Myeloproliferative Disorders Flashcards
Part of the body affected in myekoproliferaive disorders
Hematopoietic stem cell
Types of cells that proliferate in myeloproliferative disorders
Granulocytes
Ethrytocytes
Megakaryocytes
Classification based on
Lineage of predominant proliferation
Level of marrow fibrosis
Clinical data
Lab data
Clinal evolution in myeloproliferative disorder
Acquired abnormality of bone marrow stem cells
-> granulocytes precusors, red cell precursors , megakaryocytes
granulocytes precusors -> chronic myeloid leukemia -> acute myeloid leukemia
Red cell precursors -> polycythemia Vera ->acute myeloid leukemia or myeloid fibrosis
Megakaryocytes -> essential thrombocythemia or polycythemia Vera - > myelofibrosis
Is myeloproliferative disorder common in children or adults ?
Adults
Peak incidence of myeloproliferative disorder
7th
Pathogenesis
Dysregulated proliferation
Genetic abnormality
Is there bone marrow fibrosis in all MPD
Yes
What is polycythemia
Raised packed cell volume HCT
Polycythemia level in male
More than 49%
Hb more than 16.5 g/dl
Polycythemia level in female
More than 48%
Hb more than 16g/dl
Classification of MPD
Absolute
Apparent
Types of absolute MPD
Primary proliferative polycythemia (polycythemia Vera)
Secondary polycythemia
Idiopathic erythrocytosis
Type of apparent MPD
Plasma volume changes
Red cell mass changes
What is polycythemia Vera
Clonal stem cell disorder with increased red cell production
Mutation linked to polycythemia Vera
JAk2V617F
Exon 12(only 3%)
Disease phase of polycythemia Vera
Proliferative phase
Spent post polycythemia phase
Rarely become acute leukemia
Main age of polycythemia vera
55-60yo
Sometimes young adults
Clinical prevention of polycythemia Vera
Thrombosis DVT Hypertension Headache Poor vision Dizziness Skin complications like pruritus , erythomelalgia Hemorrhage due to platelet defect Hepatosplenomegaly Increased skin temp Burning sensation Redness
Lab findings of polycythemia Vera
Hb PCV Red cell mass increased Increased neutrophils and platelets Normal NAP Plasma urate high Hyper cellular bone marrow Low serum erythropoietin
Treatment of polycythemia vera
Decrease hematocrit by venesection , chemotherapy (hydroxyurea)
treat complication
What is secondary polycythemia
Increase in red cell mass due to other known -conditions in the body
When is there a compensatory y increase in erythropoietin
When there is hypoxia like in
In high altitude
pulmonary disease
Heart condition like Cyanotic heart disease
abnormal hemoglobin like high affinity hemoglobin
heavy cigarette smoker
When can you say that there is inappropriate erythropoietin production
In renal disease like carcinoma or hydronephrosis
in tumors lake fibromyoma and liver carcinoma
What is relative polycythemia
When there is an apparent polycythemia or pseudo polycythemia which is due to plasma volume contraction
What are some causes of relative polycythemia
Stress
cigarette smoking
alcohol intake dehydration
plasma loss like in burn injury
What is myelofibrosis or chronic idiopathic myelofibrosis
It is the progressive fibrosis of the marrow and increase in connective tissue element
Types of gene mutation in myelofibrosis
JAK2 55%
CALR 25%
MPL 10%
Is myeloid metaplasia Common in myelofibrosis
Yes
What is myeloid metaplasia and where does erythropoietin occur
Bone marrow replaced with fibrous tissue
It’s extramedullary erythropoiesis
mostly in the spleen and liver
What type of patient is Myelofibrosis mostly occur
Older patients
Clinical manifestation of myelofibrosis
Massive splenomegaly Hypermetabolic symptoms like loss of weight, fever ,and night sweats Bleeding problems bone pain gout
Can myelofibrosis become acute leukemia
Yes in 10 to 20% of
Lab findings of myelofibrosis
Anemia high white blood cells Late leukopenia and thrombocytopenia leucoerythroblastic blood filmed teardrop red cells bone marrow aspiration with DRY TAP due to fibrosis TREPHINEbiopsy with fibrotic hyper cellular marrow increase in NAP score
What is dry tap
In bone marrow aspiration not being able to get marrow
What are the causes of a leucoeryhtroblastic blood film
Idiopathic myelofibrosis bone marrow infiltration severe sepsis severe hemolysis sick neonates
What is the treatment of myelofibrosis
Blood transfusions ,regular folic acid therapy for anemia
Rudolitinib as oral JAK2 inhibitor to reduce spleen size
hydroxycarbamide
What is essential thrombocythemia
Clonal Myeloproliferative disease of megakaryocytic lineage. With thrombocytosis for more than six months ,increased megakaryocytes ,thrombotic or hemorrhagic episodes
What are some ways to have positive criteria for essential thrombocythemia
Platelet count of more than 450×10 ^9 per liter
Bone marrow biopsy
large and increased megakaryocytes
Mutation in essential thrombocythemia
JAK2 mutation (50-60%) CALR 75% if neg to jak 2
Diagnostic criteria for essential thrombocythemia
A1 sustain platelet count above 450×109 per liter
A2 acquired pathogenetic mutation
A3. No other myeloid malignancy primary myelofibrosis Clinic my Lloyd leukemia myelodysplastic syndrome
A4. No reactive cause for thrombocytosis and normal iron stores
A5 Bone marrow trephine histology shows increaesed megakaryocytes with large hyper lobulated forms , reticulin not generally increased
Which criteria’s are required for diagnosis of essential thrombocythemia
A1-A3
Or
A1+ A3-A5
What are some causes of reactive thrombocytosis
Bleeding Trauma Post operation chronic iron deficiency malignancy chronic infection connective tissue disorder’s post splenectomy
Clinical features of essential thrombocythemia
Hemorrhage
microvascular occlusion
splenic or hepatic vein thrombosis
hepatosplenomegaly
Treatments of essential thrombocythemia
Anticoagulants
chemotherapy with hydroxycarbamide, JAK2 inhibitors
Aspirin
Percentage of population that develop myelofibrosis in essential thrombocythemia
25%
Are acute leukemia transformation and deaths due to cardiovascular complication common disease course in essential thrombocythemia
Yes
What is leukemias
Neoplasm of white blood cells and it’s precursor with clonal proliferation and accumulation of cells in marrow
Two types of leukemias
Acute leukemias
chronic leukemia’s
What is chronic myeloid leukemia
Clonal malignant myeloproliferative disorder with increased proliferation of granulocytic cell line without loss of the capacity to differentiates
Increase in myeloid cells ,erythroidu cells and platelets in peripheral blood
marked myeloid hyperplasia in the bone marrow
Etiology of chronic myeloid leukemia
Not clear but BCR ABL fusion GENE
People at risk of chronic myeloid leukemia
Survivors of an atomic disasters of neck Nagasaki and Hiroshima
Post radiation therapy
What is the acquired cytogenetic anomaly occurring in all leukemic cells in chronic myeloid leukemia
Philadelphia chromosome
What’s translocation occurs in the Philadelphia chromosome
Translocation reciprocal between Chromosomes 22 and chromosome nine
Why is the fusion of the Protein BCR abl leading to leukemia
Has tyrosine kinase activity which transforms Hematopoietic cells To become independent of growth and survival cytokines And protect the cells from programmed cell death
Can you call features of chronic myeloid leukemia
40% asymptomatic
Chronic phase with massive splenomegaly ! hypermetabolism symptoms like weight loss ,anorexia ,lassitude ,night sweats
Anemia with pallor, dyspnoea ,tachycardia
Abnormal platelet function with bruising ,epistaxis ,menorrhagia
Hyper leukocytosis With thrombosis ,increased purine breakdown with gout, visual disturbances, priapism
Blood findings in chronic myeloid leukemia
Raised white blood cell counts Blast cell less than 10% Granulocytes at all stage High eosinophils, basophils Hb low Raised platelet
Bone marrow lab features
Hypocellular reduced fat spaces myeload to erythroid ratio 10:1 to 30:1 Myélocytes predominant Blast cells less than 10% megakaryocytes increased and dysplastic increased ridiculous fibrosis in 30 to 40%
Test for chronic myeloid leukemia
Full blood counts blood film neutrophils alkaline phosphatase urea electrolytes serum lactate dehydrogenase bone marrow aspirate bone marrow trephine biopsy (extent of fibrosis BCR ABL chimeric gene by fluorescent in situ hybridization or PCR vitamin B 12 and B12 binding capacity
What characterize the chronic phase of myeloid leukemia
Less than 10% blast cell in the blood or the marrow
basophils less than 20% in the blood
What happens in the accelerated phase which last for 3.5 to 5 years
Increased Splenomegaly because of chemotherapy
increased chemotherapy requirement
Blast cells about 10 to 19% in the blood
basophils more than 20% in the blood
persistent thrombocytopenia or thrombocytosis
cytogenetic Clonal evolution
What happens in the blastic phase of myeloid leukemia
Ressemble acute leukemia
More than 20% blessed in blood or bone marrow
2/3 myeloid blastic phase 1/3 in lymphoid blastic phase
Which has higher survival rates lymphoid or myeloid leukemia
Name for it
General management of chronic myeloid leukemia
Discussion with family about prognosis ,disease ,diagnosis ,choice of treatment (cytotoxic drug or bone marrow transplant)
What is the principle of the treatment in chronic myeloid leukemia
Relieve symptoms of hyper leukocytosis splenomegaly and thrombocytosis through hydration and chemotherapy
Control and prolong the chronic phase by , imatinib mesylate , hydroxyurea ,Alfa interferon+ chemotherapy
Eradicate malignant clone to cure with allogeneic transplant or imatinib
Action of imatinib mesilate
inhibits enhanced protein tyrosine kinase activity of BCR ABL oncoprotein
What is busulphan
Alkylating agent used in old patient which are not candidate for transplant
Side effect of busulphan
Prolonged myelosuppression
skin pigmentation
infertility
pulmonary fibrosis
Hydroxyurea action
Inhibits ribonucleotide reductase
Which treatment has the longest survival rate for chronic myeloid leukemia
Transplant with more than five years survival
Interferon and chemotherapy for six years survival
