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Acute Lymphoblastic Leukemia: Symptoms, Diagnosis and Treatment

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  • Oncology
  • 2020-09-13 02:33:58

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Acute lymphoblastic leukemia is a malignant (clonal) proliferation of early lymphoid precursors in the bone marrow with the replacement of the normal hematopoietic cells of the marrow.

For better understanding, we shall need to have an overview of what is leukemia and the classification of leukemia.

Overview of leukemia

Leukemia is a neoplastic (malignant) clonal proliferation of the hematopoietic cell lines in the bone marrow with release into circulation of abnormal cells.

It may involve any of the cell lines or a stem cell common to several cell lines.


1. Classification can be based on clinical presentation as:

a.Acute Leukemia-

It has rapid onset and progression and without treatment death in few months 2-3 months.
Acute leukemia have arrested maturation of the hemopoietic cells with a predominance of blast cells (poorly differentiated) in circulation.

b.Chronic leukemia-

It has an insidious onset and slow-progressing and less aggressive .without treatment death occur in months to years.
Mature cells and some blasts in the circulation-maturation spectrum of cells.

2. Classification can also be based on cell types

Both acute and chronic leukemias are further classified according to the prominent cell line involved in the expansion:
If the prominent cell line is of the myeloid series it is myelocytic leukemia (sometimes also called granulocytic)
If the prominent cell line is of the lymphoid series it is a lymphocytic leukemia

Therefore, there are four basic types of leukemia

  1. Acute myelocytic leukemia – AML- (includes myeloblastic, promyelocytic, monocytic, myelomonocytic, erythrocytic, and megakaryocytic)
  2. Acute lymphocytic leukemia – ALL- (includes T cell, B cell, and Null cell)
  3. Chronic myelocytic leukemia – CML - (includes myelocytic and myelomonocytic)
  4. Chronic lymphocytic leukemia-CLL - (includes plasmacytic {multiple myeloma}, Hairy cell, prolymphocytic, large granular cell lymphocytic, Sezary’s syndrome, and circulating lymphoma)

Causes of Leukemia

The exact cause is frequently not known, but predisposing factors are known:

Host factors

Some individuals have an inherited increased predisposition to develop leukemia
There is an increased incidence in those with an inherited tendency for chromosome fragility or abnormality or those with increased numbers of chromosomes (such as Down’s syndrome). Many of these diseases are characterized by chromosomal translocations.

There is an increased incidence in those with hereditary immunodeficiencies.

There is an increased incidence in those with chronic marrow dysfunction such as those with myeloproliferative diseases, myelodysplastic syndromes, aplastic anemia, or paroxysmal nocturnal hemoglobinuria.

Environmental factors:

Exposure to ionizing radiation
Exposure to mutagenic chemicals and drugs
Viral infections

In this article, we are going to discuss one type of leukemia known as Acute lymphoblastic leukemia

Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia is a malignant (clonal) proliferation of early lymphoid precursors in the bone marrow with the replacement of the normal hematopoietic cells of the marrow.

In other words, it is a result of a cancerous transformation of a stem cell leading to unregulated proliferation and arrest in maturation at the primitive blast stage.

Remember that a blast is the most immature cell that can be recognized as committed to a particular cell line


The malignant cells of ALL are lymphoid precursor cells (ie, lymphoblast) that are arrested in an early stage of development.

This arrest is caused by an abnormal expression of genes, often as a result of chromosomal translocations.

The lymphoblasts replace the normal marrow elements, resulting in a marked decrease in the production of normal blood cells. Consequently, anemia, thrombocytopenia, and neutropenia occur to varying degrees.

The lymphoblasts also proliferate in organs other than the marrow, particularly the liver, spleen, and lymph nodes.


ALL is the most common type of leukemia in children. In adults, it is less common than acute myelogenous leukemia (AML)

Only 20-40% of adults with ALL are cured with current regimens.
ALL in pediatrics is more responsive.
ALL is slightly more common in men than in women.
ALL is more common in children(2-5 years) than in adults

Signs and symptoms of acute lymphoblastic leukemia:

Physical examination

Patients commonly have physical signs of anemia, including pallor and a cardiac flow murmur.

Fever and other signs of infection, including lung findings of pneumonia, can occur.

Thrombocytopenia usually demonstrates petechiae, particularly on the lower extremities.
A large number of ecchymoses is usually an indicator of a coexistent coagulation disorder such as DIC.

Signs relating to organ infiltration with leukemia cells include hepatosplenomegaly and, to a lesser degree, lymphadenopathy.

Occasionally, patients have rashes resulting from infiltration of the skin with leukemic cells.


Patients with ALL present with either with;
(1) Symptoms relating to direct infiltration of the marrow or other organs by leukemia cells or
(2) Symptoms relating to the decreased production of normal marrow elements.

Infiltration of the marrow by massive numbers of leukemia cells frequently manifests as bone pain.
This pain can be severe and is often atypical in distribution.

Uncommonly (10-20%), patients may present with left upper quadrant fullness and early satiety due to splenomegaly.

Other patients, particularly those with T-cell ALL, present with symptoms related to a large mediastinal mass, such as shortness of breath.

Symptoms of leukostasis (eg, respiratory distress, altered mental status) because of the presence of large numbers of lymphoblasts in the peripheral circulation, leukostasis is much less common in persons with

ALL compared to AML and occurs only in patients with the highest WBC counts, ie, several hundred thousand per microliter.

Symptoms of anemia are common and include fatigue, dizziness, palpitations, and dyspnea upon even mild exertion.
Patients with ALL often have decreased neutrophil counts, despite an increased total WBC count have increased risk of infection.

Patients with ALL often have a fever without any other evidence of infection.

However, in these patients, one must assume that all fevers are from infections until proven otherwise because a failure to treat infections promptly and aggressively can be fatal. Infections are still the most common cause of death in patients undergoing treatment for ALL

Bleeding symptoms due to thrombocytopenia. The thrombocytopenia, however, tends to be less severe than that observed in patients with AML

Some may have (DIC) at the time of diagnosis, usually as a result of sepsis. Consequently, some patients may present with hemorrhagic or thrombotic complications.
Signs relating to leukostasis include respiratory distress and altered mental status

Diagnostic Procedure

Bone marrow aspiration and biopsy are the definitive diagnostic tests to confirm the diagnosis of leukemia.

Laboratory tests.

The lab diagnosis is based on two things

1.Finding a significant increase in the number of immature cells in the bone marrow including blasts, promyelocytes, promonocytes (>30% blasts is diagnostic)

2.Identification of the cell lineage of the leukemic cells

Cytochemistry help to classify the lineage of a leukemic cell. ALL is negative to myeloperoxidase.

Sudan black stains phospholipids, neutral fats and sterols found in primary and secondary granules of granulocytic cells and to a lesser extent in monocytic lysosomes. Rare positives occur in lymphoid cells, but in most cases ALL is negative.

Terminal deoxynucleotidyl transferase is a unique DNA polymerase present in stem cells and in precursor B and T lymphoid cells. High levels are found in 90% of lymphoblastic leukemias. It can also be detected using appropriate antibodies and flow cytometry.

Positive TdT-  and PAS (Periodic Acid Schiff) is the hallmark of ALL.
TdT also helps distinguish ALL from malignancies of more mature lymphocytes (ie, NHL).

Immunologic markers (immunophenotyping) are used mainly for lymphocytes, i.e., for determining B cell or T cell lineage. These tests rely on antibodies made against specific surface markers. (Fluorescent Antibody Tagging)

Flow cytometer that will determine the number of cells that have a fluorescent tag and which are thus positive for the presence of t



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