CAM FINAL - HEME L4

Acute leukemia

Unregulated production of immature blood cells called blasts that replace normal bone marrow and cause hematopoietic failure.

Major categories of acute leukemia

Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).

Acute leukemia blast threshold

≥20% blasts in bone marrow or peripheral blood.

Why acute leukemia causes anemia, thrombocytopenia, and infection

Blasts replace normal bone marrow, decreasing production of normal RBCs, platelets, and functional WBCs.

General acute leukemia risk factors

Family history, ionizing radiation, benzene exposure, and certain chemotherapy/alkylating agents.

General presentation of acute leukemia

Fatigue/pallor, bleeding/petechiae, infections, fever, bone pain, and possible hepatosplenomegaly.

Acute lymphoblastic leukemia (ALL)

Acute leukemia arising from lymphoid precursor cells.

Most common childhood cancer

ALL.

Typical age of ALL

Peak age 2-5 years.

ALL epidemiology in lecture

About 90% of cases occur in children; ALL is more common than AML in children.

ALL risk association

Down syndrome.

ALL prognosis

Generally very good/curable in children; worse in older children and adults.

ALL presentation

Bone marrow failure plus bone/joint pain, lymphadenopathy, hepatosplenomegaly, and possible extramedullary disease.

Extramedullary involvement in ALL

More common than AML; may involve mediastinum, CNS, and testes.

T-ALL classic clue

Mediastinal mass.

CNS involvement in ALL

Headache and cranial neuropathies may occur.

Testicular involvement

Can occur in ALL.

ALL marrow finding

≥20% lymphoblasts.

TdT in ALL

Positive.

Flow cytometry in ALL

Distinguishes B-ALL from T-ALL.

BCR-ABL1 in ALL

Should be checked because Philadelphia-positive ALL can occur.

ALL diagnostic workup

Morphology + flow cytometry + cytogenetics/FISH + molecular testing/NGS.

Morphology in acute leukemia

Determines whether blasts are present and what they look like.

Flow cytometry in leukemia

Determines the cell lineage of blasts.

Cytogenetics/FISH in leukemia

Identifies chromosomal abnormalities defining the leukemic clone.

NGS in leukemia

Identifies specific gene mutations that help classify disease and guide therapy.

Lumbar puncture in ALL

Used to evaluate CNS involvement.

Acute myeloid leukemia (AML)

Acute leukemia arising from myeloid precursor cells.

Typical AML patient

Older adult; median age around 60 in lecture.

AML epidemiology

About 90% of AML occurs in adults.

AML risk factors

Myelodysplastic syndrome, aplastic anemia, Down syndrome, radiation, benzene, and prior chemotherapy.

AML onset

Rapid, developing over days to weeks.

AML presentation

Fatigue, infection, bleeding/bruising, petechiae, fever, bone pain, weight loss, dyspnea, and possible hepatosplenomegaly.

Lymphadenopathy in AML

Less common than in ALL.

AML CBC clue

Anemia and thrombocytopenia with blasts.

AML diagnostic threshold

≥20% blasts.

LDH in AML

Often elevated.

Uric acid in AML

Often elevated due to high cell turnover.

AML peripheral/bone marrow clue

Auer rods.

Auer rods

Needle-like cytoplasmic inclusions in myeloid blasts; classic for AML.

Why check coagulation studies in AML

To assess for DIC, especially if APL is suspected.

AML induction chemotherapy

"7 + 3."

7 + 3 regimen

7 days cytarabine + 3 days anthracycline such as daunorubicin or idarubicin.

AML consolidation

Additional chemotherapy ± allogeneic stem cell transplant depending on risk.

AML treatment selection

Depends on ability to tolerate intensive chemotherapy and cytogenetic/molecular risk profile.

Acute promyelocytic leukemia (APL)

Highly curable subtype of AML defined by t(15;17) producing PML-RARA fusion.

APL translocation

t(15;17).

APL fusion protein

PML-RARA.

APL major emergency

DIC with high risk of intracranial hemorrhage.

APL lab pattern

High WBC, anemia, severe thrombocytopenia, prolonged PT/INR and aPTT, low fibrinogen, and elevated D-dimer.

APL morphology

Promyelocytes with multiple Auer rods or bilobed nuclei.

When to suspect APL

Acute leukemia with spontaneous DIC or intracranial bleeding.

APL treatment

ATRA + arsenic trioxide.

ATRA

All-trans retinoic acid; promotes differentiation by targeting the RARA portion of PML-RARA.

Arsenic trioxide in APL

Binds PML portion of the fusion protein, promoting degradation and apoptosis.

APL curability

Highly curable.

APL chemotherapy pearl

Lecture emphasizes ATRA + arsenic rather than standard AML chemotherapy.

Tumor lysis syndrome (TLS)

Oncologic emergency caused by rapid destruction of large numbers of tumor cells releasing intracellular contents into blood.

When TLS usually occurs

After starting chemotherapy in high tumor burden or rapidly dividing cancers, especially leukemias and lymphomas.

Can TLS occur spontaneously?

Yes, although less commonly.

TLS electrolyte pattern

↑ potassium, ↑ phosphate, ↑ uric acid, ↓ calcium.

TLS memory pattern

K↑, P↑, uric acid↑, Ca↓.

Why potassium rises in TLS

Destroyed tumor cells release intracellular potassium.

Major danger of hyperkalemia in TLS

Life-threatening cardiac arrhythmias.

Why phosphate rises in TLS

Tumor cells release intracellular phosphate.

Why calcium falls in TLS

Excess phosphate binds calcium.

Symptoms of hypocalcemia in TLS

Twitching, tetany, seizures, arrhythmias, and neuromuscular irritability.

Why uric acid rises in TLS

Nucleic acids released from destroyed cells are metabolized into uric acid.

Why TLS causes AKI

Uric acid and calcium-phosphate can precipitate in kidneys and damage renal function.

How AKI worsens TLS

Impaired kidneys cannot excrete potassium, phosphate, or uric acid, causing further accumulation.

TLS uric acid criterion

≥8 mg/dL in adults or 25% increase from baseline.

TLS potassium criterion

≥6 mmol/L.

TLS phosphorus criterion

≥4.5 mg/dL in adults.

TLS corrected calcium criterion

<7 mg/dL.

Laboratory TLS

At least 2 characteristic laboratory abnormalities within a 24-hour period from 3 days before to 7 days after therapy.

Clinical TLS

Laboratory TLS plus AKI, arrhythmia, seizure, or death.

TLS symptoms

Nausea, vomiting, diarrhea, anorexia, lethargy, hematuria, dyspnea, irregular heartbeat, cloudy urine, or joint discomfort.

TLS monitoring

Labs every 4-6 hours plus ECG monitoring.

Initial TLS treatment

Aggressive IV hydration and correction of electrolyte abnormalities.

Allopurinol in TLS

Used to reduce formation of new uric acid.

Rasburicase in TLS

Rapidly lowers uric acid; check G6PD deficiency before use.

Why screen for G6PD before rasburicase

Rasburicase is an oxidative drug and can precipitate hemolysis in G6PD deficiency.

Hyperkalemia treatment in TLS

Stop potassium intake, cardiac monitoring, insulin/glucose, beta-agonists, calcium gluconate for membrane stabilization, and dialysis if refractory.

Hyperphosphatemia treatment in TLS

Phosphate restriction and phosphate binders such as sevelamer.

Should asymptomatic hypocalcemia in TLS be routinely treated?

No; treat only if symptomatic because calcium can worsen calcium-phosphate precipitation.

Symptomatic hypocalcemia examples

Tetany, Trousseau sign, or Chvostek sign.

Myelodysplastic syndrome (MDS)

Clonal stem-cell disorder causing dysplasia, ineffective hematopoiesis, and peripheral cytopenias.

MDS vs MPN

MDS = ineffective blood production with cytopenias; MPN = effective overproduction with elevated blood counts.

Typical MDS patient

Older adult, often >70 years.

MDS marrow

Usually normocellular or hypercellular despite peripheral cytopenias.

Why MDS causes cytopenias

Cells are produced ineffectively and are morphologically abnormal.

MDS risk

MDS can progress to AML.

Blast count in MDS

Common MDS presentation

Fatigue, infections, and bleeding.

Common anemia pattern in MDS

Macrocytic anemia.

MDS diagnosis

Persistent cytopenia with morphologic dysplasia and/or defining cytogenetic/molecular abnormality.

MDS bone marrow biopsy

Hypercellular marrow with dysplasia in one or more lineages.

Prussian blue stain in MDS

May show ringed sideroblasts.

Lower-risk MDS treatment goal

Control cytopenias, reduce transfusions, and improve quality of life.

Higher-risk MDS treatment goal

Delay progression to AML and prolong survival.