Is a bone marrow biopsy necessary for all types of leukemia?

Bone Marrow Biopsy in Leukemia Diagnosis

Bone marrow biopsy is not necessary for all types of leukemia, as the requirement depends on the specific leukemia subtype, clinical presentation, and availability of diagnostic information from peripheral blood samples.

Requirements by Leukemia Type

Acute Leukemia (ALL, AML)

• Bone marrow examination is imperative for the final diagnosis of acute leukemia 1
• Bone marrow aspirate, touch imprint, cell clots, and core biopsy are recommended for morphologic examination 1
• However, if peripheral blood shows sufficient blasts, many diagnostic tests can be performed on peripheral blood specimens:
  • Manual differential count
  • Flow cytometry
  • Fluorescent in situ hybridization (FISH)
  • Next-generation sequencing (NGS) 1

Chronic Lymphocytic Leukemia (CLL)

• Bone marrow biopsy is not needed for diagnosis of CLL 1
• Diagnosis can be established through:
  • Sustained increase of peripheral blood lymphocytes ≥ 5 × 10^9 cells/L
  • Predominance of small, morphologically mature lymphocytes in blood smear
  • Characteristic immunophenotype (CD5+, CD19+, CD20+ low, CD23+, sIg low, CD79b low, FMC7–) 1
• Bone marrow biopsy is recommended only before initiating therapy to evaluate unclear cytopenia 1

Chronic Myeloid Leukemia (CML)

• Bone marrow core biopsy remains valuable in approximately 25% of CML patients 2
• It is particularly important for:
  • Establishing disease phase (chronic, accelerated, or blast phase)
  • Identifying myelofibrosis, which is associated with disease stage and outcome 2
  • Cases where aspirate smears are inadequate or misleading 2
• Bone marrow biopsy is especially indicated for patients with accelerated or blast phase disease 2

Special Considerations

When Peripheral Blood Is Diagnostic

• Additional flow cytometry on bone marrow aspirate is unnecessary when flow study has been performed on peripheral blood and is diagnostic 1
• Peripheral blood can be used for diagnosis if:
  • Bone marrow materials are inadequate
  • Bone marrow biopsy is contraindicated
  • Patient refuses bone marrow biopsy 1

When Bone Marrow Biopsy Is Essential

• When peripheral blood and bone marrow aspirate are not available or inadequate ("dry tap") 1, 3
• In hypoplastic acute myeloid leukemia 3
• For accurate assessment of:
  • Marrow cellularity
  • Pattern and extent of blast cell infiltration
  • Residual hematopoietic activity
  • Presence of myelofibrosis 2, 3

Pitfalls and Caveats

• Relying solely on peripheral blood analysis may miss bone marrow involvement in some cases
• Flow cytometric assessment of CD34+ cells is not recommended as a substitute for visual inspection of bone marrow 1
• In CML, follow-up bone marrow evaluations more often yield inadequate aspirates in patients who had inadequate aspirates at initial diagnosis 2
• In some lymphomas with leukemic presentation, bone marrow biopsy may be safely omitted in selected early-stage cases 1, 4

In summary, while bone marrow examination remains a cornerstone of leukemia diagnosis, the necessity for bone marrow biopsy varies by leukemia type, with CLL notably not requiring it for initial diagnosis, while acute leukemias and CML often benefit from the procedure, especially when peripheral blood analysis is insufficient or disease staging is critical.