Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells that is characterized by morphological dysplasia in one or more major hematopoietic cell lines. The dysplastic changes can result in varying degrees of single or multiple cytopenias, including neutropenia, anemia, and thrombocytopenia. The clinical presentation of MDS can range from asymptomatic to life-threatening, depending on the severity of cytopenias, with some  transforming to acute myeloid leukemia.

The historic  approach to diagnose MDS relied on identifying morphological dysplastic changes in the peripheral blood and bone marrow. However, due to advances in molecular technologies, the 2023 NCCN guidelines allow for diagnosis of MDS on peripheral blood alone. This enables diagnosis of MDS without the need for painful and costly bone marrow biopsy. Here we present a case where using the Omnia™ methodology, supported by advanced molecular techniques enabled the Precipio lab to diagnose a patient with MDS using only a peripheral blood sample.

Case Presentation

An 82-year old female with transfusion dependent anemia and pancytopenia presented, complaining of progressive weakness and neurological symptoms. The patient was a non-smoker, and generally in good health. CT scan of the spine showed degenerative changes (2 yrs earlier) while the head CT with contrast was negative.

Her vitamin B12 level was above the normal range at >2000 pg/ml (normal range: 180-900). The patient’s serum chloride level was elevated at 108 mmol/L (normal range: 98-107), and their serum lactate dehydrogenase (LDH) level was also elevated at 278 U/L (normal range: 140-271). Her free T4 level was below the normal range at 0.83 ng/dL (normal range: 0.88-1.64), and their iron level was high at 252 µg/dL

(normal range: 35-170). The patient’s unsaturated iron-binding capacity (UIBC) was below the normal range at <55 µg/dL (normal range: 70-275). Her ferritin level was significantly elevated at 749.5 ng/dL (normal range: 11-306.8). Table 1 presents the blood workup of the patient upon presentation.

Table 1: Blood Work Up
TestNormal RangeResults
WBC (x103/μL)4.8-10.84.73
RBC (x106/μL)4.2-5.42.17
HGB (g/dL)12-166.9
MCV (μm3)81-9998.2
MCH (pg)27-3331.8
MCHC (g/dL)32-3632.4
PLT (x103/μL)150-450143
MPV ( μm3)10.4

Case Work Up &Results:

The peripheral blood smear review showed left-shifted neutrophilic granulocytes with occasional metamyelocytes, myelocytes, and blasts.. The differential count was as follows:  Blasts 3%, polys 44%, bands 4%, metamyelocytes 9%, myelocytes 10%, lymphocytes 28%, 1% monocytes, and eosinophils 1%. Besides, there was marked anemia with mild anisopoikilocytosis. 

The flow cytometry results indicated granulocytes with a left-shift, aberrant CD56 expression, and abnormal CD13/CD16 maturation pattern suggestive of dysmyelopoiesis. Monocytes decreased from previous results. The lymphocytes (24%) included 3% polyclonal B-cells, 84% mature T-cells with a normal CD4/CD8 ratio, and 12% natural killer (NK) cells.

The findings point to an underlying myeloid stem cell disorder, including a myelodysplastic syndrome and possibly a higher grade myeloid neoplasm. 

Molecular analyses were performed using the HemeScreen® Cytopenia panel revealing positive ASXL1 (additional sex combs like 1) and WT1 (Wilms’ Tumor 1) mutations.

Clinical Implications:

ASXL1 mutations have been associated with an adverse prognostic impact on overall survival in patients with MDS and an increased likelihood of transformation to AML1

Studies2,3 of large MDS cohorts have established WT1 mutations as an independent predictor of poor prognosis. These studies have also demonstrated a correlation between WT1 mutations and lower hemoglobin levels, as well as a higher percentage of bone marrow blasts.

Obtaining accurate diagnoses through minimally invasive methods enables less painful and more efficient patient work-ups. Keeping current with the latest guidelines to support triage and testing advancements provided for more comprehensive care for this patient without prolonged, invasive sample collection visits.

This presentation is intended for educational purposes only and does not replace independent professional judgment. This document contains proprietary information belonging to Precipio, Inc. No use or disclosure of the information contained herein is permitted without the prior written consent of Precipio Inc.