The effect of Anti-HLA positivity on engraftment, graft failure, platelet and erythrocyte transfusion refractoriness and survival in patients with thalassemia major transplanted between 2015-2022

Objective: With the developments in supportive care and iron chelation for thalassemia major patients, life expectancy has improved significantly in recent years. Although HSCT has its own risks, it is currently the only curative standard treatment to avoid lifelong transfusions and complications of iron overload. Anti-HLA antibodies have been found to be associated with rejection and decreased survival, especially in solid organ transplantations, and there are studies showing that they cause graft failure, decreased survival and engraftment delay in HSCT. In this study, we aimed to evaluate the effect of anti-HLA status on graft failure, graft rejection, engraftment times, platelet and erythrocyte transfusion refractoriness and survival in patients diagnosed with transfusion dependent TM who underwent HSCT at Çukurova University Faculty of Medicine Pediatric Bone Marrow Transplantation Unit. Materials and Methods: 80 patients diagnosed with TM who underwent HSCT at Çukurova University Faculty of Medicine Pediatric Bone Marrow Transplantation Unit between January 1, 2015 and December 31, 2022 were included in the study. Data were collected retrospectively from patient files, hospital information system and national patient information system. Results: 30 (37.5%) patients were female and 60 (62.5%) were male. The median age was 7.25 years, the youngest patient was 1.5 years old and the oldest was 17 years old. Bone marrow was used as a stem cell source in 55 (68.8%) patients, peripheral stem cells in 22 (27.5%) patients, and bone marrow and peripheral stem cells together in 3 (3.8%) patients. 46 (62.2%) were anti-HLA positive. Only Class 1 was positive in 21 (28.4%) cases, only Class 2 was positive in 6 (8.1%) cases, both Class 1 and Class 2 were positive in 19 (25.7%) cases, and Anti-HLA was found to be negative in 28 (37.8) cases. In terms of AB0 blood group compatibility, 46 (59%) patients were compatible, 32 (41%) patients were blood group incompatible; 13 (16.7%) patients had minor incompatibility, 10 (12.8%) patients had major incompatibility, and 9 (11.5%) patients had bi-directional incompatibility. 22 (27.5%) underwent splenectomy. Of the 77 patients whose graft status could be evaluated, primary graft failure occurred in 12 patients (15.6%), and secondary graft failure/graft rejection in 7 (9.1%) patients. When the final status of the patients was examined, 53 (66.3%) patients were alive and 27 (33.8%) patients were dead. There was no significant relationship between anti-HLA status, graft status and patient final status between the genders (p>0.05). Although the anti-HLA positive group received more ES transfusions before transplantation (p: 0.001), there was no statistical difference between them and the anti-HLA negative group in terms of engraftment time, post-transplant TS and ES support, graft status and final status (p>0.05). Engraftment was earlier but statistically insignificant in the ABO compatible group (p>0.05). The number of post-transplant ES transfusion need was lower in AB0 compatible patients (p:0.024) and the survival of the AB0 compatible group was better on the 100th day (p: 0.021), but there was no difference in overall survival between the ABO compatible versus incompatible group (p> 0.05). Neutrophil engraftment occurred earlier in patients who underwent splenectomy than in those who did not undergo splenectomy (p:0.002), and the need for ES support after transplantation was less (p:0.030). There was no effect on graft status, patient final status and survival (p>0.05). A weak negative correlation was observed between the number of CD34+ stem cells in the product and the engraftment time (p<0.05). There was no significant difference between the groups in terms of ES and TS transfusion, graft status and patient final status after transplantation (p>0.05). Overall survival (OS) was 85% at day 100, 66.3% at 2, 5 and 8 years, and event-free survival (EFS) was 56.3% at 2 years, 5 and 8 years. Conclusion: There was no relationship between anti-HLA status and neutrophil, platelet and erythrocyte engraftment. Although anti-HLA positive patients required more post-transplant TS and ES transfusions, it was not statistically significant. In our study, no relationship was observed between anti-HLA positivity and graft status and mortality. There was no difference in survival between the anti-HLA positive and negative groups.