Haploidentical Donor Hematopoietic Cell Transplantation for Patients With Severe Aplastic Anemia

• Age less than or equal to 21 years at time of enrollment
• Confirmed diagnosis of Severe Aplastic Anemia or single lineage cytopenia with bone marrow cellularity less than 25% or hypocellular marrow for age
• Presence of one or more peripheral blood criteria: neutrophils below 0.5 x10^9/L, platelets below 20 x10^9/L or platelet transfusion dependence, hemoglobin below 8g/dL or red blood cell transfusion dependence
• No suitable HLA-matched sibling or unrelated donor available in necessary time
• Failed at least one trial of immunosuppressive therapy by being refractory or relapsed, unless very severe aplastic anemia
• Has a suitable single haplotype matched (at least 3 of 6) family member donor
• Patient or legal guardian has signed informed consent
• Adequate organ function including left ventricular ejection fraction above 40%, creatinine clearance or glomerular filtration rate at least 50 ml/min/1.73m2, forced vital capacity above 50% predicted or pulse oximetry above 92% on room air
• Karnofsky or Lansky performance score at least 50
• Bilirubin no more than 3 times upper limit of normal for age
• ALT or AST no more than 5 times upper limit of normal for age
• Agreement to use two effective methods of contraception or abstinence until after last chemotherapy dose for females and males of childbearing potential

• Diagnosis of Fanconi anemia or positive diepoxybutane (DEB) test
• Known clinical or genetic diagnosis of dyskeratosis congenita
• Clonal cytogenetic abnormalities consistent with pre-myelodysplastic syndrome or myelodysplastic syndrome (MDS)
• Diagnosis of myelodysplastic syndrome
• Presence of anti-donor HLA antibodies as defined by positive cross-match or high mean fluorescence intensity
• Prior allogeneic hematopoietic cell transplant
• Prior solid organ transplant
• Known life-threatening reaction to anti-thymocyte globulin (ATG)
• Uncontrolled bacterial, viral, or fungal infection at enrollment
• Pregnant or breastfeeding female patients
• Prior malignancies except certain treated cancers based on time since treatment
• Alemtuzumab or ATG administered within 2 weeks prior to enrollment

Inclusion criteria for haploidentical donor:

• At least single haplotype matched family member (3 of 6 or more)
• At least 18 years old
• HIV negative
• Not pregnant or breastfeeding
• Ruled out for telomere disease by appropriate clinical and diagnostic measures
• Able to sign informed consent and willing to donate peripheral blood stem cells