Allogeneic hematopoietic stem cell transplantation for children with severe aplastic anemia.

OBJECTIVE: Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative treatment for severe aplastic anemia (SAA). This is a single institutional review to study the feasibility of using allo-SCT for Thai children with SAA. MATERIAL AND METHOD: Nine children with SAA (7 matched-sibling donor-SCT, 1 matched-unrelated donor-SCT and 1 haploidentical-SCT) underwent allo-SCT between October 2002 and September 2010. Cyclophosphamide and anti-thymocyte globulin (CY/ATG) were used as conditioning regimen for 4 patients with matched-sibling donor-SCT CY/ATG and fludarabine were used for 3 patients with matched-sibling donor-SCT and one patient with haplo-identical SCT. One matched-unrelated donor-SCT received CY/ATG and total body irradiation. RESULTS: Eight of 9 patients (89%) achieved neutrophil engraftment within 13.5 days (range 6.0-22.0). One matched-sibling donor-SCT recipient who failed to achieve engraftment died from acute renal failure and gram-negative sepsis on day 21 post allo-SCT. One matched-sibling donor-SCT case developed late graft failure on day 72 and died from invasive fungal infection. For graft versus host disease (GVHD), a haplo-identical-SCT patient died from steroid refractory grade IV acute GVHD. At last follow-up, six patients (67%) alive at a median follow-up time of 76.4 months (range 2.3-88.8). Overall survival (OS) and event-free survival (EFS) at 5 year was 63% and 65%, respectively. CONCLUSION: Allo-SCT is a feasible curative treatment for children with SAA in Thailand. Graft failure and severe GVHD in alternative donors SCT are responsible for major causes of death. OS and EFS probabilities are stable after the first year post transplant.

The second mini-transplant for unstable mixed chimerism within the first 100 days after hematopoietic stem cell transplant in severe thalassemia.

Allogeneic HSCT is the only curative treatment for severe thalassemia disease. MC occurs in one-third of these patients within the first two months after HSCT; this is a major risk factor of graft rejection, especially when RHCs are more than 25%. There is still no consensus for the management of MC, especially in the early phase of HSCT. The DLI has also been described in the treatment of MC following HSCT for hemoglobinopathies, but its success is still not guaranteed. The second HSCT has been an approach used in an attempt to cure patients who reject their graft. Concern about toxicity of conditioning regimen, the second HSCT is usually delayed for at least a year after the first HSCT. We would like to demonstrate the successful use of the second mini-allogeneic HSCT in hemoglobin E/ß-thalassemia with evidence of unstable MC in the first 100 days after allogeneic HSCT to prevent further graft loss after allogeneic HSCT.

Ex vivo generation of cytokine-induced killer cells (CD3+ CD56+) from post-stem cell transplant pediatric patients against autologous-Epstein-Barr virus-transformed lymphoblastoid cell lines.

EBV-PTLDs affect as high as 20% of SCT recipients especially those with T-cell depleted grafts while high mortality rates were also noted. Adoptive allogeneic and autologous CTLs have a therapeutic potential in this setting. However, the process of expansion of these cells is tedious and time consuming in both allogeneic and autologous CTL generation. For the allogeneic SCT, another major obstacle is unavailability of donors especially in an unrelated SCT setting. The aim of the present study was therefore to investigate the efficacy of autologous CIK cells (CD3+ CD56+) against autologous EBV-LCLs from post-SCT pediatric patients. We could demonstrate that CIK cells can be generated within two wk and did show the significant cytotoxicity against autologous EBV-LCLs. CIK cells may provide a potent tool for use in post-transplantation adoptive immunotherapy.