Signs and Symptoms of Leukemia

Leukemia presents with a constellation of symptoms resulting from bone marrow failure and organ infiltration, including fatigue, fever, bleeding/bruising, pallor, lymphadenopathy, splenomegaly, and bone pain—though notably, approximately 40-50% of patients with chronic myeloid leukemia are completely asymptomatic at diagnosis. 1

Common Constitutional Symptoms

The most frequently reported systemic manifestations include:

Fatigue and malaise – resulting from anemia and the disease burden 1, 2
Fever – often without clear infectious source 1, 2
Weight loss – an important constitutional symptom across all leukemia types 1, 3
Night sweats – particularly in chronic myeloid leukemia 4

Hematologic Manifestations

Bleeding and Bruising

Petechiae and easy bruising – due to thrombocytopenia 1, 2
Bleeding complications – associated with low platelet counts and/or platelet dysfunction 1
Retinal hemorrhages – can occur in chronic myeloid leukemia from elevated histamine levels due to basophilia 1

Anemia-Related Symptoms

Pallor – visible manifestation of anemia 1
Progressive fatigue – worsening over time 1
Reduced exercise tolerance – particularly noted in chronic lymphocytic leukemia 5

Physical Examination Findings

Organomegaly

Splenomegaly – the most consistent physical sign in chronic myeloid leukemia, detected in 40-50% of cases 1
Left upper quadrant fullness or pain – from splenic enlargement 1
Hepatomegaly – less common than splenomegaly 1
Lymphadenopathy – enlarged lymph nodes, particularly prominent in lymphoid leukemias 1, 5

Musculoskeletal Symptoms

Bone pain – especially in the lower extremities, more frequent with disease transformation 1, 6
Joint pain (arthralgias) – common presenting symptom 1, 2
Muscle cramps – particularly noted in chronic myeloid leukemia patients 4

Important caveat: Musculoskeletal symptoms can initially mimic orthopedic or rheumatologic diseases such as reactive arthritis, osteomyelitis, or juvenile idiopathic arthritis, potentially delaying diagnosis. 6 Nighttime bone pain is a particularly important predictive factor for pediatric leukemia. 6

Rare but Important Manifestations

Leukostatic Symptoms

These occur from leukemic cells sludging in blood vessels, though uncommon in chronic phase despite white blood cell counts often exceeding 100 × 10⁹/L: 1

Priapism 1
Dyspnea 1
Drowsiness and confusion 1
Loss of coordination 1

Disease Stage-Specific Presentations

Chronic Phase

Asymptomatic presentation – approximately 50% of chronic myeloid leukemia patients diagnosed in Europe are asymptomatic, with disease discovered incidentally on blood tests 1
Mild symptoms – when present, typically related to anemia and splenomegaly 1

Accelerated Phase

Non-specific symptoms 1
Worsening anemia 1
Progressive splenomegaly 1
Organ infiltration 1

Blast Crisis/Transformation

Acute leukemia-like presentation – with rapidly worsening symptoms 1
Severe constitutional symptoms – including fever, weight loss, and malaise 1
Increased bleeding and infections – from profound cytopenias 1
Headaches and bone pain – more frequent with transformation 1
Pain from splenic infarction 1

Infectious Complications

Increased susceptibility to infections – from immunosuppression and neutropenia 1, 5
Opportunistic infections – particularly in advanced disease 5

Key Diagnostic Considerations

Critical point: Many symptoms are non-specific and overlap with benign conditions. 3 The combination of multiple symptoms, particularly when accompanied by abnormal blood counts (leukocytosis, cytopenias, or abnormal differential), should prompt urgent hematology-oncology referral. 2, 3

Blood examinations can sometimes be subtle or within normal limits, representing a diagnostic challenge, particularly in early disease or when musculoskeletal symptoms predominate. 6 However, the presence of leukopenia, thrombocytopenia, and nighttime pain are the most important predictive factors for pediatric leukemia. 6

What are the signs and symptoms of leukemia?

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