inpatient / hematology and oncology

Acute Leukemia

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If You Remember Nothing Else

Acute leukemia is an emergency requiring admission, and often ICU level care. You cannot miss APML, DIC, TLS, hemorrhage, or leukostasis. While all acute leukemias can be fatal, APML is unique in its proclivity to cause a bleeding subtype of DIC which can lead to fatal hemorrhage in the brain or lungs. Despite this, APML is potentially curable and patients who survive the initial encounter and induction will often have excellent outcomes with ATRA treatment. Such patients are often treated before a formal diagnosis is made if there is a clinical suspicion. A peripheral smear can also be diagnostic and is one of the most important things to send upon presentation.

In all cases of acute leukemia, watch for and manage DIC (coags, fibrinogen, dimer; give product), TLS (uric acid, LDH, BMP, phos; give fluids, allopurinol, sometimes rasburicase), leukostasis (symptoms and WBC >100k; leukopheresis and/or hyroxyurea), and neutropenic fever (ANC <500; cefepime with our without GPC coverage). In APML, watch for differentiation syndrome (presents like sepsis and/or overload; hold treatment and give steroids).

Induction chemo is dependent on the exact leukemia subtype. Once a patient is stabilized, additional studies and imaging are performed prior to initiating chemotherapy to get a baseline and further risk-stratify. Patients with acute leukemia will often be in the hospital for their induction chemotherapy for at least a month or so while they have count recovery, and are at risk of infections and often need blood products during this time.
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Clinical Pearls

• You need >20% blasts on bone marrow bx fora formal diagnosis of leukemia, but it can also be presumed based on a peripheral blast count
• APML has a median survival of 1 week if not treated (usually from hemorrhage into brain or lungs 2/2 DIC), but is curable, often presents in younger AML patients (20-50 yo), and accounts for about 5-20% of AML cases; it will take a few days for the confirmatory testing to come back, so you should look for auer rods on peripheral smear as a key quick diagnostic tip-off
• APML highest risk for DIC due to the presence of tissue factor on the surface of the promyelocytes AND Annexin II which activates tPA causing hyperfibtinolysis which causes the bleeding subtype of DIC - it's as though we treated the patient with tPA
• There is an excellent prognosis with the treatment of All-Trans Retinoic Acid (ATRA) since it holds a t(15;17) translocation which keeps the cells from differentiating - ATRA turns the blast cells into mature myeloid cells
• ATRA has low risk of toxicity (vitamin A derivative, so it is teratogenic) so many patients will be treated if they might have APML before diagnosis is confirmed since it can be rapidly life-threatening
• ICH is the most common cause of morbidity/mortality in DIC - get head imaging for any new neurological symptoms
• Differentiation Syndrome is possibly a life-threatening complication in ~25% of patients treated with ATRA therapy - watch for rapidly rising white count, SIRS, hypoxemia, pulm and peripheral edema, AKI (possibly from leukostasis); treat by holding ATRA and with high-dose steroids (dexamethasone 10mg q12); there is debate over value of prophylactic steroids, but in those who do give them, its usually pred 0.5mg/kg daily until induction therapy is complete
• Sweet Syndrome is neutrophil infiltration into the skin which can cause characteristic lesions - can be complication of differentiation syndrome due to the massive production of neutrophils
• Arsenic trioxide (ASO) is also used to treat APML - its main risk factors are arrythmia and torsades de pointes, so make sure K >4 and Mg >2; monitor QT twice weekly; can also cause pseudotumor cerebri, more commonly in younger patients - watch for headaches and vision changes
• AML is a rare cause of cancer/leukemia, is mostly a disease of the elderly, outcomes are age dependent, it is heterogeneous based on genetics of the tumor cells which also determine treatment and inform outcomes
• Induction chemo for AML is 7+3 - cytarabine infusion for 7 days with ida/daunorubicin on days 1-3; other targeted agents can be added to induction based on cytogenetics; the 7+3 regimen was first tested in a clinical trial in 1981 - we've been doing it for a long time; induction mortality in 30-60 days is ~5-10%
• Leukostasis leads to tissue hypoxia due to immature leukocytes causing microvascular obstruction
• Hyerleukocytosis will often lead to spurious hyperkalemia and low arterial PO2
• Plasma hyperviscosity is caused by elevated immunoglobulins; whole blood hyperviscosity is caused by extreme elevations in RBC and WBC count
• Plasmapheresis reduces viscosity by 20-30% per session, and is only useful for symptomatic patients; it does not affect the underlying disease process 
• Hydroxyurea reduces WBC count (cytoreduction)
• RBC and Plt transfusions can increase viscosity and should be used judiciously
• Waldenstrom Macroglobulinemia (IgM) commonly causes hyperviscosity

Trials and Literature

• AML Intensive Therapy (NEJM, 2009)
• AML non-intensive (azacitidine + venetoclax) (NEJM, 2020)
• ALL - Modern Therapy Regimens (JCO, 2011)
• ALL In Elderly with Philadelphia Chromosome - Dasatinib + Blinatumomab (NEJM 2020)
• Review of Differentiation Syndrome
• Review of Management of Hyperviscosity Syndrome

Other Resources

• Internet Book of Critical Care (IBCC) - APL
• DIC Template
• TLS Template
• Neutropenic Fever Template
• Transfusion Medicine and Reaction Template