Protocol Title: Safety and Feasibility of Autologous CD34+ Hematopoietic Stem Cells Mobilization and Apheresis in Participants With RUNX1 Familial Platelet Disorder

Eligibility Criteria

• 1. Are aged ≥ 18 to 75 years
• 2. Are willing and able to provide informed consent, as appropriate (either directly or through a legally authorized representative \[LAR\]), as described in Appendix 1, Section 13.1
• 3. Have a confirmed diagnosis of RUNX1 FPD, verified by a Clinical Laboratory Improvement Amendments (CLIA)-certified genetic sequencing report.
• 4. Clearance by apheresis team to proceed
• 5. Have systolic blood pressure ≤ 170 mm Hg and diastolic blood pressure ≤ 95 mmHg
• 6. Are eligible for HSCT per institution requirements
• 7. Have a Lansky (age \< 16 years)/Karnofsky performance status of ≥ 70 (see Appendix 2, Section 13.2).
• 8. Are willing and able to comply with protocol-defined contraceptive requirements (see Appendix 3 Section 13.3)
• 9. Have a platelet count ≥ 50,000/μL for initiation of apheresis, assessed within 24 hours prior to the procedure, or, if \< 50,000/μL are administered platelets on the day of the collection
• 10. Have hemoglobin ≥ 7.5 g/dL as assessed within 24 hours prior to the procedure
• 1. Participants with cognitive impairments and/or any serious unstable pre-existing medical condition or psychiatric disorder that can interfere with safety or with obtaining informed consent or compliance with study procedures.
• 2. Have uncontrolled bleeding
• 3. Are using supplemental oxygen
• 4. Have known severe splenomegaly (≥ 20 cm)
• 5. Have a diagnosis of MDS or hematologic malignancies, as defined by WHO hematolymphoid tumor classification fifth edition (Khourey et al 2022) hematolymphoid tumor classification fifth edition (Khourey et al 2022)
• 6. Have recent prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ Note: Cancer treated with curative intent \< 5 years previously may be allowed following approval from the study investigator. Cancer treated with curative intent \> 5 years previously is allowed.
• 7. Have any prior or current myeloproliferative or a significant coagulation or immunodeficiency disorder
• 8. Have advanced liver disease, defined as any of the following:
• 1. Persistent aspartate transaminase, alanine transaminase, or direct bilirubin value \> 5× the upper limit of normal (ULN) at screening
• 2. Screening prothrombin time (PT) or partial thromboplastin time (PTT) \> 1.5× ULN
• 9. Have had prior HSCT or gene therapy
• 10. Have history of concomitant sickle cell disease
• 11. Have been treated with an investigational drug within 30 days of screening or 5 half-lives (whichever is longer)
• 12. Have a positive test result for HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV) at screening
• 1. Participants with positive hepatitis B core antibody (HbcAb) and/or hepatitis B-e antibody (HbeAb) are eligible provided viral load is negative by quantitative polymerase chain reaction (qPCR).
• 2. Participants who are positive for anti-hepatitis C antibody are eligible as long as they have a negative HCV viral load by qPCR.
• 13. Have a positive infectious disease panel at screening for human T-lymphotropic virus 1 or 2 (HTLV-1 and HTLV-2), or syphilis (rapid plasma 24 reagin \[RPR\])
• 14. Have clinically significant and active bacterial, viral, fungal, or parasitic infection at screening
• 15. Have a white blood cell (WBC) count \< 2 × 109/L
• 16. Have a left ventricular ejection fraction \< 45%
• 17. Have a screening estimated glomerular filtration rate \< 60 mL/min/1.73 m2
• 18. Have a diagnosis of a significant psychiatric disorder that could seriously impede the ability to participate in the study
• 19. For women of childbearing potential: are pregnant or breastfeeding or lack adequate contraception
• 20. Are unable to comply with the study procedures, as assessed by the investigator