The Chronic Leukemias

Question 1

Definition of Chronic Myeloid Leukemia

Answer 1

A clonal malignant myeloproliferative disorder characterised by an increased proliferation of the granulocytic cell line( both mature and it’s precursors) resulting in an increase in myeloid, erythroid and platelet cells in pb and marked myeloid hyperplasia in the bone marrow

Question 2

The leukemias originate generally when a single hsc acquires mutations and becomes abnormal. T or F

Answer 2

T

Question 3

Epidemiology of cml

Answer 3

Median age of incidence - 45 to 55 years
Male : female….1.3:1
At presentation, 50% diagnosed during routine lab tests
85% in chronic phase

Question 4

Aetiology of cml

Answer 4

Not clear, little genetic linkage
Increased incidence is however seen in..post radiation therapy
Survivors of the atomic disasters of Nagasaki and Hiroshima

Question 5

Pathogenesis of CML

Answer 5

The Philadelphia chromosome arises due to the reciprocal translocation between the long arms of chromosomes 9 and 22 t(9,22)(q34,11). Leading to a longer chromosome 9 and a much shorter chromosome 22 known as the philadelphia chromosome which contains the abnormal fused BCR-ABL gene
A segment of the Abelson Mouse leukemia protooncogene(ABL) on ch9q34 that codes for a non receptor Tyrosine kinase is translocated to the breakpoint cluster region (BCR) on ch22q11 to form an tge bcr/abl gene transcribed into a hybrid messenger rna

Question 6

Hallmark of CML

Answer 6

The Philadelphia chromosome (95%) of patients
It is important to note that the bcr/abl protein transformations hscs so that their growth and survival becomes independent of cytokines

Question 7

Clinical Features of CML

Answer 7

Common
Anemic symptoms
Thrombocytopenic bleeding
Hypermetabolic symptoms including night sweats, weight loss
Massive spleno/hepatomegaly

Rare
Splenic infarction - due to massive splenomegaly that overwhelms blood supply
Hyperleucocytosis symptoms including leucostasis, gout , priapism, visual disturbances, fever

Question 8

Typical pbf findings in cml

Answer 8

Raised wbc count(30-400×10⁹)
Differentials show granulocytes at all stages of development
Blast cells <10% never present in normal blood

Question 9

Phases of Cml

Answer 9

Chronic phase
Accelerated phase
Blastic phase

Question 10

Chronic phase of cml is chxd by

Answer 10

Leucocytosis
All stages of granulocytes appearing in blood
Majority are myelocytes

Question 11

Accelerated phase of cml

Answer 11

Median duration is 3.5-5 years before progressing to blastic phase
Increased splenomegaly

Question 12

Blastic phase of cml

Answer 12

Resembles acute leukemias
>30% of blasts in the bm
⅔->AML( Myeloid blastic phase)
⅓->ALL
Survival 9mths vs 3mths…lymp vs myeloid

Question 13

Variants of CML

Answer 13

Philadelphia chromosome negative CML…worse prognosis
Chronic myelomonocytic leukemia
Juvenile cml
Eosinophilic leukemia

Question 14

Treatment of CML

Answer 14

Alkylating agents such as busulfan
Antimetabolite-hydroxycarbamide
Alpha interferon
Tyrosine kinase inhibitors-
Imatinib mesylate 1 gen
Nicotinic2
Dasatinib3
Bosutinib 4
Mk 0457

Question 15

Definition of Chronic lymphocytic leukemia

Answer 15

Neoplastic proliferation of mature appearing b lymphocytes in the the bm, blood spleen..etc

Question 16

Difference between sll and cll

Answer 16

The disease is called cll when there is a leukemic component in the peripheral blood

And called small lymphocytic leukemia when lymph nodes and other tissues are infiltrated with cells having the same morphological and immuniphenotypic features as cll but have no leukemic component

Question 17

Epidemiology of CLL

Answer 17

A disease of the elderly, median age of incidence 72yrs
Median age at death 79 years
Male predilection
More common in whites

Question 18

Aetiology of Cll

Answer 18

Unknown, although higher incidence in farmers, manufacturing workers etc
High familial risk- 2 fold increased risk

Question 19

Most common clonal abnormality in cll

Answer 19

Trisomy 12

Question 20

In cll, 50% of patients have a chromosomal abnormality and patients with abnormal karyotype have best prognosis. T/f

Answer 20

F, they have a worse prognosis

Question 21

Clinical presentation of cll

Answer 21

40% asymptomatic at presentation
Symptomatic patients typically present with fatigue and less commonly lymphadenopathy and infection
However ,mist that present with lymphadenopathy usually have it around cervical and supraclavicular region.
Splenomegaly
Hepatomegaly may occur
Rarely anemia or Thrombocytopenic bleeding may occur

Question 22

Bone marrow biopsy is not really required for diagnosis of cll but may be useful to determine prognostic implications. T/f

Answer 22

T

Question 23

Diagnosis of cll

Answer 23

B cell lympjocytosis of >5×10⁹/l in PB for at least 6 mths is diagnostic for Cll
Immunophenotyping

Question 24

Classic Immunophenotyping of Cll shows

Answer 24

Expression of CD5,19, 23 with dim expression of CD 20 and 79b and IgG kappa and lamda light chain restriction

Question 25

In Cll, cells in blood smears typically appear as

Answer 25

Basket or smudge cells due to ruptured lymphocytes

Question 26

Most common deletions in cll

Answer 26

del(13q14.1)
del(11q or 6q)

Question 27

The two systems of staging in Cll include

Answer 27

Rai and Binnet

Question 28

The modified Rai system

Answer 28

Low risk(0)- Absolute lymohocytosis >5×10⁹/l
Intermediate risk(1&2)- Lymphadenopathy +splenomegaly +/- hepatomegaly
Hih risk(3&4)- anemia(<10g/dl, Thrombocytopenia <100×10⁹/l)

Question 29

Binnet system of staging areas of involvement

Answer 29

Head and neck
Axillae
Groin
Palpable spleen
Palpable liver

Question 30

Binnet staging

Answer 30

Stage A hb>10g/dl , platelets >100× 10⁹/l or morewith up to 2 nodal involvement
Stage B hb, platelet same with 3 or more nodal involvement or organomegaly
Stage C hb and platelets become < , irrespective of organomegaly

Question 31

Current gold standard for Cll therapy

Answer 31

Immunochemotherapy

Question 32

Treatment of cll

Answer 32

Watch and wait for asymptomatic patients
Alemtuzumab in 17p deletions or p53 mutations
Sct useful in 1st remission in high risk patients