Allo vs Hypomethylating/Best Supportive Care in MDS (BMTCTN1102)

Inclusion Criteria:

* Patients fulfilling the following criteria will be eligible for entry into this study:

1. Patients with de novo MDS who have, or have previously had, Intermediate-2 or High risk disease as determined by the International Prognostic Scoring System (IPSS). Current Intermediate-2 or High risk disease is NOT a requirement.
2. Patients must have an acceptable MDS subtype:

* Refractory cytopenia with unilineage dysplasia (RCUD) (includes refractory anemia (RA))
* Refractory anemia with ringed sideroblasts (RARS)
* Refractory anemia with excess blasts (RAEB-1)
* Refractory anemia with excess blasts (RAEB-2)
* Refractory cytopenia with multilineage dysplasia (RCMD)
* Myelodysplastic syndrome with isolated del(5q) (5q-syndrome)
* Myelodysplastic syndrome (MDS), unclassifiable
3. Patients must have fewer than 20% marrow blasts within 60 days of consent.
4. Patients may have received prior therapy for the treatment of MDS, including but not limited to: growth factor, transfusion support, immunomodulatory (IMID) therapy, DNA hypomethylating therapy, or cytotoxic chemotherapy prior to enrollment.
5. Age 50.0-75.0 years.
6. Karnofsky performance status \> 70 or Eastern Cooperative Oncology Group (ECOG) ≤ 1.
7. Patients are eligible if no formal unrelated donor search has been activated prior to date of consent. A formal unrelated donor search begins at the time at which samples are requested from potential National Marrow Donor Program (NMDP) donors. Patients who have started a sibling donor search or who have found a matched sibling donor are eligible.
8. Patients and physicians must be willing to comply with treatment assignment:

1. No intent to proceed with alloHCT using donor sources not specified in this protocol, including human leukocyte antigen (HLA)-mismatched related or unrelated donors (\< 6/6 HLA related matched or \< 8/8 HLA unrelated matched) or umbilical cord blood unit(s).
2. No intent to use myeloablative conditioning regimens.
3. Intent to proceed with RIC alloHCT if a matched sibling or matched unrelated donor is identified. There is no requirement as to the timing of the transplantation.
9. Patients must be considered to be suitable RIC alloHCT candidates at the time of enrollment based on medical history, physical examination, and available laboratory tests. Specific testing for organ function is not required for eligibility but, if available, these tests should be used to judge eligibility.
10. Signed informed consent

Exclusion Criteria:

* Patients with the following will be ineligible for registration onto this study:

1. Therapy-related MDS (defined as the occurrence of MDS due to prior exposure to systemic chemotherapy and/or radiation for malignancy)
2. Current or prior diagnosis of AML
3. Chronic myelomonocytic leukemia or myelodysplastic/myeloproliferative neoplasm (unacceptable MDS subtypes); uncontrolled bacterial, viral or fungal infection (currently taking medication and with progression or no clinical improvement) at time of enrollment.
4. Patients with prior malignancies, except treated non-melanoma skin cancer or treated cervical carcinoma in situ. Cancer treated with curative surgery without chemotherapy/radiation therapy \> 5 years previously will be allowed. Cancer treated with curative surgery \< 5 years previously will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs.
5. Prior autologous or allogeneic HCT
6. Human Immunodeficiency Virus (HIV) infection
7. Patients of childbearing potential unwilling to use contraceptive techniques
8. Patients with psychosocial conditions that would prevent study compliance