Stem Cell Mobilization and Apheresis for Life-threatening Blood Disorders

This is a phase I, open-label, single-center study to evaluate the safety of Filgrastim plus plerixafor stem cell mobilization and apheresis in patients with BMFS. This study will include a screening period with labs, physical examination, and bone marrow evaluation at least 6 months prior to mobilization and apheresis, an intervention period that includes mobilization and apheresis of patient HSPCs, and outpatient follow-up within 7-10 days after intervention. Study staff will follow up with the participant via telephone approximately 30 days after mobilization and apheresis. A bone marrow evaluation will be done within 6 months post-intervention.

Inclusion criteria

• Participants with a bone marrow failure syndrome with an identified genetic cause willing to donate autologous HSPCs for advancing gene therapy
• Age ≥ 18 years - 25 years
• The following hematological parameters need to be met (regardless of transfusion or growth factor support)

• Hb > 8 g/dL
• ANC > 500/mm3
• Platelet > 30,000/mm3
• Bone marrow evaluation within the preceding 6 months prior to mobilization and apheresis
• Participants should either have a central venous catheter (CVC) in place, be able to undergo apheresis without requiring a CVC, or agree to having a temporary apheresis catheter placed
• Karnofsky score >80
• Negative serologic tests for syphilis, hepatitis B and C, HIV, and HTLV-1/II
• Female participants of childbearing age should have a negative serum pregnancy test within one week of beginning Filgrastim and plerixafor administration

Exclusion criteria

• Participant with sickle cell disease
• Participant who has had a prior autologous or allogeneic HSCT
• Active viral, bacterial, fungal, or parasitic infection
• Total bilirubin >2.5x ULN or transaminases >5x ULN
• Moderate or severe renal failure defined as serum/plasma creatinine >1.5 mg/dL and an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 based on the CKD-Epi equation or the St. Jude equation
• Diagnosis of MDS or other hematologic malignancy
• History of malignancy
• Known allergy to or contraindication for Filgrastim or plerixafor administration, or medications routinely administered during apheresis
• Splenomegaly (size greater than upper limit of normal on examination)
• Any disease or concomitant process that is not compatible with the study as per investigator opinion
• Concomitant treatment with alternative investigational agent or participation in another clinical trial with an investigational drug within 5 half-lives of the investigational agent
• Unwillingness to use a highly effective method of contraception for 1 month after plerixafor or GCSF
• Pregnancy
• Inability or unwillingness of research participant to give written informed consent.