The role of immunophenotyping in differential diagnosis of chronic lymphocytic leukemia

Introduction. Accurate diagnosis of chronic lymphocytic leukemia (CLL) acquires immunophenotyping by flow cytometry in order to facilitate differential diagnosis between CLL and other mature B-cell neoplasms (MBCN). Objective. The aim of this study was to define immunological profile of CLL cells. Methods. Immunophenotyping by flow cytometry was performed on peripheral blood specimens at diagnosis in the group of 211 patients with de novo MBCN. Results. Absolute count of B-cells was significantly increased in all MBCN patients comparing to healthy control group (p<0.05). B-cell monoclonality was detected in 96% of all MBCN patients, by using surface immunoglobulin (sIg) light chain restriction. B-cell antigens, CD19, CD20, CD22, were expressed with very high frequency in CLL and other MBCN. In comparison with other MBCN, in CLL group, the frequency of expression was higher for CD5 and CD23 (p<0.0001), though lower for FMC7 antigen (p<0.0001). CLL patients were characterized by lower expression patterns of CD20, CD22, CD79b, and sIg (p<0.0001) as well as higher expression pattern of CD5 antigen (p<0.05). Correlation between the final diagnosis of MBCN and values of CLL scoring system showed that the majority of CLL patients (97%) had higher values (5 or 4) whereas the majority of other MBCN patients (96%) had lower score values (0-3). Conclusion. Our results have shown that characteristic immunophenotype which differentiates CLL from other MBCN is defined by following marker combination - CD19+ CD20+low CD22+low CD5+high CD23+ FMC7- CD79b+low sIg+low. CLL score values of 5 or 4 points are highly suggestive for diagnosis of CLL

Double-hit primary unilateral adrenal lymphoma with good outcome

Introduction. Primary adrenal non-Hodgkin’s lymphoma (NHL) is a rare neoplasm with poor prognosis. On the other side, double-hit lymphomas with BCL2 and MYC translocation are characterized by advanced disease stage, extranodal and central nervous system involvements at presentation or disease progression. Case report. We reported a 73-year-old male patient with double-hit primary adrenal lymphoma and preserved adrenal function, showing a favorable clinical course. Computed tomography of abdomen showed a 9 7 cm mass of the left adrenal gland. Laparatomy with left adrenalectomy was done and histological examination revealed diagnosis of a diffuse large B-cell NHL (DLBCL), non-GCB subtype. The patient was treated with 6 cycles of R-CHOP chemotherapy with reduced doses of doxorubicin because of the decreased left verticle ejection fraction. The patient was followed up regularly for 20 months with no evidence of tumor recurrence despite the inherently poor prognostic profile and double-hit phenotype of the disease. Conclusion. R-CHOP chemotherapy in combination with adrenalectomy can be an effective first-line regimen for primary adrenal DLBCL, despite the inherently poor prognostic profile (non-GCB subtype, bulky disease, elevated lactate dehydrogenase and double-hit phenotype of the disease)

Extramedullary plasmacytoma of the tongue base: A rare presentation of head and neck plasmacytoma

Introduction. Special entities like solitary bone plasmocytoma (SBP) or extramedullary plasmacytoma (EMP) can be found in a less than 5% of patients with plasma cell disorders. EMP of the tongue represents very rare localization of the head and neck plasmacytoma. Case report. We report a case of 78-years-old woman who developed EMP of the tongue base detected by the magnetic resonance imaging (MRI) of the head and neck region. Immunohistochemical profile of the tumor tissue biopsy (CD38, IgG, kappa positivity) indicated diagnosis of EMP. The diagnosis was established with additional staging which confirmed the absence of other manifestation of the disease. The patient was treated with 40 Gy of radiotherapy in 20 doses resulting in the achievement of the complete remission of the disease. This case was discussed with the reference to the literature. Conclusion. EMP of the tongue base is a very rare entity of plasma cell dyscrasias. Appropriate irradiation results in the achievement of a long-term remission and a potential cure of the disease

Predictors of Vancomycin-Resistant Enterococcus spp. Intestinal Carriage among High-Risk Patients in University Hospitals in Serbia

The predictors of intestinal carriage of vancomycin-resistant Enterococcus spp. (VRE) among high-risk patients in the counties of the Southeast Europe Region are insufficiently investigated, yet they could be of key importance in infection control. The aim of the study was to identify risk factors associated with fecal VRE colonization among high-risk inpatients in university hospitals in Serbia. The study comprised 268 inpatients from three university hospitals. Data on patient demographics and clinical characteristics, length of hospital stay, therapy, and procedures were obtained from medical records. Chi-squared tests and univariate and multivariate logistic regressions were performed. Compared to the hemodialysis departments, stay in the geriatric departments, ICUs, and haemato-oncology departments increased the risk for VRE colonization 7.6, 5.4, and 5.5 times, respectively. Compared to inpatients who were hospitalized 48 h before stool sampling for VRE isolation, inpatients hospitalized 3–7, 8–15, and longer than 16 days before sampling had 5.0-, 4.7-, and 6.6-fold higher risk for VRE colonization, respectively. The use of cephalosporins and fluoroquinolones increased the risk for VRE colonization by 2.2 and 1.9 times, respectively. The age ≥ 65 years increased the risk for VRE colonization 2.3 times. In comparison to the University Clinical Centre of Serbia, the hospital stays at Zemun and Zvezdara University Medical Centres were identified as a protector factors. The obtained results could be valuable in predicting the fecal VRE colonization status at patient admission and consequent implementation of infection control measures targeting at-risk inpatients where VRE screening is not routinely performed

Clinical significance of TP53 aberrations and IGHV mutational status in chronic lymphocytic leukemia

Hronična limfocitna leukemija (HLL) izuzetno je heterogena bolest varijabilnog kliničkog toka. S jedne strane imamo, pacijente sa agresivnom i rezistentnom bolešću od koje umiru svega par meseci nakon dijagnoze, dok s druge strane spektra postoje pacijenti sa indolentnom, sporo progredirajućom bolešću koja ne zahteva lečenje decenijama. Razlozi su samo delimično poznati i već su decenijama unazad tema mnogobrojnih naučnih istraživanja. Tako je razvijen koncept prognostičkih i prediktivnih faktora u HLL-u, koji imaju za cilj da predvide klinički tok, odnosno terapijski ishod HLL-a. Liste prognostičkih i prediktivnih faktora su, sa boljim poznavanjem patofiziologije ove bolesti, svakom godinom sve duže, ali se i međusobno preklapaju. U ovom revijalnom radu izabrali smo aberacije TP53 gena i mutacioni status rearanžiranih IGHV (engl. immunoglobulin heavy variable) gena kao dva najznačajnija i najproučavanija faktora koji imaju i prognostički i prediktivni značaj.Chronic lymphocytic leukemia (CLL) is a very heterogeneous disease with a variable clinical course. On the one side of the spectrum, there are patients with aggressive and resistant disease, of which they die only a few months after diagnosis while, on the other side, there are patients with an indolent, slowly progressive disease that does not require treatment for decades. The reasons for this are only partially known, but they have been the subject of numerous scientific studies during the last several decades. Consequently, the concept of prognostic and predictive factors in CLL have emerged, which aims to predict the clinical course and its therapeutic outcome. With the improvement of understanding the pathophysiology of this disease, the lists of prognostic and predictive factors are getting longer every year, but they also overlap. In this review, we singled out the aberrations of the TP53 gene and the IGHV (immunoglobulin heavy variable) gene mutational status as the two most important and most studied factors that have both prognostic and predictive significance

Influence of applied CD34+ cell dose on the survival of Hodgkin's lymphoma and multiple myeloma patients following autologous stem cell transplants

Background/Aim. Autologous stem cell transplants (ASCTs) improve the rate of overall survival (OS) in patients with hematological malignancies such as multiple myeloma (MM) after induction chemotherapy, aggressive non-Hodgkin's lymphomas (NHL), and relapsed, chemotherapy-sensitive Hodgkin's lymphoma (HL). The study aim was to evaluate influence of applied CD34+ cell quantity on clinical outcome, as well as early post-transplant and overall survival (OS) of HL and MM patients following ASCT. Methods. This study included a total of 210 patients (90 HL/120 MM) who underwent ASCT. Stem cell (SC) mobilization was accomplished by granulocyte-colony stimulating factor (G-CSF) 10–16 μg/kg body mass (bm) following chemotherapy. For proven poor mobilizers, mobilization with G-CSF (16 μg/kgbm) and Plerixafor (24 or 48 mg) was performed. To our best knowledge, it was the first usage of the Plerixafor in our country in the ASCT-setting. Harvesting was initiated merely at "cut-off-value" of CD34+ cells ≥ 20 × 106/L in peripheral blood with "target-dose" of CD34+ cells ≥ 5 × 106/kgbm in harvest. The CD34+ cell count and viability was determined using flow cytometry. Results. The majority of HL patients (76.7%) were infused with > 5.0 × 106/kgbm CD34+ cells, while 68.3% of MM patients were treated by approximately 4.0–5.4 × 106/kgbm CD34+ dose, respectively. Beneficial response (complete/partial remission) was achieved in 83.3% (HL) and 94.2% (MM) patients. Among parameters that influenced survival of HL patients with positive response to the therapy, multivariate analysis (pre-ASCT performance status, CD34+ cell quantity applied, rapid hematopoietic, i.e. lymphocyte and platelet recovery) indicated that higher CD34+ cell dose used, along with pre-ASCT performance status correlated with superior event-free survival (EFS) and OS following ASCT. In MM patients, multivariate analysis (renal impairment, infused CD34+ cell quantity, early platelet recovery) indicated that the number of CD34+ cells infused was the most important parameter that influenced both EFS and OS after ASCT. Conclusion. Data obtained in this study undoubtedly confirmed that CD34+ cell dose applied is an independent factor that may contribute to superior clinical outcome and OS of HL and MM patients following ASCT

Cytomegalovirus infection may be oncoprotective against neoplasms of B-lymphocyte lineage: single-institution experience and survey of global evidence

Although cytomegalovirus (CMV) is not considered tumorigenic, there is evidence for its oncomodulatory effects and association with hematological neoplasms. Conversely, a number of experimental and clinical studies suggest its putative anti-tumour effect. We investigated the potential connection between chronic CMV infection in patients with B-lymphocyte (B-cell) malignancies in a retrospective single-center study and extracted relevant data on CMV prevalences and the incidences of B-cell cancers the world over

Electroconvulsive therapy: eighty years of Croatian and international experience

Elektrokonvulzivna terapija (EKT) i nakon više od 80 godina primjene i dalje predstavlja najučinkovitiju terapiju kod najtežih kliničkih slika psihijatrijskih poremećaja. U Hrvatskoj se EKT primjenjuje od 40-ih godina prošlog stoljeća. Danas se koristi samo u KBC-u Zagreb, najčešće u pacijenata sa shizofrenijom. Brojna istraživanja su utvrdila različite biološke učinke EKT-a koji pridonose antidepresivnom, antimaničnom, antipsihotičnom, antikonvulzivnom i antiparkinsonskom učinku. Konvulzije imaju snažan učinak na perfuziju i metabolizam pojedinih moždanih regija, povećanje propusnosti krvnomoždane barijere te imaju modulatorni učinak na glutamatnu, GABA, serotoninsku, dopaminsku i noradrenergičku neurotransmisiju, hormonalnu sekreciju, promjene u ekspresiji brojnih gena te potiču neuroplastičnost i u konačnici dovode do strukturnih promjena mozga. Neke su od ovih promjena kratkog vijeka, a neke traju mjesecima, poput neuroplastičnosti. Iako se EKT smatra medicinskim postupkom niskog rizika, mnoge teške somatske bolesti zahtijevaju pažljivu procjenu koristi i rizika. Najčešće su neželjene reakcije prolazne teškoće pamćenja i glavobolja. Prije prve aplikacije kandidati prolaze detaljnu dijagnostičku obradu u skladu s međunarodnim standardima. U postupku primjene EKT-a sudjeluje interdisciplinarni tim koji uključuje psihijatra, anesteziologa, anesteziološku sestru/tehničara i psihijatrijsku sestru/tehničara. Primjena opće anestezije omogućuje brz gubitak svijesti, kratkotrajnu mišićnu relaksaciju, smanjenje hiperdinamskog odgovora na električnu stimulaciju te brz oporavak spontane ventilacije i svijesti. Nedavno su predložene Hrvatske nacionalne smjernice o primjeni EKT-a. Zbog učinka u terapijskoj rezistenciji te kod vrlo teških kliničkih slika EKT može ostvariti značajan učinak u pažljivo odabranih bolesnika.Electroconvulsive therapy (ECT), even more than 80 years since its introduction, continues to be the most effective treatment for severe mental disorders. Croatian psychiatrists have used ECT since 1940s. Today it is performed only at the University Hospital Centre Zagreb, predominantly in patients with schizophrenia. Extensive research reported numerous biological effects of ECT, which contribute to its antidepressant, antimanic, antipsychotic, anticonvulsive and antiparkinsonian effects. Convulsions trigger changes in the cerebral blood flow and metabolism, increase the permeability of the blood-brain barrier, modulate glutamatergic, GABAergic, serotonergic, noradrenergic and dopaminergic neurotransmission, affect hormone secretion, gene expression, stimulate neuroplasticity, and eventually induce brain structural changes. Some of these effects are short-lasting and others, such a neuroplasticity, last for at least several months. While ECT is generally considered a low-risk medical treatment, patients with severe somatic comorbidity require careful risk-benefit assessment. The most commonly observed adverse events are transient forgetfulness and headache. Prior to initiation, candidates undergo comprehensive diagnostic evaluation according to international standards. The procedure is performed by an interdisciplinary team, consisting of psychiatrist, anesthesiologist, and psychiatric and anesthesiological nurses. The application of general anesthesia enables rapid loss of consciousness, short-time muscular relaxation, suppression of hyperdynamic response to electrical current and fast recovery of breathing and awareness. Recently, the Croatian expert group has proposed national guidelines for the ECT treatment. Due to its efficacy in both treatment-refractory and very severe symptomatology, ECT might be of a great benefit in carefully selected patients

Comparative analysis of International Prognostic Index for chronic lymphocytic leukemia, progression-risk score, and MD Anderson Cancer Center 2011 score: A single center experience

Uvod/Cilj Prognoza hronične limfocitne leukemije (HLL) značajno je unapređena u poslednje vreme. Među nekoliko prognostičkih modela čiji je cilj predviđanje vremena do prve terapije (eng. TTFT) izdvajaju se skor rizika od progresije (eng. PRS) i skor Centra za rak MD Anderson iz 2011. God. (eng. MDACC 2011), dok se internacionalni prognostički indeks za HLL (eng. CLL-IPI), iako primarno ustanovljen za predikciju ukupnog preživljavanja (eng. OS), dobro pokazao i u predikciji TTFT. Cilj ovog rada je da se ispita značaj pomenutih prognostičkih modela u pogledu predviđanja TTFT i OS. Metode Analizirana kohorta je obuhvatila 57 neselektovanih bolesnika sa HLL Univerzitetskog kliničkog centra Srbije sa prosečno agresivnijim profilom bolesti u odnosu na opštu populaciju de novo bolesnika sa HLL. Bolesnici su ocenjivani prema navedenim skorovima uz analizu TTFT i OS. Rezultati Bolesnici sa višim vrednostima CLL-IPI, PRS i MDACC 2011 primili su prvu terapiju značajno ranije u poređenju sa bolesnicima sa nižim vrednostima ovih skorova (p = 0,002, p = 0,019 i p lt 0,001, redom). U multivarijantnoj analizi, MDACC 2011 i CLL-IPI su zadržali prognostički značaj u predikciji TTFT (p = 0,001, odnosno p = 0,018), dok je PRS ovaj značaj izgubio. CLL-IPI je bio jedini značajan prediktor OS u univarijantnoj (p = 0,005) i u multivarijantnoj analizi (p = 0,013). Zaključak CLL-IPI, PRS i naročito MDACC 2011 su dobri prediktori TTFT čak i u kohortama bolesnika sa agresivnijom bolešću, dok je za predikciju OS od ova tri prognostička modela CLL-IPI jedini primenljiv. Ovi rezultati pokazuju da bi prognostičke modele trebalo ispitati na bolesnicima sa HLL u različitim fazama bolesti, kakvi se sreću u realnoj kliničkoj praksi.Introduction/Objective Prognostication of chronic lymphocytic leukemia (CLL) has been substantially improved in recent times. Among several prognostic models (PMs) focused on the prediction of time to first treatment (TTFT), progression-risk score (PRS), and MD Anderson Cancer Center score 2011 (MDACC 2011) are the most relevant, while CLL-International Prognostic Index (CLL-IPI), although originally developed to predict overall survival (OS), is also being used to estimate TTFT. The aim of this study was to investigate CLL-IPI, PRS, and MDACC 2011 prognostic values regarding TTFT and OS. Methods The analyzed cohort included 57 unselected Serbian CLL patients from a single institution, with the basic characteristics reflecting more aggressive disease than in the general de novo CLL population. The eligible patients were assigned investigated PMs, and TTFT and OS analyses were performed. Results Patients with higher risk scores according to CLL-IPI, PRS, and MDACC 2011 underwent treatment significantly earlier than patients with lower risk scores (p = 0.002, p = 0.019, and p lt 0.001, respectively). In multivariate analysis, MDACC 2011 and CLL-IPI retained their significance regarding TTFT (p = 0.001 and p = 0.018, respectively), while PRS did not. CLL-IPI was the only significant predictor of OS both at the univariate (p = 0.005) and multivariate (p = 0.013) levels. Conclusion CLL-IPI, PRS, and particularly MDACC 2011 are able to predict TTFT even in cohorts with more advanced-disease patients, while for prediction of OS, CLL-IPI is the only applicable among the three PMs. These results imply that PMs should be investigated in more diverse CLL populations, as it is in real-life setting