Infectious Complications Following Hematopoietic Stem Cell Transplantation Based on Fludarabine and Busulfan for Pediatric β-Thalassemia Patients
Authors: Xu Yanjun , Li Chunfu , He Yuelin , Yi Tiantian , Wen Jianyun , Chen Libai , Wu Xuedong 
Published: November 2019

Abstract
Background : Fludarabine and busulfan as a reduced-toxicity Conditioning regimen has been widely used for hematopoietic stem cell transplantation(HSCT) in pediatric β-thalassemia patients,however,the data of transplant-related infections in this population are scare.
Methods:This retrospective study assessed the clinical features of infections in 265 children who received HSCT in pediatric department of Nanfang Hospital from January 2011 to December 2015,including 151 with allogeneic hematopoietic stem cell transplantation(allo-HSCT) from unrelated donors(UDs) who are all well-matched human leukocyte antigens, 87 with HSCT from matched sibling donors(MSDs),27 with genetic haploid transplantations from matched donors(father donors=13,mother donors=13,aunt donor=1). the median age was 6 years(range:1.7 to 16 years),and the ratio of male to female patients was 1.6(163:102).The median follow-up time was 35 months(range:8-68 months).
Results: The cumulative incidence of neutrophil recovery was 97.70%,98.01% and 100% in MSD-HSCT,UD-PBSCT and genetic haploid,respectively.Most of the infections took place in the oral cavity(58.72%),respiratory tract, digestive tract and skin.Bacteremia developed in 46(17.36%) patients and 67.39% happened within 30 day of transplantation,the median time was +3 day(rang-2 to +11) when Bone marrow is barren period. G_ bacteria(68%) were the most commom causes of infections;Escherichia coli,Klebsiella pneumoniae and Pseudomonas aeruginosa accounted for the most of G- bacteria infections.Fungal turn out in 16(6.04%) patients,25% of the people was diagnosed with a probable,invasive fungal disease.The cumulative incidence of cytomegalovirus(CMV) and herpes zoster was 4.9% and17.36% .The cumulative incidence of grade II-IV aGVHD was 4.26%.17 patients died,9 of them suffered GVHD and complicated with severe pneumonia, 3 due to infection complicated with heart failure,4 of them were attributed to severe infections lead to multiple organ failure,and one appeared pancytopenia 6 months after transplantation , combined EB virus infection, cytomegalovirus infection, However, the use of MabThera treatment ineffective ,he died of liver failure,and brain hemorrhage.The estimate 5-year overall survival were 95%,94% and 84% in MSD-HSCT,UD-PBSCT and genetic haploid,respectively.
Conclusions:In conclussion,our data suggests that the myeloablative conditioning regimen transplantation based on fludarabine and busulfan provided an effective measure for pediatric β-thalassemia patients with infections comparable to other transplant center reports but higher overall survival and disease free survival. More efforts should be made to rational use of antimicrobial drugs, empirical antifungal agents and strengthen the mouth, lungs, anus and other vulnerable parts of the care ,especially after the transplant neutropenic period.

Disclosures
No relevant conflicts of interest to declare.