NMA Haplo or MUD BMT for Newly Diagnosed Severe Aplastic Anemia

This is an interventional treatment trial for Severe Aplastic Anemia focused on measuring immunosuppression, nonmyeloablative, non-myeloablative, allogeneic, tacrolimus, bone marrow, bone marrow transplant, cyclophosphamide, thymoglobulin, ATG, fludarabine Read More

Inclusion Criteria:

• Confirmed diagnosis of inherited or acquired severe aplastic anemia (SAA)

• One of the following available donors:

  1. HLA-haploidentical relative
  2. If recipient is >= 40 years old, may use HLA-matched related donor
  3. For recipients with inherited bone marrow failure syndromes (IBMFS) with clear evidence of same disorder in potential related donors, may use 10/10 matched unrelated donor
• Recipient and/or legal guardian must sign protocol informed consent
• Donor must be willing to donate bone marrow
• Left ventricular ejection fraction (LVEF) >= 40%. For recipients < 13 years old, shortening fraction >= 26% may be used instead.
• Bilirubin < 3 x upper limit of normal (ULN) for age, unless patient has Gilbert's disease
• aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 x ULN for age
• For patients >= 13 years old: estimated creatinine clearance > 50 mL/min using Cockcroft-Gault formula and actual body weight
• For patients >= 1 but < 13 years old: glomerular filtration rate (GFR) estimated by updated Schwartz formula >= 90 mL/min/1.73 m^2. If estimated GFR is < 90 mL/min/1.73 m^2, 24-hour measured creatinine clearance must be > 50 mL/min/1.73 m^2.
• For patients >= 8 years old, diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) > 40%; forced expiratory volume at one second (FEV1) > 50%; forced vital capacity (FVC) > 50%
• For patients < 8 years old or unable to undergo pulmonary function testing: no evidence of dyspnea at rest; no need for supplemental oxygen; oxygen saturation > 92% on room air
• Karnofsky/Lansky status (depending on age) >= 70%
• Females and males of childbearing potential must agree to practice 2 effective methods of contraception at the same time. If unwilling, they must agree to complete abstinence.

Exclusion Criteria:

• Previous administration of immunosuppressive therapy for SAA.
• Fanconi anemia. At minimum, this diagnosis must be excluded by diepoxybutane (DEB) or equivalent testing on peripheral blood or marrow in patients < 30 years old.
• Clonal cytogenetic abnormalities consistent with pre-myelodysplastic syndrome (pre-MDS) or MDS on bone marrow examination
• Presence of anti-donor antibodies
• Prior allogeneic stem cell transplant
• Prior solid organ transplant
• Uncontrolled bacterial, viral, or fungal infection
• HIV seropositivity
• Active hepatitis B or C infection determined by serology and/or nucleic acid testing (NAT)
• Pregnancy or active breastfeeding
• Prior malignancies except: resected basal carcinoma or treated cervical carcinoma in situ; cancer treated with curative intent > 5 years previously. Other prior cancers will not be allowed unless approved by the PI.