Leukemia is a multifaceted and complex blood cancer that affects large number of population worldwide. As a medical laboratory, science student to understand leukemia is not only important for academic, diagnosis purposes but also for raising awareness and contributing to the fight against this disease. This article will cover every feature of leukemia, including its types, causes, symptoms, diagnosis, treatment, and the latest advancements in research.

What is Leukemia?

Leukemia is a type of blood cancer, characterized by the proliferation of abnormal blood cells. This uncontrolled proliferation takes place in bone marrow, where most of body’s blood is grow. Leukemia cells are typically immature and abnormal white blood cells which crowd out healthy blood cells. The term leukemia comes from the Greek words for “white” (leukos) and “blood” (haima).

The History and Discovery of Leukemia

Leukemia’s early history dates back 200 years. A case of splenitis acutus with inexplicable milky blood was described by Peter Cullen in 1811. Alfred Velpeau noted pus in the blood arteries and described the symptoms of leukemia (1825). In 1844, Alfred Donné discovered that the white blood cells had stopped maturing.

Based on the microscopic buildup of purulent leucocytes, John Bennett gave the illness the term leucocythemia (1845). Rudolf Virchow described a reversed white and red blood cell equilibrium in the same year. In 1847, he first described the illness as leukämie. The first microscopic diagnosis of a leukemic patient was made by Henry Fuller in his lifetime (1846). Our current comprehension of this intricate illness is the result of this slow development.

Leukemia PPT / Lecture Slides

Classification of leukemias

Classification Based on Progression:

1. Acute (rapidly progressing, with immature blood cells)
2. Chronic (slow-growing, with more mature blood cells)

Classification Based on Cell Type:

1. Acute lymphoblastic leukemia (ALL)
2. Acute myelogenous leukemia (AML) (also “myeloid” or “nonlymphocytic”)
3. Chronic lymphocytic leukemia (CLL)
4. Chronic myeloid leukemia (CML)
   (Within these main categories, there are typically several subcategories)

• Any disease that arises from the myeloid elements (white cell, red cell, platelets) is a myeloid disease e.g AML, CML.
• Any disease that arises from the lymphoid elements is a lymphoid disease e.g ALL, CLL.

Acute vs. Chronic leukemia

	Acute	Chronic
Cell type	Young, immature, blast cells in the bone marrow (and often blood)	Accumulation of mature, differentiated cells in bone marrow and blood.
Presentation	More fulminant presentation Short history	Often subclinical or incidental presentation
Course	More aggressive course	In general, more indolent (slow) course
Extra medullary manifestations	Occasionally blast cells may form a tumor-like mass anywhere in the body termed “myeloid sarcoma”,”chloroma” or “granulocytic sarcoma”. This is especially true for AML.	Frequently splenomegaly
CBC	Predominance of blasts in blood WBC count is usually high due to blast cells (NOT mature WBCs) but occasionally it may be normal or low because BM can be tightly packed and cells are unable to pass into peripheral blood.	Leukocytosis with mature lymphocytosis à CLL Leukocytosis with mature neutrophilia à CML

Acute leukemia

What is Acute Leukemia?

Conditions with clonal development of precursor cells (myeloid or lymphoid) with reduced capacity to distinguish. There is maturation arrest at the blast stage and bone marrow infiltration by blast cells causing suppression of normal precursors (bone marrow failure). (> 20% blast cells in the bone marrow)

• Normal blast cell count in BM should be less than 5%.
• If blast count falls between 5-20% à Myelodysplastic syndromes (MDS), which is a group of pre-leukemic conditions usually presenting with refractory anemia and excess blast count.

Types of Acute Leukemia

• 1. Acute Myeloid Leukemia (AML)
• 2. Acute Lymphoblastic leukemia (ALL)

ALL effects >80% of children (<15 years) while AML is about four times more common than ALL in adults which effect more than 80% adults (>15 years). In children, the proportions are reversed, the lymphoblastic variety being more common.

Etiology of Acute Leukemia

• Mostly un-identifiable cause i.e., de nove (≥80%)
• Chemicals and Drugs: One of the side effect of chemotherapy is lead to secondary malignancy such as AML.
  • Alkylating agents (Chlorambucil, N mustard, Melphalan)
  • Topoisomerase inhibitors (Etoposide) Also called VP-16
  • Benzene
• Ionizing radiation. Best evidence of ionizing radiation that causes cancer is the atomic explosion in Japan.
• Myelodysplastic syndrome.
• Myeloproliferative disorders (CML, polycythemia vera, essential thrombocythemia, myelofibrosis)
• Genetic disorders: Characterized by DNA mutation and lack of repair mechanisms making them predisposed to  leukemia
  • Down’s syndrome
  • Bloom syndrome
  • Faconi anemia
  • Wiskott Aldrich syndrome

Clinical presentation of Acute Leukemia

Diagnosis of Acute Leukemia

• CBC:
  • Anemia (Hb%, RBCs Low)
• • Thrombocytopenia (Platelets decrease )
  • Low (acute)
• Coagulation Studies: Acute promyelocytic leukemia (M3) is associated with Disseminated intravascular coagulation
• Biochemical Studies (Renal function test (RFT), serum electrolytes, liver function test (LFT)).
• Peripheral Blood smear: shows blasts cells in almost all cases
• Bone Marrow Examination & Romanowsky stain:
  • Enumeration of blasts, maturing cells, recognition of dysplasia. >20% blasts à here you can establish the diagnosis of acute leukemia.
• Types of bone marrow biopsies:
  • 1. Aspirate, for cytology à useful for examination of cellular details.
  • 2. Tissue, for histology à most useful in cases of aplastic anemia or to see infiltration by tumor or fibrosis.
• Flow cytometry (Surface immunophenotype of blast cells):
  • Describes blast cell lineage commitment as myeloid, lymphoid or biphenotypic.
  • Immunophenotyping detects the presence or absence of white blood cell (WBC) antigens.
  • Most of the antigens that immunophenotyping detects are identified by a CD (clusters of differentiation or cluster designation) number, such as: CD1a, CD2, CD3, CD4, CD8, CD13, CD19, CD20, CD33, CD61, etc.
  • Flow cytometry is performed by processing blood or marrow samples and adding specific antibodies tagged with fluorescent markers. These antibodies attach to corresponding antigens on the WBCs when the antigens are present, and are analyzed.
  • Results are then graphed and compared to “normal” results and to patterns that are known to be associated with different leukemias
• Cytogenetics (chromosomal analysis) & molecular studies (FISH, PCR):
  • Detect clonal chromosomal abnormalities, including those of prognostic importance.
• CSF analysis: (all ALL patients, some AML).
• Cytochemistry: Myeloperoxidase, Sudan Black B, esterases to determine involved lineages Cytochemistry is becoming obsolete and is less used nowadays.

Differential diagnosis

1. Aplastic anemia.
2. Myelodysplastic syndromes (MDS).
3. Multiple myeloma. Plasma cell malignancy (B lymphocytes)
4. Lymphomas. Can infiltrate BM causing a drop in cell counts.
5. Severe megaloblastic anemia. May result in low cell counts however, BM biopsy will look normal, folic acid deficiency.
6. Leukemoid reaction. WBC count is about 50,000
7. If WBC count is > 100,000 = hyperleukocytosis, it raises the suspicion of leukemia.