Myeloproliferative Disorder (MYELOFIBROSIS)

1. Myeloproliferative Disorder
(MYELOFIBROSIS)
MARYAM JAMILAH BINTI ABDUL HAMID
082013100002
IMS BANGALORE

2. LEARNING OUTCOME
• Definition
• Etiology
• Pathogenesis
• Clinical features
• Investigations
• Complications
• Prognosis
• Managements

3. INTRODUCTION
WHO classification of chronic
myeloproliferative neoplasm:
Primary myelofibrosis
Essential thrombocytosis
Polycythemia vera
Mastocytosis
Myeloproliferative neoplasms,
unclassifiable
Chronic myeloid leukaemia,
bcr-abl (positive)
Chronic neutrophilic leukaemia
Chronic eosinophilic
leukaemia, NOS

4. • Primary myelofibrosis (PMF), Secondary
Myelofibrosis (malignant/nonmalignant)
• Primary myelofibrosis (PMF) is least common,
affect men > female in 6th decades or later
• PMF: absence of specific clonal marker -difficult to
establish the diagnosis
• myelofibrosis + splenomegaly seen in polycythemia
vera and CML

5. DEFINITION
• AKA Chronic primary myelofibrosis / idiopathic myelofibrosis
/ agnogenic myeloid metaplasia / myelofibrosis with myeloid
metaplasia
“A clonal disorder of a multipotent hematopoietic
progenitor cell of unknown etiology characterized by marrow
fibrosis, extramedullary hematopoiesis and splenomegaly”

6. ETIOLOGY
• PMF: unknown
nonrandom chromosome abnormalities (9p,20q-
,13q-,trisomy 8 or 9, or partial trisomy 1q)
JAK2 V617F in 50% patients
mutations in receptor Mpl in 5% patients
mutations in calreticulin gene (CALR) -alter
carboxy-terminal portion of the gene product

7. • Disorders causing myelofibrosis
Malignant Nonmalignant
• Acute leukaemia
• CML
• Hairy cell leukaemia
• Hodgkin’s disease
• Primary myelofibrosis
• Lymphoma
• Multiple myeloma
• Myelodysplasia
• Metastatic ca
• Polycythemia vera
• Systemic macrocytosis
• HIV infection
• Hyperparathyroidism
• Renal osteodystrophy
• SLE
• TB
• Vit D deficiency
• Thorium dioxide exposure
• Gray platelet syndrome

8. PATHOGENESIS
• polyclonal
• marrow initially hypercellular, with abnormal
megakaryocytes -release PDGF to the marrow
microenvironment = reactive proliferation of fibroblasts
• overproduction of transforming growth factor ß & tissue
inhibitors of metalloproteinases
• osteosclerosis- overproduction of osteoprotegerin
(osteoclast inhibitor)
• marrow angiogenesis -Increase VEGF

10. CLINICAL FEATURES
• painful splenic infarct -fever & pleuritic chest pain

11. INVESTIGATIONS
• leucoerythroblastic anemia
• Peripheral smear ; characteristics of
extramedullary hematopoiesis (teardrop-shaped
cells, nucleated red cells, myelocytes &
promyelocytes *myeloblasts may be present), giant
megakaryocytes

13. • Marrow trephine biopsy; marrow cavity replaced
by fibrosis
• Genetic analysis
• Cytogenetic analysis, IHC (exclude CML)
• Urate level

14. COMPLICATIONS
• Evolve to accelerated phase
• Marrow failure
• 10% transform into aggressive acute leukaemia

15. • Survival is less than in PV & ET (4 years after
diagnosed but range 1-20 years)
PROGNOSIS

19. MANAGEMENTS
• no specific treatment
• Ruxolitinib (JAK2 inhibitor)
• HSCT for younger patients
• PCV transfusion, folic acid
• corticosteroid (for constitutional symptoms; fever,
chills, night sweats, anorexia, weight loss)
• low dose thalidomide * combine with prednisone

20. • hydroxycarbamide (cytotoxic, to control spleen size)
• splenectomy
• erythropoietin/danazol (for anemia) *erythropoietin
can worsen splenomegaly if serum level is >125
mU/L

21. REFERENCES
• Davidson’s Principles and Practicals of Medicine,
22nd Edition, page 1048-1049
• Harrison’s Principles of Internal Medicine, 19th
Edition, page 674-676
• mayoclinic

22. THANK YOU