PS1571 EVALUATION OF RISK FACTORS OF GVHD FOLLOWING ALLOGENEIC STEM CELL TRANSPLANTATION FOR PATIENTS WITH B THALASSEMIA MAJOR:10 YEARS FOLLOW‐UP IN 568 PATIENTS
Authors: He Y. , Tan W. , Feng X. , Wu X. , Liao J. , Pei F. , Liu X. , Peng Z. , Liu H. , Li N. , Chen J. , Ruan Y. , Liu X. , Chen L. , Liu Q. , He L. , Ge H. , Wen J. , Zhang P. , Ren Y. , Li C. 
Published: June 2019

Background:

Hematopoietic stem cell transplantation (HSCT) is considered a well‐established curative therapy for β‐thalassemia major (TM),however, graft‐versus‐host disease (GVHD) is one of the major limiting factors in successful allogeneic hematopoietic stem cell transplantation (HSCT). Numerous studies have identified risk factors for GVHD,however,the impact of HLA disparity on GVHD remains unclear.

Aims:

This study was to assess risk factors for the development of acute GVHD and chronic GVHD and to explore the effect of locus‐specific allele‐level mismatching on GVHD for TM patients.

Methods:

We retrospective identified 568 patients with TM underwent allergenic HSCT between 2008–2018,with median age of 6 (1 – 23) and follow‐up of 62(1–122) months,from HLA‐identical sibling donor (SD) (n = 204; 36%), unrelated donor (UD, n = 274; 48%),sibling Cord blood(CB,n = 48,8%)and parent donor(PDn = 42,7%). Characteristics of patients was summarized in Table 1. Correlative analysis was done between donor type, disease status at transplant, locus‐specific allele levelmatching, conditioning regimen,GVHD prophylaxis, gender matching and risk of GVHD.

Results:

There were no differences in patients’ gender,donor genderor conditioning regimen groups in aGVHD (P value = 0.959, 0.845 and 0.312). Conditioning regimen in non‐ATG group was significantly higher than ATG group(P = 0.000)(figue1). Serum ferritin >5000ng/ml was correlated with higher aGVHD. Acute GVHD incidence for serum level<3000, 3000–5000 and >5000 were 10.5%, 13.6%, 17.8%, respectively (P = 0.048)l. Both aGVHD and cGVHD for Patient older than 9 years old was significantly higher than those <9 years old(16.1%vs9.4%P = 0,015) and (8.5% vs.3.1%)respectively(Figue2). Acute GVHD were much higher in UD transplant recipients than in SD, CB or PD recipients (P = 0.028, 0.000 and 0.000respectively). Risks for aGVHD were higher in HLA‐mm transplantation, particularly significant in two loci mm transplant. The corresponding incidence in one locus HLA‐mm and two loci HLA‐mm transplant were 19.8% vs.10.4%, p = 0.01 and 25%vs.10. %, p = 0.029 when compared to full matched transplant (Figure3). Similarly, cGVHD risk were also higher in recipient‐donor two loci HLA‐mmtransplant compared to HLA‐matched transplants (14.8% vs.4.2%, P = 0.049). Distribution of HLA mismatched loci and correlated effects on GVHD were shown in table 2. Patients receiving HLA‐A mismatch HSCT had a significant higher risk of aGVHD grade II–IV (19.3% vs.6.5%, P = 0.003) as shown in figure4. DR+DQ mm (8/10 matched) transplant significantly correlated with increased aGVHD and cGVHD (33.3% vs.11.4%, 16.7% vs.3.9%,P = 0.006,0.019,respectively) as shown figure5..

Summary/Conclusion:

Our data shows that donor and recipient gender disparity did not influence the risk of acute or chronic GVHD. Addition of ATG into the transplant regimen decreases the occurrence of cGVHD after PBSCT. Patient received unrelated PBSC were associated with an increased aGVHD. High serum ferritin level is also a risk factor of aGVHD for thlassemia patients. Mismatching at HLA‐A and HLA‐DR+DQ was associated with increased risk of both aGVHD and cGVHD. Older age is an independent risk factor for GVHD. We suggest that transplantation for β thalassemia major be performed before aged 9 years and iron chelation therapy pre‐HSCT is necessary. Further studies on GVHD treatment should be highlighted.

image