I. Epidemiology

  1. Incidence
    1. Annual Incidence: 13 per 100,000 people per year
    2. Lifetime Incidence: 1 in 70 people
  2. Higher Incidence in men
  3. Age distribution
    1. All Ages
      1. Acute Myelogenous Leukemia (AML)
    2. Young
      1. Acute Lymphocytic Leukemia (ALL)
    3. Elderly
      1. Chronic Lymphocytic Leukemia
      2. Hairy Cell Leukemia

III. Pathophysiology

  1. Malignant neoplasm of hematopoietic origin
  2. Origins
    1. Myeloid (Bone Marrow)
    2. Lymphoid
  3. Acute (Proliferating cell fails to mature past blast)
    1. AML: Immature clonal myeloid Cells (Myeloblast)
    2. ALL: Immature clonal lymphoid Cells (Lymphoblast)

IV. Risk Factors

  1. Idiopathic
  2. Demographics and habitus
    1. White
    2. Male
    3. Obesity
  3. Human T-Cell Leukemia Virus (HTLV-1)
  4. History of Hematologic Malignancy
  5. Congenital syndrome (risk of childhood ALL, AML)
    1. Down's Syndrome
    2. Neurofibromatosis
    3. Bloom's Syndrome
    4. Klinefelter's Syndrome
    5. Fanconi's Syndrome
    6. Wiskott-Aldrich Syndrome
  6. Environmental Factors
    1. Ionizing Radiation exposure (risk of CML, AML, ALL)
      1. Atomic bomb survivors
      2. Medical radiation workers prior to 1950
      3. Medical radiation patients
    2. Chemical exposure (risk of AML)
      1. Aromatic hydrocarbons (e.g. Benzene)
        1. Manufacturing of paints, plastics
        2. Petroleum or coal combustion
      2. Alkylating Agents
      3. Chemotherapeutic drugs

V. Labs: Initial

  1. Complete Blood Count
    1. Acute Leukemia
      1. Leukocytosis or Leukopenia
      2. Anemia
      3. Thrombocytopenia
    2. Chronic Leukemias
      1. Leukocytosis >20,000/mm3 in most cases (often >100,000/mm3)
  2. Other initial lab tests
    1. Coagulation studies
      1. ProTime (INR)
      2. Partial Thromboplastin Time (PTT)
    2. Comprehensive metabolic panel
      1. Serum electrolytes
      2. Renal Function tests including Serum Creatinine
      3. Liver Function Tests
  3. Patient febrile or otherwise ill appearing
    1. Urinalysis
    2. Urine Culture
    3. Blood Culture
    4. Chest XRay

VI. Labs: Diagnosis

  1. Studies
    1. Peripheral Blood Smear
    2. Bone Marrow Biopsy
  2. Acute Leukemia findings
    1. Blast cell predominance
    2. Auer rods on Peripheral Smear (AML, not often found)
    3. Immunophenotyping (flow cytometry, cytogenetic testing) distinguishes between AML and ALL
  3. Chronic Lymphocytic Leukemia findings
    1. Significant increase of normal appearing Lymphocytes (>50% of cells)
    2. Peripheral blood for clonal expansion of B Lymphocytes >5000/mm3
    3. Bone Marrow Biopsy is not needed for diagnosis (but defines extent of marrow involvement related to prognosis)
  4. Chronic Myelogenous Leukemia
    1. Peripheral Smear with few blast cells and increased Basophils and Eosinophils
    2. Philadelphia chromosome (BCR-ABL1 fusion gene) on peripheral blood or Bone Marrow testing

VII. Evaluation

  1. Step 0: Leukocytosis (White Blood Cell count >11,000/mm3)
    1. Confirmed with a second Complete Blood Count with differential
    2. No other obvious cause for Leukocytosis (e.g. infection, Corticosteroids)
  2. Step 1: Consider secondary causes based on white cell count differential
    1. Monocyte predominance (monocytosis)
      1. Consider chronic infection (e.g. Tuberculosis, parasitic infectikon)
      2. Consider connective tissue disease (e.g. Sarcoidosis, Inflammatory Bowel Disease)
    2. Eosinophil predominance (Eosinophilia)
      1. Consider allergic condition (e.g. Allergic Rhinitis, atopy, Asthma)
      2. Consider parasite infection
      3. Consider collagen vascular dsisease (e.g. Rheumatoid Arthritis, Systemic Lupus Erythematosus, Sarcoidosis, Addison's Disease)
      4. Consider medication causes (e.g. Methotrexate, Sulfonamides, Nitrofurantoin)
    3. Neutrophil predominance (Neutrophilia)
      1. Consider infection or inflammation
      2. Consider medication causes (e.g. Corticosteroids, Lithium, beta agonists)
      3. Consider aspenia or Splenic Sequestration
    4. Lymphocyte predominance (Lymphocytosis)
      1. Consider infections (e.g. EBV, CMV, Pertussis, Tuberculosis)
      2. Consider Asplenia or Splenic Sequestration
    5. Basophil predominance (Basophilia, rare)
      1. Consider Asplenia
      2. Consider Hypothyroidism
      3. Consider chronic inflammation (e.g. Inflammatory Bowel Disease, Chronic Sinusitis, Asthma)
  3. Step 2: Indications to proceed with Peripheral Smear
    1. Leukocytosis without other secondary cause (or despite treatment)
    2. White Blood Cell count >20,000/mm3
    3. Associated Anemia, Thrombocytopenia or Thrombocytosis
    4. Hepatomegaly, Splenomegaly or Lymphadenopathy
    5. Unexplained constitutional symptoms (e.g. fever, Fatigue or weight loss)
  4. Step 3: Based on Peripheral Smear interpretation
    1. Findings suggestive of benign cause
      1. Increased normal appearing Neutrophils
        1. Evaluate for causes of Neutrophil predominance (see above)
      2. Increased normal appearing Lymphocytes
        1. Evaluate for causes of Lymphocyte predominance (see above)
      3. Atypical lymphocytes
        1. Consider EBV, CMV or HIV
    2. Findings suggestive of Leukemia
      1. Increased blast cells
        1. Possible Acute Leukemia
        2. Test preipheral blood or Bone Marrow for immunophenotyping
      2. Few blast cells and increased Basophils and Eosinophils
        1. Possible Chronic Myelogenous Leukemia
        2. Test peripheral blood or Bone Marrow for Philadelphia chromosome testing
      3. Significant increase of normal appearing Lymphocytes (>50% of cells)
        1. Possible Chronic Lymphocytic Leukemia
        2. Test peripheral blood for clonal expansion of B Lymphocytes >5000/mm3

VIII. Management

  1. Hematology-Oncology Referral
  2. Treatment complications
    1. Neutropenic Fever
    2. Tumor Lysis Syndrome
  3. Post-cancer management
    1. See specific Leukemia
    2. See Cancer Survivor Care

Images: Related links to external sites (from Google)

Ontology: Other specified leukemia (disorder) (C0029812)

Concepts Neoplastic Process (T191)
ICD9 207, 207.8
ICD10 C94.7 , C94.80, C94.8
SnomedCT 190161003, 188751002, 188761009
English Other specified leukemia, Other specified leukaemia, Other specified leukaemia NOS, Other specified leukaemias, Other specified leukemia NOS, Other specified leukemias, [X]Other specified leukaemias, [X]Other specified leukemias, Other specified leukemia (disorder), [X]Other specified leukemias (disorder), Other specified leukemia NOS (disorder), Other specified leukemias NOS
Dutch andere gespecificeerde leukemieën, andere gespecificeerde leukemie, Overige gespecificeerde vormen van leukemie
French Autre leucémies précisées, Autre leucémie précisée
German sonstige spezifische Leukaemie, sonstige spezifische Leukaemien, Sonstige naeher bezeichnete Leukaemien
Italian Altre leucemie specifiche, Altra leucemia specificata
Portuguese Outra leucemia especificada, Outras leucemias especificadas
Spanish Otras leucemias especificadas, Otra leucemia especificada, [X]otras leucemias especificadas (trastorno), [X]otras leucemias especificadas, otra leucemia especificada (trastorno), otra leucemia especificada, SAI (trastorno), otra leucemia especificada, SAI, otra leucemia especificada
Japanese その他の明示された白血病, ソノタノメイジサレタハッケツビョウ
Czech Jiná blíže určená leukemie, Jiné blíže určená leukemie
Korean 기타 명시된 백혈병
Hungarian Egyéb meghatározott leukemia, Egyéb meghatározott leukaemia, Egyéb meghatározott leukemiák