2. 28 yr male patient came with c/o
abdominal pain-1 week in duration
involving predominantly
the left upper and
centre of the abdomen
vague dragging pain
assoc with fullness of abd
no h/o any aggravating or
relieving factors
3. h/o early satiety +
h/o loss of appetite +
No h/o loss of weight
No h/o jaundice
No h/o haematemesis
No h/o altered bowel habits
No h/o bleeding tendencies
4. PAST h/o -> No h/o Tb/HTN/DM
PERSONAL h/o -> consumes alcohol
occasionally
not a smoker
5. O/E – Pt conscious
oriented
afebrile
anemic
no Cyanosis,clubbing,icterus,
lymphadenopathy
B.P-110/70 mmHG
P.R -80 min
6. P/A –mild distention of abdomen+
no dialated viens,scars or sinuses
massive spleenomegaly(+) crossing
the umbilicus
no hepatomegaly
no FF+
7. CVS – S1S2(+)
NO murmurs
RS – NVBS+
no added sounds
CNS - NFND
12. CBC
TC – 1,60,000
SHIFT TO LEFT
BLAST 1%
HB – 9.2
PLATLET -1,80,000
Chronic phase of CML
P/S
Markedly increased TC,
showsMYELOBLAST,PR
OMYELOCYTE,METAMY
ELOCYTE,BAND FORMS
13.
14.
15. BONE MARROW FRAGMENT
SHOWING A DENSLLY CELLULAR MARROW
FRAGMENT WITH ABSENT FAT CELLS
16.
17. LOW POWER MICROSCOPE:
MYELOID HYPERPLASIA WITH RELATIVELY
REDUCED ERYTHROID PROGENITORS
18.
19.
20.
21. Patient was started on Imatinib mesylate
400mg 1-0-0
22.
23.
24. CML accounts for 15% of all cases of
leukemia.
More common in men
Peak incidence : fourth and fifth decade
25.
26. In CML the c-ABL gene is translocated from
its normal abode on chromosone 9 to
chromosone 22,where it fuses with bcr gene.
As a consequence of the fusion, c-ABL loses a
region that controls tyrosine kinase activity.
Thus the BCR-ABL protien,the product of the
fusion gene has potent and constitutive
tyrosine kinase activity.
29. EASY FATIGABILITY
DECREASE TOLERANCE TO EXERTION
ABDOMINAL DISCOMFORT AND EARLY
SATIETY( DUE TO SPLENIC ENLARGEMENT)
WIEGHT LOSS AND EXCESSIVE SWEATING
The symptoms are vague, nonspecific and
gradual in onset
30. A physical examination may detect pallor and
splenomegaly.The latter was present in 90%
of patients.
UNCOMMON PRESENTATIONS :
Dramatic hypermetabolism(night sweats,wt
loss,heat intolerance)
Acute gouty arthritis(due to hyperurecemia)
Priapism,tinnitus
Lt upper quadrant n lt shoulder pain due to
splenic infarction and perisplenitis.
31. CML is often suspected on the basis on
the complete blood count, which shows
increased granulocytes of all types, typically
including maturemyeloid cells.
Basophils and eosinophils are almost universally
increased; this feature may help differentiate
CML from a leukemoid reaction.
A bone marrow biopsy is often performed as
part of the evaluation for CML, and CML is
diagnosed by detecting the Philadelphia
chromosome.
32. 10–19% myeloblasts in the blood or bone
marrow.
>20% basophils in the blood or bone marrow
Platelet count <100,000, unrelated to therapy
Cytogenetic evolution with new abnormalities in
addition to the Philadelphia chromosome
Increasing splenomegaly or white blood cell
count, unresponsive to therapy
33. Blast crisis is the final phase in the evolution of CML, and
behaves like an acute leukemia, with rapid progression
and short survival.
Blast crisis is diagnosed if any of the following are present
in a patient with CML:
>20% myeloblasts or lymphoblasts in the blood or bone
marrow.
Large clusters of blasts in the bone marrow on biopsy.
Development of a chloroma (solid focus of leukemia
outside the bone marrow)
34. IMATINIB MESYLATE
STEM CELL TRANSPLANTATION
IFN-ALPHA
HYDROXYUREA
SECOND GENERATION TK INHIBITOR-
DASATINIB AND NILOTINIB
35. IMTINIB NOW IS USED AS INITIAL THERAPY IN
ALMOST ALL PATIENTS WITH CML.
IN CASES WHERE WBC COUNT IS MARKEDLY
ELEVATED HYDROXYUREA CAN BE USED TO
PREVENT HYPERLEUKOCYTIC SYNDROME.
36. The bcr abl oncoprotien
with a molecule of ATP in
d kinase pocket.
Phosphorylation - >
substrate .Activates
downstream molecules
Imatinib occcupies d
kinase pocket preventing
phosphorylation of its
substrates
37.
38. HAEMATOLOGIC
RESPONSE
CYTOGENETIC
RESPONSE
MOLECULAR
RESPONSE(BCR
ABL TO
CONTROL GENE
RATIO
ACCORDING TO
IS SCALE)
FREQUENCY .Every 2 weeks
until a complete
response has been
achieved and
confirmed.
every 3 months
unless othwise
required
every 6 months
until a complete
response has
been achieved
and confirmed.
then every 12
months
EVERY 3
MONTHS
METHOD complete blood
count (CBC) with
differential
Conventional
cytogenetic
examination
.FISH
(fluorescene in
situ
hybridisation)
(only before
treatment)
.RQ-PCR
(Reverse
transcription
quantitative
polymerase
chain reaction)
39. SMENT METHOD
SUBOPTIMAL RESPONSE FAILURE
tologic No Complete hematologic
response(CHR) within 3
months
No hematologic response
within 3 months
Loss of CHR at any time
enetic No MCyR (Major cytogenetic
response )within 6 months
No CCyR(Complete
cytogenetic response) within
18 months
.No cytogenetic response
within 6 months
No MCyR within 12 mont
No CCyR within 18 mont
Loss of CCyR at any time
Not applicable.
CULAR No MMR(Major molecular
response) within 8 months
Loss of MMR at any time
40.
41. Second generation TKI like
DASATINIB
NILOTINIB
Allogenic human stem cell transplant
42. Well tolerated compared to other treatment
options in CML
Superficial edema
Nausea,muscle cramps
Rash,Diarrhea
Uncommon side effects:tumour lysis in
accelerated phase,splenic rupture,cerebral
edema,Varicella Zoster infections
43. Imatinib is not recommended during
pregnancy.
Hydroxyurea has the lowest mutagenic
potential among the cytotoxic agents.
IFN can also be safely used during pregnancy.
44. Patients who are younger than 65 yrs and
who have a identical twin or a
histocompatible sibling can be transplanted
after intensive therapy usually with
cyclophosphamide.
GVHD is common.
