Myelofibrosis (MF) is a chronic disorder originating in the bone marrow, the soft tissue inside bones responsible for making blood cells. Abnormal blood cell production leads to the buildup of scar tissue, or fibrosis, within the marrow cavity. This scarring impairs the marrow’s ability to function, forcing blood cell production to shift to other organs. MF is inherently progressive, and recognizing signs of progression is important for adjusting treatment.
Worsening Constitutional Symptoms
One of the first indications of advancing myelofibrosis is a noticeable and sustained worsening of systemic, or constitutional, symptoms. These are often grouped together by physicians and referred to as “B symptoms.” The increase in frequency or intensity of these symptoms reflects a heightened inflammatory state within the body, driven by the abnormal release of signaling proteins called cytokines.
Severe, debilitating fatigue is common, often feeling relentless and out of proportion to activity. This exhaustion is often a result of anemia or the underlying inflammatory process. Patients may also experience persistent, unexplained fevers above 100.4°F (38°C) or drenching night sweats that soak clothing and bedding.
The body’s increased metabolic rate contributes to significant, unintentional weight loss, sometimes referred to as cachexia. Losing more than ten percent of body weight over six months without trying is a specific measure of progression. The rapid onset or increasing severity of these constitutional symptoms suggests the disease is becoming more active and aggressive.
Shifts in Hematological Markers
Progression is frequently signaled by significant changes in the complete blood count (CBC). Worsening anemia is a common marker, where hemoglobin levels drop further, potentially falling below 10 grams per deciliter (g/dL), often necessitating more frequent blood transfusions. The red blood cells produced can appear misshapen, known as teardrop-shaped cells, or dacryocytes, which is characteristic of diseased bone marrow.
White blood cell (WBC) counts can become unstable, either spiking to unusually high levels (leukocytosis) or dropping dangerously low (leukopenia or neutropenia). A low neutrophil count (neutropenia) weakens the immune system and increases the risk of serious infections. Similarly, platelet counts can become erratic, with a rapidly dropping count (thrombocytopenia) to below 100,000 per microliter being an unfavorable sign.
A highly concerning sign of progression is the appearance or rise in the percentage of circulating blast cells in the peripheral blood. Blasts are immature, undeveloped blood cells that should primarily remain in the bone marrow. An increasing number of these immature cells spilling into the bloodstream indicates that the disease is progressing toward a more aggressive, leukemic phase.
Physical Signs of Extramedullary Hematopoiesis
As the bone marrow becomes increasingly scarred, it fails to produce enough healthy blood cells, forcing other organs to attempt to take over this function, a process known as extramedullary hematopoiesis (EMH). The spleen and the liver are the primary sites where this compensatory blood cell production occurs. A notable and rapid increase in the size of the spleen, or splenomegaly, is a common physical sign of progression.
The enlarged spleen can cause physical symptoms such as abdominal fullness, pain in the upper left abdomen, and early satiety (feeling full after eating a small amount). The continued growth of the spleen can lead to complications like portal hypertension, which is high blood pressure in the vein that carries blood to the liver.
This complication can result in the formation of varices, or enlarged veins, in the esophagus or stomach that carry a risk of severe bleeding. Less frequently, the liver may also become enlarged (hepatomegaly), contributing to abdominal discomfort.
Progression to Accelerated Phase or AML
The most severe form of progression in myelofibrosis is the transformation to a higher-risk phase, culminating in acute myeloid leukemia (AML). This transformation is defined by a specific, measurable increase in the percentage of those immature blast cells mentioned earlier. The disease is classified as entering the accelerated phase when the percentage of blasts in the blood or bone marrow reaches a range between ten percent and nineteen percent.
The transformation is officially classified as blast phase myeloproliferative neoplasm, which is equivalent to secondary AML, once the blast count reaches twenty percent or higher. Myelofibrosis is the most common myeloproliferative neoplasm to progress to AML, with approximately twenty percent of patients experiencing this transformation within ten years of diagnosis.
Progression to this blast phase is associated with a significantly worse prognosis and a drastic change in the treatment approach, often requiring intensive therapy. Clinical clues that precede this transformation include a rapid increase in the need for red blood cell transfusions, the sudden onset of severe cytopenias, and a rapid, uncontrolled worsening of constitutional symptoms.