A Multi-Institutional Retrospective Data Analysis of Hematopoietic Cell Transplantation for Less Severe Sickle Cell Disease

Background: Outcomes of matched sibling donor (MSD) HCT for children with severe sickle cell disease have improved with disease free survival approaching 95%. As outcomes have improved, interest in extending HCT to less severely affected children has increased. However, there remains little published experience in these patients. We describe the largest multi-institutional retrospective review of MSD HCT for patients with less severe SCD.

Methods:  Patients who received MSD HCT at three centers (Children’s National Medical Center, Children’s Healthcare of Atlanta, and Columbia University Medical Center) between January 2004 – June 2014 were eligible for inclusion in the analysis.  Those with severe complications, such as stroke and recurrent acute chest syndrome, were excluded, using eligibility criteria from a recently completed trial for severe SCD (clinicaltrials.gov, NCT00968162)

Results: 25 patients (M/F: 13/12) met eligibility. 22 had HbSS and 3 HbSC. The median age was 5.3 years (1-18.3).  8 patients had no acute SCD related-complications.  The most frequent complication was vaso-occlusive pain 14/25 (56%) with a lifetime median of 1 crisis. 7 patients had splenic sequestration as the only acute complication. Twenty-four received myeloablative conditioning; 19 received BM, 3 cord blood (CB) and 3 BM + CB. Donor engraftment was achieved in all cases.  Mean peripheral whole blood or myeloid donor chimerism was 94% and 89%, at day +100 and +365 respectively.  No patients suffered severe regimen-related toxicities and none experienced seizures, encephalopathy or other neurologic complications.  One patient developed acute GVHD (grade III), which responded to therapy.  None developed chronic GVHD. Of the 17 patients who are a year or more from transplant, all are off immune suppression.  With a median follow-up of 23 months (5-130 months) all patients are alive and free of SCD.

Conclusions: HLA MSD HCT for children with less severe sickle cell appears to be highly effective.  Given that nearly all patients with SCD, regardless of their disease course during childhood, will suffer serious morbidity as adults and have a markedly shortened life expectancy, our experience suggests HCT is appropriate for children with less severe disease.  Prospective studies involving these patients are needed.