Acute Leukemias

Leukemia = white blood

Acute leukemias are a medical emergency that require fast clinical & hematological remission or else they may be fatal

Pathogenesis:  a single leukemic cell proliferates & causes an imbalance between differentiation & proliferation resulting in a “crowding out” of the bone marrow

  • Immature cells are known as “blast cells”

Risk factors for acute lymphocytic leukemia (ALL):

  • Most common childhood cancer (peaks around age 2-3), more common in males, higher incidence in Hispanics, whites > blacks, higher socioeconomic status, developed countries
  • The younger the patient, the better the survival (adults with ALL have a poorer prognosis)
  • Risk factors of Acute Leukemia
    • Genetic Disorders:  examples–Down’s Syndrome, Kleinfelter’s syndrome
    • Environmental factors:  examples–Radiation, benzene, herbicides, pesticides
    • Chemotherapy agents:  examples–Alkylating agents (nitrogen mustards–cyclophosphamide, etc;  nitrosoureas–carmustine, etc;  alkyl sulfonates–Busulfan, etc;  Platinum agents–cisplatin, etc;  procarbazine), epidophyllotoxins (etoposide, etc)
    • Recreational Drug Use:  examples–maternal smoking, alcohol use, marijuana use
    • Severely immunodeficient
    • Exposure to various viruses:  examples–Epstein-Barr, Human T Lymphocyte viruses 1 & 2

ALL prognostic risk factors: > 50,000 WBCs is high risk, chromosomal abnormalities also increase risk, being a male, having a disease of the CNS or testes, having Down’s syndrome, if the time of response to induction therapy > 4 weeks
Acute myelogenous leukemia (AML) is the most common acute leukemia in adults (older the patient, the more likely they are to get this)

  • Patients with AML will present with class B-symptoms
  • Prognostic factors: older aged ppl have less remission, CNS involvement & secondary leukemias are associated with poorer outcomes, cytogenetic abnormalities

Signs and symptoms on presentation for acute leukemia.

  • Symptoms are non-specific, may have class B symptoms (fever, night sweats, weight loss), fatigue, bruising, bleeding
  • Clinical presentation:
    • Myelosuppression: may result in anemia (fatigue, weakness, pallor), thrombocytopenia (bleeding in HI, skin, gums, urine), leukopenia related infections
    • Organ involvement: bone pain, HA, mediastinal mass, hepatomegaly, splenomegaly
  • Confirm diagnosis with a bone marrow biopsy
    • Leukemia = 30% of marrow is blasts (hypercellular)
      • Normal< 5% blasts
  • ALL
    • Goal is to achieve complete remission & eradicate the disease
    • Treatment depends on the risk of the patient (higher the risk gets more intensive therapy)
    • Remission induction (4 weeks)
      • Goal is to induce a complete clinical & hematological remission (complete remission doesn’t equal cure though)
        • No evidence of leukemia in the CNS, skin or organs
        • Absence of leukemic blasts in the peripheral blood
        • Less than 5% blasts in bone marrow & evidence of normal hematopoiesis
      • Regimen of remission induction of ALL:  IV vincristine + dexamethasone + L-asparaginase (pegaspargase)
        • If pt is high risk add daunorubicin or doxorubicin
        • The rate of clearance of blasts is important (majority of kids w/ ALL achieve complete remission within a month)
        • Managing SE:  IV antibiotics, blood products (RBCs, plasma, platelets), managing SE of tumor lysis syndrome
        • Give CNS prophylaxis to eradicate undetectable leukemia in the CNS
          • Intrathecal cytarabine, intrathecal HCT, & intrathecal methotrexate
          • Could also do a cranial irradiation or a high dose of IV methotrexate or cytarabine
      • Induction therapy is very important for ALL
    • intensifaction/consolidation (4 weeks)
      • The goal is to further eradicate residual disease & maintain remission after complete remission has been attained
      • Drugs include vincristine, mercaptopurine & intrathecal methotrexate (may add cyclophosphamide, cytarabine or pegaspargase for high risk patients)
    • delayed intensification/interim maintenance (3-9 months)
      • Goal is to maintain remission & decrease cumulative toxicity
        • Shown to prolong long-term survival in pediatric patients
      • Delayed intensification:  various regimens
      • Interim maintenance:  vincristine, dexamethasone, mercaptopurine, methotrexate
    •  maintenance (3 years)
      • Patient’s relapse after consolidation due to residual disease so the goal of maintenance therapy is further eradicate residual leukemic cells & prolong remission duration
      • Treatment:  mercaptopurine given PO daily + methotrexate given PO/IM weekly + pulses of vincristine & a steroid every month + intrathecal meds every 3 months (CNS prophylaxis)
        • Take mercaptopurine & methotrexate in the evening & don’t take mercaptopurine with dairy products
    • ALL relapse:  occurs in the bone marrow (need to do a peripheral stem cell transplant), treatment depends on how long after chemo they relapse, LT survival is poor
  • AML
    • Immediate treatment is required, including intensive high dose therapy for infections, neutropenia & bleeding
    • Remission induction (~1-2 years)
      • Goal is rapidly induce complete remission (65-85% of patients achieve this, but the older the patient, the worse the outcomes)
      • 7 + 3:  7 days of continuous infusion cytarabine + 3 days of idarubicin
        • Most pts achieve complete remission within 1-2 cycles, but this therapy may cause prolonged neutropenia
    • Consolidation (2-4 months)
      • Used b/c most patients will relapse within 4-8 months without further treatment (goal is to eradicate residual cells & prevent drug-resistant disease)
      • Usually use high dose cytarabine (for 3-4 cycles depending on risk factors)
        • SE:  conjuctivitis, cerebral toxicity
    • Bone marrow transplant
      • Use if poor prognostic factors & in younger pts
  • Expected outcomes, treatment and risk factors.
    • ALL
      • (Adult) Cure rate = 70-90%
      • (Adult) Disease free state = 30-40%
    • AML classification is known as FAB
      • 9 subclasses but basically just know subclass M3 = acute promelocytic leukemia (APL)
        • Most curable of AML subtypes
          • Use All-trans retinoic acid (ATRA) which forces differentiation
            • Has a delayed response (1-2 months)
            • Differentiation syndrome: fever, weight gain, fluid retention, respiratory distress
            • May also add arsenic trioxide or idarubicin or daunorubicin or cytarabine
            • Need to also provide supportive care for tumor lysis syndrome, renal function (increased toxicity of cytarabine), fungal infections, growth factors
    • Patients with AML have a much lower survival rate than patients with ALL.  Also older patients with AML have worse outcomes

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