Search

Uvod i svrha rada: Galektin-3 je jedini galektin kimerične strukture. Uključen je u važne stanične procese: regulaciju proliferacije stanica, apoptozu i angiogenezu.Više od 50% DLBCL-a izražava galektin-3. Preliminarni rezultati pokazuju da galektin-3 + DLBCL ima lošiju prognozu. Svrha je ovog rada usporediti biološke i kliničke karakteristike galektin3+ i galektin-3- DLBCL-a i ishode liječenja. Materijali i metode: U novodijagnosticiranih bolesnika s DLBCL-om, liječenih R-CHOP-om ili sličnim protokolom analizirali smo kliničke karakteristike (dob, spol, IPI, odgovor na liječenje, EFS i OS). Imunohistokemijski smo odredili izražaj galektina-3, BCL2, VEGF i NF-κB i stanično podrijetlo tumora. Rezultati: Uključeno je ukupno123 bolesnika uz medijan praćenja 68 mjeseci. Galektin-3 bio je pozitivan kod 69 (56,1%). Bolesnici koji su imali viši IPI (p=0,002), ABC fenotip (p=0,029) i pojačani izražaj NF-κB (p=0,016) češće su izražavali galektin-3. Izražaj galektina 3 nije značajno utjecao na OS i EFS. BCL2 + bolesnici imali su značajno lošiji ishod ukoliko su istovremeno bili galektin3+ (dvogodišnji EFS 44% vs 73% (p=0,002) i OS 50% vs 74% (p=0,006). Značajno više VEGF + tumora imalo je ABC fenotip. Značajno lošiji ishod imali su VEGF+ DLBCL GCB ali ne i ABC imunofenotipa (p=0,001).U multivarijatnoj analizi BCL2 je bio jedini značajni faktor za EFS i OS, dok izražaj galektina-3 pokazuje trend za lošiji ishod (p=0,068 za EFS i p=0,093 za OS). Zaključak: Naši rezultati u skladu su s eksperimentalnim podacima koji pokazuju da NF-κB stimulira izražaj galektina-3 i da galektin-3 dodatno potencira antiapoptotički učinak BCL2. Galektin-3 je češće izražen kod uznapredovalog stadija DLBCL-a i kod ABC fenotipa, što je u skladu s njegovim potencijalnim proliferativnim i antiapoptotičkim učinkom i njegovim izražajem na memorijskim stanicama., Introduction and aim: Galektin-3 is the only chimeric galectins. It is involved in crucial cellular processes including cell proliferation, apoptosis and angiogenesis. More than 50% of DLBCL express galectin-3. Preliminary results showed that galectin 3+ DLBCL have inferior prognosis. The purpose of this study is to compare biological and clinical characteristics of galectin-3+ and galectin-3- DLBCL and outcomes of treatment. Material and methods: In newly diagnosed DLBCL patients treated with R-CHOP like regimens we analyzed clinical characteristics (age, sex, IPI, response to treatment, EFS and OS). Expression of gal-3, BCL2, VEGF and NF-κB and cell of origin were determined by immunochemistry. Results: 123 patients were included with a median follow up 68 months. Galectin-3 was positive in 69 (56,1%). Patient with high IPI (p=0,002), ABC phenotype (p=0,029) and NF-κB + (p=0,016) expressed galektin-3 more frequently. Expression of galektin-3 did not affect OS and EFS. BCL2 + patients fared significantly worse if they coexpressed galektin-3 (2-y EFS 44% vs 73% (p=0,002) and OS 50% vs 74% (p=0,006)). Significantly higher number of VEGF + tumors were of ABC origin. Outcomes of VEGF + GCB, but not ABC DLBCLs were significantly inferior (p=0,001). In multivariant analysis BCL2 was only significant factor for EFS and OS, while galectin-3 showed trend for worse outcomes (p=0,068 for EFS and p=0,093 for OS). Conclusion: Our results are consistent with experimental data showing that NF-KB stimulates galectin-3 expression and that galectin-3 potentiates antiapoptotic effect of BCL2. Galectin-3 is more commonly expressed in advanced stage DBCL and also in ABC phenotype, which is in accordance with his potential proliferative and antiapoptotic effect and its expression on memory cells.

Purpose: Dose-adjusted EPOCH and rituximab (DA- EPOCH-R) is a regimen used for the treatment of high-risk diffuse large B-cell lymphoma (DLBCL) designed to overcome resistance to standard R-CHOP by combining prolonged exposure of lymphoma cells to cytotoxic agents and dose-adjustment based on toxicity. Data on outcomes of older patients are scarce. Patients and Methods: We collected data on patients with newly diagnosed high-risk DLBCL older than 60 years treated with DA-EPOCH-R. High-risk patients were defined by the age-adjusted international prognostic index score 2 or 3. Results: A total of 120 patients were included. Median age was 69 years (range 60–82). Response rate was 74% ; with 59% complete responses. Dose of DA-EPOCH-R was escalated in 50 patients (42%). Three-year progression-free survival (PFS) and overall survival (OS) was 53% and 58%, respectively, with treatment-related mortality (TRM) of 13%. In univariate analysis, favorable prognostic factors were performance status (PS) (0–2 vs. 3– 4), age (

Background: eBEACOPP is the most effective chemotherapy regimen for younger patients with early unfavourable (EU) and advanced stage (AS) Hodgkin lymphoma (HL), but is burdened with early and late toxicities. The original 14 days of steroids contributes to side effects, including severe osteoarticular events, like avascular bone necrosis (AVN). We have been using eBEACOPP since 2009 for AS and since 2014 also for EU patients. We started reducing the length of steroid treatment to 8–10 days in 2016, primarily to reduce the risk of AVN. Methods: We analysed outcomes of our patients, focusing on the comparison of EU and AS patients and those receiving full length and shorter steroid courses. Data was obtained retrospectively, from the hospital database. Results: 162 patients received eBEACOPP as front- line treatment, 130 with AS and 32 with EU HL. Median age was 31 y, range 19–59 ; 88 (54%) were male. After a median follow-up of 58 mo, 5-y PFS of the whole cohort was 97% and OS 98%. The outcome of EU and AS patients was indistinguishable with a 5-y PFS of 95% vs. 98%, respectively (Fig). Outcome of patients receiving full-length or shorter steroid courses was also indistinguishable, with a 5 y PFS of 98% vs. 95% respectively (Fig). The incidence of AVN was numerically, but statistically insignificantly lower in patients receiving 6 cycles of eBEACOPP with a shorter steroid course (1/42 vs. 4/72, p=0.65). There were no differences in emergency hospital admissions and episodes of febrile neutropenia between the two cohorts. Conclusion: eBEACOPP provides excellent and durable first line disease control. Our data confirms the findings of GHSG of lack of outcome differences between different prognostic groups if eBEACOPP is used as primary treatment. Reducing the duration of steroid treatment to 8 days per cycle is safe, but longer follow-up and more patients are needed to confirm that it reduces serious acute and chronic toxicities.

Indikacije i učinkovitost liječenja hospitaliziranih hematoloških bolesnika koncentratima trombocita

U ovom osvrtu prikazana su preliminarna iskustva hrvatskih hematologa sa COVID-19 u pojedinim hrvatskim hematološkim centrima.

In chronic lymphocytic leukemia, tumor flare reactions, characterized by sudden increase in tumor lesions caused by host immune effector cell infiltration, have been described exclusively after treatment with immunomodulators, most frequently lenalidomide. Here we describe a patient who had recurrence of tumor flare 6 years after the initial event, during treatment with rituximab and chemotherapy. This case report suggests that lenalidomide causes a long-lasting effect on lymph node microenvironment and host T cells.

Podnošljivost kombinacija obinutuzumaba i viših doza klorambucila u prvoj liniji liječenja kronične limfocitne leukemije

Both procedures used in our laboratory, RBC treatment with 0.2 M dithiothreitol-treated RBCs and neutralization test using DaraEx reagent, have not been shown to be sufficiently reliable in resolving the interference with the routine blood compatibility testing caused by the anti-CD38 monoclonal antibody. Therefore, for blood transfusion of these patients it is necessary to provide antigenmatched RBC units. Good collaboration between the ward and the transfusion service, with protocols in place for blood compatibility testing and blood transfusion, remains a precondition for timely and safe blood transfusion for this group of patients.

Purpose or Objective Most studies of radiotherapy in lymphoma were performed in supradiaphrgamatic localizations. Data on efficacy and toxicity of irradiation of infradiaphragmatic fields are scarce. We therefore performed this retrospective study to analyze our experience with lymphoma patients receiving radiotherapy exclusively to infradiaphragmatic fields. Material and Methods We identified 112 patients treated with external beam radiotherapy between January 2003 and December 2014. The median follow-up for all patients is 51 months (range 1-185 months). There were 69 patients irradiated with 2D technique and 43 using 3D conformal radiotherapy (3DCRT). Median dose was 36 Gy, range 4 to 54 Gy. Medium dose per fraction was 2 Gy, range 1.5 to 7 Gy. Data for long-term side effects were available for 80 patients. Results Five and 10-year overall survival (OS) rates were 69% and 58% respectively and 5 and 10- year event- free survival rates (PFS) 59% and 57% for all patients. The in-field and out- of-field recurrence rates were 5% and 21%. Patients with indolent NHL had 5 and 10-year OS rates of 84% and 63% respectively, and 5 and 10-year EFS rates of 54% and 48%. In patients with aggressive NHL 5 and 10- year OS was 75% and 64% respectively and 5 and 10- year EFS 65% and 65%. OS and EFS was significantly better in the group of patients that were irradiated after one line than after two or more lines of chemotherapy (5-years OS 87% vs. 68%, p =0.001 and EFS 72% vs. 28%, p

Background Primary and secondary myelofibrosis (PMF and SMF) are clonal hematopoietic stem cell disorders characterized by myeloproliferation, bone marrow fibrosis, splenomegaly and a strong inflammatory milieu. Glycoprotein YKL–40 emerged as an important biomarker of inflammation, angiogenesis, tissue remodeling, cell proliferation and differentiation. Serum YKL-40 levels were shown to be higher in PMF patients when compared to healthy controls. However, the clinical significance of this finding is unknown. Aims The aim of our study was to investigate serum YKL-40 levels in PMF and SMF patients and to assess its clinical correlations. Methods Using commercially available ELISA kit (R&D Systems Europe, Abingdon, UK) we analyzed serum YKL-40 levels in 30 myelofibrosis patients (13 PMF and 17 SMF) and in 25 sex- and age–matched healthy controls. Correlations with clinical parameters were made. Optimal cut - off for survival analyses was determined using the ROC curve analysis. The Kruskal-Wallis analysis of variance, the Mann-Whitney U test, the Spearman rank correlation, the log rank test and the Cox regression analysis was used. P values 2311.15 pg/mL) had inferior overall survival in comparison to patients presenting with lower YKL-40 levels (≤2311.15 pg/mL) (HR 2.91 ; p=0.034). This association remained significant in the multivariate Cox regression model after adjusting for sex, age, DIPSS score and ruxolitinib therapy (HR 5.59 ; p=0.029). Conclusion This is the first study to report clinical associations and strong prognostic properties of increased serum YKL-40 levels in patients with parimary and secondary myelofibrosis. Serum YKL-40 levels might represent a state of pronounced inflammation and increased tumor burden in myelofibrosis, as they are significantly associated with presence of constitutional symptoms, poor performance status and parameters indicative of stronger myeloproliferation. Additional studies are needed to more precisely elucidate the cell(s) of YKL–40 origin and to clarify the role of YKL-40 in promoting disease progression and bone marrow fibrosis. Prognostic properties of YKL-40 also need to be confirmed in larger prospective cohorts of uniformly treated myelofibrosis patients. Nevertheless, our results identify YKL-40 as a potential prognostic biomarker in myelofibrosis.

Nove smjernice za liječenje bolesnika s kroničnom limfocitnom leukemijom donesene su na temelju rezultata multicentričnih istraživanja za prvu liniju terapije te za liječenje relapsa/refraktorne bolesti. Nadamo se da će ove nove smjernice pridonijeti učinkovitijem liječenju naših bolesnika s kroničnim limfocitnom leukemijom.

Fanconi anemia (FA) is a rare inherited disorder associated with congenital abnormalities, progressive bone marrow failure and a predisposition for hematological and nonhematological malignant disease. Bone marrow failure initially presents with thrombocytopenia, erythrocyte macrocytosis, followed by granulocytopenia and anemia. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative option for the hemato-logical diseases of FA. We present a boy with pancytopenia as a first manifestation of the FA at the age of 5. The boy is the first FA patient in our country treated with HSCT. The bone marrow from a matched unrelated donor was transplanted. Conditioning regimen we used is based on GEFA03 protocol which includes fludara-bine, cylophosphamide and busulfan together with alemtuzumab and mycophenolate mofetil as GVHD prophy-laxis.

Sažetak. Unatrag nekoliko godina u hematologiji i onkologiji globalno sve češći problem postaje prikladna opskrba „starijim i manje zanimljivim“ kemoterapeuticima. Zbog povremene nestašice karmustina, jednog od osnovnih kemoterapeutika pri kondicioniranju prije autologne transplantacije krvotvornih matičnih stanica (ATKS) u oboljelih od limfoma, u našem se centru od 2016. godine on zamjenjuje bendamustinom. U ovom radu retrospektivno analiziramo tijek ATKS-a u 41 bolesnika koji su primili bendamustin u sklopu protokola BeEAM te ga uspoređujemo s tijekom ATKS-a u 40 bolesnika koji su primili karmustin u sklopu protokola BEAM. Medijan oporavka vrijednosti neutrofila (> 0,5 × 109/l) u skupini koja je primila bendamustin iznosio je 11 dana, dok je u skupini kondicioniranoj karmustinom iznosio 10 dana. Medijan oporavka vrijednosti trombocita (> 20 × 109/l) bio je duži kod skupine koja je primala bendamustin (16 prema 13 dana) te su ti bolesnici bili duže ovisni o transfuzijama eritrocita (7 prema 5 dana). Infektivne komplikacije nisu bile češće nakon primjene bendamustina, ali smo nakon primjene karmustina imali veću pojavu mukozitisa II. – III. stupnja (35% prema 12%). Nakon primjene bendamustina zabilježen je jedan slučaj nefrotoksičnosti i kardiotoksičnosti terapije, dok kod primjene karmustina te komplikacije nisu zabilježene. Pri upotrebi bendamustina kod kondicioniranja u naših bolesnika u ovom trenutku nije utvrđena znatnija hematološka toksičnost u odnosu prema karmustinu, ali su prisutni dulji period oporavka vrijednosti trombocita te niža incidencija mukozitisa., Summary. Inadequate supply of „old and less interesting“ chemotherapeutic agents is becoming a global issue in hemato-oncology today. In 2016 we were faced with occasional carmustin shortage, one of the most commonly used in autologous transplant conditioning regimens for lymphoma in our centre, so we decided to use bendamustin instead. We performed a retrospective analysis of 41 patients treated at our centre who had received bendamustin within BeEAM protocol and compared them with 40 patients who had received carmustin within BEAM protocol. Both protocols were used as conditioning protocols before autologous stem cell transplantation. Neutrophil recovery median following transplantation (ANC>0,5x109/l) was 11 days in the bendamustin group in comparison to 10 days in the carmustin group.Platelets recovery median following transplantation (PLT>20x109/l) was longer in the bendamustin group (16 vs.13 days) as was blood transfusion dependency (7 vs. 5 days). Infectious complications were not more frequent after bendamustin, but grade II–III mucositis was more frequent in patients who received carmustin (35% vs.12%). Following bendamustin we had one reported case of nephrotoxicity and cardiac toxicity, not reported with carmustin. Bendamustin has shown similar hematologic toxicity compared to carmustin but a longer platelet recovery period and a lower mucositis incidence.

Background: Escalated BEACOPP (eBEACOPP) is an effective but fairly toxic regimen for the treatment of Hodgkin lymphoma (HL). Avascular necrosis (AVN) of femoral head was previously reported to increase in patients treated with eBEACOPP, but so far, no systematic analysis of its frequency has been published. Aims: To analyse the frequency and identify possible risk factors for AVN development in patients treated with eBEACOPP. Methods: We identified 26 patients treated with eBEACOPP for newly diagnosed high- risk advanced-stage HL, 25 of whom were alive at the time of study. All patients were invited to participate in a cross-sectional study ; 17 patients responded and were evaluated by magnetic resonance imaging and orthopaedic examination. Results: Six patients (35.3%) were diagnosed with AVN after receiving eBEACOPP treatment. AVN was not correlated with age, gender, number of received eBEACOPP cycles, irradiation therapy or cumulative dose of steroids administered. There were significantly more cases of AVN in patients receiving methylprednisolone than prednisone (P = 0.01). Conclusion: The use of methylprednisolone was shown to be a risk factor for the development of AVN in patients treated with eBEACOPP and should not be the corticosteroid of choice in the treatment of patients with HL.

Extracellular circulating DNA in diffuse large B- cell lymphoma patients: biological correlates and prognostic impact

Inadequate supply of „old and less interesting“ chemotherapeutic agents is becoming a global issue in hemato- oncology today. In 2016 we were faced with occasional carmustin shortage, one of the most commonly used in autologous transplant conditioning regimens for lymphoma in our centre, so we decided to use bendamustin instead. We performed a retrospective analysis of 41 patients treated at our centre who had received bendamustin within BeEA M protocol and compared them with 40 patients who had received carmustin within BEA M protocol. Both protocols were used as conditioning protocols before autologous stem cell transplantation. Neutrophil recovery median following transplantation (AN C>0,5x109/l) was 11 days in the bendamustin group in comparison to 10 days in the carmustin group.Platelets recovery median following transplantation (PLT >20x109/l) was longer in the bendamustin group (16 vs.13 days) as was blood transfusion dependency (7 vs. 5 days). Infectious complications were not more frequent after bendamustin, but grade II–III mucositis was more frequent in patients who received carmustin (35% vs.12%). Following bendamustin we had one reported case of nephrotoxicity and cardiac toxicity, not reported with carmustin. Bendamustin has shown similar hematologic toxicity compared to carmustin but a longer platelet recovery period and a lower mucositis incidence.

In clinical trials the combination of fludarabine, cyclophosphamide and rituximab (FCR) demonstrated superior results and became the gold standard for first-line treatment of fit patients with chronic lymphocytic leukemia (CLL). The aim of this study was to evaluate the efficacy, toxicity and feasibility of this protocol in everyday clinical practice. We ­retrospectively analyzed the outcomes of 43 CLL patients treated at the Division of Haematology, Department of Internal Medicine, University Hospital Centre Zagreb. The dosing of rituximab differed from that in clinical trials, we administered 375mg/m2 of rituximab per cycle, in previously untreated patients for eight and in relapsed/refractory patients for six cycles. The response rate was 95% with 83% of complete remissions. Twenty–nine patients received FCR as a front–line therapy; three-year overall and progression–free survival were 90% and 80%, respectively. In relapsed/refractory disease three–year overall and progression–free survival were 86% and 62%, respectively. Severe neutropenias occurred in 46% and serious infections in 9% of patients. According to these results, the toxicity profile and treatment outcomes in everyday routine clinical practice are similar to those reported in clinical trials.

U kliničkim je studijama kombinacija fludarabina, ciklofosfamida i rituksimaba (FCR) pokazala odlične rezultate u liječenju bolesnika s kroničnom limfocitnom leukemijom (KLL) i postala zlatni standard u prvoj liniji liječenja takvih bolesnika bez znatnijih komorbiditeta. Cilj rada bio je ispitati terapijsku djelotvornost, toksičnost i provedivost ovog protokola u svakodnevnoj kliničkoj praksi. Retrospektivno su analizirani tijek i ishodi liječenja 43-oje bolesnika s KLL-om sa Zavoda za hematologiju Klinike za unutarnje bolesti Kliničkoga bolničkog centra Zagreb. Na liječenje je odgovorilo 95% bolesnika, a 83% postignulo je kompletnu remisiju. Trogodišnje preživljenje i preživljenje bez progresije bolesti u prvoj liniji liječenja (29 bolesnika) bilo je 90 i 80%, a u kasnijim linijama 86 i 62%. Teške neutropenije zabilježene su u 46% bolesnika, a teške infekcije u 9% bolesnika. Ishodi liječenja i toksični profil u svakodnevnome kliničkom radu usporedivi su s onima iz kliničkih studija.

Uvod: Tromboza je jedna od najčešćih komplikacija u bolesnika s Ph(-) mijeloproliferativnim neoplazmama, a razlozi zbog kojih nastaje još uvijek su predmet istraživanja. Cilj: Otkriti postoji li razlika u učestalosti i vrsti tromboze u V617F JAK2–pozitivnih bolesnika ovisno o njihovoj dijagnozi, dobi, spolu te opterećenju mutiranim alelom. Materijali i metode: U ovo istraživanje bila su uključena 182 V617F JAK2–pozitivna bolesnika - policitemija vera (PV) 63 bolesnika, esencijalna trombocitoza (ET) 83 bolesnika i primarna mijelofibroza (PM) 36 bolesnika. Bolesnici su bili podijeljeni prema dijagnozi, spolu, dobi pri dijagnozi te nastanku prve tromboze. Mutacija V617F JAK2 kvantificirana je iz uzorka granulocitne DNK periferne krvi metodom PCR-a u stvarnom vremenu prema Larsenu i sur. Br J Haematol 2007 ; 136:745. Rezultati: Od 182 bolesnika, 66 bolesnika razvilo je trombozu (36 %), pri čemu je arterijska tromboza bila dvostruko učestalija od venske tromboze u sve 3 grupe bolesnika. U skupini bolesnika s ET bilo je više žena (udjel žena = 0, 71), p< 0, 001. Statistički važna razlika za dob pri dijagnozi (p