4. Classification
• Myeloid versus lymphoid
• Acute versus chronic
Acute Chronic
Rapid onset of symptoms Slower onset of symptoms (or no
symptoms)
Involves blasts in bone marrow
Malignant cells are not blasts
(more mature)
5.
6.
7. among adults in western world, and the most common leukemia that occurs after age 50.
8.
9. • A type of B-cell lymphoma with the same genetic and
molecular markers as CLL that manifests primarily in
the lymph nodes, bone marrow, and other lymphatic
tissue rather than with leukocytosis
SMALL LYMPHOCYTIC LYMPHOMA (SLL)
10.
11. Risk factors
• Older age
• Environmental factors: organic solvents
• Family history
ETIOLOGY
12. • Acquired mutations in hematopoietic stem cells →
increased proliferation of leukemic B cells with impaired
maturation and differentiation in the bone marrow.
• morphologically mature but functionally defective (i.e., they
do not differentiate into antibody-manufacturing plasma
cells).
This will result in:
• Suppression of the proliferation of normal blood cells
• Immunosuppression
• Hypogammaglobulinemia
• Granulocytopenia
• Thrombocytopenia
• Anemia
• Infiltration of the lymph nodes, liver, and spleen
PATHOPHYSIOLOGY
13. COMPLICATIONS
o Occurrence: ∼ 5% of cases
o Diagnostic indicators:
Rapidly progressive lymphadenopathy → lymph node biopsy required
New onset of B symptoms
↑ LDH
o Treatment: similar to symptomatic CLL and advanced stages
4. Hyperviscosity syndrome
14. 1. Usually asymptomatic at time of diagnosis
may be discovered secondary to
abnormalities on routine labs
2. Painless lymphadenopathy (usually cervical)
3. Hepatosplenomegaly
4. Frequent respiratory or skin infections--due
to immune deficiency
5. In more advanced disease: fatigue, weight
loss, pallor, skin rashes, easy bruising, bone
CLINICAL FEATURES
15. •Laboratory studies
• Diagnostic criteria
oPersistent (≥ 3 months) lymphocytosis (≥ 5000 cells/mm3)
oCLL immunophenotype confirmed by flow cytometry, including:
Expression of CD5, CD19, CD20, CD23
Light chain restriction (kappa or lambda)
• Additional findings: may further support the diagnosis
oCytopenias
Anemia: may be caused by AIHA
Thrombocytopenia
Granulocytopenia
oPeripheral blood smear may show:
• High percentage of small mature lymphocytes
• Smudge cells (Gumprecht shadows): mature lymphocytes that rupture
easily; appear as artifacts on a blood smear
DIAGNOSIS
16. •Biopsies:
•Bone marrow aspiration
and biopsy
•Not routinely required for
diagnosis
•Consider in patients with
cytopenias to determine
the cause.
•Typical findings in aspirate
include a high percentage
DIAGNOSIS
18. •Indications for anticancer therapy: based
on disease risk (Rai staging) and disease
activity
•Low-risk disease (Rai stage 0)
•Expectant management
•Intermediate risk disease (Rai stage I or
II)
•Consider expectant management if stable
and asymptomatic.
•Medical therapy: indicated for progressive or
symptomatic disease (i.e., active disease)
TREATMENT
19. •Anticancer therapy may include:
•Targeted therapy, e.g., ibrutinib, rituximab,
alemtuzumab
•Chemoimmunotherapy, e.g., FCR:
fludarabine, cyclophosphamide, rituximab
•Allogeneic HSCT: currently the only curative
treatment option (not routinely performed)
TREATMENT
20. •Prognostic factors
•Older age is associated with a poor overall
survival rate.
•Rai staging
•Adverse prognostic markers in CLL, e.g.:
•Del(17p13)
•Elevated β2-microglobulin level
•Blood lymphocyte doubling time: Rapid doubling
is associated with a high risk of disease
PROGNOSIS
33. CHRONIC
PHASE
• Can persist for up to 10 years and is often subclinical
• When symptomatic, features include:
• Weight loss, fever, night sweats, fatigue
• Splenomegaly: abdominal discomfort in the left upper quadrant
• Lymphadenopathy is not typical in CML.
ACCELERATED
PHASE
•Erythrocytopenia: anemia
•Neutropenia: infection and fever
•Extreme pleocytosis
•Infarctions: splenic and myocardial infarctions, retinal vessel occlusion
•Leukemic priapism
•Terminal phase: myelofibrosis
•Extreme splenomegaly : palpable in lower left quadrant or pelvic cavity
BLASR CRISIS
•The blast crisis is the terminal stage of CML.
•Symptoms resemble those of acute leukemia.
•Rapid progression of bone marrow failure → pancytopenia, bone pain
•Severe malaise
•Subtypes :
•Myeloid blast crisis → AML (⅔ of cases)
•Lymphoid blast crisis → ALL (⅓ of cases)
34. Splenic rupture due to splenomegaly
The photo shows a spleen that has been
removed from a patient with CML. The
disease led to splenomegaly, which
eventually caused the spleen to rupture and
break into two parts.
35. 1. Leukocytosis with eosinophilia-WBCs from 50,000 to 200,000
2. Thrombocytosis
3. Peripheral blood smear-reveals increased numbers of immature
granulocytes, anemia, thrombocytosis, and basophilia
4. Bone marrow biopsy-increased numbers of immature granulocytes
DIAGNOSIS
36. 1. Treatment for CML is one of the great stories of modern
medicine. After the mechanism of disease was elucidated, the oral
tyrosine kinase inhibitor (TKI) imatinib was developed. This
drug targets the dysfunctional chimeric protein BCR-ABL formed
by the t(9;22) Philadelphia chromosome. Second-generation TKIs
are now available.
2. Unfortunately, patients who present in blast crisis still have very
poor outcomes. The TKIs can still be attempted in these patients.
Stem cell transplantation is also an option.
TREATMENT
37. • Survival rate without treatment:
o Chronic phase: 3.5–5 years
o Blast phase: 3–6 months
• In most patients, life expectancy can be markedly improved
through targeted therapy with imatinib. In some cases, it even
results in molecular remission
PROGNOSIS
