INCLUSION CRITERIA:
RECIPIENTS:
Must fulfill one disease category from below
Disease Specific:
Patients with sickle cell anemia (Hb SS, SC, or Sb-thal(o)) at high risk for disease related morbidity or mortality, defined by having irreversible end organ damage (A, B, or C) or potentially reversible complication(s) not ameliorated by hydroxyurea (D):
-Previous neurologic event (either symptomatic or found by imaging alone), OR
-Sickle cell related renal failure, creatinine clearance less than 20 mg/ml or requiring peritoneal or hemo-dialysis, OR
-Pulmonary hypertension, measured by tricuspid regurgitant jet velocity (TRV) of greater than 2.5m/s, OR
-any of the below complications
-more than 2 hospital admissions for pain crises per year for the last 2 years
-a previous acute chest syndrome
-stage I or II sickle chest: Stage I patients have normal oxygen saturation but 80% of predicted normal pulmonary function tests. Stage II patients also have normal oxygen saturation but 60% of predicted normal pulmonary function tests
-evidence of renal damage as defined as having an elevated creatinine of 1.5 x normal, or reduced creatinine clearance, which is still greater than 50% of normal
-osteonecrosis of multiple joints
-red cell alloimmunization
AND
-having failed hydrosyurea, as defined by a failure to achieve a hematologic response and/or clinical response where clinical/hematologic response is defined as a significant decrease in the number of crises experienced after a 6 month trial or a 2-3 fold increase in the hemoglobin F level unless has renal insufficiency preventing hydroxyurea use.
Patients with thalassemia who have grade 2 or 3 iron overload, determined by the presence of 2 or more of the following:
-portal fibrosis by liver biopsy
-inadequate chelation history (defined as failure to maintain adequate compliance with chelation with desferoxamine initiated within 18 months of the first transfusion and administered subcutaneously for 8-19 hours at least 5 days each week)
-Hepatomegaly of greater than 2 cm below the costochondral margin
Patients with Diamond Blackfan Anemia, who are refractory to or intolerant of coritcosteriods and are transfusion dependent
Non-Disease specific:
-Ages 16-65
-6/6 HLA matched family donor available
-Ability to comprehend and willing to sign an informed consent
-Negative serum B-HCG
INCLUSION CRITERIA:
DONOR
6/6 HLA identical family donor
Ages greater than or equal to 2 and weight greater than 18 kg (in so far that the weight difference between recipient and donor does not exceed a reasonable likelihood of being able to obtain an adequate cell dose from the donor within two aphereses)
Fit to receive G-CSF and give peripheral blood stem cells (normal blood counts, normotensive and no history of stroke)
Ability to comprehend and willing to sign an informed consent; assent obtained from minors
EXCLUSION CRITERIA:
RECIPIENT
(any of the following would exclude the subject from participating)
Age less than 16 years
ECOG performance status of 3 or more.
Diffusion capacity of carbon monoxide (DLCO) less than 60% predicted.
Left ventricular ejection fraction: less than 40% estimated by ECHO.
Transaminases greater than 5x upper limit of normal
Psychiatric disorder or mental deficiency severe enough as to make compliance with the BMT treatment unlikely, and making informed consent impossible.
Major anticipated illness or organ failure incompatible with survival from PBSC transplant.
Pregnant or lactating
EXCLUSION CRITERIA:
DONOR:
(any of the following would exclude the donor from participating)
Pregnant or lactating
Donor unfit to receive filgrastim G-CSF and undergo apheresis. (Uncontrolled hypertension, history of congestive heart failure or unstable angina, thrombocytopenia)
HIV positive
Hemoglobin SS, SC, or Sbeta thal0, or beta thalassemia intermedia
Abnormal Red Cell Adenosine Deaminase level collected on donors for Diamond Blackfan Anemia recipients.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 09/20/2008