Dr.Husna.Sp.

PK
INSTALASI PATOLOGI KLINIK
Myeloproliferative disorders
Nuetrophil Eryhtroid Megakaryocytic
Line Line Line
C.G.L P.R.V E.T
C.G.L
Chronic Granulocytic Leukaemia

ITS PATHOGENESIS
Philadelphia chromosome
Translocation 9:22 (t- 9:22)
Fusion 22q-/9q (Ph
1
)
New Hybridization
New Chimerism
BCR/Abl oncogene
BCR = Breakpoint Cluster Region
Abl = Abelson
New Chimeric Fusion Protein
BCR/Abl oncogene
TYROSINE KINASE-LIKE
ACTIVITY

PROLIFERATIVE EFFECT
Philadelphia Chromosome
(BCR/Abl oncogene)
Proliferation in Neutrophil line
Proliferation in eythroid line
Proliferation in megakarycytic line

NEUTROPHIL PROIFERATION produces
C.G.L
Symptoms and signs
Bloatedness (splenomegaly)
Leucocytosis (>100 x 109/l)
Thrombocytosis later thrombocytpaenia
Polycthaemia later anaemia
Loss of weight + weakness
Laboratory tests
FBCs: leucocytosis (>100 x 109/l) with
immature neutrophil (myelocytes
+metamyelocytes)
Basophilia
Neutrophil Alk Phosphatase: reduced
BMP: Ph
1
and BCR/Abl oncogene + do
HLA typing
Diagnosis
Classical CGL: clear by morphology,
confirmative with Ph
1
and BCR/Abl
In Non-classical, usually Ph
(-)
then
BCR/Abl is necessary------leucocytosis is
mild and splenomegaly is not striking
Treatment
Previously: Busulphan (leukemogenic)
Now: Hydroxyurea
Interferon (INF-)---10 Mega unit 3 x/week
BMT (Bone Marrow Transplantation)
3 Phases of C.G.L
CHRONIC phase:
ACCELERATED phase: the dose of drugs
and need of transfusion is increasing
BLASTIC CRISIS (blastic transformation):
appearance of > 5% blasts in B.M or FBCs
+ striking splenomegaly
Principles of treatment
Busulphan and Hydoxyurea: to suppress
WBCs to nearly normal and maintain
INF-: Negativity of Ph Chr but not
persistent
BMT: definite cure
Essential Thrombocythaemia
E.T
Primary proliferation of
megakaryocytic line
Pathogenesis: ?
Majority does not have Philadelphia
Chromosome
Symptoms and signs
Usually in the old age (>60 years old)
Giddiness, vertigo
AMI
Ischaemis stroke
Peripheral vascular obstruction
Diagnosis
Platelet volume study
Platelets (> 1 million/cu.mm)
Splenomegaly (although mild)
Therapy
Busulphan or Hydroxyurea
Radioactve Phosphor or I
125
(given the very
old age)
Anti-platelet if given should be with great
care. Some platelets are non-functioning
and it may give bleeding. So, it is give only
when there evidence of thrombosis
Differential diagnosis:
Secondary thrombocythaemia
Such as in bleeding e.c operation
A.M.L
Acute Myeloblastic Leukaemia
FAB classification
M-1: undifferentiated AML
M-2: well differentiated AML
M-3: acute promyelocytic leukaemia (APL)
M-4: acute myelomonoblastic leukaemia
M-5: acute monoblastic leukaemia
M-6: erythroleukaemia
M-7: acute megakaryocytic leukaemia (GpIIb/IIIa)
Diagnosis of A.M.L
(in general)
Previously 30 % myeloblasts
Now 20% myeloblasts (M-6)
Pathogenesis: ?
Except for M-3 (APL)
RAR gene
Symptoms and signs
Not specific such as weakness
Infection: fever (leucocyte abnormality)
Palor: anaemia
Bleeding: thrombocytopaenia
DO THE B.M.P, save sample for
karyotyping
Levels of risks
A. GOOD RISK: any of t (8:21), t (15:17),
inv (16)
B. STANDARD RISK: not in A or C
C. POOR RISK: 20% blast in B.M after
course 1 treatment and has no favourable
karyotyping as in A.
REMISSION INDUCTION
Course 1 and 2
ADE (Ara-C, Daunorubicin, Etoposide)
Course-1 (10+3+5), Course-2 (8+3+5)
MAE (mitoxantrone, Ara-C, Etoposide)
Course-1 (3+10+5), Course-2 (8+3+5)
Do B.M to assess
Collect PBSC if CR after course-1
Levels of risks
A. GOOD RISK: any of t (8:21), t (15:17),
inv (16)
B. STANDARD RISK: not in A or C
C. POOR RISK: 20% blast in B.M after
course 1 treatment and has no favourable
karyotyping as in A.
CONSOLIDATION
MACE (Amsacrine + Ara-C +
Etoposide day 1-5 by continuous I.v)
Do PBSC collection
Do B.M Harvest
Futher Phase
Maintenance or
2
nd
consolidation MiDAC (Mito, Ara-C) or
ICE (Ida+Ara+Eto)
PBSC
BMT allogeneic: standard or poor risk
Thats the treatment for AML
Good risk cases respond well except
for APL (M-3) t (15:17) where D.I.C
frequently happens--bleeding
t (15:17) in A.P.L
RAR- gene (retinoic acid receptor) in Chr-
17 translocate to Chr 15
Producing PML/RARA and RARA/PML
new arrangement
This new arrangement is effective for
ATRA (all-Trans Retinoic Acid)
ATRA in A.P.L
To give 5 days ATRA followed induction
chemotherapy
Continuous ATRA + Induction
chemotherapy
Whatever choice is taken ATRA seem
capable to reverse the coagulopathy.