I
. ACUTE LEUKEMIA Present with manifestations of CYTOPENIAS
Anemia: Fatigue and Dyspnea
Thrombocytopenia: Cutaneous or Mucosal Hemorrhages
Neutropenia: Fever and Infection
Leukemic Infiltration of organs: Lymphadenopathies, Splenomegaly (common in ALL), Gingival Hyperplasia and Skin Nodules (common in AML)
A. Acute Myeloid Leukemia (AML) o 80% of adult Acute Leukemia
o Characterized by predominance of Blasts (Myeloblasts and Early Promyelocyte) in the BM and PBS o Etiology: Hereditary, radiation, chemical and other occupational exposures, drugs
o Classifications: WHO Classification + FAB Classification (see harrisons) 1. Clinical Presentation
Non-Specific Symptoms that begin gradually or abruptly and are the consequence of Anemia, Leuokcytosis, Leukopenia, or Leukocyte Dysfunction, or Thrombocytopenia
Fatigue, weakness, anorexia, weight loss, fever, abnormal hemostasis, bone pain, lymphadenopathy, nonspecific cough, headache, or diaphoresis
2. On Physical Examination
Fever, Splenomegaly, Hepatomegaly, Lymphadenopathy, Sternal Tenderness, evidence of Infection &
Hemorrhage 3. Hematologic Findings
Anemia (can be severe) – Normocytic Normochromic
Decreased Erythropoiesis often results in a Reduced Reticulocyte Count
Decreased RBC survival by accelerated destruction
Active Blood Loss
Median Presenting Leukocyte Count is ~15,000u/L
Auer Rods: if present, the Myeloid Lineage is virtually certain
Platelet Counts < 100,000/uL
Elevation of Serum Uric Acid (50%) 4. Treatment: Induction + Postremission Management
Goal: to quickly induce Complete Remission (CR)
Once CR is obtained, further therapy must be used to prolong survival and achieve cure B. Acute Lymphoblastic Leukemia
o Characterized by predominance of Lymphoblasts o Occurs most often in children
o Form of Acute Leukemia that is MOST Responsive to Therapy o Common in children – ALL is NOT a common Leukemia in Adults o ALL cell origin is in the Lymphoid Line
o Most Common ALL Variant (75%) = B-Cell Lineage
II. CHRONIC LEUKEMIA
Characterized by Proliferation of Lymphoid or Hematopoietic Cells that are more mature than those of Acute Leukemia
Have a longer, less devastating Clinical Course than acute leukemia A. Chronic Lymphocytic Leukemia (CLL)
o Proliferation of neoplastic lymphoid cells (almost always B-Cells) with widespread infiltrations of BM, PBS, Lymph Node, Spleen and Liver
o Incapable of producing into Antibody-Producing Plasma Cells o Often occurs in persons > 60 y/o
o Presence of Smudge Cells in PBS
o Leukemic Cells resemble Normal Mature, Peripheral Blood Lymphocytes
o Increased Number of MATURE Lymphocytes (CD-5 B-Cells 95%) in Peripheral Blood & Bone Marrow o Males > Females
1. Complications:
Warm Antibody Autoimmune Hemolytic Anemia (AIHA)
Hypoagammaglobulinemia and Increased Susceptibility to Bacterial Infection 2. Clinical Features
Indolent Clinical Course
Generalized Lymphadenopathy and Moderate Hepatosplenomegaly
Asymptomatic or +/- Lymphadenopathy
Pallor, Signs of Bleeding, Infections 3. Treatment of Chronic Lymphocytic Leukemia
Indications for Treatment: Hemolytic Anemia, Important Cytopenias, Disfiguring Lymphadenopathy, Symptomatic Organomegalies, Marked Systemic Symptoms
Treatment / Management:
Chlorambucil + Prednisone
COP or CHOP
Mainstay of Treatment = Fludarabine +/- Chemotherapeutic Agents
HSCT (for younger patients)
IVIG B. Chronic Myeloid Leukemia (CML)
o Neoplastic Clonal Proliferation of Myeloid Stem Cells
o Characterized by reciprocal chromosomal translocation between chromosomes 1 and 2 – Philadelphia Chromosome
o Marked Leukocytosis (50,000 to 200,000)
o Reduction in Leukocyte Alkaline Phosphatase activity in the Leukemic Leukocytes o Clinical Features:
Prominent Splenomegaly
Modestly Enlarged Liver and Lymph Nodes
Terminates in Accelerated Phase (BLASTIC CRISIS) with Increasing number of Blast Cells and Promyelocyteso Diagnosis is established by identifying a Clonal Expansion of a Hematopoietic Stem Cell possessing a reciprocal translocation between Chromosomes 9 and 22
o Untreated, the disease is characterized by the inevitable transition from a Chronic Phase to an Accelerated Phase and on to Blast Crisis in a Median Time of 4 years
1. Clinical Presentation
Clinical Onset of the Chronic Phase is generally insidious
Fatigue, malaise, and weight loss, splenic enlargement (early satiety, left upper quadrant mass) 2. Physical Examination
Minimal to Moderate Splenomegaly = Most Common
Mild Hepatomegaly
3. Laboratory Hematologic Findings
Elevated WBC, with increases in both immature and mature granulocytes
Platelet Counts are almost always elevated at diagnosis
Mild Normocytic Normochromic Anemia
Bone Marrow Cellularity is Increased (at diagnosis) – Increased Myeloid to Erythroid Ratio
Disease Acceleration: defined by development of increasing degrees of anemia unaccounted for by the bleeding or therapy; cytogenetic clonal evolution; or blood marrow blasts between 10-20%, blood or marrow basophils >20%, or platelet count < 100,000/uL
Blast Crisis: defined as Acute Leukemia, with Blood or Marrow Blasts > 20%
**NOTE: Cytogenic Hallmark of CML (90-95%) = t(9;22)(q34;q11.2)
Originally, this was recognized by the presence of a shortened chromosome 22 (22q-), designated as the Philadelphia Chromosome
4. Treatment
Goal of Tx: To achieve prolonged, durable, nonneoplastic, nonclonal hematopoiesis, which entails the eradication of any residual cells containing the BCR/ABL Transcript
Hence, goal is complete molecular remission and cureIII. LYMPHOMAS
Incidence: Males > Females (3:2)
Etiology: Viral (EBV), Chemicals (Benzene Herbicides), Hereditary, Immunodeficiency A. Signs / Symptoms
o Painless Enlarged Lymphadenopathy
o With or Without Fever, Night Sweats, Weight Loss B. Hodgkin’s VS Non-Hodgkin’s Lymphoma:
HODGKIN’S LYMPHOMA NON-HODGKIN’S LYMPHOMA
Spread Orderly Spread by Contiguity Random, Hematogenous Spread
Extranodal Site Involvement RARE In UNFAVORABLE Types
Systemic Symptoms Of Prognostic Importance Less Common
Involvement Axial and Central Lymph Nodes Peripheral, Mesenteric Lymph Nodes Blood; Waldermyer’s Ring
Cure POSSIBLE for All Types RARE in Low Grade Tumors
C. Diagnosis
o Lymph Node or Extra-Nodal Mass BIOPSY o FNAB – (+) Limitations (very painful)
o Histopathology = (+) REEDSTERNBERG CELL in Hodgkin’s Lymphoma o Immunohistochemistry
D. Differential Diagnosis
o Reactive Lymph Node Hyperplasia (as in INFECTIONS) o Undifferentiated Carcinoma
E. Prognosis
o Hodgkin’s Lymphoma is BETTER than Non-Hodgkin’s Lymphoma
o International Prognostic Index (IPI) for Non-Hodgkin’s Lymphoma (FIVE Clinical Factors):
Age 60 or Above
Serum LDH Levels ELEVATED
Performance Status
Ann-Arbor Stage III or IV
Extranodal Site Involvement If Blasts > 20% Blastic Crisis
10-20% Accelerated Phase
< 10% Chronic Phase Hydroxyurea
o Given as management – action of Leukocytes Rupture