Myelodysplastic Syndromes (MDS) are bone marrow cancers where blood-forming cells become abnormal. This prevents the bone marrow from producing enough healthy blood cells, leading to conditions like anemia, easy bleeding, or frequent infections. MDS is a dynamic condition that can worsen over time.
Understanding MDS Progression
Progression in MDS signifies a worsening or advancement of the disease. This can manifest as a significant decrease in healthy blood cell counts, such as red blood cells (anemia), white blood cells (neutropenia), or platelets (thrombocytopenia). Another indicator is an increase in immature blast cells, which are early forms of blood cells, either in the bone marrow or circulating blood. New chromosomal abnormalities also point to disease progression. These changes lead to more severe symptoms and complications. Recognizing these indicators is important for monitoring the disease course and guiding treatment decisions.
Factors Driving Progression
Several factors influence the likelihood and speed at which MDS progresses. Genetic mutations play a significant role, with specific gene alterations driving disease advancement. For instance, mutations in genes like TP53, ASXL1, EZH2, RUNX1, and TET2 are frequently observed and associated with a less favorable outcome.
Chromosomal abnormalities are also powerful predictors of progression. Common abnormalities include the loss of chromosome 7, deletions of the long arm of chromosomes 5 and 7, and gains of chromosomes 8, 19, and 21. Specific cytogenetic changes, such as monosomy 7, can indicate a higher risk of transformation into acute myeloid leukemia (AML).
Risk assessment systems, such as the Revised International Prognostic Scoring System (IPSS-R) and the Molecular International Prognostic Scoring System (IPSS-M), categorize patients into different risk groups. The IPSS-R considers the percentage of blast cells in the bone marrow, the type and number of chromosomal abnormalities, and the levels of red blood cells, platelets, and neutrophils. The newer IPSS-M further refines risk stratification by incorporating molecular genetic information from 31 genes, alongside the factors included in IPSS-R. Other disease features, like the percentage of blast cells at diagnosis, the severity of low blood cell counts (cytopenias), and a patient’s age, also influence the prognosis and potential for progression.
Detecting and Tracking Progression
Healthcare professionals monitor patients for MDS progression through diagnostic tools and tests. Regular complete blood counts (CBCs) track changes in red blood cells, white blood cells, and platelets. A decline in these healthy cell counts can signal disease worsening.
Bone marrow biopsies and aspirates provide direct examination of the bone marrow, allowing for assessment of cellularity and the percentage of immature blast cells present. An increase in blast cell percentage in the bone marrow is a primary indicator of progression.
Cytogenetic and molecular testing on bone marrow samples identify new or evolving chromosomal abnormalities and gene mutations. These genetic changes can be specific indicators of disease progression. Changes in these tests, such as the emergence of new high-risk mutations or chromosomal rearrangements, alert doctors to potential progression and help guide adjustments in treatment strategies.
When MDS Becomes AML
The most significant form of MDS progression is its transformation into Acute Myeloid Leukemia (AML). This transformation occurs when the percentage of blast cells in the bone marrow or blood reaches 20% or more. This threshold marks a change in diagnosis from MDS to AML.
The development of AML is a more aggressive form of the disease. While MDS is characterized by ineffective blood cell production and maturation, AML involves a block in hematopoietic cell maturation, leading to a significant accumulation of immature blasts. Approximately 30-40% of MDS patients eventually progress to AML, with this transformation being more frequent and rapid in high-risk MDS cases. Treatment approaches shift once AML develops, often requiring more intensive therapeutic strategies.