Integrative S4

Question 1

Chronic Leukemias

Answer 1

Chronic leukemia is malignant disorder of WBC characterized by genetic defects at level of stem or progenitor cells leading to great expansion in mature looking cells rather than blast cells which seen in acute leukemia.

It broadly classify into:

• Chronic myeloproliferative disorders.
• Chronic lymphoproliferative disorders.
• Plasma cell disorders.
• Lymphomas (HD and NHL).

Question 2

Chronic myeloproliferative disorders (CMPDs)

Definition

WHO classification include:

Answer 2

Definition: are clonal hemopoietic disorders at level of stem or progenitor cells, leading to great expansion in all myeloid cells (erythroid, granulocytic and megakaryocytic) with central pathology run to more specific line.

WHO classification include:

• Chronic myeloid leukemia (CML).
• Polycythemia rubra vera (PRV).
• Essential thrombocythaemia (ET).
• Idiopathic myelofibrosis (IMF).
• Chronic neutrophilic leukemia (CNL).
• Chronic eosinophilic leukemia.
• Other forms.

Question 3

Chronic myeloid leukemia (CML)

Definition

Etiology

Answer 3

Definition: clonal hemopoietic disorder at level of stem or progenitor cells, leading to great expansion in granulocytes usually of normal morphology.

Etiology: in most cases no known predisposing factors, but may related to ionizing radiation and benzene exposure.

Question 4

Chronic myeloid leukemia (CML)

Clinical features:

Answer 4

Rare, disease of elderly 50-60s.

• 25-50 % is asymptomatic.
• Classical presentation with constitutional symptoms, anemia, bleeding, massive splenomegaly and hepatomegaly.
• Fever and LAP are rare.
• CML may progress to acute leukemia or to other forms of CMPDs.
• CML of 3 phases of disease: chronic, acceleratory and blastic phases.

Question 5

Laboratory findings (of chronic phase CML):

Answer 5

CBC: leucocytosis usually 20-200 x 109/L and may reach 800 x 109 /L. Anemia and frequently increased platelets count are seen.

• Blood film: shows the full spectrum of granulocytic maturation, from the segmented neutrophil up to blasts. The most predominant cells are neutrophils and myelocytes. Basophilia and eosinophilia are prominent features. Blasts should be less than 10 % in chronic phase.

BM examination of no diagnostic value in CML.

• Cytochemistry: Neutrophil Alkaline phosphatase (NAP) is cytochemistry stain showing low or zero score in chronic phase.
• Cytogenetics and molecular defects: Philadelphia chromosome present in more than 95% of cases. It represent reciprocal translocation t(9:22), the abnormal short chromosome 22 called Philadelphia chromosome. This translocation involving BCR-ABL genes on both chromosomes resulting in fusion oncogene of tyrosine kinase activity with continuous cell proliferation.

Question 6

Principles of treatment in chronic phase: of CML

Answer 6

• Supportive measures.
• Stem cell transplantation for young patient with appropriate donors.
• Drugs: Tyrosine kinase inhibitors with many generations consider as target therapy which change the history of CML.

Question 7

Polycythaemia (Rubra) Vera

Clinical features:

Answer 7

acquired clonal myeloproliferative disorder, characterized by generalized hyperplasia of all marrow elements, but dominated by expansion of the red cell mass.

Disease of middle aged with gradual onset.

• Headache, dizziness, plethora, purities, hypertension and gout.
• Thrombotic and hemorrhagic complications, SM and HM.
• Transformation may be to AL and other MPDs.

Question 8

Hematological findings of PRV

Answer 8

Hb, RBC count and PCV are increased. WBC and platelets usually increased. Basophilia usually present in peripheral blood.

• No additional diagnostic value for bone marrow examination.
• Serum Epo level normal or subnormal.
• JAK2 mutation found in 95% of PRV cases.

Diagnosis need specific diagnostic criteria.

Treatment : Venesection, cytoreduction agents and treatment of complications.