Dilemma: Correlation Between Serum Level of Hepcidin and IL-6 in Anemic Myeloma Patients.

INTRODUCTION: Anemia occurs in 60% to 80 % of patients with newly diagnosed myeloma multiplex (MM). The cause of anemia in MM is probably multi factorial and involved among the others hepcidin and some cytokines, especially interleukine-6. Anemia in MM is one of the risk factor used in Durie-Salmon classification for staging and prognostic score. Treatment options are set according to this score with most significant impact on survival. AIM: To estimate baseline level of serum hepcidin, IL-6 and iron metabolism markers in anemic MM patients, possible role of hepcidin and its interaction with IL-6. METHODS: 27 patients with newly diagnosed MM were enrolled in this observational, prospective study and age, gender matched 60 healthy controls. Erythrocyte count, hemoglobin, serum hepcidin, interleukin-6, iron, ferritin and transferrin were measured. RESULTS: Anemia was diagnosed in 70% of MM patients. Serum hepcidin was significantly higher in MM group (55.5 ng/mL) than in control 5.9 ng/mL (p=0000). In myeloma patients serum IL-6 was 3.59 pg/mL, anemic 3.80 pg/mL, non-anemic 0.33 pg/mL, without significant difference. It was not found significant correlation between hepcidin and IL-6 in anemic myeloma patients. CONCLUSION: High level of hepcidin probably causes anemia in MM but its high expression is not due only to IL-6.

Primary Central Nervous System Lymphoma, Treatment Outcomes - 10 Year Experience. Single Center Study.

Background: Primary central nervous system lymphoma(PCNSL) is an aggressive, rare form of Non-Hodgkin lymphoma, characterized by the absence of systemic disease. There are limited data and no strictly defined guidelines for management of PCNSL. Objective: The aim of this study was to report a 10 year experience of PCNSL treatment, to evaluate treatment outcomes and asses Progression Free and Overall Survival of these patients. Methods: Study was conducted on the Haematology Clinic, Clinical center University of Sarajevo, BH, in the period from January 2012.-December 2022. Total sample of 24 patients were enrolled. All have undergone diagnostic surgery. Patients were treated with regimens based on High dose Methotrexate, with/without whole brain radiotherapy as consolidation. Treatment response was captured by imaging techniques. Patients who have relapsed were evaluated with imaging techniques and treated according to Methotrexate-based treatment protocols. Results: We have captured equal gender distribution. The median age of patients was 59.5 years (range 20-79). Pathohistological analysis confirmed DLBCL diagnosis in 22 patients, T cell lymphoma and anaplastic large cell lymphoma, each in 1 patient. Chemotherapy, chemotherapy combined with WBRT and radiotherapy were given to 5, 18 and 1 patients, respectively. The overall complete response rate (CR) was 87,15%. Those receiving combined modality-treatment had higher CR than those receiving chemotherapy (94,4% versus 60%). Out of 24 patients, 11 of them relapsed. The median time to relapse was 29 months (from 1 to 105). After second line of the treatment, CR was 54,5%, while 45,45% of patients died during the treatment. 4 patients relapsed for the second time with median time to relapse of 9 months (from 2 to 77). 2 year OS rate was 67%, and the median OS rate was 45,9 months. 2 year PFS rate was 31%. Conclusion: The OS and PFS rates indicate the usage of new drugs and consolidation with autologous stem cell transplantation in patients with PCNSL in order to achieve better treatment outcomes.

Bone Marrow Microenvironment Interplay and Current Clinical Practice in Multiple Myeloma: A Review of the Balkan Myeloma Study Group.

The course of multiple myeloma (MM) is influenced by a variety of factors, including the specificity of the tumour microenvironment (TME). The aim of this review is to provide insight into the interplay of treatment modalities used in the current clinical practice and TME. Bortezomib-based triplets are the standard for MM first-line treatment. Bortezomib is a proteasome inhibitor (PI) which inhibits the nuclear factor kappa B (NF-κB) pathway. However, bortezomib is decreasing the expression of chemokine receptor CXCR4 as well, possibly leading to the escape of extramedullary disease. Immunomodulatory drugs (IMiDs), lenalidomide, and pomalidomide downregulate regulatory T cells (Tregs). Daratumumab, anti-cluster of differentiation 38 (anti-CD38) monoclonal antibody (MoAb), downregulates Tregs CD38+. Bisphosphonates inhibit osteoclasts and angiogenesis. Sustained suppression of bone resorption characterises the activity of MoAb denosumab. The plerixafor, used in the process of stem cell mobilisation and harvesting, block the interaction of chemokine receptors CXCR4-CXCL12, leading to disruption of MM cells' interaction with the TME, and mobilisation into the circulation. The introduction of several T-cell-based immunotherapeutic modalities, such as chimeric-antigen-receptor-transduced T cells (CAR T cells) and bispecific antibodies, represents a new perspective in MM treatment affecting TME immune evasion. The optimal treatment approach to MM patients should be adjusted to all aspects of the individual profile including the TME niche.