40 research outputs found
IMUNOHISTOKEMIJSKA IZRAŽENOST PROTEINA BORIS U TUMORIMA ZAMETNIH STANICA TESTISA
Brother of the Regulator of Imprinted Sites (BORIS) has a role in intracellular signalization and is important in epigenetic mechanism control, such as methylation/demethylation of DNA and histones. BORIS may deregulate some tumor suppressor genes. Immunohistochemical expression of BORIS was found in different tumors, some of them showing correlation with poor prognosis. The aim of this study was to determine immunohistochemical expression of BORIS in pure seminomas and different components of testicular mixed germ cell tumors (MGCT). In this study, immunohistochemical expression of BORIS in testicular germ cell tumors (TGCT) was analyzed. Staining intensity and percentage of positive staining cells were used to evaluate the level of expression. Tumor samples from 44 patients were analyzed; 26 pure seminomas and 18 MGCT. In MGCTs, seminoma component was found in 4, yolk sac in 7, teratoma in 11 and embryonal carcinoma in 13 samples. Expression of BORIS was strong in 80.8% of seminoma cases and in 76.9% of embryonal carcinoma component, 71.4% of yolk sac, 63.6% of teratoma component and 25% of seminomatous component of MGCT. In MGCT, positive correlation was found between BORIS expression in teratomatous component and presence of yolk sac component (BORIS (engl. Brother of the Regulator of Imprinted Sites) sudjeluje u unutarstaniÄnoj signalizaciji i kontrolira epigenetske mehanizme kao Å”to su metilacija/demetilacija DNK i histona. Aktivacija BORIS-a dovodi do poremeÄaja odreÄenih tumorskih supresora. Imunohistokemijska izraženost BORIS-a utvrÄena je u razliÄitim tumorima. U nekim tumorima naÄena je korelacija s loÅ”ijom prognozom. Cilj ovoga istraživanja bio je utvrditi imunohistokemijsku izraženost BORIS-a u Äistim seminomima i razliÄitim komponentama mijeÅ”anih tumora zametnih stanica testisa (engl. mixed germ cell tumors, MGCT). Materijal i metode: Analizirana je imunohistokemijska izraženost BORIS-a u tumorima zametnih stanica testisa (engl. testicular germ cell tumors, TGCT), a intenzitet bojenja i postotak reaktivnih stanica koriÅ”ten je za evaluaciju razine ekspresije. Analizirani su uzorci tumora 44 bolesnika; 26 Äistih seminoma i 18 MGCT. Kod MGCT-a komponenta seminoma naÄena je u 4, yolk sac-a u 7, teratoma u 11 te embrionalnog karcinoma u 13 uzoraka tumora. Rezultati: Imunohistokemijska izraženost bila je jaka kod 80,8% Äistih seminoma te kod 76,9% komponente embrionalnog karcinoma, 71,4% yolk sac-a, 63,6% teratoma i 25% seminomske komponente MGCT-a. Dobivena je pozitivna korelacija izraženosti BORIS-a teratomske komponente i prisutnosti komponente yolc sac
IMUNOHISTOKEMIJSKA IZRAŽENOST PROTEINA BORIS U TUMORIMA ZAMETNIH STANICA TESTISA
Brother of the Regulator of Imprinted Sites (BORIS) has a role in intracellular signalization and is important in epigenetic mechanism control, such as methylation/demethylation of DNA and histones. BORIS may deregulate some tumor suppressor genes. Immunohistochemical expression of BORIS was found in different tumors, some of them showing correlation with poor prognosis. The aim of this study was to determine immunohistochemical expression of BORIS in pure seminomas and different components of testicular mixed germ cell tumors (MGCT). In this study, immunohistochemical expression of BORIS in testicular germ cell tumors (TGCT) was analyzed. Staining intensity and percentage of positive staining cells were used to evaluate the level of expression. Tumor samples from 44 patients were analyzed; 26 pure seminomas and 18 MGCT. In MGCTs, seminoma component was found in 4, yolk sac in 7, teratoma in 11 and embryonal carcinoma in 13 samples. Expression of BORIS was strong in 80.8% of seminoma cases and in 76.9% of embryonal carcinoma component, 71.4% of yolk sac, 63.6% of teratoma component and 25% of seminomatous component of MGCT. In MGCT, positive correlation was found between BORIS expression in teratomatous component and presence of yolk sac component (BORIS (engl. Brother of the Regulator of Imprinted Sites) sudjeluje u unutarstaniÄnoj signalizaciji i kontrolira epigenetske mehanizme kao Å”to su metilacija/demetilacija DNK i histona. Aktivacija BORIS-a dovodi do poremeÄaja odreÄenih tumorskih supresora. Imunohistokemijska izraženost BORIS-a utvrÄena je u razliÄitim tumorima. U nekim tumorima naÄena je korelacija s loÅ”ijom prognozom. Cilj ovoga istraživanja bio je utvrditi imunohistokemijsku izraženost BORIS-a u Äistim seminomima i razliÄitim komponentama mijeÅ”anih tumora zametnih stanica testisa (engl. mixed germ cell tumors, MGCT). Materijal i metode: Analizirana je imunohistokemijska izraženost BORIS-a u tumorima zametnih stanica testisa (engl. testicular germ cell tumors, TGCT), a intenzitet bojenja i postotak reaktivnih stanica koriÅ”ten je za evaluaciju razine ekspresije. Analizirani su uzorci tumora 44 bolesnika; 26 Äistih seminoma i 18 MGCT. Kod MGCT-a komponenta seminoma naÄena je u 4, yolk sac-a u 7, teratoma u 11 te embrionalnog karcinoma u 13 uzoraka tumora. Rezultati: Imunohistokemijska izraženost bila je jaka kod 80,8% Äistih seminoma te kod 76,9% komponente embrionalnog karcinoma, 71,4% yolk sac-a, 63,6% teratoma i 25% seminomske komponente MGCT-a. Dobivena je pozitivna korelacija izraženosti BORIS-a teratomske komponente i prisutnosti komponente yolc sac
DIAGNOSTIC APPROACH AND TREATMENT OF IMMUNE THROMBOCYTOPENIA IN ADULTS
Cilj ovog preglednog rada jest prikazati najnovija saznanja povezana s definicijom imune trombocitopenije u odraslih (ITP), patoĀ¬fiziologijom bolesti, dijagnostiÄkim i terapijskim postupnikom. ITP je karakterizirana brojem trombocita manjim od 100x109/L te kroniÄnim tijekom u odsustvu neke druge bolesti koja bi mogla dovesti do smanjenja broja trombocita. Patogeneza ove bolesti temelji se na dva kljuÄna mehanizma: destrukciji kompleksa trombocit-protutijelo i inhibiciji sazrijevanja prekursora trombocita. Dijagnoza ITP-a temelji se na iskljuÄenju drugih moguÄih uzroka trombocitopenije. Odluka o poÄetku lijeÄenja donosi se individuĀ¬alno, prema broju trombocita (manji od 30x109/L) te riziÄnim faktorima krvarenja. Okosnica prve linije terapije su kortikosteroidi. U sluÄaju izostanka uspjeha lijeÄenja kortikosteroidima preporuÄa se primjena intravenskih imunoglobulina s brzim, ali Äesto i kratkotrajnim odgovorom. U drugoj liniji terapije su kirurÅ”ki i farmakoloÅ”ki pristupi. KirurÅ”ki pristup, splenektomija, karakteriziran je vrlo visokom stopom dugotrajnog odgovora. FarmakoloÅ”ki pristup danas znaÄi ili primjenu agonista trombopoetina (TPO) ili rituksimaba. Agonisti TPO pokazali su se kao lijekovi s visokom stopom odgovora, no potreba za kontinuiranim davanjem i cijena donekle ograniÄavaju njihovu upotrebu. Iako se rituksimab Äesto koristi u drugoj liniji lijeÄenja, za sada ne postoje randomizirana kliniÄka istraživanja koja bi poduprla njegovu primjenu. U bolesnika s refraktornim ITP-om lijeÄenje je potrebno samo u bolesniĀ¬ka s brojem trombocita manjim od 30x109/L te krvarenjem. Terapija je primjena agonista TPO, polikemoterapija, alemtuzumab te transplantacija perifernih matiÄnih stanica.The aim of this review is to provide the Croatian medical public with novel insights into the definition, pathogenesis, diagnostic algorithms and treatment approaches to immune thrombocytopenia (ITP) in adults. Recently, primary ITP has been uniformly deĀ¬fined as an autoimmune disorder characterized by an isolated platelet count lower than 100x109/L without preexisting disease or conditions, which could lead to thrombocytopenia. The recognition of primary and secondary ITP is important because they require different treatment strategies. In secondary ITP, therapeutic approach oriented towards the underlying disorder. Unlike childhood onset ITP, which is a self-limited condition with high rates of spontaneous remissions, adulthood onset ITP usually has chronic course. Previously, the pathogenesis of ITP was considered to be immune mediated destruction of platelets in liver and spleen, while recent findings have shown a novel pathophysiological pathway based on the inhibition of thrombopoiesis, leading to novel treatment approaches. The diagnosis of ITP is based on exclusion of the possible underlying causes of thrombocytopeĀ¬nia and consists of simple diagnostic procedures. The decision to treat ITP should be based individually: platelets count (lower than 30x109/L), various bleeding risk factors and patientās preference. The use of corticosteroids is the mainstay of first line therĀ¬apy. Two most commonly used corticosteroids are prednisone and dexamethasone. Prednisone is administered continuously, while dexamethasone is applied in cycles. Due to the lack of randomized clinical trials, it is not possible to recommend certain class of corticosteroid therapy. Another two agents used as first line therapy in case of corticosteroid refractoriness or the need of rapid platelet elevation, are intravenous immunoglobulins and anti-D immunoglobulin (anti-D is not approved in Europe). They are characterized by rapid onset of platelet recovery and low long-term remission rates.
Until recently, splenectomy, with adequate infectious and thromboprophylaxis, was the therapy of choice in patients who did not respond to corticosteroids due to high long-term remission rates and low relapse rates. This procedure can be offered to a younger patient without significant comorbidities after the first year of ITP duration. With advances in the understanding of ITP pathogenesis, a new class of drug has been established: thrombopoietin agonists (TPO). Eltrombopag and romiplostim, the TPO agonists currently approved for the management of ITP in patients who failed the first line therapy and are not suitable for splenectomy, are only two agents that have shown benefits in large clinical randomized trials. They are characterized by a high response rate and appropriate safety profile, but the need for continuous use, a high relapse rate after therapy withdrawal, and price limit their use in everyday practice. TPO agonists represent an appropriate treatment choice in patients who have relapse after splenectomy. Another agent, often used in everyday clinical practice, is rituximab with high response and relapse rates. Its use is based on small studies, and due to the lack of clinical randomized controlled trials, rituximab is not approved by the leadĀ¬ing medical agencies for this indication. As shown in this review article, our understanding and therapy for ITP has improved, but further research is needed to implement evidence-based therapy in clinical practice
Quality of life in Croatian Homeland war (1991-1995) veterans who suffer from post-traumatic stress disorder and chronic pain
<p>Abstract</p> <p>Background</p> <p>The aim of this study was to investigate the quality of life in Croatian homeland war veterans who suffer from post-traumatic stress disorder and chronic low back pain (LBP).</p> <p>Methods</p> <p>A total of 369 participants were included, classified in four study groups: those with post-traumatic stress disorder (PTSD; N = 59), those with both PTSD and lower back pain (PTSD+LBP; N = 80), those with isolated LBP (N = 95) and controls (N = 135). WHOQOL-BREF survey was used in the estimation of quality of life. The data were analysed using statistical methods and hierarchical clustering.</p> <p>Results</p> <p>The results indicated a general pattern of lowering quality of life in participants with both psychological (PTSD) and physical (LBP) burden. The average overall quality of life was 2.82 Ā± 1.14 for the PTSD+LBP group, 3.29 Ā± 1.28 for the PTSD group, 4.04 Ā± 1.25 for the LBP group and 4.48 Ā± 0.80 for the controls (notably, all the pair-wise comparisons were significantly different at the level of P < 0.001, except for the pair LBP-controls, which was insignificant). This result indicated that quality of life was reduced for 9.9% in patients with LBP, 26.6% in patients with PTSD and 37.1% in PTSD+LBP, suggesting strong synergistic effect of PTSD and LBP. The analysis also identified several clusters of participants with different pattern of quality of life related outcomes, reflecting the complex nature of this indicator.</p> <p>Conclusions</p> <p>The results of this study reiterate strong impact of PTSD on quality of life, which is additionally reduced if the patient also suffers from LBP. PTSD remains a substantial problem in Croatia, nearly two decades after the beginning of the 1991-1996 Homeland war.</p
PraÄenje bolesnika s klasiÄnim Hodgkinovim limfomom nakon lijeÄenja ā suvremena saznanja i nedoumice. Pregled literature [Follow-up of patients with classical Hodgin lymphoma after treatment - novel evidence and dilemmas. Literature review]
In this review we present current evidence for the follow-up of patients treated for classical Hodgkin lymphoma (HL). Nowadays introduction of novel therapies enabled successful treatment in most patients with classical HL in first remission with 5-year overall survival rate estimation of 80%. We have performed extensive literature search on the methodological approach to detection of relapse. Evidence regarding imaging clinical methods in detecting relapse on serial computed tomography and/or positron emission tomography scans is scarce. These imaging modalities are associated with considerable economic cost, unnecessary exposure to radiation and patients' stress. Furthermore, the detection of asymptomatic relapse does not seem to be associated with improved outcome in this patient group. Available data on this subject indicate that standard imaging methods, such as ultrasound, and judicious clinical examination in detecting of relapse should be the basis of HL patient follow-up. Late toxicity due to various modalities of treatment represents serious morbidity in HL. They vary from secondary solid cancers and hematologic neoplasms, associated with poor outcome, to benign disorders (fertility issues, thyroid dysfunction, cardiovascular and lung disorders). Current data on the incidence, prevalence and etiological factors do not yet provide evidence on appropriate screening methods. Most recommendations in various guidelines are associated with low level of evidence (grade IV). We, therefore, propose individually-tailored screening methods for each patient based on the modality of treatment received
The Connection between Coping Mechanisms, Depression, Anxiety and Fatigue in Multiple Sclerosis
The aim of this study was to show how different coping mechanisms influence the prevalence of anxiety and depression in people suffering from multiple sclerosis. We also aimed at showing how different coping mechanisms contribute to subjective prosperity of the patients emphasizing general health, cognitive functions and fatigue. A questionnaire was given to attendants of the VI Symposium of Patients Suffering From Multiple Sclerosis. Scales were taken from Multiple Sclerosis Quality of Life Inventory (MSQLI), Hospital Anxiety and Depression Scale (HADS) and COPE inventory. A total of 68 anonymous questionnaires were handed in. A total of 57.9% of examinees had symptoms of depression, and 63.2% suffered from symptoms of anxiety. However, majority of the examinees suffered from the combination of these entities. Hypothesis about impact of various coping factors on depression, anxiety, fatigue was validated except an impact on physical state was not proven significant. Predictors improving these states were positive reinterpretation, social emotional support and humor, Predictors worsening these states were planning, acceptance, focus on emotional ventilation and denial. Psychiatric comorbidity has a high prevalence in people suffering from MS. Different coping mechanisms can help in improvement of everyday life
ARE WE ENTERING CHEMO-FREE ERA IN CHRONIC LYMPHOCYTIC LEUKEMIA? THE ROLE OF IBRUTINIB AND VENETOCLAX AND LESSONS LEARNT FROM IDELALISIB
Glavni cilj ovog preglednog rada je predstaviti novu klasu lijekova u kroniÄnoj limfocitnoj leukemiji (KLL), najÄeÅ”Äoj leukemiji odrasle dobi, inhibitore staniÄnog signaliziranja B receptora (BCR). KLL se klasiÄno lijeÄila imunokemoterapijom, no pojedini bolesnici (poodmakla životna dob, nepovoljni bioloÅ”ki faktori) imali su loÅ”u prognozu. S boljim razumijevanjem patogeneze unutarstaniÄnih putova pojavila se moguÄnost selektivne inhibicije i ciljane terapije u KLL. Prvi lijek u svojoj klasi ibrutinib, inhibitor bruton kinaze, pokazao se superiornim u fazama III kliniÄkih pokusa te je eliminirao negativne prognostiÄke faktore u lijeÄenju KLL, pogotovo del (17p), s adekvatnim profi lom toksiÄnosti Å”to su prepoznale regulatorne agencije. Drugi BCR inhibitori idelalisib i venetoklaks su iznimno aktivni u relapsnom okruženju, no idelalisib se pokazao neprihvatljivo toksiÄnim u prvoj liniji lijeÄenja Å”to nam može poslužiti kao lekcija u dizajnu kliniÄkih pokusa s ovim lijekovima. Usprkos uÄinkovitosti, potreban je dodatni napredak u ovom podruÄju koji se nalazi u kombinacijama s imunoterapijom ili imunokemoterapijom, te moguÄoj meÄusobnoj kombinaciji kako bismo dodatno poboljÅ”ali ishode. No, najveÄa zapreka BCR inhibitorima da uÄu u Å”iroku praksu je njihova cijena i utjecaj na zdravstveni sustav Å”to nažalost ograniÄuje naÅ”u moguÄnost da lijeÄimo bolesnike s KLL u eri bez kemoterapije.The main aim of this review is to present a novel class of agents, the inhibitors of B cell receptor (BCR) signaling pathway, used in the treatment of chronic lymphocytic leukemia (CLL) as the most common leukemia in the Western world. Traditionally, CLL was treated with immunochemotherapy, but certain subpupulations (elderly, biological prognostic factors) had poor outcome. With advances in our understanding the pathogenesis of intracellular pathways, the possibility of selective inhibition and targeted therapy in CLL has arisen. The fi rst agent in the class of BCR inhibitors, ibrutinib, a Bruton kinase inhibitor, has been shown superior in phase III clinical trials eliminating negative prognostic factors such as del(17p), with adequate toxicity profi le, which was recognized by the respective regulatory agencies. Other BCR inhibitors idelalisib and venetoclax are extremely active in relapsed setting, but unfortunately, idelalisib combinations in fi rst line clinical trials resulted in unacceptable toxicity, which is a cautionary tale on designing trials. Despite their effi cacy, we are only at the beginning to improve them by combination with monoclonal antibodies, immunochemotherapy, or between each other to improve outcomes of CLL treatment even further. However, the main obstacle to chemo-free era in CLL is their price resulting in limited access to these agents and inequity in the modern treatment of CLL
FOLLOW-UP OF PATIENTS WITH CLASSICAL HODGIN LYMPHOMA AFTER TREATMENT ā NOVEL EVIDENCE AND DILEMMAS. LITERATURE REVIEW
Cilj je ovoga preglednog rada prikazati suvremeno stajaliÅ”te struke, ali i prijepore u svezi s medicinskom skrbi za bolesnike s klasiÄnim Hodgkinovim limfomom u prvoj remisiji. VeÄina bolesnika s klasiÄnim Hodgkinovim limfomom izlijeÄena je prvom linijom terapije i u nastavku je važan medicinski pristup radi otkrivanja moguÄeg relapsa. Pregledom literature nismo naÅ”li jednoznaÄne smjernice za rutinsko praÄenje bolesnika slikovnim metodama, tj. kompjutoriziranom tomografijom ili pozitronskom emisijskom tomografijom. Prema dokazima u literaturi, otkriÄe asimptomatskog relapsa nije povezano s poboljÅ”anim ishodom lijeÄenja. Za sada se može smatrati da su standardne kliniÄke i radioloÅ”ke metode Ādostatne za praÄenje ovih bolesnika. Kasne toksiÄnosti uzrokovane mnogim lijekovima i zraÄenjem znatno pridonose morbiditetu bolesnika. To ukljuÄuje pojavu sekundarnih solidnih malignoma (ponajprije karcinoma pluÄa i dojke) i hematoloÅ”kih Āneoplazma koÅ”tane srži te pojavu benignih toksiÄnosti kao Å”to su poremeÄaji funkcije Å”titnjaÄe, fertiliteta i kardiovaskularnih bolesti. Usprkos obilju literature i smjernica za praÄenje ovih bolesnika nakon zavrÅ”etka lijeÄenja, za sada ne postoje rezultati prospektivnih istraživanja koji bi pružili temelj zasnovan na dokazima za nove smjernice i preporuke. Smatramo da otkrivanje kasne toksiÄnosti treba biti prilagoÄeno pojedinaÄnom bolesniku, sukladno specifiÄnom lijeÄenju i kasnijem utjecaju te toksiÄnosti na moguÄi morbiditet u ovih bolesnika.In this review we present current evidence for the follow-up of patients treated for classical Hodgkin lymphoma (HL). Nowadays introduction of novel therapies enabled successful treatment in most patients with classical HL in first remission with 5-year overall survival rate estimation of 80%. We have performed extensive literature search on the Āmethodological approach to detection of relapse. Evidence regarding imaging clinical methods in detecting relapse on Āserial computed tomography and/or positron emission tomography scans is scarce. These imaging modalities are associated with considerable economic cost, unnecessary exposure to radiation and patientsā stress. Furthermore, the detection of Āasymptomatic relapse does not seem to be associated with improved outcome in this patient group. Available data on this subject indicate that standard imaging methods, such as ultrasound, and judicious clinical examination in detecting of Ārelapse should be the basis of HL patient follow-up. Late toxicity due to various modalities of treatment represents serious morbidity in HL. They vary from secondary solid cancers and hematologic neoplasms, associated with poor outcome, to benign disorders (fertility issues, thyroid dysfunction, cardiovascular and lung disorders). Current data on the incidence, prevalence and etiological factors do not yet provide evidence on appropriate screening methods. Most recommendations in various guidelines are associated with low level of evidence (grade IV). We, therefore, propose individually-tailored screening methods for each patient based on the modality of treatment received
ARE WE ENTERING CHEMO-FREE ERA IN CHRONIC LYMPHOCYTIC LEUKEMIA? THE ROLE OF IBRUTINIB AND VENETOCLAX AND LESSONS LEARNT FROM IDELALISIB
Glavni cilj ovog preglednog rada je predstaviti novu klasu lijekova u kroniÄnoj limfocitnoj leukemiji (KLL), najÄeÅ”Äoj leukemiji odrasle dobi, inhibitore staniÄnog signaliziranja B receptora (BCR). KLL se klasiÄno lijeÄila imunokemoterapijom, no pojedini bolesnici (poodmakla životna dob, nepovoljni bioloÅ”ki faktori) imali su loÅ”u prognozu. S boljim razumijevanjem patogeneze unutarstaniÄnih putova pojavila se moguÄnost selektivne inhibicije i ciljane terapije u KLL. Prvi lijek u svojoj klasi ibrutinib, inhibitor bruton kinaze, pokazao se superiornim u fazama III kliniÄkih pokusa te je eliminirao negativne prognostiÄke faktore u lijeÄenju KLL, pogotovo del (17p), s adekvatnim profi lom toksiÄnosti Å”to su prepoznale regulatorne agencije. Drugi BCR inhibitori idelalisib i venetoklaks su iznimno aktivni u relapsnom okruženju, no idelalisib se pokazao neprihvatljivo toksiÄnim u prvoj liniji lijeÄenja Å”to nam može poslužiti kao lekcija u dizajnu kliniÄkih pokusa s ovim lijekovima. Usprkos uÄinkovitosti, potreban je dodatni napredak u ovom podruÄju koji se nalazi u kombinacijama s imunoterapijom ili imunokemoterapijom, te moguÄoj meÄusobnoj kombinaciji kako bismo dodatno poboljÅ”ali ishode. No, najveÄa zapreka BCR inhibitorima da uÄu u Å”iroku praksu je njihova cijena i utjecaj na zdravstveni sustav Å”to nažalost ograniÄuje naÅ”u moguÄnost da lijeÄimo bolesnike s KLL u eri bez kemoterapije.The main aim of this review is to present a novel class of agents, the inhibitors of B cell receptor (BCR) signaling pathway, used in the treatment of chronic lymphocytic leukemia (CLL) as the most common leukemia in the Western world. Traditionally, CLL was treated with immunochemotherapy, but certain subpupulations (elderly, biological prognostic factors) had poor outcome. With advances in our understanding the pathogenesis of intracellular pathways, the possibility of selective inhibition and targeted therapy in CLL has arisen. The fi rst agent in the class of BCR inhibitors, ibrutinib, a Bruton kinase inhibitor, has been shown superior in phase III clinical trials eliminating negative prognostic factors such as del(17p), with adequate toxicity profi le, which was recognized by the respective regulatory agencies. Other BCR inhibitors idelalisib and venetoclax are extremely active in relapsed setting, but unfortunately, idelalisib combinations in fi rst line clinical trials resulted in unacceptable toxicity, which is a cautionary tale on designing trials. Despite their effi cacy, we are only at the beginning to improve them by combination with monoclonal antibodies, immunochemotherapy, or between each other to improve outcomes of CLL treatment even further. However, the main obstacle to chemo-free era in CLL is their price resulting in limited access to these agents and inequity in the modern treatment of CLL