Acute vs. Chronic Leukemia: Comparison

Comparison of Acute and Chronic Leukemias

• Acute leukemias (AML & ALL) have a sudden, rapid onset, while chronic leukemias (CML & CLL) have a slow, insidious progression
• Acute leukemias present with immature cells (blasts), whereas chronic leukemias have more mature appearing cells
• Bone marrow involvement is characterized by rapid marrow failure in acute leukemias and gradual marrow infiltration in chronic leukemias
• Acute myelogenous leukemia (AML) primarily affects adults, acute lymphocytic leukemia (ALL) affects children, chronic lymphocytic leukemia (CLL) affects the elderly, and chronic myelogenous leukemia (CML) affects middle-aged adults

Acute Myelogenous Leukemia (AML)

• AML most commonly affects adults around 65 years old, with risk factors including prior chemotherapy or radiation, benzene exposure, and pre-existing myelodysplastic syndromes
• AML pathophysiology involves clonal proliferation of myeloblasts in the bone marrow, impaired differentiation leading to accumulation of immature myeloid cells, and crowding out of normal hematopoiesis, resulting in pancytopenia
• Key diagnostic features of AML include Auer rods (needle-like inclusions) on peripheral smear, bone marrow with more than 20% blasts, and cytogenetic abnormalities such as t(15;17) in the APL subtype
• Clinical manifestations of AML include fatigue (anemia), infections (neutropenia), bleeding/bruising (thrombocytopenia), and leukostasis, which can cause stroke-like symptoms and respiratory distress due to WBC clumps

Acute Lymphoblastic Leukemia (ALL)

• ALL is the most common pediatric leukemia, peaking between 2–5 years, with increased risk associated with Down syndrome and exposure to environmental toxins or radiation
• Pathophysiology of ALL involves malignant transformation of lymphoid progenitor cells (mostly B cells), bone marrow failure due to blast overproduction, and common CNS infiltration
• Key diagnostic features for ALL include lymphoblasts on blood smear, more than 20% lymphoblasts on bone marrow biopsy, and positive Tdt+ (marker of immature lymphoid cells) on flow cytometry
• Clinical manifestations of ALL include bone pain, hepatosplenomegaly, CNS symptoms like seizures and headaches, and general anemia, infection, or bleeding symptoms

Chronic Myelogenous Leukemia (CML)

• CML typically affects adults aged 40–60 and is strongly associated with the Philadelphia chromosome (t(9;22), BCR-ABL fusion gene), and can also be secondary to radiation exposure
• CML pathophysiology involves BCR-ABL tyrosine kinase leading to uncontrolled proliferation of mature granulocytes and phases include chronic (indolent), accelerated (increasing blasts), and blast crisis (resembles acute leukemia)
• Key diagnostic features of CML include increased neutrophils, basophils, and eosinophils on peripheral smear, low leukocyte alkaline phosphatase (LAP), and detection of BCR-ABL via PCR or FISH
• Clinical manifestations of CML include massive splenomegaly, fatigue, weight loss, early satiety, and symptoms of hypermetabolism (sweats, weight loss)

Chronic Lymphocytic Leukemia (CLL)

• CLL is the most common leukemia in older adults, around 70 years, with a genetic predisposition involved in familial cases
• Pathophysiology of CLL involves monoclonal proliferation of functionally incompetent B cells, and impaired apoptosis leads to accumulation in blood, marrow, and lymphoid tissue
• Key diagnostic features of CLL include smudge cells on peripheral smear and CD5+, CD23+ B cells on flow cytometry, in addition to hypogammaglobulinemia
• Clinical manifestations of CLL often include asymptomatic presentation initially, painless lymphadenopathy, recurrent infections due to decreased immunoglobulins, and autoimmune hemolytic anemia or thrombocytopenia

Leukemias Compared

• AML typically affects adults, ALL affects children (2-5 years), CML affects middle-aged adults (40-60 years), and CLL affects the elderly (≥70 years)
• AML involves myeloblasts, ALL involves lymphoblasts, CML involves mature granulocytes, and CLL involves mature B-lymphocytes
• Genetic markers include t(15;17) APL subtype in AML, Tdt+ cells in ALL, Philadelphia chromosome (t9;22) in CML, and CD5+/CD23+ B cells in CLL
• Unique features of each leukemia include Auer rods and leukostasis in AML, CNS involvement in ALL, basophilia and splenomegaly in CML, and smudge cells and hypogammaglobulinemia in CLL
• AML and ALL have a rapid course, while CML progresses slowly, and CLL is often indolent and may not require treatment
• Treatment strategies include chemotherapy and bone marrow transplant (BMT) for AML, chemotherapy and CNS prophylaxis for ALL, tyrosine kinase inhibitors (TKIs) like Imatinib for CML, and observation or BTK inhibitors for CLL