Clinical Definition
Leukemia represents a heterogeneous group of malignant neoplasms arising from the hematopoietic stem cells within the bone marrow. It is characterized by the uncontrolled proliferation and accumulation of immature, dysfunctional leukocytes (blasts) or mature but abnormal white blood cells. This clonal expansion disrupts normal hematopoiesis, leading to the suppression of erythroid, myeloid, and megakaryocytic cell lines, clinically resulting in pancytopenia and organ infiltration.
Clinical Coding & Classification
| System / Category | Code(s) | Description |
|---|---|---|
| ICD-10-CM | C91.0 | Acute lymphoblastic leukemia (ALL) |
| ICD-10-CM | C92.0 | Acute myeloblastic leukemia (AML) |
| ICD-10-CM | C91.1 / C92.1 | Chronic lymphocytic leukemia (CLL) / Chronic myeloid leukemia (CML) |
| CPT (Diagnostic) | 38220 – 38222 | Diagnostic bone marrow aspiration and/or biopsy |
| CPT (Lab) | 88184 – 88189 | Flow cytometry, cell surface, cytoplasmic or nuclear marker |
Epidemiology & Statistics
Leukemia incidence exhibits a bimodal distribution. Acute Lymphoblastic Leukemia (ALL) is the most prevalent malignancy in pediatric populations, with a peak incidence between ages 2 and 5. Conversely, Acute Myeloid Leukemia (AML) and Chronic Lymphocytic Leukemia (CLL) are predominantly diseases of the elderly, with median ages of diagnosis in the late 60s to 70s. Overall, there is a slight male predominance across most subtypes. Environmental risk factors, including exposure to ionizing radiation and benzene, along with genetic syndromes (e.g., Trisomy 21), correlate with increased incidence.
Pathophysiology (Mechanism)
The pathogenesis involves somatic mutations or chromosomal translocations in hematopoietic progenitor cells that confer a survival and proliferative advantage. Key mechanisms include:
1. Differentiation Block: Mutations prevent blasts from maturing into functional cells, leading to an accumulation of immature precursors in the marrow.
2. Dysregulated Signaling: Aberrant activation of tyrosine kinases (e.g., BCR-ABL1 fusion gene in CML) drives constitutive cell growth.
3. Marrow Failure: The hypercellular marrow environment physically crowds out normal stem cells, causing the clinical triad of anemia (fatigue), neutropenia (infection), and thrombocytopenia (bleeding).
Standard Management Protocols
Therapeutic strategies are highly stratified by subtype (Myeloid vs. Lymphoid) and acuity (Acute vs. Chronic).
- Pharmacological Classes:
- Tyrosine Kinase Inhibitors (TKIs): (e.g., Imatinib, Dasatinib) Standard of care for CML and Ph+ ALL to target specific fusion proteins.
- Cytotoxic Chemotherapy: (e.g., Anthracyclines, Cytarabine) Used in induction regimens to achieve bone marrow aplasia and remission.
- Hypomethylating Agents: (e.g., Azacitidine) Used in myelodysplastic syndromes and elderly AML patients.
- Immunotherapy: (e.g., CAR-T Cell Therapy, Bi-specific T-cell engagers) Used for refractory/relapsed lymphoid leukemias.
- Surgical/Procedural Interventions:
- Hematopoietic Stem Cell Transplantation (HSCT): Allogeneic transplant remains the only curative option for many high-risk leukemias.
- Leukapheresis: Mechanical removal of white blood cells in cases of hyperleukocytosis with leukostasis.
Healthcare Resource Utilization
The economic burden of leukemia management is substantial due to:
- Inpatient Intensity: Induction chemotherapy often requires prolonged hospitalization (4-6 weeks) for monitoring of tumor lysis syndrome and management of neutropenic fevers.
- Transfusion Support: High reliance on blood products (packed red blood cells, platelets) during active treatment.
- Complex Diagnostics: Requirement for serial molecular monitoring (PCR, cytogenetics) to assess Minimal Residual Disease (MRD) status.
