A Retrospective Analysis of Transplantation Related Mortality in 515 Cases of Children β-Thalassemia Major

Objective: At present allo-genetic hematopoietic stem cell transplantation (Allo-HSCT) remains the only consolidated curative approach for β- thalassemia major. How to reduce transplantation related mortality is the key to improve the curative ratio. Hence, the aim of this study was to retrospectively analyze the clinical data of 27 cases of β- thalassemia major in children who were died related allo-HSCT, and sum up the death factors related to transplantation as well as clinical experience.

Methods: There were 515 children with β- thalassemia major who underwent transplantation in Nanfang Hospital from December 2008 to December 2017. In this study, we used the life tables and chi-square test in SPSS 20.0 statistical software to analyze the survival rate, causes of death and related factor.

Results: In our center, the nine-year disease-free survival was 90%±3%, and the transplantation related mortality was 6%±1%. A total of 27 dead patients including 20 boys and 7 girls underwent 30 transplantations at the age from 7-month-old to 14-year-old, while median age was 5-year-old, with 20 human leukocytes antigen (HLA) matched donors and 10 HLA mismatched donors. As for source of stem cell, 23 transplantations used peripheral blood stem cell (PBSC), 1 transplantation used umbilical cord blood (CB), 2 transplantations used bone marrow (BM), 1 transplantation used PBSC+CB, 2 transplantations used BM+CB and 1 transplantation used PBSC+BM+CB. Before transplantation, the mean values of cardiac ejection fraction, serum ferritin and erythrocyte infusion were 69.3%, 3555.5ng/ml and 94.5 infusions, respectively. During transplantation, the mean mononuclear cells(MNC) and CD34+ cells were 7.7×10^8/kg and 5.1×10^5/kg respectively. Granulocytes were engrafted in +17.2 days and platelets were engrafted in +22.8 days. After HSCT, 25.9% of deaths occurred within 100 days and 81.5% within one year. Thirteen cases( 48.1% ) died of graft versus host disease (GVHD) or GVHD combined with infection. Eight cases( 29.6%) died of severe infection (including 1 case of severe dengue fever). Two cases died of hepatic vein obstruction disease(HVOD). Two cases died of bone marrow failure. One case died of hypoxic ischemic encephalopathy and one case died of hemolytic uremia syndrome. Compared with the incidence of GVHD and infection, GVHD had no significant correlation with infection (χ²= 3.095, P=0.128). At last, pulmonary infection was the most common complication (24/27, 88.9%).

Conclusion: The mortality of transplantation in our center was 6%±1%. This study showed that the majority of deaths occurred within 1 year of transplantation. The most common causes of death were acute or chronic GVHD and infection. Pulmonary infection was the most common complication in the cases of death. However, there was no significant correlation between the incidence of GVHD and infection. Therefore, strategies of prophylaxis of GVHD and infection should be strengthened, and the dialectical relationship between the GVHD and infection still need to be further investigated.