Inclusion Criteria:

• Diagnosis of MDS according to World Health Organization (WHO) criteria (Appendix 2) or French-American-British (FAB) classification that must be confirmed by bone marrow (BM) aspirate and/or biopsy within 6 weeks prior to Screening.
• Myelodysplastic syndrome (MDS) classified as Low risk or Int-1 risk, according to International Prognostic Scoring System (IPSS) classification; in addition, patients should never have been classified as Int-2 or High-risk since their MDS was diagnosed;
• Transfusion dependency defined by transfusion of at least 4 units of Red blood cells (RBC) within 56 days before Screening (pre-transfusion Hgb values values must be ≤ 9 g/dL to be taken into account).
• Refractory to 8- to 12-week course of Erythropoiesis-stimulating agent (ESA) administered within the past 2 years before enrollment, or erythropoietin (EPO) level ˃ 500 mU/mL and off ESA for at least 8 weeks before Screening.
• Off all other treatments for MDS (azacitidine, decitabine, lenalidomide, chemotherapy, immunotherapy) for at least 2 weeks prior to Screening.
• Eastern Cooperative Oncology Group(ECOG) performance status of 0, 1 or 2.
• Willing to adhere to the prohibitions and restrictions specified in this protocol.
• The patient must signed an informed consent form (ICF) indicating that s/he understands the purpose of, and procedures required for, the study and is willing to participate.

Exclusion Criteria:

• Ongoing clinically significant anemia due to factors such as iron, vitamin B12, or folate deficiencies, auto-immune or hereditary hemolysis, or gastrointestinal (GI) bleeding.
• Serum ferritin < 50 ng/mL.
• Hypoplastic MDS (cellularity <10%)
• Any active malignancy within the past year, except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast.
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• Active infection not adequately responding to appropriate therapy.
• Total bilirubin ≥ 2.0 mg/dL not related to hemolysis or Gilbert's disease.
• Alanine transaminase (ALT) or aspartate transaminase (AST) ≥ 2.5 x the upper limit of normal (ULN).
• Serum creatinine ≥ 2.0 mg/dL.
• Ascites requiring active medical management including paracentesis.
• Hyponatremia (defined as serum sodium value of < 130 mEq/L).
• Female patients who are pregnant or lactating.
• Patients of childbearing potential who are unwilling to follow strict contraception requirements.
• Female patients with reproductive potential who do not have a negative blood or urine pregnancy test at Screening.
• Major surgery without full recovery or major surgery within 3 weeks of Screening.
• Uncontrolled hypertension (defined as a systolic pressure ≥ 160 mmHg and/or a diastolic pressure ≥ 110 mmHg).
• New onset seizures (within 3 months prior to the first dose of rigosertib) or poorly controlled seizures.
• Any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy.
• Chronic use (˃ 2 weeks) of corticosteroids (˃ 10 mg/24 hr equivalent prednisone) within 4 weeks of Screening.
• Investigational therapy within 4 weeks of Screening.
• Allergy to a local anaesthetic.
• Psychiatric illness or social situation that would limit the patient's ability to tolerate and/or comply with study requirements.