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.
Diagnosed with severe aplastic anemia with bone marrow cellularity <30% (excluding lymphocytes) associated with RBC or platelet transfusion dependence and/or neutropenia (absolute neutrophil count less than or equal to 1000 cells/ microL or for patients receiving granulocyte transfusions, absolute neutrophil count less than or equal to 1000 cells/microL before beginning granulocyte transfusions).
PNH that is either refractory to treatment with eculizumab/ravulizumab or occurs in patients who don t have access to treatment with eculizumab associated with either a) life- threatening thrombosis and/or b) cytopenia associated with transfusion dependence and/or c) recurrent and debilitating hemolytic crisis.
Subjects with severe aplastic anemia, hypoplastic MDS or PNH with associated bone marrow failure syndromes who have intolerance of or failure to respond to immunosuppressive therapy. This also includes patients who have failed immunosuppressive therapy with ATG and cyclosporine or therapy with cyclosporine combined with eltrombopag in those who are intolerant of or do not have access to treatment with ATG.
Availability of at least one HLA- haploidentical related donor (i.e. >= 5/10 HLA match: HLA-A, B, C, DR, and DQ loci) to serve as a stem cell donor for the allogeneic transplant.
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.