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Leukemia, Emergency Medicine

Basics

Description

- Neoplasms of WBCs that have undergone a malignant transformation - Hyperleukocytosis: - Occurs with WBC >100,000/mm3 - Leads to occlusions of small vessels primarily in brain or lungs - Present with confusion, stupor, or shortness of breath

- CML: - Lymphoma - Myeloproliferative syndromes - Systemic lupus erythematosus - Infection " ”bacterial, fungal, mycobacterial

- Treat leukostasis: - Rehydrate with 500-mL bolus (20 mL/kg) IV 0.9% NS - Administer acetazolamide to alkalinize urine. - Initiate allopurinol. - Arrange for leukapheresis. - Whole-brain radiation or dexamethasone for CNS effects - Administer hydroxyurea for CML: 20 " “30 mg/kg single dose daily

- Post-ED treatment: - CLL: - Chemotherapy - Prednisone for immune-mediated thrombocytopenia - Radiation to localized nodular masses/enlarged spleen

  • Neoplasms of WBCs that have undergone a malignant transformation
  • Hyperleukocytosis:Occurs with WBC >100,000/mm3Leads to occlusions of small vessels primarily in brain or lungsPresent with confusion, stupor, or shortness of breath

Chronic Myelogenous Leukemia

  • Overproduction of granulocytic WBCs (neutrophils)
  • Neutrophil function preserved
  • Thrombocytosis
  • Basophilia
  • Philadelphia chromosome present in bone marrow of >95%

Chronic Lymphocytic Leukemia

  • Most common leukemia in adults
  • Overproduction of monoclonal lymphocytes
  • Cells accumulate in lymph nodes, bone marrow, liver, spleen
  • Particularly prone to herpes virus infections

Acute Leukemias

  • Proliferation of undifferentiated immature cells:Acute myelogenous leukemia (AML) " ”immature myeloid cellsAcute lymphocytic leukemia (ALL) " ”immature lymphoid cells (blasts)
  • Rapidly fatal

Etiology

  • Cause unknown
  • Familial clustering in chronic lymphocytic leukemia (CLL)
  • Increased incidence of AML, ALL, and chronic myelogenous leukemia (CML) with ionizing radiation
  • Usually have ALL:Most common pediatric cancer
  • 60 " “80% remission in those who are standard risk
  • Better overall prognosis, except if <1 yr of age
  • May develop leukostasis at lower levels
  • Allopurinol dose is 3 mg/kg.
  • Ceftazidime dose is 50 mg/kg.
  • 90% of leukemias are AML or ALL.
  • Myeloid leukemias are more common.
  • CLL is very rare in pregnancy.
  • Chemotherapeutics may cause birth defects and/or preterm labor.
  • Same prognosis as nonpregnant; do not delay therapy.
  • Transfuse earlier than nonpregnant; keep hemoglobin >9.8 mg/dL.

More likely to present with CLL and CML ‚

Diagnosis

Signs and Symptoms

Chronic Myelogenous Leukemia

  • Asymptomatic
  • Fatigue
  • Weight loss
  • Left upper quadrant pain, tenderness
  • Abdominal fullness
  • Splenomegaly (most common)
  • Later stage:HeadachesBone painArthralgiasFeverLeukotactic symptoms:DyspneaDrowsinessConfusion

Chronic Lymphocytic Leukemia

  • Asymptomatic
  • Fatigue
  • Lethargy
  • Weight loss
  • Lymphadenopathy
  • Splenomegaly
  • Hepatomegaly

Acute Myelogenous Leukemia

  • Fever
  • Fatigue
  • Pallor
  • Headache
  • Angina
  • Congestive heart failure, dyspnea on exertion
  • Bone pain
  • Granulocytic sarcoma (isolated mass of leukemic blasts)
  • Easy bleeding (thrombocytopenia):PetechiaeEcchymosisEpistaxisHemorrhage
  • Infections (granulocytopenic)
  • Organ involvement with advanced ALL:LymphadenopathyHepatomegalySplenomegalyLeukemic meningitis:

History

  • Radiation exposure
  • Exposure to alkylating agents
  • Recent viral infection, particularly Epstein " “Barr

Physical Exam

  • Signs of bleeding (petechiae, purpura)
  • Hepatomegaly and splenomegaly
  • Presence of chloromas (AML blast tumors)
  • Sausage-like hemorrhagic retinal veins are pathognomic for hyperviscosity.

Essential Workup

  • CBC/platelets:CML:WBC range, 10,000 " “1 million/mm3Neutrophils predominate.Thrombocytosis in 50%
  • CLL:Absolute lymphocytosis >5,000WBC range, 40,000 " “150,000/mm3
  • Acute leukemia (AML/ALL):AnemiaThrombocytopeniaElevation/depression of WBCs

Diagnosis Tests & Interpretation

Lab

  • Electrolytes, BUN, creatinine, glucose, calcium
  • Uric acid level:Frequently elevated, especially in ALL
  • Lactate dehydrogenase:Increased in acute leukemias
  • Coagulation profile:PT/PTT, fibrinogen, fibrin-split productsIf disseminated, suspect intravascular coagulation.
  • Blood/urine cultures if fever
  • Arterial blood gases/pulse oximetry for shortness of breath

Imaging

CXR for infectious workup ‚

Diagnostic Procedures/Surgery

  • Bone marrow biopsy:Required to make diagnosisCML " ”hypercellular with myeloid hyperplasiaCLL " ”lymphocytosis (30 " “100%)Acute leukemia " ”hypercellular with blast cells, which replace normal marrow
  • Leukocyte alkaline phosphatase test:Decreased in neutrophils in CML
  • Ph1 chromosome present in CML

Differential Diagnosis

  • CML:LymphomaMyeloproliferative syndromesSystemic lupus erythematosusInfection " ”bacterial, fungal, mycobacterial
  • CLL:PertussisInfectious lymphocytosisCytomegalovirusEpstein " “Barr virus/mononucleosisHepatitisRubella
  • Acute leukemia:Aplastic anemiaLeukemoid reactions to infections

Treatment

Initial Stabilization/Therapy

  • 100% oxygen for hypoxia/shortness of breath
  • IV access with 0.9% NS
  • Initiate platelet transfusion for severe bleeding from thrombocytopenia.
  • Begin broad-spectrum antibiotics for fever and granulocytopenia.
  • Treat disseminated intravascular coagulation (see "Disseminated Intravascular Coagulation " ¯).

Ed Treatment/Procedures

  • Treat leukostasis:Rehydrate with 500-mL bolus (20 mL/kg) IV 0.9% NSAdminister acetazolamide to alkalinize urine.Initiate allopurinol.Arrange for leukapheresis.Whole-brain radiation or dexamethasone for CNS effectsAdminister hydroxyurea for CML: 20 " “30 mg/kg single dose daily
  • Transfuse packed RBCs for symptomatic anemia:May require irradiated, filtered, and HLA-type " “specific blood
  • Post-ED treatment:CLL:ChemotherapyPrednisone for immune-mediated thrombocytopeniaRadiation to localized nodular masses/enlarged spleenCML:Interferon therapyChemotherapyBone marrow transplantationALL:ChemotherapyCNS prophylaxis with intrathecal " “methotrexate/cranial radiationBone marrow transplantationAML:ChemotherapyBone marrow transplantation

Medication

First Line

  • Aggressive IVF, start with normal saline, then alkalinize
  • Packed RBC and platelets as needed

Second Line

  • Ceftazidime if febrile
  • Allopurinol or rasburicase and diuretics if at risk for tumor lysis

Follow-Up

Disposition

Admission Criteria

  • Newly diagnosed leukemia with:Symptomatic anemiaWBC >30,000Thrombocytopenia
  • ICU admission for unstable patients with disseminated intravascular coagulation, blast crisis, or bleeding

Discharge Criteria

Asymptomatic patients without significant lab abnormalities ‚

Issues for Referral

Hematology for any patient presenting with new leukemia ‚

Pearls and Pitfalls

  • Monitor for tumor lysis and secondary hyperkalemia.
  • Hyperleukocytosis may present as respiratory failure or hemorrhage.

Additional Reading

  • Abramson ‚ N, Melton ‚ B. Leukocytosis: Basics of clinical assessment. Am Fam Physician. 2000;62:2053 " “2060.
  • Higdon ‚ ML, Higdon ‚ JA. Treatment of oncologic emergencies. Am Fam Physician. 2006;74(11):1873 " “1880.
  • Hurley ‚ TJ, McKinnell ‚ JV, Irani ‚ MS. Hematologic malignancies in pregnancy. Obstet Gynecol Clin North Am. 2005;32(4):595 " “614.
  • Nazemi ‚ KJ, Malempati ‚ S. Emergency department presentation of childhood cancer. Emerg Med Clin North Am. 2009;27(3):477 " “495.
  • Pui ‚ CH, Evans ‚ WE. Acute lymphoblastic leukemia. N Engl J Med. 1998;339:605 " “615.
  • Sawyers ‚ CL. Chronic myeloid leukemia. N Engl J Med. 1999;340:1330 " “1340.
  • Tsiodras ‚ S, Samonis ‚ G, Keating ‚ MJ, et al. Infection and immunity in chronic lymphocytic leukemia. Mayo Clin Proc. 2000;75:1039 " “1054.
  • Zuckerman ‚ T, Ganzel ‚ C, Tallman ‚ MS, et al. How I treat hematologic emergencies in adults with acute leukemia. Blood. 2012;120(10):1993 " “2002.

See Also (Topic, Algorithm, Electronic Media Element)

Hyperviscosity Syndrome ‚

Codes

ICD9

  • 204.10 Chronic lymphoid leukemia, without mention of having achieved remission
  • 205.10 Chronic myeloid leukemia, without mention of having achieved remission
  • 208.90 Unspecified leukemia, without mention of having achieved remission
  • 205.00 Acute myeloid leukemia, without mention of having achieved remission
  • 204.00 Acute lymphoid leukemia without mention of having achieved remission

ICD10

  • C91.10 Chronic lymphocytic leuk of B-cell type not achieve remis
  • C92.10 Chronic myeloid leukemia, BCR/ABL-positive, not having achieved remission
  • C95.90 Leukemia, unspecified not having achieved remission
  • C92.00 Acute myeloblastic leukemia, not having achieved remission
  • C91.00 Acute lymphoblastic leukemia not having achieved remission

SNOMED

  • 93143009 Leukemia, disease (disorder)
  • 92818009 chronic myeloid leukemia, disease (disorder)
  • 92814006 chronic lymphoid leukemia, disease (disorder)
  • 91861009 Acute myeloid leukemia, disease (disorder)
  • 91857003 Acute lymphoid leukemia, disease (disorder)