NOTES

NOTES
LEUKEMIAS

GENERALLY, WHAT ARE THEY?

Neoplastic infiltration
PATHOLOGY & CAUSES ▪ Bone marrow
▫ Bone pain
▪ Malignant neoplastic monoclonal
proliferation of hematopoietic blood cells ▪ Thymus
▪ Abnormal blood cells/precursors ▫ Palpable mass, airway compression
accumulate in bone marrow → physical ▪ Liver and spleen
suppression → prevent maturation ▫ Hepatosplenomegaly
▪ Lymph nodes
TYPES ▫ Lymphadenopathy
▪ Meningeal infiltration
Acute
▫ Headaches, vomiting, nerve palsies,
▪ Acute lymphoid leukemia nuchal rigidity
▪ Acute myeloid leukemia

Chronic DIAGNOSIS
▪ Chronic lymphoid leukemia
▪ Chronic myeloid leukemia LAB RESULTS
▪ Blood count
RISK FACTORS ▪ Blood smear
▪ Numerical, structural chromosomal ▪ Bone marrow smear
aberrations ▪ Immunophenotyping
▪ Ionizing radiation, chemotherapy
▪ Benzene exposure
TREATMENT
COMPLICATIONS MEDICATIONS
▪ Infections, bleeding → death ▪ Chemotherapy

SIGNS & SYMPTOMS SURGERY

▪ Bone marrow transplantation
Cellular maturation absent
▪ Anemia → fatigue, shortness of breath, OTHER INTERVENTIONS
pallor ▪ Radiation therapy
▪ Thrombocytopenia → bruising, petechiae,
epistaxis
▪ Neutropenia → bacterial infections → fever,
pneumonia, sepsis

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ACUTE LYMPHOID LEUKEMIA (ALL)

osms.it/acute-lymphoid
▪ Neutropenia → bacterial infections → fever,
PATHOLOGY & CAUSES pneumonia, sepsis

▪ Neoplastic monoclonal proliferation of Neoplastic infiltration

lymphoid stem cells (lymphoblasts) in bone ▪ Bone marrow
marrow ▫ Bone pain
▪ Immature lymphoblasts accumulate in bone ▪ Thymus
marrow → physical suppression → prevent
▫ Palpable mass, airway compression
maturation
▪ Liver and spleen
▫ Hepatosplenomegaly
TYPES
▪ Lymph nodes
B cell acute lymphoblastic leukemia ▫ Lymphadenopathy
(B-ALL) ▪ Meningeal infiltration
▪ Most common (85%) ▫ Headaches, vomiting, nerve palsies,
▪ Origin nuchal rigidity
▫ Pre-B cells of bone marrow
▪ Associated with translocations t(12,21),
t(9,22) DIAGNOSIS
T cell acute lymphoblastic leukemia LAB RESULTS
(T-ALL)
Blood count, smear of peripheral blood
▪ Origin
▪ ↑ lymphoblasts
▫ Pre-T cells in thymus
▪ ↑ white blood cells
▪ Associated with NOTCH1 mutation
Bone marrow smear
RISK FACTORS ▪ Hypercellular bone marrow, lymphoblast
▪ Young age (most common leukemia in domination (> 20%)
children) ▪ T-ALL
▫ B-ALL: peak incidence at three years old ▫ “Starry sky” pattern produced by
▫ T-ALL: peak incidence at 15–20 years phagocytosing macrophages
old ▪ Mitotic figures
▪ Down syndrome (after age five)
Immunophenotyping
▪ Radiation exposure
▪ Terminal deoxynucleotidyl transferase (TdT)
▫ Positive nuclear staining, distinguish
SIGNS & SYMPTOMS from acute myeloid leukemia (AML)
▪ B-ALL
▪ Abrupt onset ▫ Express tumor markers CD10, CD19,
CD20
Cellular maturation absent
▪ T-ALL
▪ Anemia → fatigue, shortness of breath,
▫ Express tumor markers CD1, CD2, CD5,
pallor
CD7, CDH
▪ Thrombocytopenia → bruising, petechiae,
epistaxis

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 TREATMENT
MEDICATIONS
▪ Aggressive chemotherapy with
prophylactic injections to scrotum,
cerebrospinal fluid (CSF)
▫ 95% complete remission, 75% cure rate
▫ More successful in children > two years
old
▪ If spread to brain
▫ Intrathecal chemotherapy/radiation
therapy
▪ Tyrosine-kinase inhibitors

MNEMONIC: ABCDE
Figure 48.1 A bone marrow film from an
Characteristics of Acute
individual with acute lymphoid leukemia.
leukemias
Acute:
Blasts predominate
Children
Drastic course
Elderly
Few WBC’s (+ Fevers)

ACUTE MYELOID LEUKEMIA (AML)

osms.it/acute-myeloid
Acute megakaryocytic leukemia
PATHOLOGY & CAUSES
▪ Neoplastic monoclonal proliferation of RISK FACTORS
myelogenous stem cells (myeloblasts) in ▪ Adults age; peak at 60
bone marrow ▪ Radiation, chemotherapy
▪ Immature myeloblasts accumulate in ▪ Myeloproliferative disorders
bone marrow → physical suppression → ▪ Down syndrome (before age five)
prevents maturation

COMPLICATIONS
TYPES ▪ Disseminated intravascular coagulation
Acute promyelocytic leukemia (DIC)
▪ Associated with translocation t(15,17)
→ disruption of retinoic acid receptor → SIGNS & SYMPTOMS
promyelocytes accumulate

Acute monocytic leukemia ▪ Abrupt onset

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Cellular maturation absent SURGERY

▪ Anemia → fatigue, shortness of breath, ▪ Bone marrow transplantation
pallor
▪ Thrombocytopenia → bruising, petechiae,
epistaxis
▪ Neutropenia → bacterial infections → fever,
pneumonia, sepsis

Neoplastic infiltration
▪ Symptoms less common in AML than ALL
▪ Bone marrow
▫ Bone pain
▪ Thymus
▫ Palpable mass, airway compression
▪ Liver and spleen
▫ Hepatosplenomegaly
▪ Lymph nodes
▫ Lymphadenopathy
▪ Meningeal infiltration
▫ Headaches, vomiting, nerve palsies, Figure 48.2 The histological appearance of a
nuchal rigidity myeloid sarcoma, also known as a chloroma.
The tumor is an extramedullary manifestation
Neoplastic infiltration
of acute myeloid leukemia.
▪ Symptoms more common in AML than ALL
▪ Skin
▫ Leukemia cutis
▪ Gums
▫ Swelling (classic)

DIAGNOSIS
LAB RESULTS
Blood count, blood smear
▪ ↑ leukocytes, anemia

Bone marrow smear

▪ ↑ myeloblasts > 20%
▪ Myeloblasts containing Auer rods
(aggregates of myeloperoxidase)

Figure 48.3 A CT scan of the head in the

TREATMENT axial plane demonstrating a myeloid sarcoma,
or chloroma, of the occiput. The tumor is
MEDICATIONS extradural and destroying the overlying bone.
▪ Chemotherapy
▪ All-trans retinoic acid treatment
▫ For promyelocytic leukemia

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 MNEMONIC: ABCDE
Characteristics of Acute
leukemias
Acute:
Blasts predominate
Children
Drastic course
Elderly
Few WBC’s (+ Fevers)

CHRONIC LYMPHOID LEUKEMIA

(CLL)
osms.it/chronic-lymphoid

PATHOLOGY & CAUSES SIGNS & SYMPTOMS

▪ Neoplastic monoclonal proliferation ▪ Late onset
of mature, functionally abnormal B
lymphocytes in bone marrow, blood Cellular maturation absent
▪ Mature B lymphocytes accumulate in bone ▪ Anemia → fatigue, shortness of breath,
marrow → physical suppression → prevent pallor
maturation ▪ Thrombocytopenia → bruising, petechiae,
epistaxis
▪ Neutropenia → bacterial infections → fever,
CAUSES pneumonia, sepsis
▪ Chromosomal abnormalities
▪ Mutation of proteins involved in tyrosine Neoplastic infiltration
kinase pathway (e.g. Bruton’s tyrosine ▪ Symptoms less common in AML than ALL
kinase) ▪ Bone marrow
▫ Bone pain
RISK FACTORS ▪ Thymus
▪ Adult age; most common leukemia in adults ▫ Palpable mass, airway compression
▪ Family history ▪ Liver and spleen
▪ Agent Orange exposure ▫ Hepatosplenomegaly
▪ Lymph nodes
COMPLICATIONS ▫ Lymphadenopathy
▪ Abnormal Ig secretion ▪ Meningeal infiltration
▫ Hypogammaglobulinemia, autoimmunity ▫ Headaches, vomiting, nerve palsies,
(e.g. autoimmune hemolytic anemia) nuchal rigidity
▪ Richter syndrome
▫ Progresses into aggressive lymphoma
(e.g diffuse large B cell lymphoma)

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DIAGNOSIS
LAB RESULTS
Blood count, blood smear
▪ Lymphocytosis > 5,000 per mm3
▪ Smudge cells: disruption of fragile cell
membranes of abnormal lymphocytes

Immunophenotyping
▪ CD5, CD20, CD23

OTHER DIAGNOSTICS
Surgery
▪ Lymph node biopsy
▫ ↑ small, round lymphocytes infiltration
▫ Proliferation centers (pathognomic)
Figure 48.4 The gross pathological
appearance of the spleen in a case of chronic
TREATMENT lymphoid leukemia. The lymph nodes at the
hilum of the spleen are also involved.
MEDICATIONS
▪ Chemotherapy
▪ Immunotherapy

SURGERY
▪ Bone marrow transplant

OTHER INTERVENTIONS
▪ Radiation therapy

Figure 48.5 The histological appearance

of chronic lymphocytic leukemia. There
is a proliferation centre (also known as a
pseudofollicle) composed of malignant
lymphocytes with bigger, larger nuclei. This
proliferation centre is surrounded by small,
darker staining lymphocytes.

Figure 48.6 A CT scan in the coronal

plane demonstrating splenomegaly as a
consequence of chronic lymphoid leukemia.

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 CHRONIC MYELOID LEUKEMIA
(CML)
osms.it/chronic-myeloid
▪ Increasing anemia, thrombocytopenia,
PATHOLOGY & CAUSES basophilia
▪ Bone pain, fever
▪ Neoplastic monoclonal proliferation of
▪ Significant splenomegaly
mature granulocytes/precursors
▪ Mature granulocytes accumulate in bone
marrow → physical suppression → prevent DIAGNOSIS
maturation
▪ Associated with Philadelphia chromosome LAB RESULTS
t(9, 22) → BCR-ABL1 fusion → chimeric
protein with strong tyrosine kinase activity Blood count, blood smear
(> 90% of individuals) ▪ ↑ granulocytes (basophils, eosinophils,
neutrophils)
RISK FACTORS Bone marrow biopsy
▪ Adult age (> 40 years), radiation exposure,
▪ Hypercellularity (cells of myeloid cell line/
benzene exposure
precursors)
▪ Karyotypic analysis
SIGNS & SYMPTOMS ▫ Fluorescent in situ hybridization (FISH),
PCR: BCR-ABL1 gene mapping
▪ Classified by clinical signs, lab results ▪ Mild fibrosis

Chronic phase (85% at time of diagnosis)

▪ Leukocytosis (predominantly neutrophils)
▪ Asymptomatic/non-specific symptoms
▫ Fatigue, weight loss, loss of energy,
fever

Accelerated phase
▪ > 20% basophils in blood/bone marrow
▪ 10–19% myeloblasts in blood/bone marrow
▪ Anemia
▪ Splenomegaly, hepatomegaly,
lymphadenopathy
▪ Recurrent infections Figure 48.7 A bone marrow smear
▪ Bleeding, petechiae, ecchymoses demonstrating a small, hypolobated
▪ Treatment less effective megakaryocyte, typical of chronic
myelogenous leukemia.
Blast crisis
▪ Terminal phase; rapid progression, low
survival rate
▪ > 20% myeloblasts/lymphoblasts in blood/
bone marrow

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TREATMENT
MEDICATIONS
▪ Tyrosine kinase inhibitors

SURGERY
▪ Bone marrow transplantation

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