Updated: 4/11/2017

Acute Myelogenous Leukemia (AML)

Topic
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Questions
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Snapshot
  • A 60-year-old man presents with fever, long-standing fatigue, and shortness of breath on exertion. He also complains of easy bruising and occasional bleeding from his gums. On physical exam, he has cervical lymphadenopathy and marked hepatosplenomegaly. Peripheral blood smear shows large blasts.
Introduction

  • Acute leukemia with pancytopenia
  • Epidemiology
    • median onset 65 years of age
  • Subtypes
    • M3 aka acute promyelocytic leukemia (APML) 
      • t(15;17) 
        • disruption of retinoic acid receptor (RAR) required for myeloblast maturation 
      • associated with DIC
      • presence of Auer rods
        • peroxidase positive eosinophilic cytoplasmic inclusions
    • acute megakaryoblastic leukemia
      • associated with Down syndrome
      • < 5 years of age (recall leukemia in Down syndrome occurring in > 5 years of age = ALL)
    • acute monocytic leukemia
      • infiltration of gums
  • Risk factors
    • alkylating chemotherapy
    • radiation
    • myeloproliferative disorders
    • Down syndrome
Presentation
  • Symptoms of pancytopenia (high WBC count but WBCs are dysfunctional)
    • fatigue
    • dyspnea
    • infection due to dysfunctional blasts
    • bleeding
  • Physical exam
    • lymphadenopathy
    • fever
    • hepatosplenomegaly
Evaluation
  • Peripheral blood smear
    • > 20% blasts in blood smear
  • Most accurate test = flow cytometry
  • Bone marrow biopsy with cytogenetics     
    • myeloblasts with Auer rods in APL
    • myeloperoxidase (MPO) positive
  • CBC
    • anemia
    • thrombocytopenia
    • ↓ mature WBCs
Differential Diagnosis
  • ALL
  • Myelodysplastic syndrome
  • CML blast crisis
  • Leukemoid reaction
Treatment
  • Initial treatment with chemotherapy
    • to induce remission
    • cytarabine
  • Bone marrow transplant after remission
    • especially for cytogenetics revealing high chance of relapse
  • All-trans-retinoic acid (ATRA) to those with M3 (APL)
Prognosis, Prevention, and Complications
  • Prognosis
    • prognostic indicator is cytogenetics
    • 90% complete response rate from initial chemotherapy in those with good cytogenetics
    • relapse rate > 50% with median survival 3-12 months
  • Complications
    • febrile neutropenia
    • DIC
    • gout
    • tumor lysis syndrome
 

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Questions (4)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.ON.0) A 55-year-old male with fever, fatigue, generalized weakness, and bleeding gums for the past 3 weeks presents to his family physician. On exam, he has bilateral submandibular lymphadenopathy and hepatosplenomegaly. CBC demonstrates decreased RBCs and mature WBCs. The patient is referred to an oncologist, and a bone marrow aspiration is performed, demonstrating >20% myeloblasts with Auer rods that are myeloperoxidase positive. What is the most likely chromosomal translocation that is responsible for this patient's clinical presentation and lab results? Review Topic

QID: 106974
1

15;17

68%

(66/97)

2

9;22

14%

(14/97)

3

14;18

6%

(6/97)

4

11;14

4%

(4/97)

5

8;14

6%

(6/97)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 1

(M1.ON.72) A 35-year-old male presents to his physician with the complaint of fatigue and weakness for six months. His physician orders a CBC which demonstrates anemia and thrombocytopenia. During the subsequent work up, a bone marrow biopsy is performed which ultimately leads to the diagnosis of acute promyelocytic leukemia. Which of the following translocations and fusion genes would be present in this patient? Review Topic

QID: 106506
1

t(8;14) - BCR/Abl1

8%

(8/98)

2

t(9;22) - BCR/Abl1

6%

(6/98)

3

t(15;17) - PML/RARalpha

74%

(73/98)

4

t(14;18) - PML/RARalpha

6%

(6/98)

5

t(9;22) - PML/RARalpha

2%

(2/98)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 3

(M1.ON.49) A 62-year-old female presents to your office with a sore throat, low-grade fever, and bleeding gums. Peripheral blood smear for this patient is shown in Figure A. Which of the following is most likely to be abnormally elevated in this patient? Review Topic

QID: 101359
FIGURES:
1

Plasma cells

5%

(1/20)

2

Myeloblasts

50%

(10/20)

3

Lymphoblasts

25%

(5/20)

4

Metamyeloctes

15%

(3/20)

5

Platelets

5%

(1/20)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 2
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