Updated: 1/24/2019

Acute Lymphoblastic Leukemia (ALL)

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  • A 11-year-old girl with Down syndrome presents with a few weeks of low-grade fever. She is otherwise feeling well, with no signs of infection. Blood-work shows elevated WBCs, low neutrophil count, and anemia. Blood cultures are drawn and come back positive for Pseudomonas.
Introduction

  • Acute leukemia of lymphoid precursor cells that occurs in children
  • Crowding of bone marrow leads to bone marrow failure
  • Subtypes
    • B-cell ALL – 85% of all ALL
      • CD10+ and CD19/20+
      • TdT+ (marker of precursor T- or B-cell)
    • T-cell ALL
      • CD2+, CD8+, and CD3+
      • TdT+ (marker of precursor T- or B-cell)
      • commonly presents as mediastinal mass
        • infiltration of thymus
  • Epidemiology
    • < 15 years
    • most common type of cancer and leukemia in children
  • Associated conditions
    • Down syndrome in children > 5 years
      • leukemia in Down syndrome children < 5 years = AML
Presentation
  • Symptoms
    • most common symptom is fever
    • acute onset
      • recurrent infections
      • bleeding
      • fatigue
  • Physical exam
    • mediastinal mass from infiltration of thymus 
    • hepatosplenomegaly
    • lymphadenopathy   
Evaluation
  • Peripheral blood smear
    • ↑ lymphoblasts (high nuclei to cytoplasm ratio)
  • CBC reflects bone marrow failure
    • anemia
    • thrombocytopenia
    • ↓ mature WBCs
  • Bone marrow aspiration with cytogenetics
    • ↑ lymphoblasts
    • TdT+, a marker of pre-T and pre-B cells
    • T-cell ALL
      • CD2+
      • CD3+
    • B-cell AML
      • CD10+
      • CD19+
    • negative MPO (myeloperoxidase)
    • t(12:21) 
Differential Diagnosis
  • AML
  • B-cell lymphoma
  • Non-hodgkin lymphoma
Treatment
  • Chemotherapy
  • Prophylaxis to CNS (standard chemotherapy does not penetrate blood-brain barrier)
    • intrathecal chemotherapy
Prognosis, Prevention, and Complications
  • Prognosis
    • very responsive to therapy
  • Complications
    • likes to spread to CNS and testes
 

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Questions (6)
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.8) A 39-year-old G1P0 female at 36 weeks gestation will give birth to an infant with the following karyotype (Figure A). Which of the following will the infant be at an increased risk of developing later in life? Review Topic

QID: 107000
FIGURES:
1

Testicular cancer

2%

(1/63)

2

Gonadal blastoma

0%

(0/63)

3

Dysgerminoma ovarian tumor

2%

(1/63)

4

Acute lymphoblastic leukemia (ALL)

87%

(55/63)

5

Chronic myelogenous leukemia (CML)

8%

(5/63)

M1

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SUBMIT RESPONSE 4

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(M1.ON.72) A 33-year-old pregnant woman undergoes a routine quad-screen during her second trimester. The quad-screen results demonstrate the following: decreased alpha-fetoprotein, increased Beta-hCG, decreased estriol, and increased inhibin A. A presumptive diagnosis is made based upon these findings and is later confirmed with genetic testing. After birth, this child is at greatest risk for which of the following hematologic malignancies? Review Topic

QID: 106527
1

Chronic lymphocytic leukemia

3%

(3/112)

2

Hairy cell leukemia

4%

(4/112)

3

Acute promyelocytic leukemia

12%

(13/112)

4

Acute lymphoblastic leukemia

79%

(88/112)

5

Chronic myelogenous leukemia

2%

(2/112)

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(M1.ON.29) A mother brings her 5-year-old child to your pediatric practice for evaluation of "croup". She reports her child has a history of weight loss, fatigue, and fever over the past two weeks. On physical exam you note respirations heard in figure V and skin findings seen in Figure A. Labs reveal thrombocytopenia, anemia, and leukocytopenia with a peripheral blood smear showing abundant lymphoblasts. Given this child's physical exam findings, what cell surface marker would the blasts be expected to express? Review Topic

QID: 101693
FIGURES:
1

CD1

2%

(3/153)

2

CD3

52%

(79/153)

3

CD10

20%

(30/153)

4

CD19

12%

(19/153)

5

CD20

11%

(17/153)

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(M1.ON.72) A 5-year-old male is brought to his pediatrician after recurrent, prolonged upper respiratory infections over a period of several months. Physical exam reveals petechiae on the patient’s legs and arms. Laboratory studies show hemoglobin: 10 g/L, platelet count: 35,000/mm^3, leukocyte count: 6,600/mm^3. A bone marrow aspiration shows an abundance of lymphoblasts indicative of acute lymphoblastic leukemia (ALL). Positive immunostaining for which of the following would support a diagnosis of precursor B-cell leukemia? Review Topic

QID: 101382
1

TdT, HER-2

6%

(9/160)

2

CD2, CD8

5%

(8/160)

3

CD19, CD10

65%

(104/160)

4

CD30, CD15

13%

(21/160)

5

CD4, CD5

9%

(14/160)

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(M1.ON.41) A 15-year-old male presents to the emergency department with fever, malaise, and shortness of breath for 1 week. Further history reveals that the patient experiences swelling in his face in the morning that disappears as the day progresses. Physical exam reveals hepatosplenomegaly. A complete blood count shows WBC 84,000 cells/mL. Most of this patient's leukocytes are likely to express which of the following cell surface markers? Review Topic

QID: 101351
1

CD2

43%

(6/14)

2

CD10

21%

(3/14)

3

CD19

0%

(0/14)

4

CD20

7%

(1/14)

5

CD16

29%

(4/14)

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