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 fewer than 20% marrow blasts at the time (within 30 days) of registration and consent.
  3. 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 trial registration.
  4. Age 50.0-75.0 years.
  5. Karnofsky performance status > 70 or Eastern Cooperative Oncology Group (ECOG) ≤ 1 (see comparison scale in Appendix D).
  6. Patients are eligible if no formal unrelated donor search has been activated prior to enrollment. Patients who have started a sibling donor search or who have found a matched sibling donor are eligible.

  7. 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.
  8. 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.
  9. Signed informed consent

Exclusion Criteria:

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

  1. Therapy-related MDS
  2. Current or prior diagnosis of AML
  3. Uncontrolled bacterial, viral or fungal infection
  4. Concurrent malignancy other than superficial squamous cell or basal cell carcinoma of the skin
  5. Prior autologous or allogeneic HCT
  6. Human Immunodeficiency Virus (HIV) infection
  7. Fertile patients unwilling to use contraceptive techniques
  8. Patients with psychosocial conditions that would prevent study compliance