Family Medicine Board Review · Hematology / Oncology · Source: AAFP 2023
Leukemia: High-Yield Board Summary
Workup, the four major subtypes side-by-side, diagnostic hallmarks, and the two treatment complications that get tested every year.
Initial Evaluation Workup
Order Set
1. CBC with differential
Cornerstone first test
2. LFTs
Baseline organ function
3. Coagulation panel
Bleeding risk / DIC screen
4. Uric acid
Tumor lysis risk marker
5. Phosphorus
Tumor lysis risk marker
6. LDH
Assess for
tumor lysis syndrome if on treatment
7. UA, CXR, blood culture
If patient is
febrile8. Peripheral smear
See specific indications below
9. Bone marrow aspiration
Definitive diagnosis in most subtypes
Indications for Peripheral Smear
- Hyperleukocytosis — WBC >100,000/µL (100 × 10⁹/L) with associated anemia
- Thrombocytopenia
- Thrombocytosis
- Hepatosplenomegaly
- Lymphadenopathy
- Unexplained constitutional symptoms
Risk Factors
- Chemical exposure (e.g., benzene)
- Genetic disorders: Down syndrome, Klinefelter syndrome, Fanconi anemia
- Hepatitis C → increases risk of CLL
Board trap: Down syndrome is classically linked to ALL risk in children — but also raises AML/transient myeloproliferative disorder risk in infancy; know it as a general leukemia risk factor.
The Four Major Subtypes
Acute · Lymphoblastic
Acute Lymphoblastic Leukemia (ALL)
Mainly affects children.
Symptoms: fever, weight loss, pallor, fatigue, easy bruising/bleeding, leg and back pain, hepatosplenomegaly, lymphadenopathy.
Diagnosis: >20% lymphoblasts on bone marrow sample.
| Favorable (lower risk) | Unfavorable (higher risk) |
|---|
| Age | 1–9 years | <1 or ≥10 years |
| Initial WBC count | <50,000/mm³ | ≥50,000/mm³ |
| Ploidy | Hyperploidy | Hypoploidy |
| Cytogenetic | t(12,21) | e.g., t(4,11), t(9,22) |
| Gender | Female | Male |
| Minimal Residual Disease | Negative | Positive |
Acute · Myelogenous
Acute Myelogenous Leukemia (AML)
Mainly affects adults.
Symptoms: similar to ALL, but hepatosplenomegaly is rarely seen. May have gum infiltration.
Diagnosis: Auer rods on peripheral smear; >20% myeloblasts on peripheral smear or bone marrow biopsy.
Board trap: Auer rods = AML-specific finding. Gum/gingival infiltration is a classic clue pointing away from ALL and toward AML (especially the monocytic subtype).
Chronic · Lymphocytic
Chronic Lymphocytic Leukemia (CLL)
Mainly affects adults. Half of patients are asymptomatic at diagnosis.
Diagnosis: ≥5,000/µL (5 × 10⁹/L) monoclonal B lymphocytes on peripheral smear, confirmed with flow cytometry. Peripheral smear shows smudge cells. Bone marrow biopsy is NOT required for diagnosis.
Treatment: asymptomatic early-stage disease may be monitored without treatment ("watch and wait").
Board trap: CLL is the one leukemia where diagnosis is made from peripheral blood + flow cytometry alone — no bone marrow needed. Don't order a marrow biopsy as the "next best step" here.
Chronic · Myelogenous
Chronic Myelogenous Leukemia (CML)
Mainly affects adults. Constitutional symptoms are more common than in CLL.
Diagnosis: presence of the Philadelphia chromosome — t(9;22) — via cytogenetic or molecular testing of bone marrow or peripheral blood.
Treatment: imatinib, a BCR-ABL1 tyrosine kinase inhibitor — consistent long-term improvement with minimal side effects.
Board trap: Imatinib should not be used during pregnancy — a frequently tested safety point for reproductive-age patients on TKI therapy.
Side-by-Side Comparison
| Subtype | Groups Affected | Common Features |
|---|
| ALL |
Children and young adults (60% diagnosed before age 20) |
Symptoms: easy bruising/bleeding, fatigue, fever, joint pain, pallor. Signs: hepatosplenomegaly and lymphadenopathy |
| AML |
Adults (median age at diagnosis 68 years) |
Symptoms: central nervous system palsies, fever, pallor. Signs: flow murmur, hepatosplenomegaly, lymphadenopathy (less common) |
| CLL |
Older adults (70% of new cases diagnosed after age 65) |
Symptoms: asymptomatic (70%). Signs: hepatosplenomegaly and lymphadenopathy |
| CML |
Philadelphia chromosome (BCR-ABL1 fusion gene); adults |
Symptoms: asymptomatic (50%). Signs: splenomegaly (46%–70%) |
Treatment Complications
Emergency #1
Tumor Lysis Syndrome
- Caused by release of intracellular metabolites into the bloodstream
- Can occur spontaneously or after initiation of cytotoxic treatment
- More common in acute leukemia
- Causes: uremia, hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, possible renal failure
- Treatment: aggressive IV hydration + allopurinol
Pearl: the mnemonic is the 4 metabolic derangements — ↑K⁺, ↑uric acid, ↑phosphate, ↓Ca²⁺ — remember hypocalcemia is the odd one out (low, not high), driven by phosphate binding calcium.
Emergency #2
Neutropenic Fever
- Defined as absolute neutrophil count <0.5 (×10⁹/L) with fever
- Requires immediate evaluation
- Start empirical broad-spectrum antibiotics without delay
Pearl: neutropenic fever is a true emergency — don't wait for culture results before starting antibiotics. This pairs with UA/CXR/blood cultures from the initial workup in a febrile leukemia patient.
Diagnostic Reasoning Flow
General approach once peripheral blood smear is obtained with abnormal cell count:
- Elevated monocytes → consider infections or inflammatory conditions
- Elevated eosinophils → consider parasitic infection, allergic disease, medications, or organ/tissue involvement
- Elevated neutrophils → consider infection, stress response, tissue necrosis, medications, or asplenia
- Elevated basophils → consider inflammatory or myeloproliferative conditions
- If none apply → obtain a repeat peripheral smear; persistent leukocytosis with WBC >100,000/µL, hyperleukocytosis, hepatosplenomegaly, lymphadenopathy, or unexplained constitutional symptoms → escalate to blasts/atypical lymphocytes evaluation → bone marrow aspirate/biopsy or flow cytometry as appropriate to the suspected subtype