SALT: Alternative Donor Bone Marrow and Cord Blood Transplantation for High Risk Sickle Cell Disease

Inclusion Criteria: Hemoglobin SS, hemoglobin SC, or hemoglobin S0 thalassemia Donor available: Partially (5/6) HLA-matched relative (PMRD), matched (6/6) unrelated marrow donor or umbilical cord (5/6 or 6/6) of appropriate size (see 6.3.2) , using high-resolution HLA typing. Donor must not be homozygous for HgbS and must meet standard donor eligibility criteria of the Blood and Marrow Transplant Program. Severe SCD, defined by one of the following (modified Walters criteria): oPrevious (6 months prior) central nervous system event lasting longer than 24 hours, plus objective imaging evidence of CNS vasculopathy, with or without residual neurologic findings oFrequent (3 per year for 2 years) painful vaso-occlusive episodes (defined as episode lasting 4 hours and requiring hospitalization or outpatient treatment with parenteral narcotics) oRecurrent (3 in lifetime) acute chest syndrome events which have necessitated exchange transfusion or chronic transfusion therapy. Must have failed a good-faith trial of hydroxyurea (failure defined as a reduction of less than 50% in the incidence of vaso-occlusive events over a period of at least 18 months) or have demonstrated an inability to take the drug due to side effects. oAny combination of 3 acute chest syndrome episodes and vaso-occlusive pain episodes (defined as above) yearly for 3 years. Must have failed a good-faith trial of hydroxyurea (failure defined as a reduction of less than 50% in the incidence of vaso-occlusive events over a period of at least 18 months) or have demonstrated an inability to take the drug due to side effects. oStage I or II sickle lung disease oRed-cell alloimmunization (2 antibodies) on chronic transfusion therapy Exclusion Criteria: oSuitable HLA-identical relative donor is available oBiopsy proven chronic active hepatitis, portal fibrosis, or cirrhosis, or serologic evidence of active hepatitis. oSCD chronic lung disease stage III (see Appendix) oSevere renal dysfunction defined as <50% of predicted normal GFR for age. oSevere cardiac dysfunction defined as shortening fraction < 25%. oSevere residual neurologic impairment other than hemiplegia alone, defined as full-scale IQ 70, quadriplegia or paraplegia, inability to ambulate, inability to communicate without assistive device, or any impairment resulting in decline of Lansky performance score to <70%. oCNS event occurring within 6 months prior to transplant oKarnofsky or Lansky functional performance score < 70% (see Appendix) oConfirmed HIV seropositivity. oPatient with unspecified chronic toxicity serious enough to detrimentally affect the patient's capacity to tolerate bone marrow transplantation. oPatient or patient's guardian(s) unable to understand the nature and risks inherent in the BMT process. oHistory of lack of compliance with medical care that would jeopardize transplant course.