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.