The Myelodysplasia Transplantation-Associated Outcomes (MDS-TAO) Study

Inclusion Criteria

• Histologically-confirmed diagnosis of:
• Primary or secondary MDS using the World Health Organization (WHO) 2008 classification:
• Refractory cytopenia with unilineage dysplasia
• Refractory Anemia (RA)
• Refractory Neutropenia (RN)
• Refractory Thrombocytopenia (RT)
• Refractory Anemia with Ring Sideroblasts (RARS)
• Refractory Cytopenia with Multilineage Dysplasia (RCMD)
• Refractory Anemia with Excess Blasts-1 (RAEB-1)
• Refractory Anemia with Excess Blasts-2 (RAEB-2)
• MDS with isolated del (5q)
• MDS-Unclassified (MDS-U)
• Another of the following related disorders:
• Chronic Myelomonocytic leukemia (CMML)
• Myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPD-U)
• Age 60 to 75 years
• Any of the following (high-risk characteristics):
• Intermediate-2 or High-Risk on International Prognostic Scoring System (IPSS)
• Secondary MDS (any karyotype)
• Documented non-IPSS intermediate- or poor-prognosis karyotype including:
• +8
• t(11q23)
• Rea 3q
• +19
• 3 or greater abnormalities
• del(7q)
• -5
• t(5q)
• Documented significant cytopenia for at least four months prior to enrollment, defined by the following criteria:
• Red Blood Cell (RBC) Transfusion Dependence: four or more units of RBC transfusions within an eight-week period for symptomatic anemia with hemoglobin of ≤ 9.0 g/dL; OR
• Severe Anemia: average of two or more hemoglobin values ≤ 8 g/dL within an eight-week period not influenced by RBC transfusions (i.e., must be seven days post transfusion); OR
• Severe Thrombocytopenia: average of two or more platelet counts ≤ 50

× 109/L within an eight-week period not influenced by platelet transfusions (i.e., must be at least three days post- transfusion) or a clinically significant hemorrhage requiring platelet transfusions within the prior four months; OR

• Severe Neutropenia: average of two or more absolute neutrophil counts (ANC) ≤ 500 within an eight-week period, or a clinically significant infection requiring IV antibiotics in the setting of ANC ≤ 1000 within the prior four months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
• Adequate organ function to permit RIC HSCT as indicated by the following:
• Serum bilirubin ≤ 2.5 mg/dL (except when Gilbert's syndrome or MDS-related hemolysis suspected).
• Aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 times the upper limit of normal (ULN).
• Serum creatinine ≤ 2.0 mg/dL.
• Seemingly sufficient baseline cardiac function to undergo HSCT (no echocardiogram required).
• Seemingly sufficient baseline pulmonary function to undergo HSCT (no pulmonary function tests required).
• Seemingly sufficient neuro-psychiatric function to undergo HSCT (no specific neuro-psychiatric evaluation required).
• Willingness to undergo human leukocyte antigen (HLA)-typing and consider subsequent HSCT.
• Willingness and ability to give informed consent.

Exclusion Criteria

• Known baseline conversion to AML (eg, ≥ 20% peripheral or marrow blasts).
• Knowledge of potential donor status at study entry. Of note, knowledge of HLA status WITHOUT a related or unrelated search is allowed.
• History of prior malignancy within the past year, except for adequately-treated carcinoma in situ of uterine cervix, basal cell or squamous cell skin cancer.
• Any severe concurrent disease, infection, or comorbidity that, in the judgment of the principal investigator, would make the patient inappropriate for HSCT at the time of study entry.
• Psychiatric disorders including dementia that would preclude obtaining informed consent or the ability to participate in an ongoing research study.