Donor Stem Cell Transplant With Treosulfan, Fludarabine, and Thiotepa in Treating Patients With Non-malignant Disorders

Inclusion Criteria:

- Patient with nonmalignant disease treatable by allogenic HCT

- Patient with a known nonmalignant disease that is not clearly defined, if discussed with protocol principal investigator (PI) (Dr. Lauri Burroughs) to determine if they are eligible for HCT on the study

- DONOR: For the very few occasions where we identify a donor hematopoietic progenitor cell (HPC)-A from a non-NMDP source, we have procedures in place through our unrelated donor office to collect the information necessary to comply with donor testing, screening, and declaration of donor eligibility according to 21 CFR 1271. We require that the donor testing be performed by a United States Clinical Laboratory Improvement Amendment (CLIA) approved laboratory. In the very rare case where the donor testing is not able to be performed in a CLIA-approved laboratory, or there is confirmatory testing that needs to be performed, or for any donor identified from Europe and at risk for Creutzfeldt-Jakob disease (CJD), we note this on the donor screening form and require that the unrelated donor medical director or the attending physician approves the use of the donor HPC-A product under urgent medical need

- DONOR: Human leukocyte antigen (HLA)-identical related donor OR unrelated donor matched for HLA-A, B, C, DRB1 and DQB1 or mismatched for a single allele at HLA-A, B, C, or a single DQB1 antigen or allele mismatch by high resolution deoxyribonucleic acid (DNA) typing

- DONOR: Bone marrow is the preferred cell source (when feasible). However, PBSC is also allowed and the PI may determine if PBSC is preferred for certain patients

- DONOR: HLA-matched sibling bone marrow in combination with HLA-matched sibling umbilical cord blood if the HLA-matched sibling umbilical cord blood was collected and stored. The HLA-matched sibling bone marrow and cord blood would be matched for HLA-A, B, C, DRB1 and DQB1

Exclusion Criteria:

- Patients with idiopathic aplastic anemia and Fanconi anemia; patients with aplastic anemia associated with paroxysmal nocturnal hemoglobinuria (PNH) or inherited marrow failure syndromes (except Fanconi anemia) will be allowed

- Impaired cardiac function as evidenced by ejection fraction < 35% (or, if unable to obtain ejection fraction, shortening fraction of < 26%) or cardiac insufficiency requiring treatment or symptomatic coronary artery disease. Patients with a shortening fraction of < 26% may be enrolled if approved by a cardiologist

- Impaired pulmonary function as evidenced by carbon monoxide diffusing capability (DLCO) < 50% of predicted (or, if unable to perform pulmonary function tests, then oxygen [O2] saturation < 92% on room air)

- Impaired renal function as evidenced by creatinine-clearance < 50% for age, weight, height or serum creatinine > 2 X upper normal limit or dialysis-dependent

- Evidence of synthetic dysfunction or severe cirrhosis requiring deferral of conditioning as recommended by a gastroenterology specialist

- Active infectious disease requiring deferral of conditioning as recommended by an infectious disease specialist

- Positive for HIV (human immunodeficiency virus)

- Females who are pregnant or breast-feeding

- Known hypersensitivity to treosulfan, fludarabine, and/or thiotepa

- DONOR: Donors deemed unable to undergo marrow harvesting of PBSC mobilization and leukapheresis

- DONOR: HIV-positive donors

- DONOR: Donors with active infectious hepatitis

- DONOR: Female donor with positive pregnancy test

- DONOR: Donors are excluded if the patient has an identified antibody against a donor-specific HLA locus as specified in standard practice

- DONOR: HLA-matched sibling cord blood units that have not passed donor screening for infectious disease markers as recommended by the National Marrow Donor Project (NMDP) will not be used unless a waiver is signed by the clinical attending allowing use of cord blood unit. Cord blood units are presumed to be cytomegalovirus (CMV) negative regardless of serologic testing due to passive transmission of maternal CMV antibodies