How do you diagnose leukemia in a patient with leukocytosis (elevated white blood cell count) and a white blood cell count of 35,000 cells per microliter (hyperleukocytosis)?

From the Guidelines

Leukemia diagnosis should be approached with a combination of clinical evaluation, blood tests, and bone marrow examination, with a bone marrow aspiration and biopsy being the gold standard for diagnosis, classification, and risk stratification. For a patient with a white blood cell count of 35,000/μL (35) and possibly 1,150 blasts, the first step is to perform a complete blood count with differential to confirm the leukocytosis and identify abnormal cells. A peripheral blood smear should be examined to assess for blast cells, abnormal cell morphology, and dysplastic changes.

Key Diagnostic Steps

• Perform a complete blood count with differential to confirm leukocytosis and identify abnormal cells
• Examine a peripheral blood smear to assess for blast cells, abnormal cell morphology, and dysplastic changes
• Conduct a bone marrow aspiration and biopsy with cytogenetic analysis, flow cytometry, and molecular studies to classify the type of leukemia and determine specific genetic mutations that guide treatment
• Consider additional tests, including comprehensive metabolic panel, coagulation studies, and HLA typing if stem cell transplantation might be considered

Importance of Bone Marrow Examination

The bone marrow examination is crucial for diagnosing and classifying leukemia, as it provides information on the blast count, cell morphology, and cytogenetic abnormalities, which are essential for determining the type of leukemia and guiding treatment decisions 1.

Classification and Risk Stratification

The classification of leukemia is based on the type of cells affected, with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) being the most common types. Risk stratification is also important, as it helps determine the prognosis and guide treatment decisions. The WHO classification defines acute leukemia as 20% blasts in the marrow or blood, with exceptions for certain types of AML, such as those with t(8;21), inv(16), or t(15;17) 1.

Molecular Studies and Cytogenetic Analysis

Molecular studies and cytogenetic analysis are essential for identifying specific genetic mutations and chromosomal abnormalities that can guide treatment decisions. For example, the presence of certain genetic mutations, such as FLT3 or MLL, can affect the prognosis and treatment of AML 1.

Clinical Evaluation and Management

Clinical evaluation and management of leukemia require a multidisciplinary approach, with consideration of the patient's age, performance status, and medical history. Treatment options may include chemotherapy, targeted therapy, or stem cell transplantation, and should be individualized based on the patient's specific needs and prognosis 1.

From the Research

Diagnostic Approach for Leukemia

To diagnose leukemia, a comprehensive approach is necessary, involving various diagnostic tests and procedures. Given the patient's elevated white blood cell (WBC) count of 35, plus 1150, the following steps can be considered:

• Bone Marrow Biopsy: This procedure involves extracting a sample of bone marrow tissue for examination. According to 2, bone marrow biopsy is not required at diagnosis but is recommended before initiating treatment for chronic lymphocytic leukemia (CLL). However, it can provide important information for diagnostic purposes and elucidating CLL pathobiology.
• Bone Marrow Aspirate: This involves extracting a sample of bone marrow fluid for examination. A study by 3 compared the merits of bone marrow aspirate and biopsy in assessing bone marrow infiltration in B-cell chronic lymphocytic leukemia (CLL) and found that bone marrow histological pattern (BMP) was a more reliable and reproducible prognostic factor than lymphocytic infiltration (LI) in bone marrow aspirate.
• Histopathological Examination: The examination of bone marrow biopsy samples can provide important information on the morphology and cellularity of the bone marrow, as well as the presence of leukemic cells. A study by 4 found that certain characteristics of bone marrow biopsy, such as mitotic activity and residual hematopoiesis, were associated with a favorable outcome in adult acute lymphoblastic leukemia (ALL).
• Interpretation of Bone Marrow Biopsy: The interpretation of bone marrow biopsy results should be done in conjunction with clinical history, complete blood count, and findings in the peripheral blood and bone marrow aspirate smears. A review by 5 highlights the importance of a multidisciplinary approach to diagnosing myeloid and lymphoreticular neoplasms, incorporating flow cytometric analysis, immunohistochemistry, and molecular diagnostic studies.

Key Considerations

When diagnosing leukemia, the following factors should be considered:

• Cellularity and Morphology: The cellularity and morphology of the bone marrow can provide important information on the presence and type of leukemia.
• Immunophenotyping: Immunophenotyping can help identify the specific type of leukemia and its characteristics.
• Cytogenetic Analysis: Cytogenetic analysis can help identify genetic abnormalities associated with leukemia.
• Clinical Correlation: The interpretation of diagnostic results should be done in correlation with clinical history and other diagnostic findings.