Evaluation of the relationship between increased HLA incompatibility rate and relapse/survival in hla haploidentical stem cell transplantation

Aim : Allogeneic Hematopoietic stem cell transplantation (Allo-HSCT) is an important curative treatment option in high-risk or resistant hematological malignancies and some benign hematological diseases. In addition , it is known that transplant complications are accompanied by increased mortality and morbidity at various rates. Human leukocyte antigens (HLA) compatibility between recipient and donor in allo-HSCT has a critical impact on Graft Versus Host Disease (GVHD) relapse, disease-free survival and overall survival. However, for patients who do not have an HLA-compatible sibling donor , HLA-incompatible family (haplotype compatible) donors have become an important and frequently used option today. In this study, we aimed to retrospectively demonstrate the effect of increased rate of HLA incompatibility on relapse and survival in patients who underwent haploidentical stem cell transplantation. Equipment And Method : In this study the patients (age 18-70 years) with hematological malignancies who underwent haploidentical transplantation in Group Florence Nightingale Hospital HSCT Unit between 2013-2021 were included. The total number of patients was 95 and the follow up time was required to be at least 12 months. Patients were grouped as 4/10, 5/10, 6/10, 7/10 and 8/10 matched (antigen/allele incompatible) according to their HLA disparity. We analysed the relation between HLA mismatch rates and disease related (primary diagnosis, pre-transplant disease status), patient related (age, gender, performance status, comorbidity), donor related (age, gender, HLA compatibility) and transplant related (stem cell source, conditioning regimen, ATG and Cyclophosphamide use) factors. The correlation between these factors and the frequency of GVHD, relapse, engrafment failure, disease-free survival and overall survival was examined. SPSS statistical program was used for statistical analysis. Survival data were evaluated using Kaplan Meier P value <0.05 was considered significant. Results: Patients average age was 40.4 (age 18-70 years), female 30.5%, male 69.5%. Thirthysix patients had (37.9%) AML, 30 patients (31.6%) ALL, 2 patients (2.1%) CLL, 5 patients (5.3%) MDS, 17 patients (17.9%) NHL, 5 patients (5.3%) HL diagnosis. The remission status before transplantation was complete remission in 71 patients (74.7%), partial remission in 4 patients (4.2%) and refractory in 20 patients (21.1%). The conditioning regimen was Myeloablative in 83 patients (87.4%) and reduced intensity in 12 patients (12.6%). Stem cell source was peripheral blood in 55 patients (57.9%), bone marrow in 40 patients (42.1%). Anti HLA Antibody (PRA) was positive in 30 patients (31.6%). According to HLA incompatibility degrees; 1 patient was (1.1%) 4/10, 63 (66.3%) were 5/10, 15 (15.8%) were 6/10, 11 (11.6%) were 7/10, and 5 (5.3%) were 8/10. In GVHD prophylaxis; Post transplant cyclophosphamide in 92 patients (96.8%), anti-thymocyte globulin (ATG) in 3 patients (3.2%) along with cyclosporine (CSA) and mycophenolate mofertil (MMF) were used. Neutrophil and platelet engraftment (>500 mm3/L, and>20000 mm3/L, respectively) was 18 days for each series. Primary engraftment failure occurred in 4 patients (4.2%), secondary engrafment failure occured in 2 patients (2.1%). Full chimerism was achieved in 86 patients (90,5%) on 30 days of transplantion and in 85 patients (89,5%) on 100 days of transplantation. Thirthyfive (36.8%) patients developed Acute GVHD, 32 (33.7%) chronic GVHD. CMV activation occurred in 73 patients (76.8%). Thirteen patients 13 (13.7%) were complicated with hemorrhagic cystitis. Relapse was observed in 20 (21.1%) of the patients. The overall survival rate was 87.3%, 64.2% and 60% on days 100, 1st year, 2nd year, respectively . Conclusion : In this study we found that there was no correlation between HLA mismatch rates and GVHD, relapse, engrafment failure, disease-free survival and overall survival. Key Words : Allogeneic Haploidentical HSCT, HLA, Relapse, GVHD