Gene therapy offers hope for sickle cell patients by boosting healthy hemoglobin

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Age ≥13-55 years. 2. Patients with severe phenotype sickle cell disease (HbSS and other genotypes including HbSC); severity defined by VOE events in previous 2 years prior to enrollment on EAP a. At least 4 VOEs within the past 24 months prior to consent defined as: i. severe painful event with no medically determined cause other than vaso-occlusion requiring ≥24 hours in a hospital facility for medical management OR 2 visits to a day unit or emergency room over 72 hours with both visits requiring parenteral opioids and/or parenteral non-steroidal agents ii. acute chest syndrome defined as a new infiltrate on a chest X-ray and new concomitant hypoxia requiring hospital admission and not attributable to another cause iii. Priapism episodes requiring hospitalizations 3. Patients who meet the above criteria for disease severity, but have experienced poor mobilization, RBC alloimmunization as described below: a. Poor mobilization response to plerixafor in other trials i. Patients who were enrolled in commercial GT or trials who failed to mobilize or failed to collect sufficient stem cells to generate a drug product can be entered in the trial. Patients will be evaluated for opportunities to improve stem cell collection efficiency and by using motixafortide as a mobilization agents b. RBC alloimmunized and/or history of hyperhemolysis i. History of allo-antibodies, DHTR or hyperhemolysis limiting the ability to fully undergo preparative red cell exchanges for mobilization and collection or for conditioning and transplant. Patients would be evaluated for the ability to secure at least 8 units of red blood cells for peri-SCT support. 4. Adequate hematologic parameters (regardless of therapy) including: 1. White blood cell (WBC) count within the range of 2.5 - 25.0 x 109 /L 2. Hemoglobin within the range of 5 - 11 g/dL 3. Platelet count above 150 x 109 /L 5. Adequate organ function and performance status: 1. Karnofsky/Lansky performance status ≥ 80%. 2. Calculated creatinine clearance or GFR \>/= 40 mL/min/1.73 m2. 3. Aspartate transaminase, alanine transaminase, and direct bilirubin value \< 3 times the upper limit of normal (ULN) (per institutional upper limit of normal). 4. DLCO (corrected for hemoglobin), FEV1, and FVC \> 50% of predicted 5. Left ventricular ejection fraction \> 40% or shortening fraction \> 25% 6. Parental/guardian/participant signed informed consent Exclusion Criteria: 1. Patients who have concomitant condition or illness including, but not limited to: 1. Ongoing or active infection 2. Active malignancy 3. Major surgery in the past 30 days 4. Medical/psychiatric illness/social situations that would limit compliance with study requirements as determined by the treating physician. 2. Patients with chronic pain defined as pain requiring opioids on a majority of days in the past 6 months before consent or patients taking long-acting daily opioids for longer than 6 months prior to enrollment or patients requiring blood transfusion to manage chronic pain prior to consent. 3. Patients with history of overt CNS stroke at any time. Patients with imaging evidence of silent stroke but not on a chronic transfusion regimen are not excluded. 4. Receiving a chronic transfusion regimen for primary or secondary stroke prophylaxis. 5. Patients with history of abnormal TCD (measured with a timed average maximum mean velocity of ≥ 200 cm/second in the terminal portion of the internal carotid or proximal portion of middle cerebral artery or if the imagining TCD method is used, \> 185 cm/second plus evidence of intracranial vasculopathy) who were ever on transfusions and subsequently transitioned to hydroxyurea. 6. Patients with severe cerebral vasculopathy (defined by Moya-moya disease or occlusion or stenosis in the circle of Willis. Note: patients who have had surgical correction are not eligible). 7. Isolated recurrent priapism unresponsive to medical and surgical therapies in the absence of other qualifying VOE complications that meet inclusion criteria. 8. Contraindication to administration of conditioning medication (busulfan). 9. Patients who have undergone allogeneic hematopoietic stem cell transplant previously. 10. Known myelodysplasia of the bone marrow or abnormal bone marrow cytogenetics. For participants undergoing baseline bone marrow evaluation as part of this EAP (patients \>35 years of age), evidence of a myeloid malignancy, myelodysplastic syndrome, or other clinically significant bone marrow abnormality, including abnormal cytogenetics or molecular findings, that in the opinion of the treating physician would represent a contraindication to proceeding with gene therapy. 11. Liver MRI to document hepatic iron content is required for participants who have received ≥ 20 packed red blood cell transfusions (cumulative). Participants who have hepatic iron content ≥ 9 mg Fe/g liver dry weight by liver MRI must have a liver biopsy and histological examination/documentation of the absence of cirrhosis, moderate or severe portal fibrosis, bridging fibrosis, and active hepatitis (≤ 180 days prior to initiation of transplant conditioning). The degree of portal fibrosis and the absence of bridging fibrosis will be determined using the histological grading and staging scale as described by Ishak and colleagues (1995). Repeat liver MRI is encouraged in the event the interval between consent and initiation of BU conditioning exceeds 180 days). 12. Evidence of active HIV infection, active HTLV 2 infection, active hepatitis B infection, or active hepatitis C infection. 13. Receipt of an investigational study drug or procedure within 90 days of study enrollment. 14. Prior receipt of a genetically modified product. 15. Pregnancy, or breastfeeding in a postpartum female, or absence of adequate contraception for fertile participants. Females of child-bearing potential must agree to use a medically acceptable method of birth control such as oral contraceptive, intrauterine device, barrier and spermicide, or contraceptive implant/injection from screening through at least 6 months after drug product infusion. Male participants must agree to use effective contraception (including condoms) from screening through at least 6 months after drug product infusion. 16. Presence of a genetically-determined hypercoagulable state or personal history of prior VTE (deep vein thrombosis or pulmonary embolism) that, in the opinion of the treating physician, would represent a contraindication to proceed with central line placement and study events.