Assessment of Safety and Efficacy of Peripheral Blood Stem Cell (PBSC) Mobilization with G-CSF in Haploidentical Maternal Donors with Sickle Cell Trait Prior to Haploidentical Stem Cell Transplantation in Their Children with High-Risk Sickle Cell Disease

Background

Children with high-risk SCD have a high risk of chronic morbidity and early mortality and can only be cured following a successful allogeneic stem cell transplant (AlloSCT) (Talano/Cairo et al, EJH, 2014). We previously demonstrated 100% EFS/overall survival in 18 children with SCD following reduced toxicity conditioning and HLA matched sibling or cord blood (CB) AlloSCT (Bhatia/Cairo, et al, BMT, 2014). All sibling donors with SCD trait were mobilized with G-CSF without serious adverse events. Unfortunately, high-risk SCD patients have only a 16% chance of having an unaffected HLA matched sibling donor (Freed/Cairo et al, BMT, 2012). Previous studies by our group and others utilizing unrelated CB as alternative donors had unsatisfactory results (Radhakrishnan/Cairo et al, BBMT, 2013; Kamani/Shenoy et al, BBMT, 2012). Few 8/8 HLA matched unrelated donors have been identified in the unrelated donor registries. Haploidentical maternal donors with SCD trait open up a major opportunity to identify a new donor source in children with high-risk SCD. Past studies reported serious toxicity of G-CSF mobilization in patients with homozygous SCD (Adler/Prchal et al, Blood, 2001). There is a paucity of information of safety and efficacy of G-CSF PBSC mobilization from haploidentical adult maternal donors with SCD trait.

 

Objective

To determine the safety and efficacy of G-CSF PBSC mobilization in haploidentical parental donors with sickle cell trait.

 

Methods

G-CSF (15mcg/kg/d divided bid x 4 days) was administered to seven haploidentical maternal donors with sickle cell trait; PBSC collection was on day 5. Donors underwent ≥1 rounds of PBSC leukapheresis using the Spectra Optia (n=6) or Spectra (n=1) Apheresis System.  A minimum of 10 x 10⁶ CD34/kg and 2 x 10⁵ CD3/kg were obtained and cryopreserved prior to beginning of recipient myeloablative conditioning prior to Day -59.  PBSCs were selected by the CliniMACS^® System (Miltenyi Biotec) and 2 x 10⁵ CD3/kg was added back prior to infusion (Fig. 1A). 

 

Results

Seven haploidentical adult maternal donors were mobilized with G-CSF x4 days (median age 46 [34-55] yrs) with a mean±SEM CD34/kg (recipient weight) was of 20.9 ± 3.32 x 10⁶/kg and a final mean±SEM selection of 14.5 ± 1.54 x 10⁶/kg (Fig. 1B). There was Grade 1 generalized bone pain (NIH CTCAE, V4.0,) but no episodes of SCD-related venoocclusive crisis, stroke, acute chest syndrome or other adverse events (Fig. 1B).

Conclusion

These preliminary data suggest that G-CSF mobilization of PBSC in haploidentical adult maternal donors with SCD trait was safe, well-tolerated and resulted in desired efficacy. A larger cohort and with longer follow-up will be required to confirm the preliminary findings. (This study was supported by grants from the FDA [5R01FD004090] and Otsuka and CliniMACS^® supplies from Miltenyi Biotec) (IND#14359 and NCT01461837; http://www.sicklecelltransplantconsortium.org).