Non-Myeloablative Conditioning and Bone Marrow Transplantation

RECIPIENT INCLUSION CRITERIA

- Patients who are ineligible for BMT from an HLA-matched sibling donor can proceed to a
haplo-BMT. Patients with an HLA-matched related donor will proceed to a matched BMT.

- Age 2-70 years

- Good performance status (ECOG 0 or 1; Karnofsky and Lansky 70-100)

- Patients and donors must be able to sign consent forms. First degree relative should
be willing to donate

- Patients must be geographically accessible and willing to participate in all stages of
treatment.

- Eligible diagnoses: Patients with sickle cell anemia such as sickle cell anemia (Hb
SS), Hb Sβ° thalassemia, Hb Sβ+thalassemia, Hb SC disease, Hb SE disease, Hb SD
disease, Hemoglobin SO- Arab disease HbS with hereditary persistence of fetal
hemoglobin. Other significant hemoglobinopathies.

Plus one of the following:

- Attenuation of progressive disease (adults):

- Severe and debilitating vaso-occlusive pain despite hydroxyurea or regular blood
transfusion therapy.

- Stroke and silent infarct; stroke or central nervous system event lasting more than 24
hours; MRI changes indicative of brain parenchyma damage and MRA evidence of
cerebrovascular disease.

- Recurrent acute chest syndrome requiring exchange hospitalization.

- Chronic lung disease as defined by progressive restrictive disease irrespective of
oxygen requirements.

- Chronic kidney disease, CKD stage II - IV

- Transfusion dépendent thalassemia

RECIPIENT EXCLUSION CRITERIA:

- Poor performance status (ECOG>1).

- Poor cardiac function: left ventricular ejection fraction<35%.

- Poor pulmonary function: FEV1 and FVC<40% predicted.

- Pulmonary hypertension moderate to severe by echocardiographic standards.

- Poor liver function: direct bilirubin >3.1 mg/dl

- HIV-positive

- Minor (donor anti-recipient) ABO incompatibility if an ABO compatible donor is
available.

- Prior transfusions from donor or recipient if caused alloimmunization vs. donor cells.

- Women of childbearing potential who currently are pregnant (Beta-HCG+) or who are not
practicing adequate contraception.

- Patients who have any debilitating medical or psychiatric illness that would preclude
their giving informed consent or their receiving optimal treatment and follow-up.
However, patients with history of stroke and significant cognitive deficit,that would
preclude giving informed consent or assent will not be excluded, if they have a family
member or significant other with Power of Attorney to also consent of their behalf.

CRITERIA FOR DONOR ELIGIBILITY:

- Weight ≥ 20kg and age ≥ 18 years or per institutional guidelines

- Donors must meet the selection criteria as defined by the Foundation for the
Accreditation of Hematopoietic Cell Therapy (FAHCT) and will be screened per the
American Association of Blood Banks (AABB). (AABB guidelines and the recipients will
be informed of any deviations.)

- HLA-haploidentical first-degree relatives of the patient. Participants must be HLA
typed at high resolution using DNA based typing at HLA-A, -B, -C and DRB1 and have
available: An HLA haploidentical first degree relative donor (parents, siblings or
half siblings, or children) with 2, 3, or 4 (out of 8) HLA-mismatches who is willing
and able to donate bone marrow. A unidirectional mismatch in either the graft versus
host or host versus graft direction is considered a mismatch. The donor and recipient
must be HLA identical for at least one antigen (using high resolution DNA based
typing) at the following genetic loci: HLA-A, HLA-B, HLA-C, and HLA-DRB1. Fulfillment
of this criterion shall be considered sufficient evidence that the donor and recipient
share one HLA haplotype, and typing of additional family members is not required.

When more than one donor is available, the donor with the lowest number of HLA allele
mismatches will be chosen, unless there is HLA cross-match incompatibility or a medical
reason to select otherwise, in which case donor selection is the responsibility of the PI,
in consultation with the immunogenetics laboratory. In cases where there is more than one
donor with the least degree of mismatch, donors will be selected based on the most
favorable combination of:

- HLA compatibility in cross-match testing and

- ABO compatibility

- Donor age <40 years

- Avoid female donors for male recipients and

- Avoid CMV mismatched donor-recipient transplants:

HLA cross-matching (in order of priority):

- Mutually compatible (no cross-matching antibodies)

- Recipient non-cross-reactive with donor, donor cross-reactive with recipient

- Mutually cross-reactive

ABO compatibility (in order of priority):

- Compatible

- Major incompatibility

- Minor incompatibility

- Major and minor incompatibility

- Donors will be selected to minimize HLA mismatch in the Host-versus-graft direction.

- Donors fulfilling the following criteria are ineligible for registration onto this
study:

- All donors will be screened by hemoglobin electrophoresis; donors with a clinically
significant hemoglobinopathy are ineligible. Sickle trait is acceptable.