patients (76%) had previous aGVHD. Ten patients (48%) had oral cGVHD ; 6 patients had moderate or severe NIH oral cGVHD score. Nine patients (43%) had moderate and 12 (57%) had severe NIH global cGVHD score. Six patients (29%) were positive for C. albicans and 3 patients for C. krusei by standard cultivating methods. When using real- time PCR method, 13 patients (61%) were positive for C. albicans, 4 patients for C. krusei, 2 patients with C. dubliensis, 1 patient with C. tropicalis and 1 patient with C. glabrata. Coinfection with 2 or 3 different Candida sp. was found in 6 patients. Ten samples were analyzed by proteomics with 5 samples confirmed as C. albicans. Although more patients were positive for C. albicans and C. non albicans sp by multiplex PCR than cultivation, this was not statistically significant (P¼0.335 and 0.184, respectively). Nine patients with oral cGVHD (90%) had colonization with at least one Candida sp, while 7 patients without oral cGVHD (64%) had colonization with Candida sp (P¼0.311). Ten patients with global severe cGVHD (83%) and 5 patients with moderate cGVHD (55.5%) had Candida sp colonization (P¼0.331). Conclusion: Significant proportion of patients with cGVHD, especially patients with severe global cGVHD were colonized with Candida sp. Use of molecular methods is important in diagnosing C.non albicans (3 new species identified only by PCR). Majority (90%) of patients with oral cGVHD were colonized with Candida sp, however larger studies are needed to determine association between cGVHD global severity and organ involvement with Candida colonization. Considering significant proportion of cGVHD patients colonized with Candida sp, further studies investigating its possible role in pathogenesis of cGVHD, as well as possible prophylactic/therapeutic are needed. Disclosure of Interest: None declared.

Danas se u svijetu sve veći broj bolesnika s malignim i nemalignim bolestima liječi transplantacijom alogeničnih krvotvornih matičnih stanica (aloTKMS). Kronična bolest presatka protiv primatelja (eng. Chronic graft versus host disease - cGVHD) vodeći je uzrok morbiditeta i mortaliteta koji nije povezan s relapsom osnovne bolesti u osoba nakon aloTKMS‑a. Na KBC Zagreb u 2013. godini formiran je multidisciplinarni tim za liječenje cGVHD-a i dugotrajnih komplikacija nakon aloTKMS-a u suradnji s National Cancer Institute (NCI), NIH, SAD.

Previous studies reported independent associations of hematological parameters with insulin resistance. The aim of this study was to explore the associations of hematological parameters, including red blood cell count (RBC), hemoglobin (Hgb), white blood cell count (WBC), and platelets with insulin resistance in type 1 diabetes. Study included 353 patients with type 1 diabetes. None showed signs of acute or chronic inflammatory, renal and cardiovascular diseases. Insulin sensitivity was measured with estimated glucose disposal rate (eGDR) calculated with the equation: eGDR=24.31-(12.22xWHR)-(3.29xAHT)- (0.57xHbA1c). The units were mg.kg-1min-1 ; WHR=waist to hip ratio ; AHT=hypertension. RBC, Hgb, and WBC significantly correlated with insulin resistance measured by eGDR (r=-0.12, -0.21, and -0.14, respectively, all P≤0.01), and its components disorders, most notably WHR (r=0.38, 0.44, and 0.16, respectively, all P≤0.001). In a multiple logistic regression analysis after adjustment for age, sex, duration of diabetes and BMI, the presence of insulin resistance was independently associated with WBC count (odds ratio=1.28, P

Background: Up to now there have been missing data in the literature concerning relationship of galactomannan (GM) detected in bronchoalveolar lavage (BAL) fluid and type of abnormality on pulmonary high resolution computer tomography (HRCT) in patients (pts.) with pulmonary invasive aspergillosis (IPA). Aims: To evaluate relationship between sensitivity of GM detected in BAL fluid and serum (S-GM) and type of abnormality on pulmonary HRCT in pts. with IPA. Methods: We retrospectively analyzed mentioned relationship in pts. with IPA entered in „Fungal InfectioN Database (FIND)“ aspergillus between 2001 and 2012.

Diabetes mellitus is a well known risk factor for infections, which remain a major cause of morbidity and mortality in patients treated with autologous peripheral blood stem cell transplantation (PBSCT). We have evaluated infectious complications following transplantation in 132 consecutive patients with relapsed or refractory Non-Hodgkin’ s lymphoma (n=101) and Hodgkin’ s disease (n=31) treated with PBSCT. Febrile neutropenia occurred in 86 (65.6%) patients at a mean of 6 days after transplantation (range 1-9, SD 1.59). Patients with diabetes mellitus had a clear predisposition for infectious complications following PBSCT. All 10 patients with diabetes developed febrile neutropenia. Compared to patients not having diabetes mellitus, they also had significantly longer median time to defervescence (4 days vs. 2 days, Logrank p=0.03). Furthermore, diabetic patients had a higher incidence of serious infections: 60% of febrile episodes in these patients (vs. 30.3% in non- diabetics) were microbiologically proven bacteremias (p=0.07). Gram positive microorganisms were responsible for the majority of documented infections with Staphylococcus epidermidis being the most frequently isolated pathogen. Infections are serious but manageable complications of PBSCT, even in patients with unfavorable risk factors. Patients with lymphoma and diabetes mellitus undergoing stem cell transplantation are especially prone to infections during the neutropenic period following transplantation. Early empirical antimicrobial therapy, tailored according to local microbiological epidemiology is essential for their optimal treatment.

B-cell chronic lymphocytic leukemia (B-CLL) cells are variably distributed among the major lymphoid compartments contributing to the heterogeneous clinical presentation and course of this disease. In order to evaluate this variable distribution we propose a model for its clinical assessment. We introduce the model for tumor distribution (TD) assessment based on TTM scoring system, where TD value represents percentage of total tumor mass infiltrating peripheral blood and bone marrow (TD=TM(1)/TTM). TD in B-CLL can be categorized into 3 subgroups: pure leukemia if TD=100%, predominantly leukemia if TD=50-99% and predominantly lymphoma TD

Imunofenotipizacija u dijagnostici bolesti limfnog čvora zauzima značajno mjesto. S jedne strane je od velike pomoći pri razlikovanju reaktivnih hiperplazija od B NHL, a s druge strane u subtipizaciji limfoma, koja se temelji na određivanju diferencijacijskih biljega limfatičnih stanica. Cilj rada je bio: 1. analizirati adekvatnost uzoraka punktata limfnih čvorova na protočnom citometru; 2. analizirati prisustvo klonalnosti u svrhu odvajanja reaktivnih od B klonalnih poremećaja; 3. analizirati podudarnost citološke i histološke subtipizacije s imunofenotipom učinjenim na protočnom citometru; 4. analizirati mogućnost subtipizacije ALCL od HB te velikostaničnih limfoma od slabo diferenciranih tumora drugog staničnog podrijetla imunocitokemijskom analizom na razmazima upotrebom kombinacije staničnih biljega. U KB "Merkur" u razdoblju od 3 godine učinjena je 201 analiza punktata limfnih čvorova na protočnom citometru. Određivana je prvenstveno klonalnost, a u slučajevima monoklonalnih neoplazmi i subtipizacija. Adekvatnost uzorka za analizu iznosila je 95.1%. Poliklonalnost u citološki dijagnosticiranih reaktivnih hiperplazija iznosila je 98.9% (91/93) što daje veliku sigurnost u odvajanju malignih limfoma B fenotipa od reaktivnih hiperplazija. Podudarnost imunofenotipa (odvajanje T i B neoplazmi) u odnosu na citološku dijagnozu iznosila je 97.1% (102/105), te 94.2 (65/69) za patohistološku dijagnozu. Sukladnost subtipizacije limfoma imunološki, citološki i patohistološki pokazala je znatno nižu reproducibilnost od svega 50.7% (35/69). Imunofenotipizacija protočnim citometrom nije nam pomogla u dijagnostici perifernih T limfoma i Hodgkinove bolesti. U slučajevima kad je limfni čvor nedostupan eksciziji i patohistološkoj analizi, kod infiltracije tjelesnih tekućina limfomskim stanicama, tijekom praćenja bolesti, razlikovanju ALCL od HB te velikostaničnih limfoma od slabo diferenciranih tumora drugog biološkog podrijetla pomaže nam imunocitokemijska analiza na citološkim razmazima upotrebom kombinacije staničnih biljega.

Apsolutna limfocitoza u perifernoj krvi, infiltracija koštane srži, limfnih čvorova i/ili slezene malim limfocitima karakterizira kroničnu limfocitnu leukemiju (CLL). Istraživanjem je obuhvaćeno 10 uzorka periferne krvi i koštane srži kod normalnih osoba, 10 uzoraka periferne krvi i koštane srži bolesnika s CLL-om te 4 punktata limfnih čvorova kod istih bolesnika. Ukupno je analizirano 1000 limfocita periferne krvi kod normalnih osoba i bolesnika s CLL-om, 1000 limfocita koštane srži kod normalnih osoba i bolesnika s CLL-om te 400 limfocita punktata limfnih čvorova kod bolesnika s CLL-om. Morfometrijski su analizirani parametri cijele stanice te posebno jezgre: oblik, površina, konveksitet te faktori pravilnosti (faktor opsega, faktor konveksiteta te faktor izduženosti). Nije nađena statistički značajna razlika niti u jednom od navedenih parametara između normalnih limfocita i limfocita u bolesnika s CLL-om. Isto tako, nije uočena heterogenost limfocita u različitim odjeljcima tumorske mase (perifernoj krvi, koštanoj srži i limfnim čvorovima) najvjerojatnije zbog malog broja uzoraka, ali i zbog odabira tipičnih oblika CLL-a. Sama morfometrija limfocita nije dovoljna, kao posebni kriterij, za diferencijaciju normalnih od neoplastičnih limfocita u CLL-u te su osim samog izgleda, potrebne i dodatne pretrage: apsolutna limfocitoza (> 5x109/L), infiltracija koštane srži, određivanje fenotipa te klonalnost limfocita.

Neke specifične kromosomske abnormalnosti u akutnim leukemijama udružene su s karakterističnom morfologijom i imaju različitu kliničku sliku (WHO 2000). Specifične kategorije definiraju se kao: AML t(8;21)(q22;q22), 2. akutna promijelocitna leukemija s t(15;17)(q22;q11-12) i varijanta, 3. AML s abnormalnim eozinofilima u koštanoj srži inv (16)(p13:q22) ili t (16;16)(p13;q22), 4. AML s 11q23 (MLL) abnormalnosti, 4. Burkitt cell leukemija i translokacija 8;14 itd. U KB ŤMerkurť je liječeno 317 akutnih leukemija citogenetskih tipiziranih u Zavodu za citogenetiku Klinike za dječje bolesti KBC Rebro. U svega 10 slučajeva (3.1%) analiza nije bila moguća ili je bila manjkava. 47% akutnih leukemija je bilo bez kromosomskih abnormalnosti. U 53% svih leukemija (podjednako AML i ALL) nađene su citogenetske abnormalnosti. Potvrđena je dobra korelacija između morfološke slike i pripadajuće abnormalnosti kod akutne promijelocitne leukemije i translokacije 15;17, te Burkitt cell leukemije i translokacije 8;14, kao i u akutnoj mijeloičnoj leukemiji s tanslokacijom 8;21 ako se dovoljno na to misli, nešto manja kod AML s abnormalnim eozinofilima u koštanoj srži i inverziji 16, dok je akutnu leukemiju s kromosomskom promjenom 11q23 nemoguće morfološki prepoznati. Morfologija i imunofenotipizacija nijsu ame dovoljne za klasifikaciju akutnih leukemija te je citogenentska analiza obavezna u subtipiziranju specifičnih kategorija.

Malignitet karakterizira promjena sadržaja DNA - aneuploidija. Morfološke karakteristike jezgara malignih stanica vidljive u standardnim May- Grunwald-Giemsa bojenim preparatima, svojom hiperkromazijom upućuju na promjenu sadržaja DNA. Budući su te promjene nedostupne vizualnoj kvantifikaciji u njihovoj analizi koristi se automatski analizator slike, koji se sastoji od mikroskopa, video kamere i računala s odgovarajućim programom za analizu slike SFORM, koji omogućuje numeričku objektivizaciju promjene intenziteta obojenja. Analizirali smo 31 punktat limfnog čvora bolesnika oboljelih od velikostaničnih limfoma - 6 bolesnik s Burkitt i Burkitt-like limfom, 4 bolesnika FC III, 10 bolesnika ALCL-om ( T ili 0) te 11 bolesnika s DLBCL. Preparati su obojeni metodom po Feulgenu. Rezultati su pokazali da postoji heterogenost u količini DNA unutar istovjetnih morfloških podskupina velikostaničnih limfoma. Postotak stanica >30 u S+G2M fazi ili >30% stanica sa DNA> 2N govori za brzi relaps bolesti, kraće preživljenje ili pak korelaira s kompleksim kromosomskim abnormalnostima. Precizno kvantificiranje količine DNA koristi se ne samo u dijagnozi, već i u klasifikaciji i prognozi različitih bolesti, prvenstveno malignih tumora.

Bolesnik star 18 godina dolazi ambulantno zbog povećanog čvora na vratu u veljači 1999. godine. Citološkom punkcijom postavi se dijagnoza slabo diferenciranog tumora i preporuči imunocitokemijska tipizacija. Ostali klinički i laboratorijski nalazi nisu pokazivali odstupanja od normale. Pacijent se hospitalizira, učini se imunofenotipizacija na protočnom citometru te nađu stanice koje nisu limfoidnog podrijetla. Patohistološki nalaz ekstirpiranog dijela čvora nije pokazivao elemente za neoplastični proces. Nakon mjesec dana dolazi do lokanog recidiva na istom mjestu. Citološkom i opsežnom imunocitokemijskom obradom nađu se slabo diferencirane stanice pozitivne na HMB 45, S-100 i vimentin, a negativne na sve limoidne biljege (CD 45, CD 20, CD 3 I CD 30) te se postavi dijagnoza amelanotičnog melanoma. Većina malignih melanoma je pigmentirana. Međutim dijagnoza primarnog ili metastatskog amelanotičnog melanoma predstavlja veliki problem za citologa i patohistologa obzirom na različite morfološke entitete. Dva nespecifična antitijela S 100 protein i HMB 45 te vimentin kao i negativna reakcija na citokeratin i limfoidne markere mogu pomoći u odvajanju od tumora drugog biološkog podrijetla. No situacija nije jednostavna budući maligni melanociti mogu pokazivati različiti stupanj imunoreaktivnosti i s NSE, nekim citokeratinima i CEA. S druge strane nemelanotične stanice kao Schwannove stanice i C stanice štitnjače, primitivne neuroektodermalne stanice kao meduloblasti mogu također sintetizirati melanin. Opsežna imunocitokemijska obrada, uz ultrastrukturalnu elektronskomikroskopsku analizu, jedini je izlaz u dvojbenim slučajevima.

Bolesnica 39 godina hospitalizirana je u više navrata u MC Karlovac te Klinici za unutarnje bolesti KB" Merkur" zbog sumnje na mastocitozu. Klinički bolesnica je patila od napadaja koji se javljaju više puta tjedno, a počinju kao osjećaj gušenja, nakon čega slijedi lupanje srca, crvenilo lica praćeno gubitkom svijesti. Nakon napada obično uslijedi temperatura, ginekološko krvarenje i nekontrolirana stolica. Bolesnica ja smršavila 10 kilograma u 6 mjeseci i javio se svrbež kože, osobito dlanova i tabana. Status je uredan. Od nalaza prisutna je ubrzana sedimentacija, leukocitoza ( 21×109/L ), anemija. U leukogramu se nađe 14% eozinofilnih granulocita, a punkcijom koštane srži 36% eozinofilnih granulocita i 24% toluidin pozitivnih stanica - mastocita. Uz ordiniranu terapiju kortikosteroidima, antihistaminicima, nakon 8 mjeseci dolazi do pogoršanja bolesti uz svakodnevnu pojavu napada i leukocitozu ( 64 - 107× 109/L ). Pogoršanje se verificira u punktatu i bioptičkom uzorku kosti - porast broja atipičnih mastocita 44%, uz pojavu mastocita i u perifernoj krvi. Kariogram iz stanica koštane srži nije pokazao klonske abnormalnosti.U terapiju se uvode i citostatici, a bolesnica nakon 3 mjeseca umire pod slikom hemoragijske dijateze i sepse. Sistemska mastocitoza često je udružena s eozinofilijom, dok pojava limfadenopatije, izostanak infiltracije kože i udruženost s mijeloproliferativnim i mijelodisplastičnim bolestima upučuje na lošu prognozu. Sistemska mastocitoza može preći u akutnu leukemiju obično u M1, M2 ili M4 rijeđe u M6 i M7, a najrjeđe u mastocitnu leukemiju. Mastocitna leukemija najčešće nastaje de novo, arijeđe iz urtikarije pigmentoze odnosno sistemske mastocitoze.

Flow cytometry techniques (FCM) immunophenotyping, which can be readily performed on the limited size obtained by fine-needle aspirates (FNA), provides more objective information then FNA cytology alone. 87 lymph node FNA specimens from patients suspected having hematological malignancy were analyzed by FCM. Obtained results by FCM were interpreted according either to the normal values for lymph node lymphoid cells reported previously by Bryan et all (Ann. N.Y. Academ.Sci. 1993. 84: 404-406) or to the REAL classification of lymphoid neoplasms. Table 1 presents comparative results obtained by two methods on 87 lymph node FNA specimens: final diagnosisproved by: non-malignant hyperplasia malignant disorder: Hodgkin's disease B-chronic lymphocytic leukemia B-NonHodgkin lymphoma T-Non Hodgkin lymphoma FCM 36 48 0 3 36 6 cytology 36 51 3 3 37 8 agreement 100% 94% 0% 100% 97% 75% In conclusion, FCM is reliable and useful tools for distiguishing reactive and neoplastic processes, in asigment of malignant cells to the B or T cell lineage, even for futher subclassification of disease, but it is not diagnostically helpful in the case of Hodgkin's disease (without agreement with cytomorphology analyses).

Objectives: “Fungal InfectioN Database” (FIND) represents international database of invasive fungal infections in Czech and Slovak hematooncological departments. FIND - aspergillus covers all case of invasive aspergillosis (IA) in participating centers since 2001. Methods: The goal of our retrospective analysis was to evaluate incidence, early diagnostic procedures and effect of antifungal therapy in proven and probable IA that occurred in 16 institutions participating in FIND database between 2001–2011. Till 2009 we followed EORTC/MSG 2002 and from 2010 EORTC/MSG 2008 criteria in evaluation of IA diagnosis and therapy response. Results: 256 probable and 58 proven IA (91% isolated pulmonary IA, IPA) have been documented. Prolonged and profound neutropenia (61%) and long-term use of corticosteroids (28%) were identified as the major risk factors of IA. 68% pts. had consecutive positivity of serum-galactomannan (S-GM) (OD index >0.5). 83% pts. with IPA and bronchoalveolar lavage (BAL) had positive GM in BAL fluid (OD index >0.5). In pts. with IPA only 7.6% BAL fluids and 8.4% sputum samples had positive microscopic result for filamentous fungi and 2.2% BAL fluids and 1.8% sputum samples had positive culture for Aspergillus spp. The primary antifungal therapy of IA was used in 89% pts. - 41% voriconazole (VORI), 7% echinocandins (ECHINO), 23% VORI+ECHINO, 7% amphotericine B deoxycholate (C-AMB) and 9% lipid- based AMB (LBA). Overall RR to primary therapy of IA was 46% - VORI 55%, VORI+ECHINO 54%, C-AMB 35%, LBA 39%, ECHINO 25%. There was a statistically significant difference in overall RR to targeted therapy in pts. with neutrophil count 1.0x10e9/L at the end of therapy (21% vs. 71%). The overall mortality rate was 61%, with 39% attributable to IA. Conclusion: On the basis of our analysis we confirm typical risk factors for IA and critical role of S-GM and CT for early diagnosis and prompt start of antifungal therapy of IA. A reasonable treatment response was achieved using VORI, VORI+ECHINO or LBA in primary therapy of IA. We have confirmed neutropenia at the end of antifungal therapy as the major predictive factor for therapeutic response. On behalf of CELL - The Czech leukemia study group for life.

Anaplastic Large Cell Lymphoma (ALCL) is described as a distinct clinico-pathological entity but recent studies suggest it to be a heterogeneous disorder. Pathomorphological similarities to some subtypes of Hodgkin’s Lymphoma (HL) contribute to such impression. Oncogenic marker, a fusion gene Nucleophosmin/Anaplastic Lymhoma Kinase (NPM/ALK) is reported to be specifically associated with ALCL. Resulting activity of a receptor tyrosine kinase ALK is considered responsible for lymphomagenesis. In a series of 121 consecutive CD30+ lymphoma patients, classified by experienced hematopathologist based on routine morphological and immunophenotypic analyses as either ALCL (49) or HL (72), ALK protein expression and incidence of NPM/ALK rearrangement was investigated to evaluate whether this marker has clinical prognostic power and whether adding ALK to other clinical and laboratory parameters will make a difference in discriminating ALCLs from HLs. ALK1+ immunostaining was found in 12/72 HLs and 13/49 ALCLs. Molecular analysis by RT-PCR in 46 available diagnostic lymph nodes revealed NPM-ALK fusion transcript in 2 ALCLs (1 also ALK1+) and 4 HDs. There is a discrepancy in the number of ALK1 immunoreactive cases and molecular results. However, molecular event of NPM-ALK rearrangement is not the only possible mechanism of ALK gene upregulation as more parter genes coming into fusion with ALK are being reported. On the other hand in six NPM-ALK gene positive but ALK protein negative cases a posttranslational modification of protein conformation might have impaired immunobinding properties of ALK1 antibody. Hematological and clinical characteristics were further compared in 111 patients (66 HL and 45 ALCL) where univariate analysis showed difference between the two groups for the presence of constitutional symptoms, performance status, ESR, WBC count, serum copper and LDH. There was no difference for the treatment modality, response, survival and DFS. ALK protein-positive patients, irrespective of lymphoma type, did not have better survival although in some previous reports ALK positivity conferred better prognosis. International Prognostic Index (IPI) has a significant prognostic power for ALCL with p=0.0440 among the 4 risk groups. In conclusion, our study found that evaluating ALK protein/gene expression did not show clinical prognostic value nor did it contribute to differentiation ALCLs from HD variants

Invasive aspergillosis in patients with hematological malignancies in Czech, Slovak and Croatian hematooncological departments: Fungal INfection Database (FIND) analysis (2001-2014) - an update