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Autologous stem cell transplantation (ASCT) is considered standard therapeutic approach for patients with relapsed and refractory (R/R) diffuse large B cell lymphoma (DLBCL) that are transplant eligible. For transplant ineligible patients there are few therapeutic options and novel targeted therapies and immunotherapy that are still in development. Treatment of such patients with poor prognosis is considered to be a challenge and there is constant need for new salvage treatment regimens. The aim of this study was to evaluate patients’ characteristics and treatment strategies and considerations for diffuse large B cell lymphoma in our department, and to promote new therapeutic possibilities for R/R patients with NHL DLBCL. A total of 308 patients with NHL were treated at University Clinic for hematology from 2008 until 2020 and 49% (151) of patients with NHL DLBCL were included in this study. Survival analysis of all analyzed relapsed/refractory NHL patients revealed statistically significant better survival in patients with low risk IPI score, disease stage I/II and patients with age

Acute promyelocytic leukemia (APL) is a subtype of acute leukemia (AL) with distinct cytogenetics, clinical and biological characteristics. APL was considered as one of the most rapidly lethal forms of acute myeloblastic leukemia (AML), but recently, with the introduction of all-trans retinoic acid (ATRA) it has become the most curable subtype of AL. The main difficulty with APL is early death (ED), defined as death because of any cause within 30 days after diagnosis, and it has emerged as the most important cause of treatment failure. Our retrospective-prospective study was realized at the University Clinic for Hematology from January 2004 until December 2020. It included 46 patients with APL, according to FAB and WHO classification with confirmed molecular diagnosis. The following patients’ risk stratification factors were analyzed: age, Sanz risk score, WBC, PL, clinical presentation of the disease, levels of fibrinogen and D-dimers. During the study period, APL was diagnosed in 46 patients, 24 females (52.2%) and 22 males (47.8%), with mean age of 45 years. The overall survival showed that 24 patients (52.1%) were alive and 22 (47.8%) had lethal outcome. Regarding treatment, five patients (10.9%) died before starting the chemo-treatment. But, still, ED was observed in 13 patients (59%), and in 9 patients (40.9%) death occurred 30 days after establishing the diagnosis. The main reasons of mortality were also analyzed. To prevent ED prior to treatment, suspected APL patients should be immediately hospitalized and treated as medical emergency. Keywords: acute promyelocytic leukemia, early death, all-trans retinoic acid

The Multiple myeloma (MM) is a plasma cell malignancy in which monoclonal plasma cells proliferate in bone marrow, resulting in an overabundance of monoclonal paraprotein (M protein), destruction of bone, and displacement of other hematopoietic cell lines. This retrospective-prospective study was conducted at the University Clinic for Hematology in Skopje, North Macedonia, in the period between January 2009 and December 2019. Patients younger than 65 years, without comorbidities, fit for autologous peripheral blood stem cell transplantation (PBSCT), were treated with Cyclophosphamide-Thalidomide-Dexamethasone (CyThalDex) protocol divided into two daily doses which were maintained until complete remission. Patients over 65 years of age, unfit for more aggressive treatment options like peripheral blood stem cells (PBSCT) with comorbidities and renal failure, were treated with Melphalan-Prednisone-Thalidomide (MPT) protocol. The third group of patients was treated without new immunomodulators such as thalidomide, but instead a salvage therapy was given consisted of chemotherapy and corticosteroids. The use of thalidomide can lead to more undesirable effects such as deep vein thrombosis and renal neuropathy. The results obtained in our study showed no high percentage of these effects. However, a better survival rate was registered along with a longer period without progression of the underlying disease (PFS). Moreover, a higher percentage of complete remission (CR) was achieved and a very good partial response (VGPR) in general. Myeloma multiplex is still incurable disease with pattern of regression and remission followed by multiple relapses rising from the residual myeloma cells, but in the future still many unsolved questions has to be answered. Keywords: myeloma multiplex, autologous stem cell transplantation, thalidomide

The concept generated by biological expression profile divided patients with diffuse large B-cell lymphoma (DLBCL) into two subtypes. This concept has been presented in the recent editions of WHO classification and became a prognostic tool. Aim of the study was introduction of new three-marker model for immunohistochemical and prognostic subclasification of patients with DLBCL. Our retrospective study enrolled 200 adult patients with DLBCL diagnosed and treated in the period between January 2013 to January 2021. They were all treated with chemoimmunotherapy with R+/-CHOP regimen and the median follow-up of the patients was 48 months. We analysed the biopsy samples immunohistochemically with the markers of germinal (BCL6) and post-germinal centre (MUM1), and the marker of apoptosis (BCL2). Using the immunohistochemical three-marker model, which consisted of BCL-2, BCL-6, and MUM1, we distributed the patients with DLBCL into 2 subgroups: germinal centre – like (GCL) and activated centre-like lymphoma (ACL). The GCL and ACL patients were comparable regarding age, gender and all other already established prognostic parameters. Patients with GCL had overall survival of 140 months, and patients with ACL had overall survival of 88 months. ACL patients with BCL2 expression had a shorter survival compared to ACL patients without BCL2 expression. The difference in survival was statistically significant for p=0.01914. The study introduced the new three-marker model for immunohistochemical subclasification of patients with DLBCL treated with immunochemotherapy. Apoptotic marker BCL2 is a strong survival predictor. In the present study, we confirmed the prognostic importance of BCL2 protein expression, which showed a predictive capacity in ACL. Keywords: DLBCL, three - marker model, immunohistochemical, BCL2