Aleksandra Sretenovic

Intravascular large B-cell lymphoma of central nervous system - a report of two cases and literature review.

Intravascular large B-cell lymphoma (IVL) is a rare form of diffuse large B cell lymphoma (DBCL) frequently presenting with skin and/or central nervous system (CNS) involvement. IVL involves CNS in 75 - 85% of patients and neurological symptoms include sensory and motor deficits or neuropathies, meningoradiculitis, paresthesia, hypostenia, aphasia, dysarthria, hemiparesis, seizures, transient visual loss, vertigo and impaired cognitive function. Neuroimaging discloses CNS involvement only in half of patients with neurological symptoms because there are no pathognomonic neuroradiological findings for IVL; ischemic foci are the most common presentation pattern and therefore vasculitis is the most common differential diagnosis. According to all mentioned data, diagnosis of CNS IVL requires a histopathological confirmation. Brain biopsy is absolutely indicated in patients with progressive neurological deterioration with unclear abnormalities in cerebral MR imaging. A general policy is that patients with IVL should be considered to have disseminated disease and should be treated with systemic chemotherapy. In younger patients with unfavorable features the high-dose chemotherapy with autologous stem cell transplantation should be used. Nevertheless, the course of IVL is rapidly progressive and ultimately fatal.

Prognostic effect of comorbidity indices in elderly patients with multiple myeloma.

BACKGROUND Consideration of comorbidity, disability, and frailty represents a significant part of the treatment of elderly multiple myeloma (MM) patients. The aim of study was to analyze the effect of the Charlson Comorbidity Index (CCI) and scale of Instrumental Activities of Daily Living (IADL) on the course of disease. PATIENTS AND METHODS The study included 110 newly diagnosed MM patients older than 65 years of age. According to the CCI most patients had at least 1 comorbidity (CCI score of 1) and most of them (51 of 110 patients; 46.4%) had an age-adjusted CCI (aaCCI) score of 5 to 6. Most of our patients were capable of performing routine daily activities (IADL ≥ 6). Patients were treated with thalidomide- and bortezomib- based combinations, or with conventional chemotherapy. RESULTS International Staging System (ISS) score 3 correlated with high scores of CCI or aaCCI (R = 0.314, P < .003; R = .317, P < .002, respectively), and lower IADL (R = 0.259, P < .007). The probability of adverse events was 70% greater for CCI score ≥ 2 (odds ratio [OR], 1.72); 28% for aaCCI ≥ 5 (OR, 1.28) and 22% higher for IADL < 3 (OR, 2.25). The patients with a CCI score of 0 to 1 had significantly longer overall survival (OS; log rank, 6.538; P < .011). The patients with aaCCI ≥ 5 had significantly shorter OS (log rank, 4.209; P < .040), and the patients with IADL > 3 had significantly longer OS (log rank, 6.62; P < .001). In the proposed model, aaCCI ≥ 5 and IADL > 3 scores had a major effect on the OS (χ(2), 8.46; P = .037). CONCLUSION CCI, aaCCI, and IADL scale are clinical parameters of prognostic significance. A proposed model for a personalized treatment approach is based on variables such as scores for aaCCI ≥ 5 and IADL > 3.

Development and validation of multivariable predictive model for thromboembolic events in lymphoma patients.

Lymphoma patients are at increased risk of thromboembolic events but thromboprophylaxis in these patients is largely underused. We sought to develop and validate a simple model, based on individual clinical and laboratory patient characteristics that would designate lymphoma patients at risk for thromboembolic event. The study population included 1,820 lymphoma patients who were treated in the Lymphoma Departments at the Clinics of Hematology, Clinical Center of Serbia and Clinical Center Kragujevac. The model was developed using data from a derivation cohort (n = 1,236), and further assessed in the validation cohort (n = 584). Sixty‐five patients (5.3%) in the derivation cohort and 34 (5.8%) patients in the validation cohort developed thromboembolic events. The variables independently associated with risk for thromboembolism were: previous venous and/or arterial events, mediastinal involvement, BMI>30 kg/m2, reduced mobility, extranodal localization, development of neutropenia and hemoglobin level < 100g/L. Based on the risk model score, the population was divided into the following risk categories: low (score 0‐1), intermediate (score 2‐3), and high (score >3). For patients classified at risk (intermediate and high‐risk scores), the model produced negative predictive value of 98.5%, positive predictive value of 25.1%, sensitivity of 75.4%, and specificity of 87.5%. A high‐risk score had positive predictive value of 65.2%. The diagnostic performance measures retained similar values in the validation cohort. Developed prognostic Thrombosis Lymphoma – ThroLy score is more specific for lymphoma patients than any other available score targeting thrombosis in cancer patients. Am. J. Hematol. 91:1014–1019, 2016.

The possible benefit from total tumour resection in primary diffuse large B-cell lymphoma of central nervous system – a one-decade single-centre experience

Background and methods. The aim of the study was to evaluate retrospectively clinical course of 27 patients with primary central nervous system lymphoma (PCNSL) diagnosed and treated by different surgical approaches. Initial therapy-diagnostic approach included surgery with total tumour reduction (TTR) performed in 12 patients (44.4%), while partial reduction and biopsy were performed in 8 (29.7%) and 7 (25.9%) patients, respectively. All patients were treated with chemotherapy based on high-dose methotrexate (HD-MTX) with/without whole-brain radiotherapy (WBRT). Results. The median overall survival (OS) and event-free survival were 37 and 31 months, respectively, with overall response rate of 74%. The patients who underwent an open surgery with TTR had significantly longer OS (median not reached), comparing with partial tumour reduction or biopsy only (Log-Rank χ2 6.08, p = 0.014) when median OS was 23 months. In patients with performance status according to Eastern Cooperative Oncology Group (ECOG PS) ≥ 3, OS was 23 months, contrary to ECOG PS 1–2 when median was not reached. The International Extranodal Lymphoma Study Group score (low, intermediate and high) also influenced OS between three risk groups (Log-Rank χ2 12.5, p = 0.002). Conclusion. The treatment of PCNSL still remains doubtful, however possible benefit from the TTR followed with HD-MTX with/without WBRT should be reconsidered.

The Revised International Staging System Compared to the Classical International Staging System Better Discriminates Risk Groups among Transplant-Ineligible Multiple Myeloma Patients

Background: The Revised International Staging System (R-ISS) has recently been introduced as a comprehensive prognostic score for multiple myeloma (MM). Validation of the R-ISS in patients treated outside of clinical trials is the focus of current investigations. The aim of this study was to test the prognostic role of the R-ISS in MM patients ineligible for autologous stem cell transplantation. Patients and Methods: A total of 102 newly diagnosed MM patients were analyzed. All patients were initially treated with thalidomide-based combinations. Results: An overall response rate was achieved in 77.4% patients. Both the International Staging System (ISS) and the R-ISS influenced the event-free survival and the overall survival (OS). However, the ISS was unable to discriminate patients in stages ISS1 and ISS2 regarding OS. On the contrary, the R-ISS clearly differentiated risk categories regarding OS and provided an improved discriminative power of 6.3% compared to the ISS. Furthermore, among the parameters that were significant in univariate analysis (presence of renal impairment, anemia, platelet count < 130 × 109/l, and R-ISS), the multivariate model pointed to the R-ISS (p = 0.001) as the most important parameter influencing OS. Conclusion: The R-ISS represents a useful tool for risk stratification of transplant-ineligible MM patients and should be considered as a prognostic index in daily clinical practice.

A case of primary peripheral T-cell type non-Hodgkin lymphoma originating in the iris: Clinico-pathological findings

BACKGROUND The ocular adnexal region is the primary localization of extranodal lymphoma in 5% to 15% of all Non-Hodgkin lymphoma. Intraocular lymphoma of T-cell origin is extremely rare and such sites of infiltration have been rarely observed in clinical examination. CASE REPORT We presented a 56-year-old man with iris infiltration by primary intraocular peripheral T-cell lymphoma. The patient was in clinical stage I BE and the treatment was initiated according to cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone (CHOP) regimen. When the second course of the therapy was scheduled, the patient developed central nervous system lymphoma infiltration. Although De Angelis regimen was used, 3 months after the diagnosis was established, lethal outcome ensued due to disease progression. CONCLUSION According to our experience we can conclude that further therapeutical approach to patients with primary intraocular T-cell lymphoma requires modification of conventional treatment regimens. The lower median survival in these patients suggests that the disease may be of more aggressive course.

CHRONIC LYMPHOCYTIC LEUKEMIA INVOLVEMENT OF CENTRAL NERVOUS SYSTEM: A SINGLE CENTRE EXPERIENCE

using p < 0.05 determined statistical significance. Results: Compared to pre‐treatment baseline samples, both Ibrutinib and Venetoclax treatment resulted in a significant increase in the frequency and absolute number of both MDSC (HLADRCD11bCD33) and normal monocytes (HLADRCD11bCD33+) to the same level (Ibrutinib) or in excess (Venetoclax) to those seen in healthy controls (Fig. 1). The frequency of mDC (HLADRCD11c) was significantly increased following Ibrutinib (but not Venetoclax) treatment. Following both Ibrutinib and Venetoclax treatment, a significant increase in the frequency of NK cells (CD3CD56) was seen, although only Venetoclax treatment resulted in a normalisation of NK cells comparable to healthy controls. Both Ibrutinib and Venetoclax treatment resulted in a significant increase in the frequency of γδ T cells. Conclusion: BTK and Bcl‐2 inhibitors have different effects on innate immune subsets. Whist the immunological profile of patients improves with both, immunological recovery is greatest in those treated with Venetoclax. This provides an opportunity for the potential introduction of immunotherapies following small molecule therapy to promote anti‐ CLL immunity and improve durability of responses.

COMPARATIVE ANALYSIS OF PREDICTIVE MODELS FOR THROMBOEMBOLIC EVENTS IN LYMPHOMA PATIENTS

ing the side effect profile. Methods: Data from 2012 to 2016 were collected retrospectively from pharmacy records for all lymphoma patients treated with thalidomide. The majority of these patients were multiply relapsed. Patients were all started on 50 mg daily, with dose escalation to 200 mg daily as tolerated, in addition to pulsed dexamethasone. Results: 27 patients were treated: ‐ 11 DLBCL (2 transformed low‐ grade) ‐ 3 Follicular lymphoma‐ 2 B‐NHL unspecified‐ 3 Hodgkins disease‐ 2 Waldenströms macroglobulinaemia‐ 1 mantle cell‐ 5 angioimmunoblastic T cell‐ Age range of patients 52–58 (median age 75)‐ Line of treatment was 1–5 (median 2)‐ 17/27 patients were treated for >4 weeks (others stopped due to SEs or early relapse/ death)‐ 7 of those 17 achieved disease control for >6 months. Conclusion: The patients examined in this study were all multiply relapsed and/or too frail for conventional chemotherapy. Prognosis in such a cohort is very poor and, unsurprisingly, many of the cases we looked at died shortly after starting treatment. However, a subset of these patients achieved long disease control—one patient is still alive 5 years after starting thalidomide. Thalidomide has a variety of mechanisms including immunomodulatory and anti‐angiogenic properties so it is a logical choice of treatment in chemotherapy‐resistant cases. Given the generally well‐tolerated side effect profile and low cost of thalidomide not to mention the ease of administration, a trial of thalidomide is worth considering when no other options remain, where it may buy precious months, or even years, of life.