Assessment of Safety and Efficacy of PBSC Mobilization with G-CSF and CD34+ Enrichment and Pbmnc (CD3+) Addback in Familial Haploidentical (FHI) Adult Donors with Sickle Cell Disease Trait (SCDT) Prior to Allogeneic HSCT of High-Risk SCD Patients

Background We and others have previously reported the safety of allogeneic stem cell transplantation in children with SCD without sibling HLA matched bone marrow donors who commonly have SCDT. The majority of the sibling donors donated bone marrow and received G-CSF mobilized PBSCs (Bhatia/Cairo et al, BMT 2014; Gluckman et al, Blood 2017). Furthermore, only 14-18% of siblings can serve as donors based on HLA match and presence of SCD (Mentzer, Am J Ped Hem/Onc 1994; Walters, BBMT 1996). Unrelated cord blood as a donor source for SCD patients was associated with unacceptable primary graft failure rates (Radhakrishnan/Cairo, BBMT 2013). MUD HSCT resulted in unacceptably high rates of CGVHD (Shenoy et al, Blood 2016). Parental FHI SCDT PBSCs represent an alternative donor source. However, little is known about G-CSF PBSC mobilization in older donors with SCDT. GCSF mobilization of PBSC in homozygous SCD patients in the past has been reported to be associated with major toxicity and death (Adler et al, Blood 2001). Objective To determine if FHI PBSC mobilization in older adult donors with SCDT is safe and effective. Methods Eighteen FHI donors with SCDT received 15mg/kg/d GCSF divided BID x4 days. PBSC leukapheresis on day 5, repeating qd until 10 × 10 6 CD34/kg and 2 × 10 5 CD3/kg (minimum) were cryopreserved. CD34+ enrichment utilized the CliniMACS® System (generously provided by Miltenyi), with 2 × 10 5 CD3/kg T-cell add-back before HSCT as we have previously described (Geyer/Cairo, BJH 2011). Donor chimerism assays for whole blood CD3, CD71, and CD56 were performed post-HSCT. Results Fifteen female/3 male FHI donors with SCDT were mobilized: mean age 41 yrs (30-55). The most common donor side effect was grade 1 bone pain (n = 11). Other side effects were grade 1 nausea/vomiting (n = 3), grade 1 headache (n = 2), grade 1 dizziness (n = 1), grade 1 fatigue (n = 2), grade 1 abdominal pain (n = 2), grade 3 bone pain (n = 1), and grade 3 thrombocytopenia (n = 1). The mean ± SEM cryopreserved CD34 count was 12.9 ± 0.8 × 10 6 /kg recipient wt with the mean ± SEM yield 533.69 ± 48.9 × 10 6 . Mean ± SD log T-cell (CD3) depletion was 4.84 ± 0.58 (Fig. 1). 100% of patients achieved neutrophil engraftment at a median of 9 days (range 6-13), and 92.1% of patients achieved platelet engraftment at a median of 19 days (range 8-90) (Fig 2A/2B, respectively). Mean ± SEM Blood and CD71+ (RBC) donor chimerism was 97 · 1 ± 1.4 and 96 · 4 ± 2.0%, respectively. Conclusion These data suggest that adult FHI stem cell donors with SCDT undergoing GCSF mobilization for PBSC collection is safe and well-tolerated with only minor temporary adverse events. PBSC collection and CD34 enrichment was effective and resulted in successful SCD recipient engraftment and long-term donor chimerism. Further studies are needed to evaluate the long-term outcome of high-risk SCD patients undergoing FHI AlloHSCT R01FD004090.