Leukemias & Lymphomas (Clinical)
Blasts that crash the marrow, nodes that spread by the rules, and one true emergency
Acute leukemia: presentation and diagnosis
Blasts crowd out three cell lines. Acute leukemia is a clonal expansion of blasts (≥20% of marrow or blood cells) that crowds out normal hematopoiesis over weeks, producing pancytopenia: anemia (fatigue), thrombocytopenia (bruising, petechiae), and neutropenia (infection), even when the total WBC is high. Bone pain and hepatosplenomegaly are common. The smear shows circulating blasts; marrow biopsy with flow cytometry and cytogenetics confirms the lineage and risk group.
High-count complications. Very high blast counts (typically AML with WBC >100,000/μL) cause leukostasis, with hypoxia, confusion, and stroke from sludging blasts; treat with urgent cytoreduction (hydroxyurea, leukapheresis, induction chemotherapy). Tumor lysis is the other threat. Fever with an absolute neutrophil count <500/μL needs immediate empiric antipseudomonal antibiotics.
| Feature | ALL | AML |
|---|---|---|
| Typical patient | Children, peak age 2–5 | Adults, median age ~65 |
| Blast markers | Lymphoblasts, TdT-positive | Myeloblasts, myeloperoxidase-positive, Auer rods |
| Distinctive features | Seeds CNS and testes; T-ALL presents with an anterior mediastinal mass | Gum and skin infiltration in monocytic subtypes; APL causes DIC |
| Genetics | t(12;21) and hyperdiploidy favorable; t(9;22) unfavorable | t(15;17), t(8;21), inv(16) favorable |
| Treatment | Multiagent chemotherapy with intrathecal CNS prophylaxis; add a TKI if Philadelphia-positive | Induction with cytarabine plus an anthracycline; transplant for high-risk disease |
Acute promyelocytic leukemia: the same-day emergency
APL (AML M3) carries t(15;17), which fuses PML with the retinoic acid receptor α gene (PML-RARA) and arrests cells at the promyelocyte stage. The abnormal promyelocytes, packed with Auer rods (bundled in "faggot cells"), release procoagulants that trigger DIC with low fibrinogen, high D-dimer, and life-threatening hemorrhage. The classic patient is a young adult with gingival bleeding, fatigue, and fever.
- t(15;17) PML-RARAMaturation arrest; abnormal promyelocytes accumulate.
- Procoagulant releaseAuer rods and faggot cells.
- DICConsumption of clotting factors, fibrinogen, and platelets.
- HemorrhageGive ATRA plus arsenic now.
Treat on suspicion. Start all-trans retinoic acid (ATRA) immediately, before genetic confirmation, with arsenic trioxide; both differentiate the promyelocytes and reverse the coagulopathy. Support with fibrinogen (cryoprecipitate) and platelets. Treated fast, APL is highly curable.
ATRA can cause differentiation syndrome (fever, dyspnea, pulmonary infiltrates, edema); treat with dexamethasone. Arsenic prolongs the QT interval.
Chronic leukemias: CLL and CML
CLL is the most common adult leukemia in the West: an older patient, often with asymptomatic lymphocytosis found incidentally. Mature small lymphocytes and smudge cells fill the smear, and flow cytometry shows CD5+, CD19+, CD23+ B cells. Early asymptomatic disease is observed; treat for symptoms, progressive cytopenias, or bulky disease (BTK inhibitors such as ibrutinib, or venetoclax).
CML is driven by t(9;22), the Philadelphia chromosome, which creates the BCR-ABL tyrosine kinase. It presents with a markedly elevated WBC showing the full spectrum of myeloid maturation, basophilia, and splenomegaly. Confirm BCR-ABL1 by FISH or RT-PCR (a low leukocyte alkaline phosphatase score is a historical clue, no longer used) and treat with a BCR-ABL tyrosine kinase inhibitor: imatinib, dasatinib, nilotinib, or bosutinib. Untreated, it progresses to blast crisis, which behaves like acute leukemia.
| Feature | CLL | CML | Leukemoid reaction |
|---|---|---|---|
| Cells | Mature B lymphocytes, smudge cells | Full myeloid spectrum, basophilia | Neutrophils with left shift, toxic granulation |
| Key test | CD5+, CD19+, CD23+ | t(9;22) BCR-ABL1 by FISH or RT-PCR | No BCR-ABL1 |
| Complications | Autoimmune hemolytic anemia, hypogammaglobulinemia, Richter transformation to DLBCL | Blast crisis | Resolves with the cause (infection) |
| Treatment | Observe early disease; BTK inhibitor or venetoclax | BCR-ABL TKI (imatinib, dasatinib, nilotinib, or bosutinib) | Treat the underlying cause |
Hodgkin vs non-Hodgkin lymphoma
Hodgkin lymphoma is defined by Reed-Sternberg cells: large, binucleate "owl-eye" cells that are CD15+ and CD30+. It has bimodal age peaks, spreads contiguously node to node, is usually localized at diagnosis, and has a good prognosis. Nodular sclerosis is the most common subtype, and EBV is linked. It often presents with painless cervical or mediastinal lymphadenopathy and B symptoms. ABVD chemotherapy with or without radiation cures most early-stage patients; for advanced stage, nivolumab-AVD or brentuximab vedotin-AVD is now preferred. Cure comes at the cost of late effects (secondary cancers, bleomycin lung toxicity, anthracycline cardiotoxicity).
Non-Hodgkin lymphoma is more common, spreads non-contiguously, and frequently involves extranodal sites; HIV and immunosuppression raise the risk. Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive type (R-CHOP). Translocation signatures:
- Follicular, t(14;18): BCL2 overexpression; indolent.
- Burkitt, t(8;14): c-myc; "starry-sky" histology, the fastest-growing human tumor.
- Mantle cell, t(11;14): cyclin D1; aggressive.
| Feature | Hodgkin | Non-Hodgkin |
|---|---|---|
| Hallmark | Reed-Sternberg cells (CD15+, CD30+) | No Reed-Sternberg cells; B or T cell |
| Spread | Contiguous, orderly; often localized | Non-contiguous, extranodal; often disseminated |
| Patients | Bimodal age; EBV linked | Older adults; HIV linked |
| Prognosis | Better | Variable by subtype |
Screen for hepatitis B (HBsAg and anti-HBc, plus HCV and HIV) before rituximab: anti-CD20 therapy can reactivate HBV, so give antiviral prophylaxis if HBsAg or anti-HBc is positive.
Lymphoma workup and staging
Excisional biopsy, not FNA. Evaluate persistent, painless, firm nodes larger than 2 cm or lasting over 4 weeks. Diagnose lymphoma with an excisional lymph node biopsy, because fine-needle aspiration destroys the architecture needed for classification; core needle biopsy is acceptable when excision is impractical. Stage with PET-CT and often bone marrow biopsy; an elevated LDH reflects tumor burden and prognosis.
- Stage IA single lymph node region.
- Stage IITwo or more regions on the same side of the diaphragm.
- Stage IIINodes on both sides of the diaphragm.
- Stage IVDisseminated extranodal disease (marrow, liver, lung).
A vs B. Suffix A means no systemic symptoms; B means B symptoms are present. The B suffix does not change the stage number, but it worsens prognosis and often intensifies treatment. Pruritus and Pel-Ebstein (cyclical) fever are Hodgkin systemic features, not formal B symptoms.
Tumor lysis syndrome
Three highs, one low. TLS follows chemotherapy of bulky, rapidly dividing tumors (Burkitt lymphoma, ALL, high-count AML). Cell breakdown releases potassium, phosphate, and uric acid, and phosphate precipitates calcium. Uric acid and calcium-phosphate crystals cause acute kidney injury; hyperkalemia causes arrhythmias.
Prevent by risk. Hydrate every patient aggressively and monitor electrolytes closely. Allopurinol (a xanthine oxidase inhibitor) blocks new uric acid formation but does not remove the existing load. Rasburicase (recombinant urate oxidase) converts uric acid to soluble allantoin and works faster, so give it for high uric acid, bulky disease, or high-risk tumors.
Avoid rasburicase in G6PD deficiency (hemolysis). Give calcium only for symptomatic hypocalcemia, because it promotes calcium-phosphate deposition; refractory hyperkalemia or renal failure calls for dialysis.