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Acute Leukemia

Robert Corty

Background

  • Hematological malignancy caused by unchecked proliferation of WBC precursors in the bone marrow
  • Pt’s with suspected acute leukemia require hospitalization for urgent diagnosis & treatment
  • Types:
    • AML = Acute Myeloid Leukemia
      • APL = Acute Promyelocytic Leukemia defined by translocation (15;17) PML-RARA
    • ALL = Acute Lymphocytic Leukemia
  • Risk Factors:
    • radiation, chemical exposures (e.g benzene), chemotherapy (esp alkylating agents)
    • HIV, immunosuppression, smoking
    • myeloproliferative disorders, aplastic anemia

Presentation

  • Leukocytosis, leukemia cutis, gingival hypertrophy, leukostasis
  • Functional Leukopenia, often neutropenia: recurrent infections
  • Anemia: fatigue, pallor, dyspnea
  • Thrombocytopenia: gingival bleeding, epistaxis, petechiae, ecchymoses, menorrhagia
  • Extramedullary hematopoiesis: splenomegaly, hepatomegaly, lymphadenopathy

Evaluation

  • Diagnosis of acute leukemia requires one of the following:
    • 20% blasts in peripheral blood

    • 20% blasts in bone marrow biopsy

    • Any pathognomonic cytogenetic abnormality of t(8;21), inv(16), t(15;17)
  • Check for the presence of these time-sensitive conditions.
    • DIC – check fibrinogen, PT, PTT, platelets
    • TLS – check uric acid, phosphate, K+
    • Neutropenic fever – check temp, neutrophil count
    • Leukostasis (see below)
    • Presumptive APL – promyelocytes on diff, DIC or Auer rods on smear
  • Confirm if peripheral flow cytometry ordered/in process
  • Use hematology admission order set
  • Set RBC and Plt transfusion thresholds
  • Order nurse-driven electrolyte repletion
  • ECG and TTE to establish pre-chemotherapy cardiac function
  • Daily labs: CBC, TLS, DIC
  • TLS prophylaxis

Management

  • Consult hematology
  • Discuss chemo plan and order double lumen PICC for reliable access
  • If findings suggest APL start ATRA
  • Subspecialized lab tests: bone marrow biopsy, cytogenetics, FISH
  • Monitor for Common Complications/Emergencies: (see individual sections)
    • TLS, DIC, Febrile Neutropenia, Leukostasis

Additional Information

  • Obtain blood product consent on admission
  • APL Specific findings: promyelocytes on differential or Auer rods on smear
  • Differentiation syndrome: promyelocytes differentiate
    • Symptoms and signs: fever, SOB, Hypotn, 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

Leukemia Treatment Overview

  • General strategy is to use “induction” chemo to try to induce clinicopathologic (as opposed to molecular) “remission”
  • Defined as absence of symptoms, normal CBC, and <5% blasts in bone marrow (on day 28)
  • Then waiting in hospital until neutrophil count >500 (typically ~3 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. idrarubicin on days 1-3 and cytarabine on days 1-7
    • 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
    • If low-risk dz (t(8;21) or inv(16)), use cytarabine on days 1-7, and 3 days of low-dose daunorubicin + gemtuzumab-ozogamicin
    • There are other induction regimens that can be used depending on specific cytogenetics and patient 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) (known as Philadelphia chromosome), use tyrosine kinase inhibitor (TKI)
  • If CD20+, use rituximab

Common Chemotherapy Regimens for Leukemia Encountered as Inpatient

Regimen Components Use

7+3

 

 Cytarabine (Ara-C) x 7 d & 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)

 APL (APML)
HyperCVAD/MA

CVAD = Cyclophosphamide, vincristine, doxorubicin, dexamethasone

MA = methotrexate/cytarabine 

(Given as alternating cycles)

 ALL
R-CHOP Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone NHL
R-EPOCH

Etoposide plus the drugs above

(dosing is different)

 NHL
ABVD Doxorubicin, bleomycin, vinblastine, dacarbazine HL
Last update: 2022-06-25 02:05:01