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.

Small Intestine Posttransplant Lymphoproliferative Disorder in a Kidney Transplant Recipient: A Case Report.

Posttransplant lymphoproliferative disorder is a serious, life-threatening complication in organ transplant patients receiving immunosuppressive therapy. Isolated posttransplant lymphoproliferative disorder of the gastrointestinal tract is rare. Posttransplant lymphoproliferative disorder encompasses a spectrum of clinical manifestations, in addition to a wide range of histopathological findings, from B-cell hyperplasia to lymphoma. Renal transplant patients with small intestinal posttransplant lymphoproliferative disorder are more likely to be of younger age, but less frequently represent Hodgkin and Hodgkin-like lesions. They also have better patient survival compared with transplant recipients with posttransplant lymphoproliferative disorder in other locations. We report on the treatment of a kidney transplant recipient with confirmed isolated posttransplant lymphoproliferative disorder in the small intestine. The patient presented with acute abdomen and small intestine perforation, 17 years after kidney transplant, despite being without calcineurin inhibitor in immunosuppressive therapy, to mitigate previous ductal breast carcinoma. Pathological examinations revealed isolated EpsteinBarr virus-positive diffuse large B-cell non-Hodgkin lymphoma of small intestine, clinical stage IV A E. The patient was treated with reduction of immunosuppression, rituximab, and the CHOP regimen (ie, cyclophosphamide, doxorubicin, vincristine, and prednisone). A complete remission was achieved. Kidney allograft function was stable throughout the follow-up period. Physicians should consider isolated gastrointestinal posttransplant lymphoproliferative disorder as a possible etiology in posttransplant, immunocompromised patients who present with different gastrointestinal symptoms. Given good clinical response to treatment, early identification of posttransplant lymphoproliferative disorder has a key role in monitoring and treatment.

Gaucher disease in Montenegro - genotype/phenotype correlations: Five cases report.

BACKGROUND: The most common lysosomal storage disorder is Gaucher disease (GD). It is a deficiency of lysosomal glucocerebrosidase (GBA) due to biallelic mutations in the GBA gene, characterized by the deposition of glucocerebroside in macrophage-monocyte system cells. The report targets clinical phenotypes of GD in order to correlate them with GBA gene mutations, as well as to identify GBA gene mutation in patients in Montenegro that are diagnosed with GD. CASES SUMMARY: Five patients (4 male, 1 female) of type 1 GD (GD1) are reported. The age at diagnosis ranged from 7 to 40. Patients experienced delays of 1-12 years in diagnosis after the original onset of symptoms. The most common mode of presentation was a variable degree of splenomegaly and thrombocytopenia, while other symptoms included bone pain, hepatomegaly, abdominal pain and fatigue. Osteopenia was present in a majority of the patients: 4/5. All patients were found to have an asymptomatic Erlenmeyer flask deformity of the distal femur. On enzyme replacement therapy (ERT), the hematological and visceral parameters showed significant improvement, but no significant progression in bone mineral density was noticed. GBA gene sequencing revealed homozygosity for the N370S mutation in one patient. The genotypes of the other patients were N370S/55bp deletion, N370S/D409H (2 patients), and H255Q/N370S (1 patient). CONCLUSION: The phenotypes of the GD1 encountered in Montenegro were severe but all responded well to ERT.