Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia and Other Bone Marrow Failure Syndromes Using G-CSF Mobilized CD34+ Selected Hematopoietic Precursor Cells Co-Infused With a Reduced Dose of Non-Mobilized Donor T-cells

• INCLUSION CRITERIA:

• Recipient:

• Patients diagnosed with one of the following hematologic diseases which areassociated with reasonable longevity, shown to be curable by allogeneic BMT butwhere concern for a high procedural mortality with conventional BMT may delayor prevent such treatment:

1. Paroxysmal nocturnal hemoglobinuria (PNH) associated withlife-threatening thrombosis, and/or cytopenia, and/or transfusiondependence and/or recurrent and debilitating hemolytic crisis

2. Severe aplastic anemia (SAA) or pure red cell aplasia (PRCA [acquiredor congenital]) with bone marrow cellularity <30% (excludinglymphocytes) associated with RBC or platelet transfusion dependenceand/or neutropenia (absolute neutrophil count <=1000 cells/uL or forpatients receiving granulocyte transfusions, absolute neutrophilcount <=1000 cells/ uL before beginning granulocyte transfusions). innewly diagnosed patients and/or in patients who have failedimmunosuppressive therapy.

3. Refractory anemia (RA) or RARS MDS patients who have associatedtransfusion dependence and/or neutropenia.

• Ages 4 to 80 (both inclusive), and weight >15 kg

• Availability of HLA identical or single HLA locus mismatched family donor or 10/10 matched unrelated donor at the allelic level (HLA alleles A, B, C, DR,and DQ).

• 9/10 donors where all the HLA sequences have the same antigen/peptide bindingdomains in key exons to the patient. This can result in identical proteinsequences between patient and donor. Allele mismatches in p and g groups can beconsidered acceptable due to the exact matching which exists in the bindingdomains.

• Telomere Length Testing

• Germline/Inherited gene panel in patients where a suspicion for a familial bonemarrow failure syndrome (BMFS) exist, hTERC and hTERT, GATA2 mutation testingwill be performed on protocol 04-H-0012 or performed elsewhere prior toenrolling on 04-H-0012.

EXCLUSION CRITERIA:

• Recipient: any of the following

• Major anticipated illness or organ failure incompatible with survival from PBSCtransplant

• Diffusion capacity of carbon monoxide (DLCO) <40% predicted (patients under the ageof 10 may be excluded from this criterion if they have difficulty performing thetest correctly and thus are unable to have their DLCO assessed) using DL Adj andDL/VA/Adj.

• Left ventricular ejection fraction <40% (evaluated by ECHO)

• Serum creatinine greater than 2.5mg/dl or creatinine clearance less than 50 ml/minby 24 hr urine collection

• Serum bilirubin greater than 4 mg/dl, transaminases greater than 5 times the upperlimit of normal

• Pregnant or lactating

• Fanconi s anemia (test to be performed at a CLIA-certified laboratory)

• ECOG performance status of 3 or more (See NIH Bone & Marrow Transplant ConsortiumSupportive Care Guidelines for HSCT Recipients or Institutional Guidelines for boneand marrow transplants)

• Other malignant diseases liable to relapse or progress within 5 years, with theexception of a separate hematologic malignancy where allogeneic stem cell transplanthas been shown to be potentially curative.

• Presence of an active infection not adequately responding to appropriate therapy.

• Inability to comprehend the investigational nature of the study and provide informedconsent. The procedure will be explained to subjects age 8 -17 years with formalconsent being obtained from parents or legal guardian.

INCLUSION CRITERIA:

-Related Donor:

• Related donor deemed suitable and eligible, and willing to donate, per clinicalevaluations who are additionally willing to donate blood samples for research.Related donors will be evaluated in accordance with existing Standard Policies andProcedures for determination of eligibility and suitability for clinical donation.Note that participation in this study is offered to all related donors, but studyparticipation is not required for a donor to make a stem cell donation, so it ispossible that not all related donors will enroll onto this study

• Age greater than or equal to 4 and less than or equal to 80 years old

EXCLUSION CRITERIA:

-Related Donor: None

INCLUSION CRITERIA & EXCLUSION CRITERIA: Unrelated Donor

• The NMDP unrelated donor inclusion criteria will be used as outlined in document (http://bethematch.org/WorkArea/DownloadAsset.aspx?id=1960). Donor eligibility willbe completed per NMDP standards and in accordance with most recent and stringent FDAguidelines.