Changes in patients population and characteristics of hematopoietic stem cell transplantation for relapsed/refractory Hodgkin lymphoma: an analysis of the Lymphoma Working Party of the EBMT.

Indications for autologous (auto-HCT) and allogeneic transplantation (allo-HCT) in relapsed/refractory Hodgkin lymphoma (rrHL) have been long established. The expectation is that long-term outcomes have significantly improved over time with increased experience in these procedures. The objective of this study was to assess whether this is the case and to identify further areas of improvement. A total of 13,639 adult patients receiving an auto-HCT or allo-HCT for rrHL were reported to the European Society for Blood and Marrow Transplantation (EBMT) over a 25-year period. Regarding auto-HCT, recipients are younger, interval between diagnosis and transplant shorter, peripheral blood has become the universal stem cell source and the use of total body irradiation is almost non-existent in recent years. Allo-HCT is currently mostly used as a second transplant; recipients are younger, fitter and less frequently, chemorefractory. Reduced intensity conditioning protocols have vastly replaced myeloablative protocols. Increasing numbers of haplo-HCT have been reported. Both in auto-HCT and allo-HCT, NRM, PFS and OS have significantly improved but relapse remains the main cause of treatment failure. A better selection of patients and improvements in the supportive care has resulted in a reduction in the NRM. Relapse after HCT remains unchanged and further research is needed.

HLA profile of the donors in the Macedonian Bone Marrow Donor Registry.

The importance of HLA alleles in the process of haematopoietic stem cell transplantation, especially the process of unrelated donor search, is enormous. Macedonian Bone Marrow Donor Registry was established in 2010 and has registered volunteer donors from different nationalities that live in the Republic of Macedonia. The aim of this study was to determine the HLA allele and haplotype frequencies of the volunteer donors from the Macedonian Bone Marrow Donor Registry and to compare this results with the Macedonians from a family study. We analyzed 1,541 donors, with different nationalities, Macedonian, Albanian and Macedonian Muslims that were most numerous in MBMDR, and typed them for HLA-A, -B, -C, -DRB1, whereas Macedonian also for HLA-DQA1 and HLA-DQB1 by SSO method (One Lambda, CA, USA). The most frequent alleles in Macedonians were HLA-A*02, 01, 24; HLA-B*35, 18, 51; HLA-C*07, 04, 12; HLA-DRB1*11, 16, 13; HLA-DQA1*01, 05 and HLA-DQB1*05, 03, 06; in Albanians they were HLA-A*02, 24,01; HLA-B*51, 18, 35; HLA-C*07, 04, 12, HLA-DRB1*11, 13,16; and in Macedonian Muslims they were HLA-A*02, 01, 24; HLA-B*18, 51, 35, HLA-C*07, 04, 02 and HLA-DRB1*11, 16, 14. The most common haplotype in Macedonian was HLA-A*01-B*08-C*07-DRB1*03, whilst in Albanian and Macedonian Muslims HLA-A*02-B*18-C*07-DRB1*11. The comparison of the HLA allele groups between Macedonian from MBMDR and family study showed similar distribution. This study confirmed the close relationship between the populations that live in the Balkan Peninsula.

HLA-A, -B, -C and -DRB1 allele and haplotype frequencies in the Macedonian population based on a family study.

AIM: The aim of this study was to determine HLA allele and 2-, 3- and 4-loci haplotype frequencies in a sample from Macedonian population with defined haplotypes based on family history. MATERIAL AND METHODS: We analysed 286 unrelated individuals with Macedonian origin, parents of patients who needed stem cell transplantation, in the period of 01.01.2003 till 31.12.2016. Allele and haplotype frequencies, as well as Hardy-Weinberg equilibrium were calculated using the Arlequin3.5 software. Population comparison was calculated using the PHYLIP software. RESULTS: We identified 18 HLA-A, 26 HLA-B, 13 HLA-C and 13 HLA-DRB1 allele group families. The most frequent allele groups in our population were HLA-A*02 (29.0%), HLA-A*24 (13.8%), HLA-B*35 (16.1%), HLA-B*51 (14.7%), HLA-B*18 (14.7%), HLA-C*07 (27.9%), HLA-DRB1*11 (25.5%) and HLA-DRB1*16 (14.8%). The most frequent four loci haplotype was HLA-A*01-B*08-C*07-DRB1*03 (2.7%). Our comparison showed that the Macedonian population is closely related to the neighbouring countries in the Balkan Peninsula. CONCLUSION: This study provides data about the HLA diversity in the Macedonian population, which can be very important in the process of unrelated donor search, and in addition yields control group for future disease association studies in our population.

Adverse effects of thalidomide administration, in patients with myeloma multiplex?

INTRODUCTION: Myeloma multiplex is defined by the presence of monoclonal plasma cell population in the bone marrow>10%,M protein in the serum and/or urine ,and clinical evidence of end organ damage like hypercalcemia ,renal failure, anemia, or bone lesions. In the most hematologic malignancies the role of induction treatment is to achieve complete remission (CR). Thalidomide became a new therapeutic approach but use of Thalidomide as a single agent or combination with steroids or chemotherapy is associated with several side effects like deep vein thrombosis (DVT), peripheral neuropathy (PN), constipation, somnolence, pyrexia, pain, fatigue osteonecrosis of jaw, and teratogenicity that is the most worrying adverse event. Risk of appearance of DVT increased if we use combination of Thalidomide plus Dexamethasone plus cytotoxic chemotherapy such Cyclophosphamide. >30% DVT usually occurs during the first months of treatment and is more frequent in newly diagnosed patients with a high tumor burden. The second side effect is peripheral neuropathy (PN) which occurs in 50% of patients with MM treated with Thalidomide plus Dexamethasone and chemotherapy. PATIENTS AND METHODS: Eighty patients of both sexes (43 males and 37 females) at the age of 31-81 (median range 58 years) with MM, were treated-one group with combinations of Thalidomide plus Dexamethasone plus Cyclophosphamide (CyThalDex) 4 cycle(>4months), and the other group with Thalidomide plus Dexamethasone plus Melphalan (MPT), (>4month) and third group with high dose of chemotherapy and continue with ThalDex (TD), the fourth group with CyThalDex, > than 5 cycles, and the fifth group with ThalDex (TD) only. RESULTS: It is obvious while myelo-suppression is very rare, the incidence of nonhematologic side effects is high and dose dependent. Eight (or 10%) patients that developed DVT and CVI were initially treated with antiaggregation therapy of Aspirin 100mg per day, but those that already developed were treated with low dose of Heparin 40000 iE per day in ten days and continued with oral anticoagulans therapy. However, besides the given therapy in four (or 5 %) patients there was exitus letalis. PN was developed in twentyone patients (or 26.25%) from the total number of patients treated with Thalidomide, in ten patients the dosage of Thalidomide was decreased to 50mg per day, in one patient with Epi attacks it was interrupted and the other was with paresis n.occulomotorius and n.abducens. CONCLUSIONS: Patients treated with thalidomide have an increased risk of arterial thromboembolism, including myocardial infarction and cerebrovascular events, in addition to the established risk of venous thromboembolism, but most patients who presenting DVT or some of thromboembolic events have had identifiable risk factors. The prolonged exposure to Thalidomide seems to induce resistance of MM reducing overall survival (OS). We must evaluate consolidation and maintenance therapies with Thalidomide, determinate which regimens provide a highness benefit with favorable side effect profiles in specific subgroups of patients.