Case StudyCase StudyMICR 410 - HematologyMICR 410 - Hematology

Spring, 2011Spring, 2011

Case # 5Hee Jin Kim, Hooman Nikizad

and Arthur Omuro

Case SummaryCase SummaryGregory, a healthy 25-year-old man, has a

routine physical examination and laboratory studies for new employment. He is asymptomatic.

Laboratory Findings: ◦Total white blood cell count: 30,000 x 109/L◦The differential white blood cell count:

7% blasts, 3% promyelocytes, 25% myelocytes, 10% metamyelocytes, 5% bands, 25% segmented neutrophils, 10% basophils, 5% eosinophils, and 10% lymphocytes.

Cytogenetic analysis: ◦All cells had the karyotype of 46,XY,t(9;22)

(q34:q11.2)

Key Information Pointing to Key Information Pointing to Diagnosis Diagnosis Significant increase in white

blood cell count: 30,000 x 109 /L Left shift:

◦7% blast, 3% promyelocytes, 25% myelocytes, 10% metamyelocytes

Increased number of granulocytes:◦10% basophils, 5% eosinophils

Philadelphia Chromosome

The Diagnosis for Case # The Diagnosis for Case # 55

Increased WBC count and the left shift in the WBC in the peripheral blood suggest the possibilities of : ◦Chronic Myelocytic Leukemia, Leukemoid

Reaction, and essential thrombocythemia.

Cytogenetic finding of the Philadelphia chromosome (46, XY, t(9;22)(q34:q11.2)) suggests that Gregory has Chronic Myelocytic Leukemia.

Pathophysiology of Chronic Pathophysiology of Chronic Myelocytic Leukemia (CML)Myelocytic Leukemia (CML)

Philadelphia Chromosome t(9;22): reciprocal translocation on the long arms of chromosome 9 and 22◦BCR gene from chromosome 22 fuses

with ABL gene on chromosome 9.◦BCR/ABL produces a tyrosine kinase,

inhibits DNA repair, and enhances cell division.

◦As a result of the Philadelphia Chromosome that exists in the stem cells, the dividing abnormal cells are clonal.

Diagnostic Tests for CMLDiagnostic Tests for CML

Cytogenetic karyotype studies detect the presence of Philadelphia chromosome in 90% of CML case.

The remaining 5-10% of CML with undetectable translocation can be checked with more sensitive DNA studies such as RT-PCR or fluorescent in situ hybridization (FISH).

Other tests may be performed post bone marrow transplant to provide information regarding the recipient’s cells: ◦FISH, RT-PCR, Leukocyte Alkaline

Phosphatase scoring

Therapy for Chronic Myelocytic Therapy for Chronic Myelocytic LeukemiaLeukemia

Treatment: ◦Single agent chemotherapy◦Bone marrow transplant after eradication of

the leukemic cell mass is the best therapy – however, cells with Philadelphia chromosome will remain in the bone marrow 3 months after receiving a bone marrow

transplant from his sister (46, XX), the karyotype of the patient was completely replaced by that of the sister’s, pointing to a successful transplant.

◦New drug: Gleevec

Prognosis for Chronic Prognosis for Chronic Myelocytic LeukemiaMyelocytic Leukemia5 Years after the transplant,

cytogenetic analysis revealed: ◦5 cells: 46, XX◦15 cells: 47, XY,+8,t(9:22)

(q34:q11.2),i(17q)Chromosome 8 has a trisomy while

chromosome 17 has become an isochromosome.

Based on the abundance of abnormal cells, the patient is not in great condition.

Prevention of Chronic Prevention of Chronic Myelocytic LeukemiaMyelocytic Leukemia

CML is not an inherited disease. It is rather acquired disease, often with unknown cause (95%).

However, some identified leukemogens that are known to increase the risk of translocation and formation of Philadelphia chromosome are: ◦Ionizing radiation, cytotoxic drugs

(especially alkylating agents) and biologically active chemicals such as benzene. Avoiding exposure to these agents might help preventing CML.

Take Home MessageTake Home MessageThe diagnosis is: Chronic Myelogenous

LeukemiaTypical symptoms are: fatigue, fever,

malaise, weight loss, sweating, bone aches, fullness in upper abdomen, bleeding, petechiae

The cause of the disease is: unknown, exposure to radiation and chemicals

Diagnostic tests include: CBC, bone marrow biopsy, FISH, RT-PCR

Treatment is: bone marrow transplant, drugs, chemotherapy

Prognosis is: variable dependent on treatment and progression of disease

Prevention is: avoid radiation/chemicals

ReferencesReferencesHarmening, Denise M. “Clinical

Hematology and Fundamentals of Hemostasis.” Philadelphia, Pennsylvania: FA Davis, 2009: 373 – 380

Meng, Chin Y. “Cytogenetics and Molecular Studies in Chronic Myeloid Leukemia.” St. Clements University Dissertation, 2001.

McQueen, Nancy. Class Lecture. Hematology. CSULA, 19 May 2011.

Branford, S. et al. “Diagnosis and Monitoring of Chronic Myeloid Leukemia by Qualitative and Quantitative RT-PCR.” Methods Mol Med.2006: 69-92

Point SpreadPoint SpreadCase summary 5

Key Information pointing to Diagnosis 15

Diagnosis 5

Pathophysiology of the disease 25

Diagnostic tests 10

Therapy 5

Prognosis 5

Prevention 5

Take home message 5

Are all questions addressed? 10

Appearance 5

Presentation skills (individual) 5

Total 100