Eltrombopag for the Treatment of Poor Graft Function Following Haematopoietic Cell Transplantation: Real-Life Data

Background: Eltrombopag has an off-label indication for haematopoietic cell transplantation in patients experiencing delayed thrombocyte recovery and/or thrombocytopaenia. Aims: To present our centre's experience of using this agent not only for post- haematopoietic cell transplantation thrombocytopaenia but also for poor graft functioning in the post-haematopoietic cell transplantation setting. Study Design: Retrospective cross-sectional study. Methods: Thirty-nine patients who had persistent cytopaenia following haematopoietic cell transplantation and treated with eltrombopag at our centre between October 2011 and December 2021 were retrospectively identified. During this period, 9 (23.1%) and 30 (76.9%) patients who underwent allogeneic transplantations, respectively, received eltrombopag. Results: The female-to-male ratio was 12:27, and the median transplant age was 49 (18-70) years. Eight (20.5%) patients had isolated thrombocytopaenia, 19 (49.4%) had bi-lineage cytopaenia and 12 (30.1%) had pancytopaenia. Patients received a median of 50 mg/day (25-150 mg/day) of eltrombopagfor a median duration of 82 (24-386) days. Nine (23.1%) patients had autologous haematopoietic cell transplantation, and 30 (76.9%) had allogeneic haematopoietic cell transplantation (14 unrelated, 9 sibling and 7 haploidentical). The median donor age was 32 (20-67) years. The median follow-up was 16.4 (1.8-84.3) months. The median pre-treatment platelet count was 11x109/l (1-23), which increased to 41x109/l (6-150). The median platelet count increment was 29.5x109/l (p = 0.001). The pre-treatment median neutrophil count was 1.19x109/l (0.39-5.1), which increased to 2.35 x109/l (0.1-5.33) (p = 0.05), and the pre-treatment median haemoglobin was 8.3 (6.2-14) g/dl, which increased to 10 (6.2-14) g/dl (p = 0.001) with eltrombopag. No eltrombopag-related hepatotoxicity occurred; however, 1 (2.6%) patient failed to continue treatment because of two consecutive episodes of deep venous thrombosis. Six (15.4%) patients were unresponsive to eltrombopag and dependent on blood product transfusions. After a median time of 82 days, 61.5% of the patients discontinued eltrombopag successfully. Conclusion: The results confirmed that eltrombopag could provide a rapid, sustained response in patients with poor graft functioning after haematopoietic cell transplantation. This finding is essential given the high rate of non-relapse mortality caused by poor graft functioning after haematopoietic cell transplantation.

Dynamic thiol-disulfide homeostasis as an oxidative stress marker in ankylosing spondylitis and undifferentiated spondyloarthropathy.

Background/aim: Seronegative spondyloarthropathies (SpA) are a group of chronic diseases characterized by axial inflammation, oligoarthritis, and enthesitis. Oxidative stress may contribute to a wide range of rheumatologic diseases, including SpA. This prospective case-control study was designed to compare thiol-disulfide levels as a marker of oxidative stress between SpA patients and healthy controls. Materials and methods: A total of 144 patients diagnosed with undifferentiated spondyloarthropathy (USpA, n = 97) or ankylosing spondylitis (AS, n = 47) were included along with 80 healthy controls. Serum native thiol (NT), total thiol (TT), and disulfide (D) levels were measured using the fully automated Erel method. The ratios NT/TT, D/TT, and D/NT were calculated. Thiol-disulfide levels were compared between the SpA groups and the healthy controls. Results: The NT and NT/TT ratios were found to be significantly lower in the SpA group (p < 0.001). The disulfide, D/NT, and D/TT ratios were found to be significantly higher in the SpA group (p < 0.001). In pairwise comparisons between the SpA subgroups, the NT and TT levels were lower in the USpA group than in the AS group (p = 0.021), but serum disulfide levels were higher in the USpA group than in the AS group (p = 0.004). Among the patients with SpA, the group taking antitumor necrosis factor (anti-TNF) had lower TT measurements compared to the group taking conventional disease modifying antirheumatic drugs (DMARD) (p = 0.039). Conclusion: The thiol-disulfide balance is disturbed in favor of disulfide in SpA patients compared to healthy volunteers. Native and total thiol measurements correlate with acute phase reactants and might be used to monitor disease activity. Anti-TNF therapy might control the oxidative degenerative process better than the conventional DMARD in SpA patients.

Dynamic Thiol/Disulphide Homeostasis as Oxidative Stress Marker in Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy.

AIM: Seronegative spondyloarthropathies (SpA) are a group of chronic diseases, characterized by axial inflammation, oligoarthritis, and enthesitis. Oxidative stress may contribute to a wide range of diseases such as rheumatologic diseases including SpA. This prospective case-control study was designed to compare the thiol-disulfide levels as a marker of oxidative stress in SpA patients with healthy controls. METHODS: A total of 144 patients who were diagnosed as undifferentiated spondyloarthropathy (UspA, n=97), ankylosing spondylitis (AS, n=47), and 80 healthy controls were included. Serum native thiol (NT), total thiol (TT), disulfide (D) levels were measured with the fully automated Erel?s method. NT/TT, D/TT, and D/NT ratios were calculated. Thiol-disulfide levels were compared between SpA groups and healthy controls. RESULTS: NT and NT/TT ratios were found to be significantly lower in the SpA group. (p<0.001). Disulfide, D/NT, and D/TT ratios were found to be significantly higher in the SpA group (p <0.001 for each comparison). In pairwise comparisons between SpA subgroups, NT and TT levels were lower in USpA group compared to AS group (P=0.021). Serum disulfide levels were higher in USpA group compared to AS group (P=0,004). Anti-tumor necrosis factor (Anti-TNF) group had lower TT measurements compared to the classical disease-modifying anti-rheumatic drugs (cDMARD) group in patients with SpA (P=0.039). CONCLUSION: Thiol-disulfide balance is disturbed in favor of disulfide in SpAs patients compared to healthy volunteers. Native and total thiol measurements correlate with acute phase reactants and might be used to monitor disease activity. Anti-TNF therapy might control the oxidative degenerative process better than the classical DMARD in SpA patients.

Highlighting the Prognostic Importance of Measurable Residual Disease Among Acute Myeloid Leukemia Risk Factors

Objective: The optimal timing of measurable residual disease (MRD) evaluation in acute myeloid leukemia (AML) patients has not been well defined yet. We aimed to investigate the impact of MRD in pre- and post-allogeneic hematopoietic stem cell transplantation (AHSCT) periods on prognostic parameters. Materials and Methods: Seventy-seven AML patients who underwent AHSCT in complete morphological remission were included. MRD analyses were performed by 10-color MFC and 10-4 was defined as positive. Relapse risk and survival outcomes were assessed based on pre- and post-AHSCT MRD positivity. Results: The median age of the patients was 46 (range: 18-71) years, and 41 (53.2%) were male while 36 (46.8%) were female. The median follow-up after AHSCT was 12.2 months (range: 0.2-73.0). The 2-year overall survival (OS) in the entire cohort was 37.0%, with a significant difference between patients who were MRD-negative and MRD-positive before AHSCT, estimated as 63.0% versus 16.0%, respectively (p=0.005). MRD positivity at +28 days after AHSCT was also associated with significantly inferior 2-year OS when compared to MRD negativity (p=0.03). The risk of relapse at 1 year was 2.4 times higher (95% confidence interval: 1.1-5.6; p=0.04) in the pre-AHSCT MRD-positive group when compared to the MRD-negative group regardless of other transplant-related factors, including pre-AHSCT disease status (i.e., complete remission 1 and 2). Event-free survival (EFS) was significantly shorter in patients who were pre-AHSCT MRD-positive (p=0.016). Post-AHSCT MRD positivity was also related to an increased relapse risk. OS and EFS were significantly inferior among MRD-positive patients at +28 days after AHSCT (p=0.03 and p=0.019). Conclusion: Our results indicate the importance of MRD before and after AHSCT independently of other factors.