Myeloproliferative disorders

myeloproliferative disorder

-blood cancers: producing blood cells uncontrollably

-JAK2 mutation most common

Polycythemia Vera (PV)

-acquired

-overproduction of all three hematopoietic cell lines (mostly RBC)

-males

->60

PV pathogenesis

mutation in JAK2 gene > abnormal JAK2 tyrosine kinase activity > neoplastic proliferation of the hematopoietic cells > myeloproliferative > PV

-acquired mutation in exon 14 of JAK2 molecule

PV symptoms

-too many of all cell types

-pruritis after bath

PV signs

-dilated retinal veins

-splenomegaly

-ARTERIAL THROMBOSIS- MMC of death

PV diagnosis

CBC: Hematocrit: exceed 49% male, 48% females, increase vitamin B12

Screening: JAK2 mutation

PBS: basophil and eosinophil present

bone marrow: hypocellular

PV treatment

first line: phlebotomy

hydroxyurea 500 QD PO

-cause cell death

second line: myelosuppressive therapy

aspirin: given to all to reduce thrombosis

PV education/prognosis

-slow growing

-mortality cause = thrombosis

Essential Thrombocythemia (ET)

-proliferation of megakaryocytes in bone marrow = more platelets

-50-60

-female

ET pathogenesis

-et clonal stem cell disorder > extensive platelet production and not prolonged platelet survival in peripheral blood

ET symptoms

- accidentally discovered

-NO ITCHING

-erythromelalgia: burning hands

ET signs

MCC- thrombosis

ET diagnosis

CBC: ELEVATED PLATELETS >2 mil

PBS: large platelets

Bone marrow: increase megakaryocytes nothing else

philadelphia chromosome = neg

ET treatment

Firstline: hydroxyurea 500mg QD

Low dose aspirin 81mg BID for thrombosis

-high risk if >60, JAK2 mutation, history

Primary Myelofibrosis (PMF)

proliferation of abnormal bone marrow megakaryocytes and granulocytes, bone marrow fibrosis

- >50

PMF Pathophysiology

-acquired genetic mutation = increased secretion of platelet derived growth factor, cytokine, megakaryocytes, monocytes > fibrosis of bone marrow > PMF

bone marrow fibrosis takes place in

liver, spleen, lymph nodes

-mesenchymal cells can be reactivated in fetal

PMF symptoms

> 50

-severe fatigue- common

-abdominal fullness

PMF signs

-splenomegaly - massive

-enlarged liver 50%

-extramedullary hematopoiesis more prominent

PMF diagnosis

PBS: teardrop poikilocytosis, leukoerythroblastic blood, giant abnormal platelets

-bone marrow: dry tap

CBC: anemia

PMF treatment

low risk: observe

moderate: hydroxyurea 500mg QD

high: allogenic stem cell transplant

PMF education/prognosis

-survival 5 years after diagnosis

Plasma Cell Myeloma (MM)

-malignancy of hematopoietic stem cells terminally differentiated as plasma cells

-make specific immunoglobulins

-male

-african

- 65-74

MM pathophysiology

mutation in oncogene cyclin D1 or D3 on chromosome 14 or deletion of TP53 on chromosome 7 > malignant proliferation of B cells > cause excess secretion of M proteins > end organ damage

M protein

-monoclonal antibody, produced in excess by B cells

-can be detected in blood or urine of myeloma patients

light chains= bence-jones

MM classification

-two heavy chains: G, A, D, E, M

-two light chains: kappa, lambda

MCC- IgG kappa: two IgG heavy, two kappa light

15% only have light chains= bence-jones myeloma

MM symptoms

-symptoms represent end organ damage

C- hyperCalcemia: bone demineralization

R- Renal dysfunction: free light chain nephropathy

A- Anemia

B- Bone pain w lytic lesions: fractures

interaction between myeloma and bone microenvironment lead to

activation of osteoclasts and suppression of osteoblasts = bone loss

MM Tests

CBC: anemia

PBS: rouleaux formation

metabolic panel: elevated total protein

SPEP, UPEP, IFE: done all together to see proteins and Ig

-60% IgG

Free light chain analysis: elevated

MM imaging studies

Bone Xray or CT: lytic lesions

MM bone marrow biopsy

Clonal bone marrow plasma cells > 10%

MM confirmative diagnosis

-clonal plasma cell >10

-Biopsy + plasmacytoma (plasma tumor of bone or soft tissue

-SLiM-CRAB

MM treatment

-treat CRAB symptoms

D-VRd:

Daratumumab

Velcade:protease inhibitor chemo

Revlimid: immunomodulatory chemo

dexamethasone: corticosteroid

Autologous stem cell transplant

Smoldering Multiple Myeloma (SMM)

low risk: low risk to get MM

smoldering: asymptomatic, no CRAB, clonal plasma cells in bone marrow

-observe

MM education/prognosis

-no cure

-untreated= 5-12 mon survival

-treated= 5 year survival