New stem cell transplant trial offers hope for rare blood diseases

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

* INCLUSION CRITERIA - RECIPIENT: * 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). OR --History of severe aplastic anemia transformed to MDS. that meet the following criteria: a) International Prognostic Scoring System (IPSS) risk category of INT-1 or greater, b) \<5% myeloblasts and \<30% of cellularity in the bone marrow on screening morphologic analysis. OR * 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 a backup stem cell source in the event of graft rejection: * at least one additional haploidentical related alternative donor (i.e. HLA- haploidentical related donor (i.e. \>= 5/10 HLA match: HLA-A, B, C, DR, and DQ loci) or \>= 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) \<40% using DLCO corrected for Hgb or lung volumes (patients under the age of 10 may be excluded from this criterion if they have difficulty performing the test correctly and thus are unable to have their DLCO assessed). * Left ventricular ejection fraction \<40% (evaluated by ECHO) * Transaminases \> 5x upper limit of normal. * Direct bilirubin \>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