Risk-Adjusted Combination Chemotherapy Alone in Treating Patients with Fanconi Anemia Undergoing Hematopoietic Stem Cell Transplantation

Inclusion Criteria

• Patients must have a diagnosis of Fanconi anemia (confirmed by mitomycin C or diepoxybutane [DEB] chromosomal breakage testing at a Clinical Laboratory Improvement Amendments [CLIA] approved laboratory).
• Patients must have one of the following hematologic diagnoses: * Severe aplastic anemia (SAA), with bone marrow cellularity of < 25% OR severe isolated single lineage cytopenia AND at least one of the following features: ** Platelet count < 20 x 10^9 /L or platelet transfusion dependence. ** Absolute neutrophil count (ANC) < 1000 x 10^9/L. ** Hemoglobin (Hgb) < 8 gm/dl or red cell transfusion dependence. * Myelodysplastic syndrome (MDS): MDS at any stage, based on either one of the following classifications: ** World Health Organization (WHO) Classification. *** Refractory anemia and transfusion dependence. *** Any of other stages. ** International Prognostic Scoring System (IPSS) Classification. *** Low risk (score 0) and transfusion dependence. *** Any other risk groups Score >= 0.5. ** Note that patients with chromosome 1q cytogenetic abnormalities in the absence of morphologic dysplasia will not be considered to have MDS. * Acute myelogenous leukemia. ** Patients with acute leukemia are included in this trial untreated, in remission or with refractory or relapsed disease. (Transfusion dependence will be defined as greater than ONE transfusion of platelets or red blood cells in the last year prior to evaluation on protocol).
• Donor choices will be determined by the investigators according to institutional criteria. Patients who will be enrolled on this protocol must have one of the following donor choices: * Human leukocyte antigen (HLA)-compatible unrelated volunteer donors. ** Patients who do not have a related HLA-matched donor but have an unrelated donor who is either matched at all A, B, C and DRB1 (8/8) loci or who is mismatched at no more than 2/8 loci (A, B, C or DRB1) (6/8) as tested by deoxyribonucleic acid (DNA) analysis (high resolution), will be eligible for entry on this protocol. * HLA-mismatched related donors. ** Patients who do not have a related or unrelated HLA-compatible donor must have a healthy family member who is at least HLA-haplotype identical to the recipient. First degree related donors must have a normal diepoxybutane (DEB) test. ** The donor must be healthy and willing and able to receive a 4-6 day course of granulocyte colony-stimulating factor (G-CSF) and undergo 1-3 daily leukaphereses, as per institutional guidelines. ** Related and unrelated donors must be medically evaluated and fulfill the criteria for collection of peripheral blood stem cell (PBSC)s as per institutional guidelines.
• Patients and donors may be of either gender or any ethnic background.
• Patients must have a Karnofsky adult, or Lansky pediatric performance scale status >= 70%.
• Asymptomatic or if symptomatic then * Left ventricular ejection fraction (LVEF) at rest must be >= 50% and must improve with exercise or * Shortening fraction >= 29%.
• < 5 x upper limit of normal (ULN) alanine transaminase (ALT).
• < 2.0 mg/dl total serum bilirubin.
• Serum creatinine =< 1.5 mg/dl or if serum creatinine is outside the normal range, then creatinine clearance (CrCl) > 50 ml/min/1.73 m^2.
• Asymptomatic or if symptomatic, diffusing capacity of the lungs for carbon monoxide (DLCO) > 50% of predicted (corrected for hemoglobin).
• Each patient must be willing to participate as a research subject and must sign an informed consent form. Parent or legal guardians of patients who are minors will sign the informed consent form. Assents will be obtained as per institutional guidelines.
• Female patients and donors must not be pregnant or breastfeeding at the time of signing consent. Women must be willing to undergo a pregnancy test prior to transplant and avoid becoming pregnant while on study. Positive pregnancy test results will be reported to the parent(s) or guardian of minor participants, as required per institutional guidelines.

Exclusion Criteria

• Active central nervous system (CNS) leukemia.
• Female patients who are pregnant (positive serum or urine human chorionic gonadotropin [HCG]) or breast-feeding. Women of childbearing age must avoid becoming pregnant while on study.
• Active uncontrolled viral, bacterial or fungal infection.
• Patient seropositive for human immunodeficiency virus (HIV)-I/II; human T-lymphotropic virus (HTLV)-I/II.