Bone Marrow for Hemoglobinopathy Research
Bone Marrow for Hemoglobinopathy Research
Human participants affected with sickle cell disease or thalassemia will donate bone marrow
 for use in experimental laboratory models to study potential new treatments. This is an
 observational study using bone marrow from human participants. The investigators will use
 sickle cell and thalassemia mouse models to observe and evaluate the possibility of
 correcting these disorders through genetic alterations or drug treatment.
These studies are designed to evaluate the potential of retroviral vector mediated gene
 transfer, gene editing, or drug treatment to correct the pathophysiology of sickle cell
 anemia and β-thalassemia. CD34+ cells purified from bone marrow of research participants with
 a sickle cell syndrome or a thalassemia syndrome will be subjected to genetic editing, drug
 treatment, or transduced with retroviral vectors containing γ-globin coding sequences under
 the control of the β-globin gene promoter and including various regulatory elements chosen to
 enhance gene expression and to insulate regulatory elements from cellular genes at or near
 the integration sites. The efficiency of gene transfer and the function of the globin
 transgene will be evaluated in erythroid cells derived from transduced progenitors and from
 the progenitors in the bone marrow of immunodeficient mice engrafted with transduced,
 primitive hematopoietic cells. The hypothesis to be tested in this research is that a gene
 therapy vector, gene editing strategy, or drug modality can be designed to achieve a
 potentially therapeutic level of globin gene expression in maturing erythroid cells.
Inclusion Criteria:

 -  Patients with homozygous S/S disease or doubly heterozygous for S and β thalassemia
 who are 2 years or older are eligible. Patients with HbE- β- thalassemia or homozygous
 (severe) β-thalassemia are also eligible. Patients with thalassemia include those who
 are transfusion dependent (major) or severely anemic but relatively transfusion
 independent (intermedia). Diagnostic criteria include standard hematological
 parameters, red cell indices, hemoglobin electrophoresis and quantitative
 determination of HbF and HbA2.

 -  Patients are eligible for participation in the protocol only if they are currently
 clinically stable and have been free of all acute disease manifestations for a minimum
 of 14 days.

 -  Patients may participate while continuing their current therapeutic regimen including
 regular transfusion therapy or hydroxyurea administration.

 -  In general, two categories of patients will be considered as research participants in
 this protocol.

 1. Patients who are 18 years or older and therefore able to provide informed consent
 will be eligible. Such individuals will be recruited from among patients followed
 at SJCRH. In addition, individuals followed in an outside clinic who are
 recruited will be asked to come to the Hematology Clinic at SJCRH to enroll and
 have the procedure performed. Alternatively, if a patient who is 18 or older is
 to undergo a diagnostic or surgical procedure under general anesthesia, and they
 agree to participate in the study, the bone marrow aspirate will be obtained at
 that time.

 2. Patients between the ages of 2 and 17 years who are scheduled for a diagnostic or
 surgical procedure at SJCRH or LeBonheur Children's Medical Center for which
 sedation or general anesthesia is indicated will be eligible for protocol
 enrollment. A bone marrow aspiration will be performed during the sedation or
 general anesthesia for the diagnostic or surgical procedure.

 Exclusion Criteria:

 -  Active, acute manifestations of sickle cell disease including painful crisis, acute
 chest syndrome, cerebrovascular events or active infection.

 -  Pregnant women will not be eligible for study enrollment.

 -  Inability or unwillingness of the research participant or legal
 guardian/representative to give written informed consent will preclude enrollment on
 this research protocol.

 -  Platelet count < 150,000/mm^3

 -  Neutrophil count < 2000/mm^3 (unless on hydroxyurea therapy)

 -  Neutrophil count < 1000/mm^3 for patients on hydroxyurea therapy

 -  Prothrombin Time > 17 seconds

 -  Partial thromboplastin Time > 43 seconds

 -  History of excessive bleeding in the context of previous procedures including surgery
 and dental extractions