Acute Basophilic Leukemia - Causes, Symptoms, Diagnosis and Treatment

What Is Leukemia?

Leukemia refers to the cancer of blood cells and associated blood-forming tissues. The most common types of leukemia are cancers involving white blood cells. There are various types of leukemia based on the type of affected white cells (myeloid cells or lymphoid cells). Also based on the rate of progression, leukemias are classified into acute (fast-growing) and chronic (slow-growing), and whether it starts in myeloid cells or lymphoid cells. The clinical symptoms, diagnostic tests, and treatment strategies differ depending on the type of leukemia acquired.

What Is Acute Basophilic Leukemia?

Basophils are a type of mature white blood cells that belong to the subtype of granulocytes. These granulocytes develop from the myeloblasts (a specific type of blood-forming cells present in the bone marrow). basophils have distinct granules that contain inflammatory mediators and enzymes to destroy foreign substances such as parasites, allergens, etc. they are predominantly activated as an inflammatory response during allergic reactions.

Acute basophilic leukemia (ABL) is a rare subtype of acute myeloid leukemia (AML) or acute granulocytic leukemia. Its clinical manifestations resemble severe basophilia (increased number of basophils) or hyper histaminemia (elevated levels of histamine in the blood). Patients generally exhibit bone marrow failure. The cancerous blast cells (myeloblasts) invade and infiltrate throughout the bone marrow leading to rapid progression. In 2008, WHO (world health organization) considered acute basophilic leukemia as a discrete, rare entity and placed it under ‘acute myeloid leukemia not otherwise specified’.

What Causes Acute Basophilic Leukemia?

The exact cause for the occurrence of acute basophilic leukemia is not well defined. Clinical studies suggest that its primary cause could be de novo or as mutational abnormalities due to chemotherapy or radiation (secondary causes). Some of the reported causes are as follows -

• De novo origin - the first cancer of its type whose cause of occurrence is not identified. Primarily it occurs due to unknown genetic changes.

• Mutagenic (defects in gene) stimulation secondary to chemotherapy that is given to treat other carcinomas.

• Radiation therapy.

• Prolonged immunosuppressive therapy.

• Frequent exposure to cytotoxic agents.

What Are the Signs and Symptoms of Acute Basophilic Leukemia?

The signs and symptoms of acute basophilic leukemia of primary patients (who develop ABL without prior cancer history) often show clinical features of severe allergic or hypersensitivity reactions (similar to basophilia). Whereas patients with already existing cancerous conditions show mixed clinical symptoms which should not be misinterpreted during a general clinical examination. Some of the common clinical manifestations of acute basophilic leukemia are as follows -

• Abdominal pain.

• Generalized tiredness and weakness.

• Cutaneous involvement.

• Pruritis.

• Urticarial rash.

• Elevated levels of histamine levels lead to osteolytic lesions in the bone.

• Severe bone pain and increased risk of fractures.

• Gastroesophageal disturbances such as dyspepsia and nausea.

• Vomiting.

• Diarrhea.

• Abdominal swelling.

• Ulcers.

• Organomegaly (enlargement of the liver or spleen).

• Pallor with clubbing (enlargement of nails).

• Ascites.

• Symptoms of bone marrow failure such as anemia or decreased immunity.

How Is Acute Basophilic Leukemia Diagnosed?

Acute basophilic leukemia (ABL) is a rare type of leukemia that does develop from tumor outgrowths. It originates from the bone marrow and spreads to other parts rapidly. Hence staging or grading ABL is not possible. Also, its diagnosis is crucial because it should be differentiated from other commonly occurring leukemias such as acute myeloid leukemia. Detailed clinical examination and specific laboratory investigations along with imaging techniques help in the confirmatory diagnosis of acute basophilic leukemia. The commonly employed diagnostic procedures are as follows -

Clinical Examination

• Signs of anemia such as marked pallor (grade III) with clubbing in fingernails and toes.

• Tense ascites which often show positive fluid thrill and shifting dullness.

• Decreased bone density and weak bones.

• Enlargement of liver and spleen detected.

Laboratory Tests

• Complete blood count (CBC) helps in detecting increased basophils and conditions associated with bone marrow failure (cytopenias).

• Reactive increase in the total number of basophils.

• Microscopic examination of peripheral blood smear and bone marrow aspirate.

• In acute basophilic leukemia, basophilic blast cells (myeloblasts from which basophils develop) are seen more in number than mature basophils in peripheral smear.

• In bone marrow aspirate these blast cells are more than 80 % of the normal range.

• The blast cells in ABL show an increased nucleocytoplasmic ratio (N:C) with irregular nucleus morphology.

• Basophilic differentiation is confirmed under light microscopy where blast cells show heterogeneous chromatin granules and very rough basophilic granules.

• Mature basophils are seen in low numbers.

• Ultrastructural analysis of blast cells is done as confirmatory tests.

• Cytochemistry analysis of basophilic granules stains positive in Toluidine blue staining methods.

• Immunophenotyping of myeloid markers like CD33, CD117, and CD31 shows positivity in leukemic blast cells whereas monocytic markers are negative.

• Genetic typing and molecular profile are usually done to rule out other known leukemias and in the differential diagnosis.

• In some cases, cytogenetic studies show that acute basophilic leukemia is often associated with the Philadelphia chromosome (an abnormality in chromosome 22 which results in leukemic changes).

Imaging Techniques

• Ultrasonography (USG) confirms hepatomegaly and splenomegaly.

• X-ray scans reveal weak areas in bones that occur due to reduced bone density.

How Is Acute Basophilic Leukemia Treated?

Clinical progression of acute basophilic leukemia is very rapid and usually shows a poor prognosis. Treatment of acute basophilic leukemia becomes challenging because ABL commonly occurs in patients already undergoing cancer therapies. Complications are more fatal in these groups than de novo type. Bone marrow failure resulting in abnormal hematopoiesis is the main cause of poor prognosis. Supportive care and symptomatic management are the standard treatment strategies followed in acute basophilic leukemia.

• Nucleic acid synthesis inhibitors such as Decitabine show improvement in ABL patients.

• Stem cell transplantation is advised in severe cytopenic conditions.

• Prophylactic therapy to reduce symptoms related to high histamine levels.

• Histamine receptor blockers, steroids, and proton pump inhibitors are also administered.

Conclusion

Acute basophilic leukemia is a rare type of leukemia associated with diverse clinical manifestations, rapid progression, and poor treatment outcomes. Bone marrow failure and increased histamine levels are the important distinctive features for confirmatory diagnosis of acute basophilic leukemia. Symptomatic management and supportive treatment interventions help in better outcomes of acute basophilic leukemia.