Leukocyte Disorders Diagnosis

Question 1

Acute Lymphoblastic Leukemia (ALL)

Answer 1

CBC – does not r/o or confirm
-decreased RBC, platelet and neutrophils
-WBC may be normal, high or low
Complete Metabolic Panel (CMP) - kidney/liver function
Blood Cultures - if signs of infection
Initial Imaging
* CXR - r/o pneumonia as a source of infection, assess for signs of mediastinal widening (mass there, lost borders of mediastinum on xr)
* CT/MRI Brain (without contrast) – Headache symptom indicates to check for hemorrhage complication
* if neurologic s/s are present or leukostasis is suspected

Question 2

Acute lymphoblastic Leukemia ALL
Additional Work up

Answer 2

Peripheral smear - **confirms **CBC findings
-Hallmark: pancytopenia with circulating lymphoblasts

Lactic dehydrogenase level (LDH)¹ - ↑ due to tissue destruction
CT chest with contrast - assess lymphadenopathy, further assess mediastinal mass

Cerebrospinal Fluid (CSF) Analysis
* required in all patients to evaluate CNS involvement & severity of disease
* (+) lymphoblast cells in CSF - with spinal infiltration of dz.

Flow-cytometry- just know atypical antigens present

Bone Marrow Aspiration & Biopsy
* definitive diagnosis - > 20% lymphoblasts (WHO classification)

Question 3

Chronic Lymphocytic Leukemia

Answer 3

CBC
WBC >20,000 cell/µL
isolated absolute lymphocytosis (hallmark)
persists for > 3 months
+/- decreased RBC, platelets

• Peripheral smear
  predominantly small mature lymphocytes, (+) smudge cells¹, may see prolymphocytes

CMP
-assess liver/renal function

Peripheral blood via flow cytometry - confirms diagnosis
-confirms the presence of various abnormal B-lymphocyte surface antigens¹

Bone marrow aspiration/biopsy
-infiltrated with small lymphocytes
-not always required to make diagnosis

Question 4

Staging CLL (Chronic Lymphocytic Leukemia)

Answer 4

Staging CLL: Revised Rai staging system
Low risk
Stage 0: Lymphocytosis alone – Tx not indicated
lymphocyte > 15,000/μL, and > 40% lymphocytes in the bone marrow
Intermediate risk
Stage I: Lymphocytosis with enlarged node(s) in any site,
Stage II: splenomegaly or hepatomegaly or both
High risk
Stage III: Anemia (hemoglobin level < 11.0 g/dL)
Stage IV: Thrombocytopenia (platelets < 100,000/μL)

Question 5

Acute Myelogenous Leukemia

Answer 5

CBC - decreased RBC, platelet and neutrophils
* WBC may be normal, high or low

Peripheral smear
* Hallmark: pancytopenia with predominantly circulating myeloblasts
* Auer rod - eosinophilic needle-like inclusion in the cytoplasm of myeloblasts
*`` Result from abnormal fusion of primary granules
* Never found in lymphoblasts
* Confirms the presence of AML
————————————-

• Complete Metabolic Panel (CMP) - assess kidney/liver function
• Blood Cultures - indicated if signs of infection
• Lactic dehydrogenase level (LDH) - ↑ with tissue destruction
• Bone Marrow - hypercellular, predominant myeloblasts
• Flow Cytometry
  differentiates AML from ALL by detecting myeloid antigens on cell surface

Imaging Studies
Brain MRI/CT - indicated for neurologic symptoms (leukostasis)

Lumbar Puncture - symptomatic patients only
LP is performed to look for leukemic (myeloblast) cells

Routine evaluation of CNS is not recommended for asymptomatic patients as CNS infiltration is rare.

Question 6

Chronic Myeloid Leukemia

Answer 6

CBC
* chronic phase - average white count 100,000-150,000 cells/μL (all go to spleen which enlarges)
* granulocytosis with marked increase in mature neutrophils, mild increase in basophils and eosinophils¹
* accelerated phase - reduced platelets, RBC, increase in myeloblasts

Peripheral Smear
* chronic phase - confirmation of CBC findings
* accelerated phase - peripheral myeloblast cells, promyelocytes visualized

Leukocyte Alkaline Phosphatase (LAP) stain
- a type of alkaline phosphatase found inside WBC’s
high LAP activity shows up as a dark stain on testing
- No longer utilized due to the discovery of the bcr/abl gene via cytogenetic testing
- LAP is low inside the WBC in CML

CMP
* assess liver/renal function
Bone Marrow Aspiration/Biopsy
* hypercellular with increased granulocyte cells and their progenitors
* Blast phase: >20% blasts compromise BM cells

Polymerase chain reaction (PCR) ¹- (the genetic test for Philadelphia chromosome)
* can be performed on blood or marrow aspirate
* identifies bcr/abl DNA segment (aka Philadelphia Chromosome)
*

Question 7

Multiple Myeloma

Answer 7

CBC - pancytopenia
* anemia, neutropenia, thrombocytopenia

Peripheral blood smear
* confirms CBC; RBC rouleaux formation¹

CMP - abnormalities depend on organ(s) affected
* hypercalcemia, elevated BUN/Cr

Bone marrow aspiration/biopsy
* infiltration by monoclonal plasma cells which are often morphologically abnormal²

Serum protein electrophoresis¹ (SPEP)
(+) paraprotein (M-protein) found

24 hour urine collection with urine protein electrophoresis (UPEP)
(+) Bence Jones protein²

Quantitative immunoglobulin levels
suppression of the non-myelomatous immunoglobulins (IgG, IgA, IgM)

Prognostic testing
Beta-2 microglobulin³elevated - level is directly related to tumor burden

x-rays - complete skeletal survey
assess for lytic lesions and pathologic fractures
MC seen in skull, spine, long bones

CT scan
utilized to monitor patients for neoplastic bone disease once the dx of MM is made

MRI spine
assess spinal nerve compression