Outcomes of Bone Marrow or Cord Blood Matched Related Transplantation for Children with Sickle Cell Disease: Experience of a Canadian Center

Introduction:Hematopoietic stem cell transplantation (HSCT) still remains the only curative treatment for patients suffering from severe forms of sickle cell disease (SCD). The aim of this study was to review the indications and outcomes of SCD children transplanted with a matched sibling donor at a medium sized pediatric institution in Canada.

Methods:From 2003 to 2014, 17 children received a HSCT at our institution. Data were retrospectively extracted from medical charts.

Results:All children had severe forms of SCD including stroke (3/17), silent strokes (7/17), cerebral arteries stenosis (9/17), acute chest syndrome (10/17), splenic sequestration (5/17) and recurrent vaso-occlusive crisis requiring up to 41 hospital admissions for one patient. Neurocognitive impairment was documented for 7 out of 11 children tested. Before HSCT, 10/17 children had been treated by programmed blood transfusions and 12/17 had received Hydroxyurea. Children transplanted after 2010 tended to be younger and to have less brain damages. The median age at HSCT was 10y (2 to 15y). The myeloablative conditioning regimen was based on Busulfan, Cyclophosphamide and rabbit antithymoglobulin. The source of stem cells was a bone marrow for 11 patients and a cord blood for 6.

The median follow-up was 56 months (128 to 4m). All patients engrafted. Stable mixed chimerism (less than 95% of donor cells) was common (13/17). No patient experienced new onset of SCD complications. Previous organ damages did not progressed after HSCT. No grade 2-4 acute graft versus host disease (GVHD) was observed. Extensive chronic GVHD was noted for 2 out of 16 patients and evolved favourably on treatment. At 12 months after HSCT, 10 out of 11 children were free from immunosuppressive drugs. Opportunistic infections were common such as CMV (12/17) or EBV (13/13), and evolved favourably with or without treatment. One death not related to HSCT occurred 42 months after HSCT. Among 5 evaluable women, 2 have primary amenorrhea, 2 have some signs of ovarian insufficiency and the youngest one (5 years old at HSCT) has a normal ovarian function.

Conclusion: HSCT with a matched sibling donor is safe and effective to cure children suffering from SCD, whatever the graft source is a bone marrow or a cord blood. The outcomes at our medium-sized Canadian institution are identical to the best results from larger institutions. A younger age at HSCT may enhance the functional prognosis of severe SCD and may decrease the risk of long term gonadal toxicity related to HSCT.