To compare the outcomes of Croatian patients with mantle cell lymphoma (MCL) who started treatment in 2007 and 2008 (historical cohort) and of those who started treatment between 2015 and 2017 ...(recent cohort).
The historical cohort consisted of 40 patients who started treatment with rituximab in 2007 and 2008. Data on the recent cohort, consisting of 89 patients, were collected retrospectively from the electronic databases of Croatian hospitals with hematology units. Demographic characteristics and data on induction regimens, autologous stem cell transplantation (ASCT), and rituximab maintenance in the first remission, event-free survival (EFS), and overall survival (OS) were available for both cohorts, and data on cell morphology, mantle cell international prognostic index (MIPI), and Ki67 expression only for the recent cohort.
The recent cohort had significantly better two-year EFS and OS (EFS 58% vs 40%, P=0.014; OS 80% vs 56%, P=0.009), especially in patients below 65. In univariate analysis, induction regimen, ASCT, and maintenance were significant prognostic factors for EFS and the former two for OS. In the multivariate analysis, only ASCT remained significant. Bendamustine+rituximab (BR) induction improved the outcomes of non-transplantable patients over R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, steroid). Blastoid morphology and high MIPI were adverse prognostic factors for EFS and OS.
In the last decade, the outcome of newly diagnosed MCL patients improved. ASCT in the first remission was the main contributor in transplantable patients and BR in non-transplantable. Regularly updated national guidelines may help in a timely adoption of new treatments, thus improving the results.
Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder characterized by a specific expansion of mature B-cell clones. We hypothesized that the disease has a heterogeneous clinical ...outcome that depends on the genes and signaling pathways active in the malignant clone of the individual patient. It was found that several signaling pathways are active in CLL, namely, NOTCH1, the Ikaros family genes, BCL2, and NF-κB, all of which contribute to cell survival and the proliferation of the leukemic clone. Therefore, we analyzed primary CLL cells for the gene and protein expression of NOTCH1, DELTEX1, HES1, and AIOLOS in both peripheral blood lymphocytes (PBLs) and the bone marrow (BM) of patients, as well as the expression of BCL2 and miRNAs to see if they correlate with any of these genes. BCL2 and AIOLOS were highly expressed in all CLL samples as previously described, but we show here for the first time that AIOLOS expression was higher in the PBLs than in the BM. On the other hand, NOTCH1 activation was higher in the BM. In addition, miR-15a, miR-181, and miR-146 were decreased and miR-155 had increased expression in most samples. The activation of the NOTCH pathway in vitro increases the susceptibility of primary CLL cells to apoptosis despite high BCL2 expression.
Utilization of somatic healthcare services is highly predictive of the development of chronic physical illnesses and increased mortality risks. The objective of this study was to assess the ...differences in healthcare utilization among patients with schizophrenia spectrum disorders (SSD), major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) and the general population in Croatia.
We enrolled 566 Croatian participants from the general population, 282 with SSD, 178 with MDD, and 86 with PTSD. The primary outcome was a self-reported specialist consultation for non-psychiatric (e.g., somatic) causes within the previous 12 months.
Although SSD patients with chronic physical illnesses were significantly more often hospitalized for physical illness than the general population, the proportion of patients who had a specialist consultation were equal in SSD and the general population. MDD and PTSD patients had significantly higher adjusted odds for specialist consultation than the general population and SSD patients (MDD compared to SSD: OR = 2.14; 95% CI 1.27-3.59; PTSD compared to SSD: OR = 2.03; 95% CI 1.00-4.10).
SSD patients' utilization of somatic healthcare is equal to the general population, despite their increased healthcare needs. However, their utilization is lower than in MDD and PTSD patients and, therefore, probably not adequate.
The study protocol was registered at ClinicalTrials.gov ( NCT02773108 ) on May 16, 2016.
Mukozitis označava bolnu upalu i oštećenje sluznice usta i gastrointestinalnog trakta koja se javlja kao komplikacija kemoterapijskog i/ili radioterapijskog liječenja i tijekom transplantacije ...krvotvornih matičnih stanica u bolesnika oboljelih od zloćudnih hematoloških bolesti. Navedeno stanje uvelike utječe na kvalitetu života i ishode liječenja bolesnika. U ovom preglednom radu opisani su čimbenici rizika za pojavu mukozitisa, učestalost, klinička slika, mjere prevencije i liječenja mukozitisa u bolesnika sa zloćudnim hematološkim bolestima te je na temelju aktualne literature i važećih svjetskih smjernica iznesen pregled područja i stav Hrvatske kooperativne grupe za hematološke bolesti (KROHEM).
Mucositis is the painful inflammation with lesions of the mucous membranes of the mouth and the gastrointestinal tract that commonly arises as an adverse effect of high dose chemotherapy and/or radiotherapy and during hematopoietic stem cell transplantation in patients suffering from malignant hematological diseases. Mucositis affects the patients’ quality of life and the outcome of treatment. This review article describes the risk factors, prevalence, clinical picture, prevention measures and treatment of mucositis in patients suffering from malignant hematological diseases, and contains an overview of the subject matter and the attitude of the Croatian Cooperative Group for Hematological Diseases KROHEM, in accordance with the current literature and valid global guidelines.
Elderly patients make up a significant number of cases of newly diagnosed Hodgkin lymphoma. However, unlike in young patients, the outcomes of elderly patients are poor, and they are ...under-represented in phase III trials. Prior to treatment initiation, geriatric assessment should ideally be performed to address the patient's fitness and decide whether to pursue a curative or palliative approach. The ABVD regimen is poorly tolerated in unfit patients, with high treatment-related mortality. Alternative chemotherapy approaches have been explored, with mixed results obtained concerning their feasibility and toxicity in phase II trials. The introduction of brentuximab vedotin-based regimens led to a paradigm shift in first- and further-line treatment of elderly Hodgkin lymphoma patients, providing adequate disease control within a broader patient population. As far as checkpoint inhibitors are concerned, we are only just beginning to understand the role in the treatment of this population. In relapsed/refractory settings there are few options, ranging from autologous stem cell transplantation in selected patients to pembrolizumab, but unfortunately, palliative care is the most common modality. Importantly, published studies are frequently burdened with numerous biases (such as low numbers of patients, selection bias and lack of geriatric assessment), leading to low level of evidence. Furthermore, there are few ongoing studies on this topic. Thus, elderly Hodgkin lymphoma patients are hard to treat and represent an unmet need in hematologic oncology. In conclusion, treatment needs to be personalized and tailored on a case-by-case basis. In this article, we outline treatment options for elderly Hodgkin lymphoma patients.
Summary Notch signaling is implicated in the pathogenesis of multiple myeloma expressing high level of active Notch proteins NOTCH1 and JAGGED1 in tumor plasma cells. We investigated expression of ...NOTCH1 and JAGGED1 in bone marrow trephine biopsies of 80 newly diagnosed multiple myeloma and 20 monoclonal gammopathy of undetermined significance patients using immunohistochemical methods. The number of positive tumor cells was counted per 1000 tumor cells and the intensity of staining was assessed semi quantitatively. Multiple myelomas expressed NOTCH1 in 92.31% (72/78) and JAGGED1 in 92.21% (71/77) cases. NOTCH1 staining was strong in the majority of cases (59.7%), whereas JAGGED1 was predominately weak (67.6% of cases). In contrast, both markers were negative in all monoclonal gammopathy of undetermined significance cases. However, upon progression of disease from monoclonal gammopathy of undetermined significance to multiple myeloma (seen in 4 patients), analysis of the subsequent bone marrow biopsy showed weak expression of both markers in tumorous plasma cells. Immunohistochemistry results were compared with the pattern of bone marrow infiltration, plasma cell differentiation, and the presence of t(11;14)(q13,q32), t(14;16)(q32;q23),and t(4;14)(p16.3;q23) and overall survival in multiple myeloma patients. A significant correlation was found between strong NOTCH1 staining in multiple myeloma plasma cells and the diffuse type of bone marrow infiltration ( P = .002) and an immature morphologic type of plasma cells ( P = .043). After a median follow-up of 20.3 months, in multiple myeloma patients no difference in overall survival between NOTCH1 ( P = .484) and JAGGED1 ( P = .822) positive and negative cases were found. In conclusion, our results indicate importance of NOTCH1 and JAGGED1 expression in plasma cell neoplasia and a possible diagnostic value of their immunohistochemical evaluation of bone marrow infiltrates for multiple myeloma.
Mijelodisplastični sindrom (MDS) klonski je poremećaj krvotvorne matične stanice karakteriziran neučinkovitom hematopoezom i citopenijom u perifernoj krvi, a u oko trećine bolesnika može doći do ...progresije poremećaja u akutnu mijeloičnu leukemiju (AML). Dijagnoza MDS-a postavlja se nakon analize periferne krvi i koštane srži, a ovisno o postotku blasta u koštanoj srži, broju citopenija te citogenetičkim abnormalnostima, određuju se prognostički indeksi (engl. International Prognostic Scoring System – IPSS, Revised International Prognostic
Scoring System – IPSS-R, WHO Prognostic Scoring System – WPSS). Dosad su provedena brojna istraživanja o molekularnim mehanizmima i epigenetičkim putovima u mijelodisplastičnom sindromu te njihovu prognostičkom i terapijskom značenju, ali je malo studija o važnosti mikroRNK (miRNK) u MDS-u. U posljednjih nekoliko godina objavljeni su brojni rezultati o utjecaju aberantnog izražaja miRNK u malignim poremećajima, pri čemu su se miRNK-i pokazali kao geni koji suprimiraju tumor ili onkogeni. U pojedinim su tumorima miRNK-i prepoznati kao dijagnostički i prognostički parametri te mogući terapijski ciljevi. U ovom radu donosimo pregled dosadašnjih rezultata o ulozi miRNK u MDS-u.
Mijelodisplastični sindrom heterogena je grupa bolesti koje dijele neka klinička i morfološka obilježja. Uzrok im je nepoznat. Budući da brz razvoj molekularne genetike omogućuje uvid u uzročne ...genske aberacije,
danas se mogu odrediti neki patogenetski mehanizmi u nastanku mijelodisplastičnog sindroma. U ovom radu pokušat ćemo objasniti neka otkrića u tom području i njihovu vezu s citomorfološkim obilježjima, fenotipom mijelodisplastičnog sindroma.
Dijagnostička kategorija mijelodisplastične/mijeloproliferativne neoplazme (MDS/MPN) obuhvaća klonske hematopoetske neoplazme koje u vrijeme postavljanja dijagnoze istodobno pokazuju klinička, ...laboratorijska i/ili morfološka obilježja i mijelodisplastičnog sindroma (MDS) i mijeloproliferativne neoplazme (MPN). Citopenija i displazija jedne ili više mijeloidnih loza (obilježja MDS-a) mogu se vidjeti istodobno s leukocitozom, trombocitozom i/ili organomegalijom (obilježja koja su češće povezana s MPN-om). Bolesnici s prije dijagnosticiranim MPN-om, kod kojih se razviju mijelodisplastične promjene kao posljedica evolucije bolesti ili kemoterapije, ne ubrajaju se u ovu dijagnostičku kategoriju. Prema klasifikaciji Svjetske zdravstvene organizacije (engl. World Health Organization – WHO) iz 2008. godine te njezinoj reviziji iz 2016. godine, MDS/MPN obuhvaća pet entiteta: kroničnu mijelomonocitnu leukemiju (engl. chronic myelomonocytic leukemia – CMML), juvenilnu mijelomonocitnu leukemiju (engl. juvenile myelomonocytic leukemia – JMML), atipičnu kroničnu mijeloičnu leukemiju, BCR-ABL1- (engl. atypical chronic myeloid leukemia – aCML), MDS/MPN s prstenastim sideroblastima i trombocitozom (engl. MDS/MPN with ring sideroblasts and thrombocytosis – MDS/MPN-RS-T) i neklasificirani MDS/MPN (engl. MDS/MPN, unclassifiable – MDS/MPN, U).
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