Replacing Bone Marrow Diagnostics With Peripheral Blood Analysis in Cytopenia Patients

This observational, multi-center study aims to collect data in order to develop a novel, minimally invasive diagnostic tool for MDS based on peripheral blood profiling of circulating hematopoietic stem and progenitor cells (cHSPCs) using single-cell RNA sequencing and DNA sequencing. Current MDS diagnosis relies on bone marrow (BM) aspiration and biopsy, which is invasive, technically challenging, and sometimes inconclusive, particularly in early or low-risk disease. Our prior research established a healthy reference map of cHSPC subtypes and developed a computational pipeline that distinguishes MDS from non-clonal cytopenias based on deviations from this reference. In this study, patients referred, as part of standard care, for BM evaluation due to unexplained cytopenias or abnormal blood counts and undergo PB collection for genomic profiling. The study's primary objective is to develop a PB-based test by comparing the developed test diagnoses to the conventional BM-based one. Secondary objectives include evaluating its potential for MDS risk stratification and assessing its ability to reduce the need for BM evaluations.

Inclusion criteria

• Patients aged 18 and up with suspected/confirmed MDS cases referred to BM evaluation either for diagnosis or risk assessment due to cytopenia
• Platelets < 150 × 10E9/L or
• Absolute neutrophil count < 1.8 × 10E9/L or
• Hemoglobin (Hgb) < 13 g/dL (males) and < 12 g/dL (female) and
• For both sexes, no evidence of Iron, folinic acid, or B12 deficiency

Exclusion criteria

• Women who are pregnant
• Previous diagnosis of leukemia; AML, MPN, ALL, CLL, MGUS/MM or any other gammopathy
• Lymphocytes > 5000/ul
• Patients who are on disease-related therapy are excluded, unless they are treated with Erythropoietin or Prednisone. See Appendix 2 for the list of excluded treatments.
• Patients who have undergone a bone marrow transplant.