Clinical Trials

Eligibility Criteria:

• Suspected (e.g., persistent unexplained cytopenia, circulating peripheral blasts etc.) MDS or MDS/MPN overlap disorders and undergoing diagnostic work-up with planned bone marrow assessments; OR
• Diagnosed with de novo or therapy-related MDS within 12-months of enrollment per the World Health Organization (WHO) criteria1 and undergoing clinical evaluation and planned bone marrow assessments to confirm MDS or to evaluate disease status.
• Bone marrow aspirate expected to be performed within 1 week of registration, and in all cases must be performed no later than 4 weeks after enrollment
• Age 18 or older.
• No prior treatment for MDS at entry and through the time of the entry bone marrow aspirate.
• No treatment with hematopoietic growth factors in prior 6 months.
• If anemic without prior MDS diagnosis, the following tests within the prior 6 months. Values that are significantly outside of normal range do not exclude participation but should prompt investigation of alternative etiologies for anemia:
  • B12 level;
  • Serum folate;
  • Mean corpuscular volume (MCV);
  • Red cell distribution width (RDW);
  • Ferritin;
  • Iron studies (Iron, Total Iron-Binding Capacity (TIBC) Test, Percent Saturation).
• No diagnosis of a solid tumor or hematologic malignancy within two years prior to enrollment except for in situ cancer of the skin (basal or squamous cell), cervix, bladder, breast, or prostate
• No treatment with radiation therapy in the two years prior to registration
• No non-hormonal treatment for malignancy within the two years prior to registration.
• No established hereditary bone marrow failure syndrome.
• No known primary diagnosis of aplastic anemia, classical paroxysmal nocturnal hemoglobinuria, amegakaryocytic thrombocytopenic purpura, or large granular lymphocyte leukemia.
• Not enrolled in the Connect® MDS/AML Disease Registry.

1See Appendix III for WHO peripheral blood and bone marrow findings in MDS.

• In participants with suspected MDS and prior to registration with subsequent bone marrow evaluation, alternative causes for the cytopenias should be considered (e.g., internal bleeding, autoimmune cytopenias, thyroid disorders, other causes of anemia etc.). In select individuals, the following tests could be performed to assist in the diagnostic work-up. These evaluations are not required by the protocol; however, abnormal results in advance of enrollment may reduce the number of non-MDS cases:
  • Copper, serum level;
  • Direct Antiglobulin Test;
  • Antinuclear Antibody (ANA) Test;
  • Creatinine;
  • Calculated Glomerular filtration rate (GFR);
  • Thyroid-Stimulating Hormone (TSH) tests performed in prior 6 months.

    Based on centralized pathology review, participants will be classified into the longitudinal cohort of cases (MDS; MDS/MPN overlap disorders; AML with < 30% blasts without core binding factor or acute promyelocytic leukemia [AML < 30% blasts including chromosomal rearrangements between chromosomes 8 and 21 and within chromosome 16 as well as t(15;17)]; ICUS, or at risk based on selected genetic markers (described in Section 5.1) of the protocol) and the cross-sectional cohort (all others). It is not known in advance what percentages of individuals will fall into each cohort. In addition to baseline biological samples, longitudinal samples and data will be collected for approximately 2000 Cases of MDS or MDS/MPN overlap disorders and 500 Cases of ICUS assigned to the longitudinal cohort. Sample and data collection will cease at baseline for all cases assigned to the cross-sectional cohort. Submitted samples will be reviewed by a central pathologist to determine eligibility for the longitudinal cohort (i.e., an MDS, MDS/MPN, AML with < 30% blasts without core binding factor or acute promyelocytic leukemia, or ICUS diagnosis). Should a discrepancy in diagnosis occur between the central review and study site, the study site will be notified to allow for additional information to be submitted to clarify the diagnosis. Such notifications will not occur in real time, and are not intended to assist in patient care. Additional central sequencing of selected genetic targets will be performed.

Re-screening Subjects

• Subjects that are not entered in the longitudinal study are eligible to be re-screened for participation in this study if progression of signs or symptoms provides evidence to support a probable diagnosis of MDS, MDS/MPN overlap disorders or ICUS.