Chronic Myeloproliferative disorders

What other conditions are associated with chronic myeloproliferative disorders?

- spleen or liver enlargement
- cytogenetic abnormalities
- disorders of coagulation (DIC)

RBC count for CML, PMF, PV and ET

CML and PMF: Decreased
PV and ET: Increased

WBC count for CML, PV and ET

CML: very inc
PV: increased
ET: normal

Plt count for CML, PV and ET

CML: inc in beg, dec in late
PV: increased
ET: very inc

Which myeloproliferative disorder presents with dacrocytes?

primary myelofibrosis

LAP score for CML, PV and ET

CML: decreased
PV: increased
ET: normal/inc

Chronic Myelogenous Leukemia (CML)

- males > females
- high prevalence in US (1500 deaths each year)
- Philadelphia chromosome (Ph1)

What are the 3 phases of CML?

- initial chronic phase (blasts <20%, treatable)
- accelerated phase (basos, anemia, R to treatment)
- acute blast crisis (blasts > 30%, looks like acute)

What is the translocation for the Philadelphia chromosome? What does it make?

t(9;22), makes the BCR-ABL gene and protein

What does the BCR-ABL protein do?

provides sustained kinase activity which stimulates CML cell proliferation

What are the clinical symptoms of CML?

fever, weight loss, fatigue, abdominal pain, anemia, bleeding, infection

Blood profile for CML

WBC > 50-300, <20% blast, basophilia, N/N anemia, thrombocytosis, NRBCs

Bone marrow profile for CML

hypercellular (all stages), Increased M:E ratio

Lab findings for CML

Inc B12 and B12 binding, serum uric acid, muramidase, LDH
RT-PCR and flow cytometry (CD11b an CD33 +)

What is the prognosis for CML?

after remission, disease progresses to aggressive/accelerated phase (if blast > 30% 6 mos to live)

Treatments for CML?

chemo: hydroxyurea (also for sickle), cytarabine
Gleevec: tyrosine kinase inhibitor (best for those not stem cell transplant eligible)
Interferon, stem cell transplant

Minimal Residual Disease (MRD) and how to monitor

small amount of cancer cells remain after treatment (use flow RT-PCR, Next-gen sequencing)

What is the genetic mutation that leads to PV, ET, and PMF?

JAK2 (proliferation advantage)

Polycythemia Vera (PV)

clonal hyperproliferation characterized by excessive proliferation of ERYTHROID, granulocytes, and megas

What are common symptoms associated with PV?

headache, weakness, pruritis, fatigue, plethora (redness)

PV lab findings

inc hematocrit, WBC, plt, LAP
normal/low EPO

What are the complications associated with PV?

acute leukemia or myelofibrosis due to alkylating drugs and radiation

Primary Myelofibrosis (PMF) early vs. late

early: abnromal myeloprolif (esp. megas)
later: BM failure pancytopenia bc BM replacement by connective tissue

What do proliferating megakaryocytes secrete?

cytokines and growth factors

What is the major finding for PMF?

extramedullary hematopoiesis (cannot compensate)

What are the typical symptoms of PMF?

weight loss, anemia, abdominal discomfort, jaundice, > 40% osteosclerosis

What would you find in a PMF smear?

N/N anemia, aniso/poiki, DACROs, abnormal plts

The bone marrow aspirate in PMF would look like what?

dry due to increase in reticulum fibers and patchy fibrosis

What is the usual course of PMF?

progressive anemia, splenomegaly, opportunistic infections

What is the median survival for PMF and what factors can influences this?

4-5 years (degree of anemia, abnormal karyotype, plt count, osteomyelosclerosis)

Essential Thrombocythemia (ET)

predominance of megakaryocytic proliferation in the marrow (spontaneous hemorrhage, less common splenomegaly, neurologic symptoms)

What are the neurological symptoms caused by in ET?

vascular obstruction of the cerebral blood vessels by plt plugs

Laboratory profile for ET

^^ Plts (900-1400), hypochrom/microcyt, LAP normal/inc, inc B12 and uric acid, dec plt function, hypercellular marrow

What is the clinical course for Essential thrombocythemia?

stable for many years but may develop into other myeloproliferative disorders