INCLUSION CRITERIA - RECIPIENT:
-Diagnosed with severe aplastic anemia characterized by all of the following:
a) Bone marrow cellularity less than 30% (excluding lymphocytes)
b) Transfusion dependence for platelets and/or RBCs
c) Neutropenia (absolute neutrophil count less than 500 cells/ uL)
OR
-Diagnosed with myelodysplastic syndrome characterized by:
a) Refractory Anemia (RA) OR (Refractory anemia with ringed sideroblasts (RARS)
b) Neutropenia (absolute neutrophil count less than 500 cells/ uL)
c) History of 1 or more opportunistic infections related to neutropenia
-Intolerance of or failure to respond after at least 6 months standard immunosuppressive therapy.
-Availability of at least one HLA-haploidentical related family member donor (2-75 years old)
-Availability of at least one 4/6 HLA-matched (HLA-A, B, and DR loci) cord blood unit from the NMDP. The cord blood unit must contain a minimum TNC (prior to thawing) of at least 1.5 x 10(7) cells per kilogram of recipient body weight with the following exception: if the minimum criterion of TNC is not met the cord unit must contain at least 1.7 x 10(5) CD34 plus cells/kg (prior to thawing).
-Ages 8-55 years inclusive
-Ability to comprehend the investigational nature of the study and provide informed consent. The procedure will be explained to patients aged 8-17 years with formal consent being obtained from parents or legal guardian.
EXCLUSION CRITERIA - RECIPIENT:
-Availability of an HLA identical or 5/6 HLA matched-relative to serve as a stem cell donor
-The patient is deemed to be a candidate for a 6/6 HLA matched unrelated stem cell transplant (availability of a donor and resources required for such a transplant).
-ECOG performance status of 2 or more
-Major anticipated illness or organ failure incompatible with survival from transplant
-Severe psychiatric illness. Mental deficiency sufficiently severe as to make compliance with the transplant treatment unlikely and making informed consent impossible.
-Positive pregnancy test for women of childbearing age.
-HIV positive
-Diagnosis of Fanconi's anemia or dyskeratosis congenita.
-Diffusion capacity of carbon monoxide (DLCO) less than 40 percent predicted
-Left ventricular ejection fraction less than 40 percent (evaluated by ECHO) or less than 30 percent (evaluated by MUGA)
-Transaminases greater than 5x upper limit of normal (when transaminases are elevated, the patient may be excluded at the discretion of the PI)
-Serum bilirubin greater than 4 mg/dl
-Creatinine clearance less than 50 cc/min by 24 hr urine collection (adjusted for body surface area, i.e.50 ml/min/1.73m(2))
-Failure to collect an adequate number of CD34+ cells (i.e. greater than or equal 2 x 10(6) CD34+ cells/kg) for transplantation from the patient's haploidentical relative
-Presence of an active infection not adequately responding to appropriate therapy
-History of a malignant diseases liable to relapse or progress within 5 years
INCLUSION CRITERIA - RELATED DONOR DONATING PURIFIED CD34 PLUS CELLS:
-HLA haploidentical (i.e. greater than 3/6 HLA match) family donor available to donate CD34+ cells
-Ages 7-75 inclusive
-Weight greater than or equal to 18 kg
-For adults: Ability to comprehend the investigational nature of the study and provide informed consent. For minors: Written informed consent from one parent or guardian who is not the recipient of the transplant and informed assent: The process will be explained to the minor on a level of complexity appropriate for their age and ability to comprehend.
EXCLUSION CRITERIA - RELATED DONOR (ANY OF THE FOLLOWING):
-Pregnant or lactating
-A pediatric haplo-identical donor will be excluded if a suitable adult haplo-identical donor is available.
-Unfit to receive filgrastim (G-CSF) and undergo apheresis (history of stroke, MI, unstable angina, uncontrolled hypertension, severe heart disease or palpable spleen)
-HIV positive (Donors who are positive for HBV, HCV or HTLV I/II may be used at the discretion of the investigator following counseling and approval from the recipient)
-Sickling hemoglobinopathies including HbSS, HbAS, HbSC
-Severe psychiatric illness. Mental deficiency sufficiently severe as to make compliance with the BMT treatment unlikely and making informed consent impossible.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 01/30/2009