inpatient / hematology and oncology

Acute Leukemia

Last Updated: 1/18/2023

# Acute Leukemia

-- ABCs: 
does the patient need to be intubated for either hypoxemia or AMS? is there evidence of sepsis or shock requiring ICU? get blood consent in case patient in DIC or anemic and needs product; if WBC >100k and concern for leukostasis the patient may beed emergent leukopheresis (will need a line for this)
-- Chart Check: prior leukemia workup, evidence of TLS or DIC
-- HPI Intake: ***
-- Can't Miss: APML, leukostasis, TLS, DIC, intracerebral hemorrhage (ICH)
-- Admission Orders: *** CBC with Diff, peripheral smear, T+S, uric acid, LDH, BMP, phos q8; coags fibrinoge, dimer q8; EKG, continuous telemetry, LFTs
-- Initial Treatment to Consider: fluids and allopurinol for TLS, product (mostly cryoprecipitate) for DIC/bleeding

-- History: ***
-- Clinical: *** weight loss, night sweats, fever, loss of appetite, lymphadenopathy, fatigue/weakness, dyspnea
-- Exam: *** fever, bleeding, lymphdenopathy, WOB, crackles, hypoxia, focal neuro deficits, evidence of DVT, bruising, petechiae, leukemia cutis
-- Data: *** WBC, Hgb, Plt, creatinine
-- Etiology/DDx: *** AML, CML

The patient's HPI is notable for ***. Exam showed ***. Labwork and data were notable for ***. Taken together, the patient's presentation is most concerning for ***, with a differential including ***.

-- f/u CBC with diff, peripheral blood smear, viscosity studies, SPEP, SFLC
-- Leukemia workup - flow cytometry, cytogenetics, molecular testing for new dx
-- f/u TLS labs q6-8 (Uric Acid, LDH, BMP, Phos)
-- f/u DIC labs q6-8 (Coags, fibrinogen, D-dimer, T+S)
-- f/u EKG; Continuous telemetry
-- Additional Screening labs - LFTs, UA, bHCG, HBV, HCV, HIV, CMV IgG; G6PD quantitative
-- if fevering, send infectious workup
-- CT chest without contrast for all patients
-- TTE (will need for baseline before induction chemo with anthracycline)
-- Consider CT Head and LP if severe CNS symptoms
-- Consider sperm-banking for young men prior to chemo
-- consult oral medicine if poor dentition to prevent abscess as source of future neutropenic fever

-- IVF: *** often 125-200cc/hr for TLS ppx, but do not overload
-- O2: currently ***, continuous pulse ox with goal >92%
-- Abx: *** cefepime if neutropenic fever, with addition of vancomycin for severe sepsis
-- Transfuse: Hgb > 8 Plt > 10 (50 if bleeding) fibrinogen >150; careful if c/f leukostasis as may make worse
-- Ppx: *** allopurinol 300mg daily (TLS), omeprazole (GI), VZV, peridex mouthwash; acyclovir and fluconazole if on 7+3
-- induction chemo per cancer type and patient's age/functional status
-- hydroxyurea 3g once vs leukapheresis if c/f leukostasis with WBC >100K
-- consider rasburicase if AKI or uric acid >8 or rapidly rising (do not need to wait for G6PD testing if active TLS, but watch for hemolysis)

AML Treatment

Day 1 - Induction

AML - Intensive Induction Candidate
-- 7+3 - 7 days of continuous cytarabine, 3 days of daunorubicin
-- FLT3 - add midostaurin
-- CD33 positive - add gemtuzumab
-- t-AML/MDS - liposomal cytarabine/daunorubicin (Vyxeos)

AML - greater than 75 years old or co-morbidities preclude intensive induction
-- Venotoclax and azacitadine


Day 14 and 28 - Bone Marrow Biopsy

Favorable risk - HiDAC - high dose cytarabine (Ara-C)
-- Unfavorable Risk - Allo HSCT vs Clinical Trial

FLT3 - gilteritinib
-- IDH-1 - ivosidenib
-- IDH-2 - enasidenib

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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.

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