Allogeneic Stem Cell Transplantation Is Superior to Immunosuppressive Therapy in Children with Aplastic Anaemia – a Single Centre Analysis from India

Introduction: Allogeneic stem cell transplantation (HSCT) and immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG) are standard treatment options for a child with aplastic anaemia (AA). Response to ATG however is much lower in developing countries.

Patients and Methods: Retrospective analysis of paediatric patients with AA (age < 15 years) who underwent sibling donor HSCT or received IST at Christian Medical College, Vellore India between 1990 and March 2014. Fanconi anaemia was excluded with stress cytogenetics. IST consisted of either ALG (Pasteur Merieux) for 5 days or ATGAM (Pharmacia Upjohn) for 4 days followed by steroids and cyclosporine for 12 months. Response was assessed at 6 months after IST. Patients undergoing HSCT used either Cy/ATG or a Fludarabine based regimen for conditioning

Results: 196 children [119 males and 77 females; median age 10.2 years (range: 2-15)] were analysed of which 119 received IST and 77 underwent HSCT. Response to IST at 6 months was 36.1% with CR in 14.3% and PR in 21.8%. Response rates were 7.7% in children with age < 5 years, 46.6% between ages 6-10 and 43.1% between 11-15 years. Of the 43 responders, 13(30.2%) had relapse or clonal evolution [9 had AA, 3 had AML and 1 had MDS]. Six patients had a repeat course of ATG while another 6 underwent BMT. The 3 year OS for the entire group is 50 + 4.7%. Of the 77 who underwent HSCT, 12 had conditioning with Cy/ATG, 6 had Flu/Bu/ATG and 59 had Flu/Cy + ATG or TBI 200Cg. Graft source was bone marrow in 20 and PBSC in 57.  Engraftment was seen in 62 (80.5%) while 15 had either primary graft failure or expired due to sepsis within first 2 weeks of HSCT. Acute GVHD was seen in 32.2% of patients and chronic GVHD in 59.6% - mostly limited. The 3 year OS for the entire group was 71.1 + 5.2% while for a cohort of 59 patients who had Flu/Cy conditioning, the 3 yr OS was 77.6 + 5.5%.

A Superior 3 yr OS was seen with the use of Flu/Cy conditioning for HSCT compared to ATG in all age groups. It was 83.3 + 10.8 vs 15.4 + 1.2 for age < 5 yrs and 74.1 +5.7 vs 52.6 + 3.7 for age > 5 years for HSCT and ATG respectively.

Conclusion: Sibling donor allogeneic HSCT is superior to IST across all age groups in a large cohort of Indian children with aplastic anemia. Alternative donor transplants need to be explored in patients who do not have a HLA identical sibling donor.