Search

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.

Introduction. Autoimmune diseases are a family of more than 100 heterogeneous conditions that affect 5 to 8% of the world’s population. The etiology is still un-known but the disregulation of the regulatory T-lymphocytes play a central role inthe autoimmunity and the success of the long-term remission. Although conventional immunosuppression and new biological agents can provide disease control in severely affected patients, such treatments are rarely curative and alternative strategies are needed. Indeed, severe forms of systemic autoimmune diseases, such as multiple sclerosis (MS), systemic sclerosis (SSc), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA), hematologic immune cytopenia (HIC) and Crohn’s disease are difficult to be treated. High-dose immunosuppressive therapy followed by autologous stem cells transplantation is reliable option for a successive treatment of this group of patients. Aim. To determine the safety of the procedure of autologous stem cell transplantation in patients with autoimmune diseases and concomitant malignant hematological disorders. Methods. During a period of 15 years (from September 2000 to September 2015) at the University Clinic of Hematology in Skopje we have treated 6 patients with autoimmune disease and concomitant hematological neoplasm. None of the patients was treated for primary autoimmune diseases. Two men and 4 women, with median age of 47 years were treated. Sjogren syndrome and multiple myeloma were found in 2 patients, polyartheritis nodosa and multiple myeloma in 1 patient, rheumatoid arthritis and acute myeloblastic leukemia in 1, systemic lupus erythematosus and non-Hodgkin lymphoma in 1; severe psoriasis and acute myeloblastic leukemia in 1 patient. Results. All treated patients are alive after trans-planted procedure, with transplant related mortality day +100: 0. Conclusion. Autologous stem cell transplantation is safe and recommended option for treatment ofpatients with autoimmune disease and hematologic neoplasm.

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.

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.

e19502 Background: Autologous stem cell transplantation (ASCT) improves survival in patients with myeloma and lymphoma but is associated with morbidity and nonrelapse mortality (NRM). Hematopoietic cell transplant comorbidity index (HCT-CI) was shown to predict risk of NRM and survival after allogeneic transplantation. We tested the utility of HCT-CI as a predictor of NRM and overall survival (OS) in patients undergoing ASCT. Methods: We analyzed outcomes of 220 patients after high-dose melphalan and high –dose anti lymphoma chemotherapy during year 2000 to 2015. Individual comorbidities were prospectively collected at the time of ASCT. The impact of HCT-CI and other potential prognostic factors, including Karnofsky performance score (KPS), on NRM and survival were studied in multivariate Cox regression models. Results: HCT-CI score was 0, 1, 2, 3, and >3 in 42%, 18%, 13%, 13%, and 14% of the study cohort, respectively. Subjects were stratified into 3 risk groups: HCT-CI score of 0 (42%) versus HCT-CI score of 1 to 2 (32%) versus HCT-CI score > 2 (26%). Higher HCT-CI was associated with lower KPS < 90 (33% of subject’s score of 0 versus 50% in HCT-CI score > 2). HCT-CI score > 2 was associated with melphalan dose reduction (22% versus 10% in score 0 cohorts). One-year NRM was low at 2% (95% confidence interval, 1% to 4%). On multivariate analysis, overall survival was inferior in groups with HCT-CI score of 1 to 2 (relative risk, 1.37, [95% confidence interval, 1.01 to 1.87], P = .04) and HCT-CI score > 2 (relative risk, 1.5 [95% confidence interval, 1.09 to 2.08], P = .01). Factors that affect OS in the autologous recipients among lymphoma and myeloma patients were: HCT-CI, Karnofsky score, number of CD34+ cells/kg and time from diagnosis until transplant (p

8023Background: Considering the high prevalence of comorbidities in multiple myeloma (MM) patients, comorbidity has an important issue for the management of myeloma. However, the impact of comorbid...

Introduction. Allogeneic stem cell transplantation (allo-SCT) is a well established therapeutic alternative for those patients with refractory Hodgkin’s lymphoma (HL) who relapse after an autologous stem cell transplantation (ASCT), have chemosensitive disease and a HLA compatible donor available. The impact of the intensity of the conditioning regimen in the outcome of this procedure is still not well understood. An initial retrospective analysis from the European Group for Blood and Marrow Transplantation (EBMT) Lymphoma Working Party (LWP) (Sureda et al, JCO 2010) that compared myeloablative (MAC) with reduced intensity conditioning (RIC) protocols indicated that the high non-relapse mortality (NRM) associated to MAC-SCT translated into a non-significant improvement in progression free survival (PFS) for RIC recipients in spite of the higher relapse rate of the latter. As NRM for MAC-SCT might have decreased over time due to better patient selection, HLA typing and peri-transplant supportive measures, we hypothesize that overall results of more intensive protocols could compare better to RIC-SCT in recent years. Patients and Methods. We have included in this analysis adult patients with multiply relapsed classical HL treated with an allo-SCT between January 2006 and December 2010 and reported to the EBMT Database. Only first and second allo-SCT was included. Tandem ASCT-allo-SCT was excluded as well as cord blood transplantations and haplo-identical SCT. A total of 313 patients met the inclusion criteria (63 patients treated with a MAC and 250 patients treated with a RIC, definitions following the EBMT criteria). There were 173 males (55%) and 140 females (45%) with a mean age at diagnosis of 29 years and at SCT of 33 years. Mean time from diagnosis to SCT was of 43.3 months. 153 patients (49%) were chemorefractory at the time of allo-SCT and 166 patients (53%) had already failed a prior ASCT. Peripheral blood (PB) was used as the source of stem cells in 88% of the patients. Comparing MAC with RIC groups, the latter one was significantly older at allo-SCT (31 years vs 34 years, p=0.01), had a longer time interval between diagnosis and allo-SCT and preferentially received mobilized PB stem cells (82% vs 91%, p=0.01). There were also more prior autograft failures in the RIC group (56% vs 42%, p=0.006). Results. With a median follow up for alive patients of 32.5 (9.7 – 52.9) months, overall survival (OS) was 75% and 65%, PFS, 54% and 39%, NRM 11% and 12% and relapse rate after SCT of 37% at 1 year. There were no significant differences in NRM between MAC and RIC patients. Relapse rate was higher in the RIC group, although these differences did not reach statistical significance (55% vs 40% at 24 months, p=0.1). This lower relapse rate translated into an improvement in PFS for the MAC group (48% vs 37% at 24 months, p=0.08) with no differences in terms of OS (71% for MAC vs 61% for RIC at 24 months, p=0.4). Multivariate analysis after adjusting for disease status at the time of SCT showed that the use of RIC protocols was the only independent adverse prognostic factor associated to a higher relapse rate after SCT [HR 0.68, 95%CI (0.38 – 0.98), p=0.04] and to a lower PFS after the procedure [HR 0.65, 95%CI (0.43 – 0.98), p=0.04]. The intensity of the conditioning regimen did not have any impact n NRM in the multivariate analysis. Chemosensitive disease at SCT was the only independent prognostic factor for OS after SCT in the multivariate analysis [HR 1.70, 95%CI (1.17 – 2.46), p=0.005]. Conclusions. This retrospective analysis shows that NRM after MAC protocols is not a significant clinical issue when allografting patients with HL nowadays. On the other hand, using MAC decreases the relapse risk in this highly resistant population of patients, translating into a significant improvement of PFS. MAC protocols should be considered when designing prospective clinical trials in patients with HL candidates for an allogeneic stem cell procedure. Disclosures No relevant conflicts of interest to declare.