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

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 cells
- Acute 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:
- Headaches
- Bone pain
- Arthralgias
- Fever
- Leukotactic symptoms:
  - Dyspnea
  - Drowsiness
  - Confusion

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):
- Petechiae
- Ecchymosis
- Epistaxis
- Hemorrhage
Infections (granulocytopenic)
Organ involvement with advanced ALL:
- Lymphadenopathy
- Hepatomegaly
- Splenomegaly
- Leukemic meningitis:
  - Headache
  - Nausea
  - Seizures

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/mm3
- Neutrophils predominate.
- Thrombocytosis in 50%
CLL:
- Absolute lymphocytosis >5,000
- WBC range, 40,000 " “150,000/mm3
Acute leukemia (AML/ALL):
- Anemia
- Thrombocytopenia
- Elevation/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 products
- If 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 diagnosis
- CML " ”hypercellular with myeloid hyperplasia
- CLL " ”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:
- Lymphoma
- Myeloproliferative syndromes
- Systemic lupus erythematosus
- Infection " ”bacterial, fungal, mycobacterial
CLL:
- Pertussis
- Infectious lymphocytosis
- Cytomegalovirus
- Epstein " “Barr virus/mononucleosis
- Hepatitis
- Rubella
Acute leukemia:
- Aplastic anemia
- Leukemoid 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% 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
Transfuse packed RBCs for symptomatic anemia:
- May require irradiated, filtered, and HLA-type " “specific blood
Post-ED treatment:
- CLL:
  - Chemotherapy
  - Prednisone for immune-mediated thrombocytopenia
  - Radiation to localized nodular masses/enlarged spleen
- CML:
  - Interferon therapy
  - Chemotherapy
  - Bone marrow transplantation
- ALL:
  - Chemotherapy
  - CNS prophylaxis with intrathecal " “methotrexate/cranial radiation
  - Bone marrow transplantation
- AML:
  - Chemotherapy
  - Bone 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 anemia
- WBC >30,000
- Thrombocytopenia
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.

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)

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