Outcome of Hematopoietic Stem Cell Transplantation (HSCT) for Pediatric Patients with Hemoglobinopathy. Fifteen Years Experience in One Pediatric Transplant Center

 Allogeneic HSCT remains the only curative option for patients with B- Thalassemia major. Outcome of Thalassemia patients depend on class of Thalassemia, type of donor and type of preparative conditioning regimen. Our objective herein was to review the outcome of all children who received HSCT for different types of hemoglobinopathy between the years 1998-2014 in Rambam Medical Center, Israel.

Patients and methods: 45 HSCT were done  to 37 children, 33 Thalassemia and 4 Sickle Cell Anemia patients. Median age at HSCT was 7.8 years (range 0.5-22 yr). Of total 33 Thalassemia patients, 25 had 1 HSCT and 8 children needed second HSCT. 15 patients had class 1 or 2 and 18  had class 3 of Thalassemia. 38 patients received stem cells  from matched related donors, 4-from matched unrelated donors  and 3  from unrelated cord blood. Conditioning regimen included Protocol P26 in 24 patients, 2 of  them received  modified Protocol P26 with Treosulphan instead of Busulphan; 10 patients were conditioned with protocol Busulphan, Cyclophosphamide, with or without  Antitymoglobulin ; 7 children had partially T-cell depleted protocol  with Busulphan, Cyclophosphamide, Fludarabine and ATG without immunosuppression after infusion of graft and 3 patients received protocol with Treosulphan, Fludarabine, Thiotepa.

Results: Overall survival for the whole group was 88% and event free survival 80%. 9 patients rejected the graft: 5 had primary rejection and 4 had secondary engraftment  failure with median time of rejection 8.7 months (range 1-17 months). 2 of 9 rejected patients successfully engrafted after second HSCT and 2-rejected second HSCT as well.  75%  of all successfully engrafted patients have full donor chimerism, 25%  mixed stable chimerism. Incidence of acute graft versus host disease (GVHD) was 24%, grade 3-4 was 11%. Incidence of chronic GVHD was 20%, severe chronic GVHD was 4%. 5 children  died due to transplant related mortality (TRM), all of them were class 3 Thalassemia; 2 patients transplanted from unrelated donor and unrelated cord and 2 died after second HSCT.  Causes of deaths were severe  infections secondary to engraftment failure; severe hemorrhagic cystitis and multiorgan failure;  pulmonary and intracranial bleeding during engraftment and TTP. 1 child died 3.5 years after HSCT from severe multisystemic GVHD and complications of immunosuppressive therapy.

Conclusion: Our results showed that children with hemoglobinopathy who received HSCT had excellent results with survival above 80% despite of majority of patients with class 3 thalassemia and number of children who underwent second HSCT. Factors affecting prognosis were: advanced class of Thalassemia ,type of donor and second HSCT with myeloablative regimen. Engraftment failure continues to be a problem for Thalassemia patients. There is a need for controlled trials to evaluate the effectiveness of different  treatment regimens for specific group of patients.