What are the signs and symptoms of leukemia?

Signs and Symptoms of Leukemia

Approximately 50% of patients with chronic myeloid leukemia (CML) are asymptomatic at diagnosis, with the disease discovered incidentally on routine blood work, while symptomatic patients most commonly present with fatigue, splenomegaly, and constitutional symptoms. 1

Chronic Myeloid Leukemia (CML) - Chronic Phase

Most Common Presentations (>40% of patients)

• Asymptomatic presentation occurs in approximately 50% of European CML patients, discovered through abnormal blood counts obtained for unrelated reasons 1
• Splenomegaly is the most consistent physical finding, detected in 40-50% of cases 1
• Fatigue is a primary symptom resulting from anemia 1
• Weight loss and malaise are common constitutional symptoms 1
• Left upper quadrant fullness or pain related to splenomegaly 1

Less Common Manifestations (Rare)

• Bleeding associated with low platelet count and/or platelet dysfunction 1
• Thrombosis related to thrombocytosis and/or marked leukocytosis 1
• Gouty arthritis from elevated uric acid levels 1
• Retinal hemorrhages 1
• Upper gastrointestinal ulceration from elevated histamine levels due to basophilia 1
• Leukostatic symptoms (priapism, dyspnea, drowsiness, loss of coordination, confusion) are uncommon in chronic phase despite white blood cell counts often exceeding 100 × 10⁹/L 1

Physical Examination Findings

• Splenomegaly in 40-50% of patients 1
• Hepatomegaly is less common than splenomegaly 1
• Extramedullary infiltration (apart from spleen and liver) is rare in chronic phase 1

CML - Accelerated Phase

Accelerated phase presents with non-specific symptoms, worsening anemia, progressive splenomegaly, and organ infiltration. 1

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

CML - Blast Crisis

Blast crisis presents as an acute leukemia with rapidly worsening constitutional symptoms, bleeding, fever, and infections. 1

• Worsening constitutional symptoms (more severe than chronic phase) 1
• Bleeding complications 1
• Fever 1
• Infections due to immunosuppression 1
• Headaches 1
• Bone pain 1
• Arthralgias 1
• Pain from splenic infarction 1

Chronic Lymphocytic Leukemia (CLL)

Common Presentations

• Cervical lymphadenopathy is the most common initial finding 2
• Splenomegaly 2
• General fatigue 2
• Night sweats, fever, weight loss (B symptoms) 2
• Frequent infections 2
• Reduced exercise tolerance 3

Autoimmune Complications

• Autoimmune hemolytic anemia (AIHA) 2
• Immune thrombocytopenia (ITP) 2

Advanced Disease Features

• Anemia 3
• Bleeding from thrombocytopenia 3
• Susceptibility to infection from immunodeficiency 3

Acute Leukemia (General Features)

Constitutional Symptoms

• Fever present in 53% of childhood cases 4
• Fatigue in 46% of cases 4
• Weight loss 5

Hematologic Manifestations

• Pallor present in 54% of childhood cases 4
• Bruising in 52% of cases 4
• Bleeding tendency in 38% of cases 4
• Petechiae 4
• Recurrent infections in 49% of cases 4

Organomegaly

• Hepatomegaly in 64% of childhood cases 4
• Splenomegaly in 61% of cases 4
• Hepatosplenomegaly in 42% of cases 4
• Lymphadenopathy in 41% of cases 4

Musculoskeletal Symptoms

• Limb pain in 43% of childhood cases 4
• Bone pain 5
• Joint pain 4
• Limp 4

Other Manifestations

• Rash in 35% of cases 4
• Abdominal pain 4
• Anorexia 4
• Abdominal distension 4

Critical Clinical Pearls

Approximately 6% of children with leukemia are completely asymptomatic at diagnosis. 4

Key Diagnostic Indicators

• Multiple concurrent symptoms and signs should heighten suspicion for leukemia 4
• Leukocytosis with basophilia and immature granulocytes (metamyelocytes, myelocytes, promyelocytes) is the hallmark of CML diagnosis 1
• Thrombocytosis is frequent in CML 1
• Severe anemia is rare at CML diagnosis 1

Important Caveats

• Blood examinations can sometimes be subtle or within normal limits, particularly in acute leukemia presenting with musculoskeletal symptoms, representing a diagnostic challenge 6
• Musculoskeletal presentations may initially be misdiagnosed as reactive arthritis, osteomyelitis, or juvenile idiopathic arthritis 6
• Leukopenia, thrombocytopenia, and nighttime pain are the most important predictive factors for pediatric leukemia 6
• Radiological findings of leukemic bone involvement may appear before hematologic abnormalities 6

Essential Physical Examination Components

A thorough examination must include abdominal palpation for organomegaly, palpation for lymphadenopathy, and careful scrutiny of the skin for petechiae, bruising, or rash. 4