Myeloproliferative Neoplasms

Background

-Clonal myeloid conditions in which blood production is deregulated and independent of growth factors

-Caused by acquired genetic defects in myeloid cells

-May present with unusual thromboses, plenomegaly, or constitutional symptoms

-Each has a chronic phase that may progress to an acute leukemia

What is Polycythemia Vera?

A condition characterized by the overproduction of all three hematopoietic cell lines, most prominently red blood cells, independent of erythropoietin (EPO).

What percentage of Polycythemia Vera cases are male?

60%

What is the median age of diagnosis for Polycythemia Vera?

60 years

What genetic mutation is commonly associated with Polycythemia Vera?

JAK2 mutation

What is the median survival time after diagnosis of Polycythemia Vera?

15 years

What is a major cause of death in patients with Polycythemia Vera?

Arterial thrombosis

What is the risk associated with Polycythemia Vera regarding disease transformation?

Risk of transformation to Chronic Myeloid Leukemia (CML)

Clinical Manifestation of Polycythemia Vera

-Headache

-Dizziness

-Tinnitus

-Blurred Vision

-Fatigue

-Facial Plethora

-Engorged Retinal Veins

-Thrombosis

-Splenomegaly

-Aquagenic Puritus

SecondaryPolycythemia Vera

-No leukocytosis or thrombocytosis

-No splenomegaly

-Sources include OSA, Smoking, or other myeloproliferative disorders

-No need for treatment

Polycythemia Vera Treatment

-Avoid iron supplementation

-Phlebotomy (decreases thrombosis risk)

-Asprin

-Hydrea (to decrease RBC volume)

-Jakafi

What is Essential Thrombocytosis?

An uncommon disorder with marked proliferation of megakaryocytes in the bone marrow leading to platelet elevation.

What is the etiology of Essential Thrombocytosis?

Unknown etiology.

Which mutations are common in Essential Thrombocytosis?

Jak2, CALR, and MPL mutations.

What is the median age of diagnosis for Essential Thrombocytosis?

50-60 years old.

What is the risk associated with Essential Thrombocytosis?

Increased risk of thrombosis.

What bleeding risk is associated with Essential Thrombocytosis?

Bleeding risk from platelet defects.

Essential Thrombocytosis Clinical Manifestations

-Paresthesia

-Erythromelalgia (painful burning in the hands and feet)

-Splenomegaly

-Leukocytosis

-No erythrocytosis

-Smear with large platelets

Essential Thrombocytosis Labs

-Platelet count over 2,000,000

-WBC elevated

-Bone marrow biopsy to show increased megakaryocytes

Essential Thrombocytosis Treatment

-Aspirin

-Hydrea

-Survival greater than 15 years from dx

Lymphoma

-Aberrant proliferations of white cells in lymphatic tissue

-Wide spectrum of disease ranging from indolent to very aggressive

Lymphoma Pathophysiology

-Recurring genetic abnormalities at a variety of levels

-Gross chromosomal changes

-Rearrangement of specific genes

-Changes in oncogenes leading to overexpression

-Environmental factors play a role

Hodgkin Lymphoma

-B Cell lymphoma with painless lymphadenopathy typically cervical, axillary and groin

-Will find Reed-Sternberg Cells on biopsy

-Bimodal age distribution (20 and then 50's)

-Classical Hodgkin Lymphoma include nodular sclerosis, mixed cellularity, lymphocyte rich/depleted

Hodgkin Lymphoma Epidemiology/Etiology

-3 times elevated risk after mono infection

-Increased incidence with immunodeficiency and personal or family history of autoimmune disease

What are B symptoms in Hodgkin Lymphoma?

Fever, night sweats, and weight loss

What is a common skin symptom of Hodgkin Lymphoma?

Generalized pruritus

How does Hodgkin Lymphoma typically spread?

From a single lymph node group to contiguous areas

What unusual symptom can occur with lymph nodes in Hodgkin Lymphoma after alcohol ingestion?

Pain involved with lymph nodes

Hodgkin Lymphoma Exam Findings

-Diffuse/puffy swelling rather than a mass that is typically a cervical lymph node

-Can involve the spleen

-Rare paraneoplastic syndromes have been described in cHL at time of dx

Hodgkin Lymphoma Work up/Diagnosis

-Must get an excisional lymph node biopsy

-ID of immune markers of Hodgkin Lymphoma

-Labs include CBC w/ Diff, CMP< LDH, and uric acid

-CT scans and PET scans

-Bone Marrow Biopsy

What does Stage 1 of Hodgkin Lymphoma indicate?

Involvement of a single lymphatic site

What does Stage 2 of Hodgkin Lymphoma indicate?

Involvement of two or more lymphatic sites above the diaphragm

What does Stage 3 of Hodgkin Lymphoma indicate?

Involvement of two or more lymphatic sites on both sides of the diaphragm

What does Stage 4 of Hodgkin Lymphoma indicate?

Involvement of more than one lymph organ

What does the letter A signify in Hodgkin Lymphoma staging?

No symptoms

What does the letter B signify in Hodgkin Lymphoma staging?

B symptoms

What does the letter E signify in Hodgkin Lymphoma staging?

Involvement of a single extra nodal site

What does the letter S signify in Hodgkin Lymphoma staging?

Splenic involvement

Hodgkin Lymphoma Treament

-Early stages chemo with or without radiation

-Late stages get radiation

-Relapse disease get chemo and radiation with possible HCT

Hodgkin Lymphoma Prognosis

-10 year survival over 90% for those under 44

-10 year survival of 80% for those under 45-54

-10 year survival of 70% for those under 55-64

-Relapse in 10-15% of patients

Diffuse Large B Cell Non-Hodgkin Lymphoma Epidemiology

-Most common NHL

-25% are double hit lymphomas (over expression of MYC and BCL2 proteins and very aggressive)

-Incidence increases with age

-May arise through the transformation of many different types of low grade B cell lymphomas

-Associated with EBV

What is a common clinical manifestation of Diffuse Large B Cell Non-Hodgkin Lymphoma?

Rapidly enlarging symptomatic mass

What are B symptoms in the context of Diffuse Large B Cell Non-Hodgkin Lymphoma?

Fever, night sweats, and weight loss

What percentage of patients with Diffuse Large B Cell Non-Hodgkin Lymphoma present with advanced disease?

60%

What percentage of patients with Diffuse Large B Cell Non-Hodgkin Lymphoma present with localized disease?

40%

In what percentage of Diffuse Large B Cell Non-Hodgkin Lymphoma cases is there bone marrow involvement?

30%

What percentage of Diffuse Large B Cell Non-Hodgkin Lymphoma cases arise in extranodal extramedullary tissues?

40%

What is the most common site for extranodal extramedullary involvement in Diffuse Large B Cell Non-Hodgkin Lymphoma?

Gastrointestinal tract

Diffuse Large B Cell Non-Hodgkin Lymphoma Diagnosis/Workup

-Excisional tissue biopsy

-PET and CT scans

-Bone marrow biopsy

-Lab testing includes CBCD, CMP, LDH, uric acid, SPEP, beta-2 micrglobulin, hepatitis serologies, HIV testing

-Echo

-Lumbar puncture if risk of CNS involvement

Diffuse Large B Cell Non-Hodgkin Lymphoma Treatment

-Early stage chemo with or without radiation

-Late stage is chemo with rituximab

Diffuse Large B Cell Non-Hodgkin Lymphoma Prognosis

-Curable in 50% of cases

-Consider CAR T-cell therapy if 2nd treatment fails

Folicular Non-Hodgkin Lymphoma

-Derived from mutated germinal center B cells

-Median age 59

-Aggressive cases in 30-40% of cases

Folicular Non-Hodgkin Lymphoma Signs and Symptoms

-Patients often asymptomatic

-Painless diffuse lymphadenopathy

-Hepatosplenomegaly

-Marrow infiltration

-Peripheral lymphoma cells

Folicular Non-Hodgkin Lymphoma Treatment

-Watch and wait approach

-Do not treat until symptomatic

-Once symptomatic then treat with rituximab and localized radiation

What type of lymphoma is Burkitt Non-Hodgkin Lymphoma?

Highly aggressive

What chromosomal translocation is associated with Burkitt Non-Hodgkin Lymphoma?

MYC gene

What is the endemic form of Burkitt Non-Hodgkin Lymphoma associated with?

Jaw or facial bone tumor and +EBV

What characterizes the non-endemic forms of Burkitt Non-Hodgkin Lymphoma?

Sporadic and immunodeficiency-associated, with abdominal mass common

What can Burkitt Non-Hodgkin Lymphoma progress to?

Burkitt Leukemia

What percentage of Burkitt Non-Hodgkin Lymphoma cases will develop leptomeningeal involvement?

30%

What treatment option can be considered for relapsed Burkitt Non-Hodgkin Lymphoma patients?

Stem cell transplant