Survival in Dialysis or Plasma Exchange Treated Patients for Multiple Myeloma – A Single Centre 25 Year Experience

Aim: Multiple myeloma (MM) patients might require haemodialysis (HD) and/or plasma exchange (PE) in cases of acute kidney injury (AKI) and/or chronic kidney disease (CKD) and/or other indications. The study analysed the survival of MM patients who required HD and/or PE. Subjects and methods: All 144 patients treated for MM at the University Hospital Centre Osijek between 1994 and 2018 (of whom 47.9 % were men) were included in the study. Data were collected from medical records. MedCalc Statistical Software version 17.8.2 was used for the statistical analysis, with significance set at α = 0.05. Results: Forty-three of 144 MM patients (29.9 %) were treated with HD and/or PE. Male patients required HD or PE more often than female patients (62.8 % vs 37.2 %, P = 0.02). Patients who did not require HD or PE were significantly older at the time of their death than the patients treated with HD or PE [75 (interquartile range, IQR, 72 – 77) vs 72 (IQR 66 – 75) years; P = 0.009, Mann-Whitney test]. Among all patients who required acute or chronic HD, PE or a combination of the treatments, the longest life span was found in 17 patients who were treated with chronic HD (median 12 months, IQR 8 – 58). Conclusion: Kidney failure requiring HD or PE in MM was associated with a significantly shorter life span in comparison with other MM patients. Chronic HD patients had the longest survival among patients who required acute or chronic HD, PE or a combination of the treatments. In general, MM patients in need for HD and/or PE had poor survival. (Smajić* P, Schönberger E, Periša V, Sinčić Petričević J, Zibar L, Kralik K. Survival of Multiple Myeloma Patients Undergoing Dialysis or Plasma Exchange - A Single Centre’s 25-Year Experience. SEEMEDJ 2020; 4(1); 25-31

A Coincidence of HLA-B27 Negative Spondyloarthritis and Paravertebral Non-Hodgkin’s Lymphoma – A Lesson to be Learned from the Past Experience

We reported a case of a 71-year-old woman with progressive low back pain and neurologic symptoms of lower extremities, who in the background had the coexistence of spondyloarthritis (SpA) and non Hodgkin’s lymphoma of the paravertebral location. This example describes a situation where SpA with minimal sacroiliac joints affection has nevertheless led to the overt axial SpA. This situation included undifferentiated or reactive SpA, as well as unusual disease context, presented with late-life disease onset, older age, female gender and no obvious hereditary predisposition. This combination of comorbid factors could allow environmental and disease-specifi c factors to accumulate over time and to, by modifying the primary, low-penetrant genetic background, lead to the development of lymphoma. By achieving better understanding of disease pathophysiology dynamic, we will be able to improve our capabilities to navigate biologic therapy in the future, in order to prevent the development of both, overt SpA and lymphoproliferative disease

Red blood cell distribution width as a simple negative prognostic factor in patients with diffuse large B-cell lymphoma: a retrospective study

Aim To determine the prognostic value of baseline red blood cell distribution width (RDW) in diffuse large B cell lymphoma (DLBCL) patients. Methods Data from 81 DLBCL patients diagnosed from 2006 to 2013 at the University Hospital Center Osijek, Osijek, Croatia, were reviewed. We evaluated disease outcome, overall survival (OS) and event-free survival (EFS), and demographic, clinical and laboratory factors affecting outcome. Univariate analysis and Cox regression analysis were used. Results Median age of patients was 64 years, 29 were men (35.8%). Higher RDW levels (%) were found in patients with advanced Ann Arbor clinical stage (14.94 ± 1.82 vs 13.55 ± 1.54, P = 0.001) and in those with poor response to therapy (14.94 ± 1.82 vs 13.55 ± 1.54, P = 0.001). Patients with RDW>15% (cut-off was calculated by receiver operating characteristics) had significantly worse OS (median [range], 33 months [20-46] vs 74 months [65-82], P < 0.001) and EFS (27 months [15-40] vs 68 months [59-77], P < 0.001). Cox regression analysis showed that RDW>15% was an independent prognostic factor for OS (HR 3.654, 95% CI 1.128-11.836) and EFS (HR 2.611, 95% CI 1.012-6-739). Conclusion High baseline RDW is an independent prognostic marker of poor outcome in patients with DLBCL. RDW could be an easily available and inexpensive marker for the risk stratification in patients with DLBCL

Clinical Characteristics of Patients with Spondyloarthritides and HLA-B27 Positive Antigen

The aim of this study was to present our experiences in diagnosing spondyloarthritides (SpA), and to list the most common clinical features of HLA-B 27 positive patients.The study included 65 HLA-B 27 positive patients with confirmed diagnosis of ankylosing spondylitis(AS) and psoriatic arthritis (PsA) who were analyzed between 2009 and 2010 in Clinic of Internal Medicine in Osijek. The diagnosis of seronegative spondyloarthritides was based on the ASAS (Assessment in AS Working Group) classification criteria for axial and then supplemented with ASAS criteria for peripheral SpA and was confirmed by radiological techniques. For diagnosing the ankylosing spondylitis (AS), there have been applied the modified New York criteria. Radiological criteria for definite sacroiliitis according to the modified New York criteria is bilateral sacroiliitis, grade 2–4 (2) or unilateral sacroiliitis, grade 3–4. For diagnosing the psoriatic arthritis (PsA), there were used CASPAR diagnostic criteria. Other features of SpA are defined within the existing classification criteria. HLA-B27 antigen was determined by direct immune-fluorescence technique using flow cytometer. The average age of patients was 50.34 years, of whom 27 female (41.53%), 38 male (58.46%). Duration of illness was 15.79 years on average.With 75.38% of patients, there had been determined the diagnosis of AS; 24.62% of patients had the diagnosis of PsA. The most common clinical characteristics that patients had were: inflammatory back pain (pain Inflammation along the lumbosacral spine), peripheral arthritis, intermittent pain in the gluteus, sacroiliitis, enthesitis, uveitis, dactilitis

Smjernice za dijagnostiku i liječenje kronične limfocitne leukemije – Krohem B-CLL 2017.

Recent developments in the diagnosis and treatment of chronic lymphocytic leukemia (B-CLL) have led to change of approach in clinical practice. New treatments have been approved based on the results of randomized multicenter trials for first line and for salvage therapy, and the results of numerous ongoing clinical trials are permanently providing new answers and further refining of therapeutic strategies. This is paralleled by substantial increase in understanding the disease genetics due to major advances in the next generation sequencing (NGS) technology. We define current position of the Croatian Cooperative Group for Hematologic Disease on diagnosis and treatment of CLL in the transition from chemo-immunotherapy paradigm into a new one that is based on new diagnostic stratification and unprecedented therapeutic results of B-cell receptor inhibitors (BRI) and Bcl-2 antagonists. This is a rapidly evolving field as a great number of ongoing clinical trials constantly accumulate and provide new knowledge. We believe that novel therapy research including genomic diagnosis is likely to offer new options that will eventually lead to time limited therapies without chemotherapy and more effective clinical care for B-CLL based on individualized precision medicine.Nedavni događaji u dijagnostici i liječenju kronične limfocitne leukemije (B-KLL) doveli su do promjene pristupa u kliničkoj praksi. Nova liječenja su odobrena na temelju rezultata randomiziranih multicentričnih pokusa za prvu liniju terapije i za liječenje relapsa/refraktorne bolesti, a rezultati brojnih kliničkih pokusa u tijeku trajno doprinose daljnjem unaprjeđenju terapijskih strategija. Uz to prisutan je bitan porast razumijevanja genskih promjena bolesti zbog velikog napretka tehnologije nove generacije sekvencioniranja. Definiramo trenutni stav Hrvatske suradne skupine za hematološke bolesti o dijagnostici i liječenju B-KLL u sadašnjoj tranziciji iz kemo-imunoterapijske paradigme u novu koja se temelji na novoj dijagnostičkoj slojevitosti i izvrsnim terapijskim rezultatima inhibitora B-staničnih receptora (BRI) i Bcl-2 antagonista. To se područje brzo razvija kako velik broj kliničkih ispitivanja koja su u tijeku neprestance doprinosi i pruža nova znanja. Vjerujemo da će istraživanje novih terapija uz genomsku dijagnostiku pružiti nove mogućnosti koje će na kraju dovesti do vremenski ograničenog liječenja bez kemoterapije i do učinkovitije kliničke skrbi B-KLL na temelju individualizirane i precizne medicine

DIAGNOSIS AND THERAPY FOR PATIENTS WITH ESSENTIAL THROMBOCYTHEMIA Guidelines of Croatian Cooperative Group for hematologic disorders – KROHEM

Esencijalna trombocitopenija (ET) klonski je mijeloproliferativni zloćudni tumor. Hrvatska kooperativna grupa za hematološke bolesti, KROHEM, predlaže smjernice dijagnostičkog i terapijskog pristupa. Dijagnoza ET temelji se na kriterijima dijagnostike i podjele mijeloidnih zloćudnih tumora Svjetske zdravstvene organizacije (SZO). Razina terapijskih preporuka polazi od pokazatelja predloženih od elektronskog izvora medicinskih informacija, UpToDate®. Za dijagnozu ET potrebno je dokazati trajan porast broja trombocita (>450×109/L), uz tipičnu histološku sliku megakariocitopoeze u koštanoj srži te isključiti postojanje sekundarne trombocitoze ili drugih kroničnih mijeloproliferativnih zloćudnih tumora. Liječenje se temelji na pokazateljima rizika od bolesti koji je određen brojen trombocita, dobi bolesnika te prisutnošću rizika ili znakova tromboze i krvarenja. Bolesnike niskog rizika (dob 60 godina) prva linija terapije je hidroksiureja, a anagrelid se primjenjuje u bolesnika s nepotpunim odgovorom na hidroksiureju. U trudnica, kada je potrebno liječenje, preporučuje se alfa-interferon.Essential thrombocythemia (ET) is a clonal myeloproliferative neoplasm. Croatian Cooperative Group for hematologic disorders, KROHEM proposes the diagnostic and treatment guidelines for ET. Diagnosis of ET is based on the criteria and classification of World Health Organization (WHO). The level of treatment recommendation is based on the UpToDate® (web based medical community database) criteria. For ET diagnosis it is mandatory to show sustained increased number of platelets with typical histomorphological changes of megakaryopoiesis in bone marrow. Secondaly thrombocytosis and other chronic myeloproliferative neoplasms have to be excluded. Therapy is based on risk factors for ET. The risk factors are number of platelets, patient’s age, and the risk levels for thrombosis and bleeding. Patients with low risk (age <60 years and platelets <1000×109/L) arw not candidates for therapy. In younger group of patients with platelets between 1000 and 1500×109/L or more than 1500×109/L treatment with anagrelide or hydroxyurea is recommended respectively. In high risk patients hydroxyurea is the first line treatment. Anagrelide is indicated in these patients in the absence of treatment response. Alpha-interferon is recommended for pregnant women with ET and high platelet counts

Prognostic Nutritional Index as a Predictor of Prognosis in Patients with Diffuse Large B cell Lymphoma

BACKGROUND: The prognostic nutritional index (PNI), an indicator of nutritional status and systemic inflammation, is associated with short-term and long-term outcomes of various malignancies. The prognostic value of PNI in diffuse large B cell lymphoma (DLBCL) remains unknown. The aim of the present study was to determine the prognostic value of baseline PNI in DLBCL patients. METHODS: We retrospectively analyzed data from 103 DLBCL patients treated with R‑CHOP or R‑CHOP-like regimens. We evaluated the significance of PNI as a predictor of response to treatment, overall survival (OS) and event-free survival (EFS). RESULTS: Patients with a PNI ≤ 44.55, where the cut-off was calculated by receiver operating characteristics (Youden index) and the same was obtained for response to treatment with 76.2 % sensitivity and a specificity of 85.4 %, for OS with 72.4 % sensitivity and a specificity of 90.5 % and for EFS with 65.6 % sensitivity and a specificity of 90.1 %, had significantly worse 5‑year OS (18.3 % vs 86.4 %, P < 0.001, log rank test) and 5‑year EFS (15.1 % vs 82.3 %, P < 0.001, log rank test). Regression analysis showed that PNI ≤ 44.55 was an independent prognostic factor for response to treatment with an odds ratio (OR) of 4.88 for treatment failure, 95 % confidence interval (CI) 1.077-22.105, OS hazard ratio (HR) 4.24, 95 % CI 1.451-12.392 and EFS HR 4.007, 95 % CI 1.48-10.852. Lower PNI levels were found in patients with advanced Ann Arbor clinical stage (46.6 ± 7.77 vs. 52.7 ± 5.43) and in those with poor response to therapy (40.58 ± 7.26 vs. 50.67 ± 6.26). CONCLUSIONS: The PNI is a simple and useful marker to predict long-term survival outcome in DLBCL patients. Low PNI predicted poor outcome. A limitation of the study is its retrospective design in which the prognostic value was tested in the derivation cohort only. Notwithstanding, this is the first study suggesting that PNI is an important prognostic factor in DLBCL

A Coincidence of HLA-B27 Negative Spondyloarthritis and Paravertebral Non-Hodgkin’s Lymphoma – A Lesson to be Learned from the Past Experience

We reported a case of a 71-year-old woman with progressive low back pain and neurologic symptoms of lower extremities, who in the background had the coexistence of spondyloarthritis (SpA) and non Hodgkin’s lymphoma of the paravertebral location. This example describes a situation where SpA with minimal sacroiliac joints affection has nevertheless led to the overt axial SpA. This situation included undifferentiated or reactive SpA, as well as unusual disease context, presented with late-life disease onset, older age, female gender and no obvious hereditary predisposition. This combination of comorbid factors could allow environmental and disease-specifi c factors to accumulate over time and to, by modifying the primary, low-penetrant genetic background, lead to the development of lymphoma. By achieving better understanding of disease pathophysiology dynamic, we will be able to improve our capabilities to navigate biologic therapy in the future, in order to prevent the development of both, overt SpA and lymphoproliferative disease

Koincidencija između HLA-B27 negativnog spondiloartritisa i paravertebraline lokalizacije Non-Hodgkin-ovog limfoma - Lekcija koju bi trebalo naučiti iz prošlosti

We reported a case of a 71-year-old woman with progressive low back pain and neurologic symptoms of lower extremities, who in the background had the coexistence of spondyloarthritis (SpA) and non Hodgkin’s lymphoma of the paravertebral location. This example describes a situation where SpA with minimal sacroiliac joints affection has nevertheless led to the overt axial SpA. This situation included undifferentiated or reactive SpA, as well as unusual disease context, presented with late-life disease onset, older age, female gender and no obvious hereditary predisposition. This combination of comorbid factors could allow environmental and disease-specifi c factors to accumulate over time and to, by modifying the primary, low-penetrant genetic background, lead to the development of lymphoma. By achieving better understanding of disease pathophysiology dynamic, we will be able to improve our capabilities to navigate biologic therapy in the future, in order to prevent the development of both, overt SpA and lymphoproliferative disease.Prikazali smo slučaj 71-godišnje žene s progresivnim bolom u križima i neurološkim simptomima donjih ekstremiteta, čiju je pozadinu činila koegzistencija spondiloartritisa (SpA) i ne-Hodgkin-ova limfoma paravertebralne lokalizacije. Taj slučaj opisuje situaciju gdje je SpA s minimalnim promjenama na sakroilijačnim zglobovima ipak doveo do razvija uznapredovalog oblika aksijalnog SpA. Ta situacija je uključivala nediferencirani ili reaktivni SpA, kao i neuobičajeni klinički kontekst predstavljen kasnim početkom bolesti, starijom dobi, ženskim spolom i odsustvom nasljedne predispozicije bolesti. Takva kombinacija ko-morbiditetnih čimbenika je bila pogodna da omogući okolišnim i za bolest specifi čnim čimbenicima da se nakupljaju kroz vrijeme i da, modifi cirajući primarnu, slabo penetrirajuću genetsku podlogu, dovedu do razvoja limfoma. S boljim razumijevanjem patofi ziološke dinamike bolesti, poboljšat ćemo i našu sposobnost da specifi čno usmjeravamo biološku terapiju u budućnosti, da bi spriječili razvoj, kako uznapredovalog oblika SpA, tako i limfoproliferativne bolesti

Comparison of the Prognostic Impact of Neutrophil/Lymphocyte Ratio, Platelet/Lymphocyte Ratio, and Glasgow Prognostic Score in Diffuse Large B-Cell Lymphoma

Background: Given the role of inflammation in tumor progression, as well as in diffuse large B-cell lymphoma (DLBCL), researchers are trying to identify easily applicable, easy accessible prognostic markers for individual risk assessment. The most frequently used inflammatory prognostic markers are the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR),andthe Glasgow prognostic score (GPS). Objectives: To determine and compare the prognostic value of the baseline inflammatory biomarkers NLR, PLR, and GPS in patients with DLBCL. Methods: We retrospectively analyzed data from 103 DLBCL patients treated with R-CHOP or R-CHOP-like regimens. We evaluated the significance of NLR, PLR, and GPS as a predictor of response to treatment, overall survival (OS), and event-free survival (EFS). Results: Higher NLR levels were found in patients with a poorer response to therapy (median [range] 2.87 [0.56 - 26.33] vs. 4 [0.62 - 29.66], P = 0.026). Patients with NLR values of > 2.63 (cutoff value calculated by receiver-operating characteristic) had significantly worse two-year OS (65.1% vs. 87.2%, P = 0.002) and two-year EFS (59.8% vs. 87.1%, P = 0.001). PLR values were not significant for survival. The two-year OS rates for patients with GPS = 0, GPS = 1, and GPS = 2 were 93.3%, 63.9%, and 33.3%, respectively (P 2.63 were an independent prognostic factor for OS (hazard ratio [HR] = 2.857; 95% confidence interval [CI] 1.022 - 8.699; P = 0.048] and EFS (HR = 4.06; 95% CI 1.357 - 12.151; P = 0.012). Conclusions: Our research confirmed NLR as useful independent prognostic marker for survival. PLR and GPS did not show independent prognostic value, although they were also associated with the patients’ clinical features. The easy availability and inexpensiveness of inflammatory biomarkers should encourage their use in clinical practice