Haploidentical Transplantation With Pre-Transplant Immunosuppressive Therapy for Patients With Sickle Cell Disease

Inclusion criteria

• Diagnosis: Patients with sickle cell anemia (Hgb SS or SB° Thalassemia) withbaseline Hgb S more than 60%.

• Disease status:

• Significant neurologic event (stroke) or any neurological deficit lasting > 24hours; or increased transcranial Doppler velocity (>200 m/s).

• History of one or more episodes of acute chest syndrome (ACS) in the 2-year periodpreceding enrollment despite the institution of supportive care measures (i.e.asthma therapy and/or hydroxyurea).

• History of one or more severe vaso-occlusive pain crises per year in the 2-yearperiod preceding enrollment despite the institution of supportive care measures (i.e. a pain management plan and/or treatment with hydroxyurea).

• Recurrent priapism requiring medical therapy.

• Osteonecrosis of two or more joints despite the institution of supportive caremeasures.

• Prior treatment with regular RBC transfusion therapy, defined as receiving 8 or moretransfusions per year for > 1 year to prevent vaso-occlusive clinical complications (i.e. pain, stroke, and acute chest syndrome)

• Echocardiograph finding of tricuspid valve regurgitation jet (TRJ) velocity ≥ 2.5m/sec.

• Ages 1 to 30.

• Child Bearing Potential- Transplantation could be teratogenic and/or lethal to thedeveloping fetus. For this reason, women of child-bearing potential and men mustagree to use adequate contraception (hormonal or barrier method of birth control orabstinence) prior to study entry and for six months following duration of studyparticipation. Should a woman become pregnant or suspect that she is pregnant whileparticipating on the trial, she should inform her treating physician immediately.

• Informed Consent/Assent: All subjects must have the ability to understand and thewillingness to sign a written informed consent.

• The recipient must have a related donor who is genotypically haploidentical onHLA-A, B, C and DRB1 loci.

• No HLA matched sibling or 10/10 matched unrelated donor is available.

Exclusion criteria:

• Any uncontrolled illness including ongoing or active bacterial, viral or fungalinfection.

• Patients may not be receiving any other investigational agents, or concurrentbiological, chemotherapy, or radiation therapy.

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to any in the pre- or post-transplant regimen.

• Pregnant women are excluded from this study.

• Patients with any active malignancy are ineligible for this study, other thannon-melanoma skin cancers.

• Medical problem or neurologic/psychiatric dysfunction which would impair patientability to be compliant with the medical regimen and to tolerate transplantation orwould prolong hematologic recovery which in the opinion of the principalinvestigator would place the recipient at unacceptable risk.

• Prior autologous or allogeneic transplant.

• Fully HLA-matched related or unrelated donor is available to donate.

• Non-Compliance: Subjects, who in the opinion of the investigator, may not be able tocomply with the safety monitoring requirements of the study.