Lymphoblastic Leukemia: Clinical Presentation and Laboratory Findings
Clinical Symptoms
Patients with acute lymphoblastic leukemia (ALL) present with symptoms resulting from bone marrow infiltration and extramedullary involvement, most commonly including fatigue, bleeding manifestations, fever, and infections. 1
Primary Presenting Symptoms
- Fatigue and lethargy are among the most common presenting complaints, resulting from anemia secondary to bone marrow failure 1
- Easy bruising or bleeding occurs due to thrombocytopenia and platelet dysfunction 1
- Fever and recurrent infections develop from neutropenia and leukocyte dysfunction 1
- Constitutional symptoms including night sweats and unintentional weight loss are frequently present 1
- Dyspnea and dizziness relate directly to anemia 1
Age-Specific Presentations
- In children, bone or joint pain may be the only presenting symptom, which can lead to diagnostic delays 1
- Chin numbness or facial palsy may indicate cranial nerve or CNS involvement 1
Physical Examination Findings
- Lymphadenopathy, splenomegaly, and/or hepatomegaly are found in approximately 20% of patients on physical examination 1
- Mediastinal mass is particularly common in T-cell ALL due to thymic involvement 1
- Abdominal masses from gastrointestinal involvement are more suggestive of mature B-cell ALL (Burkitt lymphoma) rather than typical ALL 1
Oncologic Emergencies
Patients may present with life-threatening complications requiring immediate intervention 1:
- Tumor lysis syndrome from rapid cell turnover
- Superior vena cava syndrome from mediastinal masses
- Respiratory compromise from thoracic involvement
- Spinal cord compression from CNS disease
Laboratory Values
The diagnosis of ALL requires ≥20% lymphoblasts in the bone marrow, though ≥25% is often used in treatment protocols to definitively establish leukemia. 1
Diagnostic Criteria
- Bone marrow lymphoblasts ≥20% on aspirate and biopsy is the standard diagnostic threshold 1
- Peripheral blood can substitute for bone marrow when there are ≥1,000 circulating lymphoblasts per microliter OR ≥20% lymphoblasts, particularly in cases of hyperleukocytosis (≥100,000 leukocytes/μL) or when bone marrow aspiration is not feasible 1
- Flow cytometry confirmation of clonality is essential for diagnosis 1
Complete Blood Count Abnormalities
- Anemia (low hemoglobin) from bone marrow replacement 1
- Thrombocytopenia (low platelet count <100 × 10⁹/L) is common 1
- Variable white blood cell count: can be low, normal, or markedly elevated with circulating blasts 1
- Neutropenia leading to increased infection risk 1
Essential Baseline Laboratory Studies
The following tests should be obtained at diagnosis 1:
- Complete blood count with differential to assess cytopenias and circulating blasts 1
- Comprehensive metabolic panel to monitor for tumor lysis syndrome, particularly important at diagnosis and during induction therapy 1
- Lactate dehydrogenase (LDH) as a marker of tumor burden and cell turnover 1
- Uric acid and phosphate levels to assess tumor lysis syndrome risk 1
- Coagulation panel (PT, PTT, fibrinogen) to detect disseminated intravascular coagulation 1
Immunophenotyping Requirements
Flow cytometry is mandatory to establish lineage and clonality 1:
- B-cell ALL markers: CD19, CD20 (often dim), CD10 (in most cases), surface immunoglobulin light chain restriction (kappa or lambda) 1
- T-cell ALL markers: CD3, CD5, CD7, with absence of B-cell markers 1
- Terminal deoxynucleotidyl transferase (TdT) is typically positive in ALL, distinguishing it from mature lymphomas 1
- CD20 expression helps guide immunotherapy decisions 1
Cytogenetic and Molecular Studies
FISH and cytogenetic analysis are essential before initiating therapy to identify prognostically important abnormalities 1:
- Philadelphia chromosome (BCR-ABL1) detection is critical as it fundamentally changes treatment approach 1, 2
- High-risk cytogenetics including KMT2A (MLL) rearrangements, hypodiploidy, and complex karyotype 1
- Favorable cytogenetics such as hyperdiploidy and ETV6-RUNX1 (TEL-AML1) fusion 1
- Baseline characterization of leukemic clone by flow cytometry or immunoglobulin/T-cell receptor gene rearrangements to facilitate minimal residual disease monitoring 1
Important Diagnostic Distinctions
Chronic Lymphocytic Leukemia vs. Acute Lymphoblastic Leukemia
CLL requires ≥5,000 monoclonal B lymphocytes/μL for ≥3 months and presents with mature-appearing lymphocytes, fundamentally different from ALL 1:
- CLL cells are small, mature lymphocytes with dense nuclei lacking nucleoli, versus ALL blasts which are larger with immature features 1
- CLL immunophenotype: CD5+, CD23+, CD19+, CD20 dim, surface immunoglobulin dim 1
- CLL typically presents in older adults (median age 69-72 years) with indolent course, versus ALL which is more aggressive 1
Lymphoblastic Lymphoma vs. ALL
When disease is restricted to mass lesions with <20% bone marrow lymphoblasts, the diagnosis is lymphoblastic lymphoma rather than ALL, though treatment approaches are identical 1:
- Both entities are biologically identical, distinguished only by primary disease location 1
- Lymphoblastic lymphoma patients benefit from ALL-like treatment regimens 1
Critical Pitfalls to Avoid
- Do not diagnose ALL with <20% marrow blasts unless there is compelling clinical evidence, as this threshold is important for distinguishing from other lymphoproliferative disorders 1
- Do not delay cytogenetic and molecular testing, as results directly impact initial treatment decisions, particularly for Philadelphia chromosome-positive disease 1, 2
- Do not omit tumor lysis syndrome monitoring in patients with high disease burden, as this is a life-threatening complication requiring prophylaxis 1
- Ensure adequate sample collection for flow cytometry, cytogenetics, and molecular studies at diagnosis, as repeat bone marrow procedures may be difficult after treatment initiation 1