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Acute Leukemia

Kenna Koehler

Background

  • AML: proliferation of myeloid blasts
    • Most common acute leukemia in adults
    • Median age of diagnosis is 65 years old
    • AML has been associated with environmental factors (e.g. exposure to chemicals, radiation, tobacco, chemotherapy) and genetic abnormalities (e.g. trisomy 21; Fanconi anemia; Bloom's syndrome; various familial mutations)
    • Pts with clonal hematopoiesis (MDS, myeloproliferative neoplasms, paroxysmal nocturnal hemoglobinuria, aplastic anemia) are at risk of transforming into AML
  • APML
  • ALL: proliferation of lymphoid blasts
    • ⅔ of cases are B-cell ALL
  • Blasts accumulate in the bone marrow, blood, and other tissues

Presentation

  • Various cytopenias: anemia, thrombocytopenia, leukopenia, neutropenia
    • Can have elevated, normal, or low WBC
  • Weakness, fatigue, infections, gingival bleeding, weight loss, ecchymosis, epistaxis, bone pain, fever, leukemia cutis
  • Electrolyte abnormalities (tumor lysis syndrome)
  • Extramedullary hematopoiesis: splenomegaly, hepatomegaly, lymphadenopathy

Evaluation

  • Diagnosis of acute leukemia requires one of the following
    • 20% blasts in the bone marrow
    • 20% blasts in the peripheral blood
    • Presence of specific cytogenetic abnormality: t(8;21), inv(16), or t(15;17)
  • Diagnosis of APML
    • Should suspect APML based on presence of atypical promyelocytes in bone marrow or peripheral blood (these cells typically have finely dispersed chromatin, prominent nucleoli, high nuclear to cytoplasmic ratio, and creased, folded, bilobed, kidney-shaped, or dumb-bell shaped nuclei) or the presence of Auer rods
    • Diagnosis is confirmed with presence of PML::RARA fusion gene and/or the associated chromosomal translocation t(15;17)(q24.1;q21.2)
  • DIC: PT/INR, PTT, fibrinogen
  • TLS: potassium, uric acid, phosphorous
  • Neutropenic fever
  • Leukostasis

Management

  • Consult Hematology early
  • Obtain blood consent and double lumen PICC for access
  • Telemetry,TTE
  • Daily labs: CBC w/ diff, CMP, coags
  • Monitor for TLS, DIC, neutropenic fever
  • TLS prophylaxis with allopurinol
  • If concerned for APML, start ATRA right away (can start this before definitive diagnosis)
  • Can use hematology order set for nurse-driven PRBC, platelet, and electrolyte repletion
  • Will need specialized testing: bone marrow biopsy, molecular testing

Additional information

  • APML is a medical emergency due to high rate of mortality, especially from massive hemorrhage due to coagulopathy. This is why it’s extremely important to start ATRA as soon as possible, even before definitive diagnosis is made
  • Differentiation syndrome: promyelocytes differentiate
    • Signs and symptoms: fever, SOB, hypotension, peripheral edema, pleural effusion, AKI
    • Diagnosis: No defined criteria. If suspicious, discuss with hematology fellow
    • Management: Steroids. If critically ill, hold ATRA and ATO and consider hydroxyurea
  • AML is broken down into 3 risk categories based on molecular studies:
    • Good risk: t(8;21), inv(18), t(16;16), NPM1+
    • Intermediate risk: normal karyotype, FLT3+
      • FLT3 inhibitors are midostaurin and gilteritinib
    • Poor risk: TP53, everything else

Leukemia treatment overview

  • General strategy is to use “induction” chemotherapy to try to induce clinicopathologic (as opposed to molecular) “remission”
  • Defined as count recovery and <5% blasts in bone marrow (on day 28)
  • Pts stay in hospital until neutrophil count >500 (typically ~4 weeks)
  • From there, bone marrow transplant (for high-risk disease) or “consolidation” chemo for normal-risk or low-risk disease

AML treatment

  • Induction
    • Typical is “7+3” i.e. cytarabine on days 1-7 and idarubicin on days 1-3
    • If therapy-related AML, MDS-related AML, or AML with cytogenetics similar to MDS, use “Vyxeos” which is liposomal daunorubicin and cytarabine on days 1, 3, and 5
    • There are other induction regimens that can be used depending on specific cytogenetics and pt frailty, which is beyond the scope of the handbook
  • Consolidation
    • Typically “HiDAC”(high-dose Ara-C i.e. cytarabine)
      • Generally too toxic for pts with age > 60, so a dose reduction is used
    • In the case of relapse, typical treatment is a different high-dose chemo and BMT if possible

ALL treatment

  • Typical induction is “HyperCVAD” (hyper-fractionated cyclophosphamide, vincristine, doxorubicin (“A” due to trade name Adriamycin), and dexamethasone
  • If t(9;22) (Philadelphia chromosome), use tyrosine kinase inhibitor (TKI)
  • If CD20+, use rituximab

Overview of Common Chemotherapy Regimens:

Regimen Components Use
7+3 Cytarabine (Ara-C) x 7 d and anthracycline (e.g. idarubicin x3 d) AML Induction
Vyxeos Cytarabine + liposomal daunorubicin AML-MRC or t-AML
CLAG-M Cladribine, cytarabine (Ara-C), Filgrastim (G-CSF), mitoxantrone AML induction (relapsed/refractory)
HIDAC high-dose cytarabine AML consolidation
ATRA All-trans retinoic acid given with arsenic trioxide (ATO) APML
HyperCVAD/MA CVAD = Cyclophosphamide, vincristine, doxorubicin, dexamethasone
MA = methotrexate/cytarabine (Given as alternating cycles)		 ALL