Hematological Disorders Overview: Lymphoma, CML, PMF, and Hyperleukocytosis

Mayta
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1. Anemia in Lymphoma: Mechanisms and Clinical Insight

Lymphoma, a malignancy of the lymphatic system, can lead to anemia through several distinct pathophysiological mechanisms:

1.1 Bone Marrow Infiltration

Mechanism: Lymphoma cells infiltrate the bone marrow and crowd out erythropoietic precursors.
Effect: Impaired hematopoiesis leads to pancytopenia, including normocytic normochromic anemia.
Diagnostic Clue: Bone marrow biopsy shows lymphoma cells replacing hematopoietic tissue.

1.2 Autoimmune Hemolytic Anemia (AIHA)

Common in: Non-Hodgkin lymphoma (especially CLL-like types).
Mechanism: The lymphoma drives production of autoantibodies against red cells.
Effect: Increased red cell destruction with spherocytes seen on smear, elevated LDH, indirect bilirubin, and reticulocytosis.
Confirmatory Test: Positive direct Coombs test.

1.3 Anemia of Chronic Disease (ACD)

Mechanism: Inflammatory cytokines (IL-6, TNF-α) interfere with iron metabolism, reducing erythropoietin response and trapping iron in macrophages.
Labs: Low serum iron, low TIBC, high ferritin.

1.4 Chemotherapy-Induced Anemia

Mechanism: Cytotoxic damage to proliferating marrow cells.
Management: Often managed supportively or with erythropoiesis-stimulating agents.

1.5 Nutritional Deficiencies

Mechanism: Poor appetite or GI toxicity may lead to deficiencies in folate, vitamin B12, or iron.

2. Peripheral Blood Smear: CML vs. PMF

A core hematology diagnostic skill is distinguishing CML (Chronic Myeloid Leukemia) from PMF (Primary Myelofibrosis) based on PBS findings:

Feature	CML	PMF
WBC Count	Very high (>100,000/µL)	Normal to mildly elevated (early), decreased in late
Granulocytic Series	Full spectrum of myeloid precursors: "myelocyte bulge"	Left shift with nRBCs and immature myeloids
Basophilia	Present	Rare
Platelets	Often high	Giant platelets; variable count
Teardrop Cells	Rare	Classic feature of PMF
Leukoerythroblastosis	Rare	Present
Blasts in Chronic Phase	<10%	Mild
Bone Marrow	Hypercellular with myeloid hyperplasia	Fibrotic with abnormal megakaryocytes

3. Splenomegaly: CML vs. PMF

CML:

Massive splenomegaly due to infiltration by proliferating granulocytes and extramedullary hematopoiesis.
Often presents with left upper quadrant fullness or early satiety.
Very high WBC count accompanies splenomegaly.

PMF:

Splenomegaly due to extramedullary hematopoiesis secondary to bone marrow fibrosis.
WBC count not typically extremely elevated, and may fall in late stages.

4. Hyperleukocytosis Syndrome

4.1 Definition

WBC > 100,000/µL.
Most common in acute leukemias (AML, ALL) and CML blast crisis.

4.2 Pathophysiology

Large, rigid leukemic blasts occlude small vessels → microcirculatory stasis.
Affects high-flow areas like brain and lungs → organ dysfunction.

4.3 Clinical Manifestations

CNS: Headache, dizziness, confusion, seizures, coma.
Lungs: Dyspnea, hypoxia, acute respiratory failure.
Other: Priapism, visual disturbances, renal failure (TLS).

4.4 Management

Emergency!
Start with hydration (0.9% saline) to prevent tumor lysis and renal failure.
Avoid transfusing PRBCs unless symptomatic anemia exists.
Leukapheresis: Immediate cytoreduction.
Hydroxyurea: 50–100 mg/kg/day for cytoreduction.
Rasburicase/allopurinol: Prevent tumor lysis syndrome.
Start definitive chemotherapy once stable.

5. Diagnostic Criteria for Chronic Myeloid Leukemia (CML)

5.1 Clinical Features

Fatigue, weight loss, night sweats, splenomegaly.
Hypermetabolism due to high cell turnover.

5.2 Peripheral Blood Findings

Leukocytosis >100,000 cells/µL.
Full spectrum of myeloid precursors.
Basophilia and eosinophilia.
Thrombocytosis (early); thrombocytopenia (late).

5.3 Bone Marrow

Hypercellular with granulocytic hyperplasia.
Increased myeloid:erythroid ratio.
Giant, dysplastic megakaryocytes.

5.4 Cytogenetic & Molecular Testing

Philadelphia chromosome: t(9;22)(q34;q11).
BCR-ABL1 fusion gene → constitutively active tyrosine kinase.
Detected via FISH, PCR, or karyotyping.

5.5 Phases of CML

Phase	Blast %	Clinical Picture
Chronic	<10%	Stable, asymptomatic or mild symptoms
Accelerated	10–19%	Symptoms worsen, resistant to therapy
Blast Crisis	≥20%	Resembles acute leukemia, poor prognosis

5.6 Ancillary Tests

LDH: Elevated from high turnover.
Uric acid: High, risk of gout or TLS.
CBC + smear: Essential for monitoring.

6. Summary Table

Disorder	Key Feature	PBS	Splenomegaly	Genetic Hallmark
CML	Myeloid cell proliferation	Myelocyte bulge, basophilia	Massive	BCR-ABL1 (t9;22)
PMF	Marrow fibrosis	Teardrop cells, nRBCs	Massive	JAK2/CALR/MPL mutations
Lymphoma	Lymphatic malignancy	Anemia, possibly AIHA	Possible	Varies by type
Hyperleukocytosis	WBC >100,000	Blasts (AML/ALL)	May be present	Often no specific cytogenetics; depends on leukemia

🧠 Medical Student Takeaways

Memorize PBS patterns to distinguish CML from PMF.
Recognize anemia mechanisms in cancer: marrow infiltration, hemolysis, chronic inflammation.
Treat hyperleukocytosis as a true hematologic emergency.
Know that BCR-ABL1 fusion is pathognomonic for CML, and targeted therapy with TKIs (e.g., imatinib) revolutionized its treatment.