Myelofibrosis

Dimas Bayu
A. Fachruddin Benyamin

Division of Hematology & Oncology, Dept. of Internal Medicine

Faculty of Medicine, Hasanuddin University

Introduction:

Myeloproliferative disorders describes a group

of conditions characterized by clonal proliferation
of one or more haemopoietic components in the
bone marrow & sometime the liver & the spleen.
These disorders are closely related .

Division of Hematology & Oncology, Dept. of Internal Medicine

Introduction
Myeloproliferative disorders :
1

Polycythemia Vera ( PV )

Essential Thrombocytemia (ET )

Chronic Myelocytic Leukemia

Myelofibrosis ( MF )

Division of Hematology & Oncology, Dept. of Internal Medicine

Hematopoetic stem cel

Prekursor
granulosit

CML

Prekursor
eritrosit

Prekursor
magakariosit

Fibrosis
reaktif

PV

TE

MF

AML
Division of Hematology & Oncology, Dept. of Internal Medicine

Introduction:
Other designations (angogenic myeloid
metaplasia,myelofibrosis with myeloid metaplasia).
Is a clonal disorder of hematopoeitc progenitor cell
of unknown etiology characterize by marrow
fibrosis,myeloid metaplasia ,with extramedullary
hematopoiesis & hepatosplenomegally.
There is over production of collagen.

Division of Hematology & Oncology, Dept. of Internal Medicine

Myelofibrosis

Bone marrow fibrosis

Splenomegaly & Hepatomegaly

Characterized by

Blood smear :
leuco-erithroblastic
( immature leucocyte & erythrocyte ),
poikilositosis: tear-drops cells

Division of Hematology & Oncology, Dept. of Internal Medicine

Etiology:

The etiology is unknown.

No specific cytogenitc abnormality has been identified.

Division of Hematology & Oncology, Dept. of Internal Medicine

Pathogenesis
Platelet Derived Growth Factor (PDGF) secretion
& other cytokine >>

bone marrow fibrosis

extramedullary hematopoesis
in the spleen, liver, limph-node
(reactivation of the mesenchymal tissue
which was active for hematopoesis in foetus)
Division of Hematology & Oncology, Dept. of Internal Medicine

Clinical features:
Age > 50 years old
No specific sign or symptoms.
Most patients are asympotomatic at presentation
&usually recognized by splenic enlargement &/or
abnormal blood count .
Blood smear revels the characteristic feature of
extramedullary hematopiesis.
Mild hepatomegally.
LDH&Alkaline phosphatase can be high.
BM aspirate will give dry tape.

Division of Hematology & Oncology, Dept. of Internal Medicine

Diagnosis:
The diagnosis is by exclusion.
Peripheral blood film (teardrop-shaped red
cells,nucleated red cells,myelocytes,and promyelocytes)
establishes the presence of extramedullary
hematopoeisis.
Bone marrow is usually not aspirable due to increase
marrow reticulin.
Marrow biopsy:hyper cellular marrow,with trilineage
hyperplasia&in particular megakaryocytes.

Division of Hematology & Oncology, Dept. of Internal Medicine

Clinical Sign
In the late phase ( bane marrow failure due to fibrosis ):

Severe Anemia transfusion

Severe thrombocytopenia bleeding

Spleenomegaly >> early satiety

Spleen Infarction pain/ shock (surgery)

Cachexia
Division of Hematology & Oncology, Dept. of Internal Medicine

Clinical Sign
6

Bone pain (lower extremity)

Hematopoesis in the liver portal hypertension

(ascites & esophageal varices)

Abnormal myelopoesis in epidural cavity

Transversal Myelitis

Division of Hematology & Oncology, Dept. of Internal Medicine

Laboratorium
1. Mostly anemia
2. Leucocyte could be < , normal, atau >
(sometimes 50.000 / mm3)
3. Thrombocyte count is vary
Abnormal thrombocyte (giant)
4. Blood smear: poikilositosis,tear-drop cell
(abnormal erythrocyte)

Division of Hematology & Oncology, Dept. of Internal Medicine

Laboratorium

Teardrop cells & nucleated red blood cells

Division of Hematology & Oncology, Dept. of Internal Medicine

Laboratorium
immature erythrocyte & myeloid cell
(mieloblast / promielosit)
Bone Marrow: dry-tap, initial phase:
hypercellular bone marrow
Early phase: reticulin, late phase: collagen
Chromosome abnormality (-)

Division of Hematology & Oncology, Dept. of Internal Medicine

Laboratorium

Myelofibrosis of the bone marrow. Total replacement of marrow precursors

and fat cells by a dense infiltrate of reticulin fibers and collagen (H&E stain).
Division of Hematology & Oncology, Dept. of Internal Medicine

Laboratorium

Reticulin stain of marrow myelofibrosis. Silver stain of a myelofibrotic

marrow showing an increase in reticulin fibers (black-staining threads).
Division of Hematology & Oncology, Dept. of Internal Medicine

Differential Diagnosis

MF
Leuco-erythroblastic :
Found in severe infection,
severe inflammation, bone
marrow infiltration (no teardrops cells & giant
thrombocyte)

Bone Marrow Fibrosis :

Found in metastatic
carcinoma, Hodgkin,
Hairy cell leukemia

Division of Hematology & Oncology, Dept. of Internal Medicine

Complication:

Chronic disease of a median survival of 5years.

The patients are prone to deep-seated tissue infections
particularly of the lung.
Can transform to accelerated phase with constitutional
symptoms and marrow failure.
In 10% of patients the disorder terminates in a rapidly
progressive form of acute leukemia for which therapy is
usually is ineffective.

Division of Hematology & Oncology, Dept. of Internal Medicine

Management
No specific treatment.
1. Anemia transfussion
2. Androgen (Oxymetholone 200 mg p.o/ day,
or testosterone)
3. Splenectomy, if the patients experienced
pain, severe thrombocytopenia, or
transfussion dependent >>
4. Interferon Alfa, 2-5 MU, Sub-Cutaneous,
three times a week
5. Allogenic bone marrow transplantation
( young patients ) 50 % long-term survival
Division of Hematology & Oncology, Dept. of Internal Medicine

Prognosis

Median survival: 5 years after first diagnosis

Late phase: General weakness, liver failure,
bleeding due to thrombocytopenia
Several cases transform into Acute Myeloid Leukemia

Division of Hematology & Oncology, Dept. of Internal Medicine