Treo/Flu/TBI With Donor Stem Cell Transplant for Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia

Inclusion Criteria:

MDS, myelodysplastic syndrome/myeloproliferative neoplasia overlap disorders (including chronic myelomonocytic leukemia [CMML], and MDS/myeloproliferative neoplasm [MPN] unclassifiable syndromes)
AML, other than acute promyelocytic leukemia (APL), in first or second remission or with minimal residual disease
With Karnofsky index or Lansky Play-Performance scale > 70% on pre-transplant evaluation
Able to give informed consent (if > 18 years), or with a legal guardian capable of giving informed consent (if < 18 years)
Patients with previous autologous or allogeneic HCT are allowed to enroll
DONOR: Human leukocyte antigen (HLA)-identical related donors or
DONOR: Unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 as defined by high resolution deoxyribonucleic acid (DNA) typing; mismatch for one HLA allele is allowed
DONOR: Donors able to undergo peripheral blood stem cell collection or bone marrow harvest
DONOR: Donors in good general health, with a Karnofsky or Lansky play performance score > 90%
DONOR: Donors able to give informed consent (if > 18 years), or with a legal guardian capable of giving informed consent (if < 18 years)

Exclusion Criteria:

Receiving umbilical cord blood
With 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 < 26% may be enrolled if approved by a cardiologist
With impaired pulmonary function as evidenced by partial pressure of oxygen (pO2) < 70 mm Hg and carbon monoxide diffusing capability test (DLCO) < 70% of predicted or pO2 < 80 mm Hg and DLCO < 60% of predicted; (or, for pediatric patients unable to perform pulmonary function tests, then oxygen (O2) saturation < 92% on room air), or receiving supplementary continuous oxygen
With impaired renal function as evidenced by creatinine-clearance < 50% for age, weight, height or serum creatinine > 2 x upper limit of normal or dialysis-dependent
With hepatic dysfunction as evidenced by total bilirubin > 2.0 x upper limit of normal or evidence of synthetic dysfunction or severe cirrhosis
With hepatic dysfunction as evidenced by aspartate aminotransferase (AST) > 2.0 x upper limit of normal or evidence of synthetic dysfunction or severe cirrhosis
With active infectious disease requiring deferral of conditioning, as recommended by an infectious disease specialist
With human immunodeficiency virus (HIV)-positivity or active infectious hepatitis
With central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy, cranial irradiation or both prior to initiating conditioning (day -6)
Patients with active non-hematological malignancies (except non-melanoma skin cancers) or those with non-hematological malignancies who have been rendered with no evidence of disease, but have a greater than 20% chance of having disease recurrence within 5 years; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy
With life expectancy severely limited by diseases other than malignancy
Women who are pregnant or lactating
With known hypersensitivity to treosulfan or fludarabine (fludarabine phosphate)
Receiving another experimental drug within 4 weeks before initiation of conditioning (day -6)
Unable to give informed consent (if > 18 years) or with a legal guardian (if < 18 years) unable to give informed consent
DONOR: Individuals deemed unable to undergo marrow harvesting or PBSC mobilization and leukapheresis
DONOR: Individuals who are HIV-positive
DONOR: Individuals with active infectious hepatitis
DONOR: Females with a positive pregnancy test
DONOR: Persons unable to give informed consent (if > 18 years) or with a legal guardian (if < 18 years) unable to give informed consent