Peripheral Blood Stem Cell Collection for Sickle Cell Disease (SCD) Patients

The constitution of blood relies upon hematopoietic stem cells (HSCs), which stay in the bone
marrow and differentiate to all lineages of peripheral blood cells. HSC transplantation is
the only curative option currently available for sickle cell disease (SCD) patients either
via allogeneic HSC transplantation or HSC-targeted gene therapy. Granulocyte-colony
stimulating factor (G-CSF)- mobilized HSCs are frequently utilized in the adult setting of
HSC transplantation because of the faster hematologic recovery as compared to bone marrow. As
an autologous HSC source for gene therapy, bone marrow harvest has been generally employed
since G-CSF has been prohibitive in SCD patients due to granulocyte stimulation and the
associated reports of vaso-occlusive crises, multi-organ failure, and death. However, when
bone marrow harvest is used, the amounts of collected cells are limited and anesthesia is
required. In order to obtain HSCs in large numbers without anesthesia, patients will undergo
mobilization followed by large volume apheresis. Plerixafor is an alternative treatment for
mobilization without direct stimulation to granulocytes, and it is theoretically applicable
for SCD patients. The primary endpoint of this study is to obtain sufficient amounts of HSCs
collected from the peripheral blood in SCD patients after plerixafor mobilization with an
acceptable safety profile. The harvested products will be stored as backup for patients
undergoing gene therapy as well as allogeneic HSC transplantation.

- INCLUSION CRITERIA:

- SCD patients who are 18 or older, and (a) planned to enroll in an active allogeneic
HSCT study where back-up autologous HSCs are needed; OR (b) are eligible for an
allogeneic HSCT study (i.e. have the same disease severity as group (a), but no active
allogeneic HSCT study is available), and are willing to donate autologous HSCs for a
future gene therapy, gene editing, or allogeneic HSCT study.

- Adequate renal function: serum/plasma creatinine <1.5 mg/dL.

- Adequate liver function: direct bilirubin and ALT <5 times the upper limit of normal
range.

- Blood counts: WBC >3,000/mm^3, granulocytes >1,000/mm^3, hemoglobin>7.0g/dL,
platelets>150,000/mm^3.

- Female patients of childbearing age should have a negative serum pregnancy test within
one week of beginning plerixafor administration, have had a hysterectomy,
post-menopausal, or absence of a menses for over a year.

- Meets NIH Department of Transfusion Medicine (DTM) eligibility criteria for blood
component donation for in vitro research use (negative serologic tests for syphilis,
hepatitis B and C, HIV, and HTLV-1).

- Ability to give informed consent to participate in the protocol.

- Female and male individuals of reproductive potential must agree to one of the
contraceptive regimens stated above if sexually active

EXCLUSION CRITERIA:

- Pregnancy. Female patients of childbearing age should have a negative serum pregnancy
test within one week of beginning plerixafor administration, except those that have
had a hysterectomy, post-menopausal, or an absence of a menses for over a year.

- Active viral, bacterial, fungal, or parasitic infection.

- History of cancer, excluding squamous carcinoma of the skin and cervical carcinoma in
situ.

- Active and painful splenomegaly or splenomegaly (size greater than upper limit of
normal) determined by ultrasound.

- Allergy to plerixafor.