Upfront Alternate Donor HSCT for Children with Severe Aplastic Anemia: A Single Center Prospective Clinical Trail Outcome

Background: Alternate donor (AD) hematopoietic stem cell transplantation (HSCT) for children with severe aplastic anemia (SAA) remains challenges mainly associated with graft failure and Graft versus Host Disease (GVHD). So it has been considered in the second choice of treatment status. But the survival outcomes from AD HSCT in childhood SAA have improved steadily over the past decade. To answer the question whether the AD HSCT can be the first line therapy for SAA children we start this single center prospective upfront AD HSCT study. Methods: Based on the success of the AD HSCT for children with SAA previously in our center, the upfront AD HSCT protocols were approved by the local Ethics Committees. This trail was registered in ChiCTR (www.chictr.org) in 2010. Fludarabine (180mg/m2-200mg/m2) +Cyclophosphamide (120mg/kg) +Anti-thymocyte globulin (ATG, thymoglobulin 10mg/kg) +TBI 3GY were the conditioning regimen and peripherial blood stem cell was as the stem cell source for all the HSCT children. Results: 56 children with acquired SAA (include 15VSAA) were recruited in this upfront AD HSCT study in our center between Jan 2010 to Jun 2014 with the average age 7.5（1.8~17）years old. 21 patients with 10/10 matched unrelated donor (MUD), 23 patients with 8-9/10 mismatched unrelated donor (MMUD) and 9 patients with 5-8/10 mismatched related donor (MMRD). All patients did not receive ATG before HSCT. The average interval from diagnosis to HSCT was 6.5（1-102）months. The median nucleated cell doses were (11.2±3.4 )×10⁸/kg and the CD34⁺ cell doses were (4.73±2.37) ×10⁶/kg. Except 1 graft failure (rescued by second HSCT) 55 (98.2%) were engrafted with neutrophil and platelet recovery occurring at a median of 12 days (range, 9-18) and 14（7-68）post-transplant. The cumulative incidence was 39% and 7% for grade I-II and III-IV acute GVHD, 19% and 2% for mild and moderate chronic GVHD. Compared to our previous study this intensified conditioning regimen with lower graft failure but high post-transplant lymphoproliferative disease (PTLD). After median follow up 21.75（2.2-54）months, 4 of 56 patients died (2 died of PTLD, 1 died of severe aGVHD and another 1 died of CNS infection). 2 patients suffered poor graft function with long interval from diagnosis to HSCT (84 months and 102 months respectively). 5 VSAA patents under uncontrolled infection were rescued by AD HSCT. The estimated 5-year OS and FFS of the entire cohort was 92.6% and 88.6%, with no difference between the MUD, MMUD and MMRD cohort (97.7%, 92.3% and 88.9% respectively). Conclusions: These excellent outcomes suggest that unmanipulated AD PBSC is a good HSCT source for children with SAA. It's reasonable to consider AD HSCT as first line therapy for SAA children if suitable donor can be found quickly. HSCT rescued therapy was important for some under uncontrolled infection VSAA children. Better strategies are required to prevent PTLD.