myeloproliferative neoplasms Flashcards
Myeloproliferative Neoplasms (MPN)
Definition
MPN: clonal myeloid conditions in which blood production is deregulated and independent of growth factors
* Caused by acquired genetic defects in myeloid stem cells
* May present with unusual thromboses, splenomegaly, constitutional symptoms
* Each has a chronic phase that may progress to an acute leukemia
Polycythemia Vera (PCV)
general
Acquired MPN
60% males
Median age: 60
Median survival 15 years from dx
Arterial thrombosis major cause of mortality
Risk of transformation to myelofibrosis or CML. Rarely to AML
essentially too many RBCs
PCV
Clinical manifestations
Engorged Retinal Veins
Thrombosis
Gouty arthritis
Headache
Fatigue
Blurred vision
Facial plethora- constant facial redness
Palpable splenomegaly in 75% of pts
Erythromelalgia. This is a burning pain in the hands or feet, usually accompanied by a reddish or bluish coloration of the skin. Caused by an ↑ platelet count or ↑ platelet aggregation, resulting in formation of tiny blood clots in the vessels of the extremity; responds rapidly to aspirin.
pts are often itchy after a hot shower
PCV
Laboratory findings
Genetic testing
↑RBCs
↑ Hct
might be increased slightly Basophilia or eosinophilia
↓EPO low
JAK2 mutation- 95% of cases
Bone marrow biopsy- Hypercellular
PCV
major and minor criteria
PCV
Primary Tx
Avoid iron supplements
Phlebotomy
Decrease thrombosis risk
ASA 81mg PO daily
Hydrea (Hydroxyurea)- also for sickle cell
500-1500mg PO daily
Jakafi (Ruxolitinib)
Oral Jak 2 inhibitor for those who fail or are intolerant of Hydrea
pts with JAK2
PCV
secondary Tx
Likely hypoxemia related
Fix underlying etiology
Phlebotomy for Hct >55%
pts with hypoxia, COPD, smokers, sleep apnea
Essential Thrombocytosis or -themia (ET)
general
Unknown etiology
Jak2, CALR, MPL mutation common
Median age: 50-60
Female > Male
Risk of thrombosis:
Age > 60yr
WBC ≥ 11,000/mcL
History of thrombosis
Bleeding risk from platelet defects
ET
Clin man
Paresthesia
Erythromelalgia -Painful burning of hands with erythema
Splenomegaly
May have concurrent leukocytosis
No erythrocytosis!
Peripheral smear with large platelets
ET
Tx
ASA 81mg daily
Hydrea (Hydroxyurea) 500-1,000mg PO daily
Keep platelet < 500,00/mcL
Lymphoma
definition
Aberrant proliferations of white cells in lymphatic tissue such as
Lymph nodes, spleen
Some also invade extra-nodal sites
Wide spectrum of disease ranging from indolent to very aggressive
WHO classification identifies 3 major categories of lymphoid malignancies:
Non-Hodgkin lymphoma
B-cell neoplasms
T and natural killer (NK) cell neoplasms
Hodgkin lymphoma
lymphomas
Lymphoma
Pathophysiology
Recurring genetic abnormalities at a variety of levels
Gross chromosomal changes
Rearrangement of specific genes
Changes in oncogenes leading to overexpression
Altered expressions/mutation of proteins
Environmental factors implicated
Infectious agents
Chemical exposures
Medical treatments
Lymphoma
severity of disease determinants
The differentiation stage of a malignant lymphoma does not predict its natural history
Cell surface phenotyping aids in differential diagnosis (benign versus malignant)
Hodgkin Lymphoma
general
B-cell in origin
Reed-Sternberg cells
Beware: can be seen in other conditions
Types
Classical Hodgkin Lymphoma (cHL)
Nodular sclerosis
Mixed cellularity
Lymphocyte rich/depleted
Nodular lymphocyte predominant
Hodgkin lymphoma:
Epidemiology/Etiology
Bimodal incidence
20s and > 50
A 3x ↑ risk in young adults with prior history of serologically confirmed infectious **mononucleosis **
Increased incidence of HL associated with
Immunodeficiency
Personal or family history of autoimmune diseases
Hodgkin lymphoma
clin man
“B” symptoms present in approx. 30% of cases:
Fever > 38°C (100.4°F)
Drenching night sweats
Weight loss (>10% of body weight)
Generalized pruritus
Single LN group and spreads to contiguous areas- Late disseminated
Pain in involved lymph nodes immediately after the ingestion of alcohol - occurs in fewer than 10% of patients but specific to cHL
Hodgkin lymphoma
PE findings
Diffuse/puffy swelling rather than a discrete mass may be apparent in the supraclavicular, infraclavicular, or anterior chest wall regions
~70% cervical node involvement
12% axillary nodes
9% in the inguinal nodes
Involvement of the spleen strongly dependent on histologic subtype
Rare paraneoplastic syndromes have been described in cHL at the time of diagnosis.
Hodgkin lymphoma:
Workup/Diagnosis
Diagnosis of HL is made by the evaluation of involved tissue, usually an excisional lymph node biopsy
Identification of immune markers of Hodgkin lymphoma
Reed-Sternberg cells
Laboratory testing: CBCD, CMP, LDH, uric acid
CT scans and FDG-PET imaging
Bone marrow biopsy
Hodgkin lymphoma
Tx for early, avdanced, and relapse
Early stage (I-II)
Chemotherapy +/- radiation
Advanced stage (III-IV)
Chemotherapy
Relapsed disease (HL returns after prior treatment)
Conventional chemo + radiation therapy
High dose chemo and autologous hematopoietic cell transplantation (HCT) +/- radiation therapy
hodgkin lymphoma stages
follicular lymphoma
general
Indolent lymphoma derived from mutated germinal center B cells
Median age: 59 years
Histologic transformation to aggressive lymphoma occurs in 30 to 40% of patients
Usually leads to death within a few years of transformation
follicular lymphoma
S/Sx
Patients are often asymptomatic
Presentation
Painless, diffuse lymphadenopathy
Marrow infiltration (40-70%)
Hepatosplenomegaly
Peripherally circulating lymphoma cells
May live for many years in good health without therapy
Most patients eventually develop progressive lymphadenopathy causing symptoms
follicular lymphoma
Tx
“Watch-and-wait” approach is the standard for asymptomatic disease
Treatment does not change overall survival
Treat once symptomatic
Many regimens effective at inducing remissions
Rituximab (CD-20 directed)
Localized radiation
Mantle cell lymphoma
general
Most commonly involves lymph nodes
May involve extranodal sites, including the GI tract (lymphomatous polyposis)
Male patients age >60
Widespread disease
10-15% present with a more indolent, chronic course
Splenomegaly in 40%
Bone marrow involved in majority of patients
50% present with blood involvement, sometimes overt leukemic phase
Despite high initial response rates, early relapses frequent
Median survival 3-5 years
Burkitt Lymphoma
general
common on pance
Highly aggressive lymphoma with characteristic chromosomal translocations of MYC gene
Presents in three clinically distinct forms:
* Endemic
Jaw or facial bone tumor
May spread to extranodal sites, especially to the marrow and meninges
Almost all cases are EBV-positive
* Nonendemic forms (Sporadic and Immunodeficiency- associated- HIV involvement)
Abdominal mass in approximately 65% of cases, often with ascites.
Extranodal sites, such as the kidneys, gonads, breast, marrow, and CNS, may be involved.
Patients with more than 25% marrow involvement with malignant cells often are referred to as having Burkitt cell leukemia
Burkitt lymphoma
In the absence of CNS prophylaxis
up to 30 percent of patients with Burkitt lymphoma/leukemia will develop leptomeningeal involvement/recurrence regardless of HIV status
Most receive intrathecal chemotherapy prophylaxis
Burkitt Lymphoma
Tx
For patients with relapsed or refractory disease – possibly stem cell transplant
There is no agreed upon standard treatment for Burkitt lymphoma/leukemia in the HIV seronegative population, and limited data for HIV positive patients.
