Haplo-identical Transplantation for Severe Aplastic Anemia, Hypo-plastic MDS and PNH Using Peripheral Blood Stem Cells and Post-transplant Cyclophosphamide for GVHD Prophylaxis

Background: Severe aplastic anemia (SAA), and myelodysplastic syndrome (MDS), and paroxysmal nocturnal hemoglobinuria (PNH) cause serious blood problems. Stem cell transplants using bone marrow or blood plus chemotherapy can help. Researchers want to see if using peripheral blood stem cells (PBSCs) rather than bone marrow cells works too. PBSCs are easier to collect and have more cells that help transplants. Objectives: To see how safely and effectively SAA, MDS and PNH are treated using peripheral blood hematopoietic stem cells from a family member plus chemotherapy. Eligibility: Recipients ages 4-60 with SAA, MDS or PNH and their relative donors ages 4-75 Design: Recipients will have: * Blood, urine, heart, and lung tests * Scans * Bone marrow sample Recipients will need a caregiver for several months. They may make fertility plans and a power of attorney. Donors will have blood and tissue tests, then injections to boost stem cells for 5-7 days. Donors will have blood collected from a tube in an arm or leg vein. A machine will separate stem cells and maybe white blood cells. The rest of the blood will be returned into the other arm or leg. In the hospital for about 1 month, recipients will have: * Central line inserted in the neck or chest * Medicines for side effects * Chemotherapy over 8 days and radiation 1 time * Stem cell transplant over 4 hours Up to 6 months after transplant, recipients will stay near NIH for weekly physical exams and blood tests. At day 180, recipients will go home. They will have tests at their doctor s office and NIH several times over 5 years.

* INCLUSION CRITERIA - RECIPIENT: * Diagnosed with severe aplastic anemia with bone marrow cellularity \= 9/10 HLA matched unrelated donor who is available to serve as a stem cell donor for a salvage allogeneic transplant in the event that the haplo-transplant has been rejected. * umbilical cord blood unit/s that can be used for a salvage cord blood transplant in the event that the haplo-transplant has been rejected * The patient does not have any HLA antibodies detectable against any of the mismatched HLA alleles expressed by the haplo-donor. * Ages 4-60 years inclusive. * Ability to comprehend the investigational nature of the study and provide informed consent. The procedure will be explained to subjects aged 4-17 years with formal consent being obtained from parents or legal guardian. EXCLUSION CRITERIA - RECIPIENT (ANY OF THE FOLLOWING): * Availability of an HLA identical (12/12) matched related or unrelated donor who is available within optimal timeline and suitable considering graft source and established donor selection factors (e.g. age, sex, viral exposure, ABO compatibility, pregnancy status, etc) per PI discretion. * The patient is deemed to be a candidate for a 12/12 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. * Current pregnancy, or unwillingness to take oral contraceptives or use a barrier method of birth control or practice abstinence to refrain from pregnancy, if of childbearing potential for one year. * HIV positive. * Diagnosis of Fanconi s anemia (by chromosome breakage study). * Diffusion capacity of carbon monoxide (DLCO) \3 mg/dl. * Creatinine clearance \< 50 cc/min/BSAm\^2 by 24-hour urine collection adjusted by body surface area. * Serum creatinine \> 2.5 mg/dl * Presence of an active infection not adequately responding to appropriate therapy. * History of a malignant disease liable to relapse or progress within 5 years. INCLUSION CRITERIA - DONOR: Donor deemed suitable and eligible, and willing to donate, per clinical evaluations who are additionally willing to donate blood for research. Donors will be evaluated in accordance with existing Standard NIH Policies and Procedures for determination of eligibility and suitability for clinical donation. Note that participation in this study is offered to all donors, but is not required for a donor to make a stem cell donation, so it is possible that not all donors will enroll onto this study. EXCLUSION CRITERIA - RELATED DONOR: None