Hematologic Malignancies Flashcards
Types of Heme Malignancies
Leukemia
Lymphoma
Myeloma
Myelodysplastic Syndrome
Myeloproliferative Disorder
What is leukemia?
cancer of the blood and bone marrow characterized by the uncontrolled accumulation of malignant white blood cells
Leukemia
Acute vs. Chronic
Acute
- block in differentiation of immature WBC
- rapid course
- death within days to weeks if untreated
Chronic
- excess proliferation of more mature WBCs
- indolent course
- may survive for years even if untreated
Leukemia
Signs and Symptoms
Can be asymptomatic to sudden, severe illness
Initally presentation is often non-specific
- fatigue
- infection (recurrent, persistent)
- mild bleeding symptoms (bruising, epistaxis)
- these patients will generally get bounced around before getting their final dx
Abnormal CBC
- pancytopenia
- marked leukocytosis
Leukemia
Diagnosis
Get it done ASAP!
Detail H&P
Labs: CBC, renal and liver function, coags, peripheral blood immunophenotyping
Bone marrow aspirate and biopsy (within 24hrs)
Imaging studies as directed by H&P
Classification of Leukemia
Myeloid vs. Lymphoid
- from which stem cell arises from
- determines treatment options
Acute vs. Chronic
- determines urgency of treatment
Leukemia
Risk Factors
**In most cases, the cause is unknown **
AML
- Radiation exposure
- Chemotherapy
- Benzene
- Tobacco smoke
- Genetic disorders - Down and Fanconi anemia
- Preexisting MDS
ALL
- Radiation exposure
- Viral infection - EBV, HTLV-1
- Genetic disorders - Down
**CML **
- Radiation exposure
**CLL **
- Race/genetics (white males >70)
Secondary Leukemia
Causes
Arises from pre-existing MDS/MPD or following exposure to radiation or chemotherapy
Latent period approximately 5 years
Almost always myeloid, and usually preceded by dysplastic changes in all 3 cell lines
Abnormalities in multiple chromosomes and complex karyotypes common
Prognosis is worse than for de novo AML
Leukemia
Age that it affects
Bimodal distrubition - >20, <65 MC
Older pts more likely to die from leukemia
Leukemia
Treatment
- Little role for surgery or radiation
- Chemo is the main treatment modality
- Stem cell transplant
- Prognosis varies widely
Leukemia
Treatment and Prognosis of Each Type
ALL
- MC in kids; highly curable with chemo
- Adults: less common, nasty, usually requires transplant to cure
AML
- uncommon in kids
- several subtypes so prognosis is variable
Generally, tx - induction, consolidation, maintenance
CLL
- Not seen in kids, common in elderly
- Don’t treat until sxs develop
- Goal is to control disease with chemo, true cure unlikely
CML
- very uncommon in kids
- chronic, accelerated, adn blast crisis phases
- up to 70% cure if transplanted in chronic phase
- Philadelphia chromosome: Gleevec and other TKIs block faulty protein that signals cells to grow out of control
Leukemia
Histology
Bone marrow - Increase in cellularity
AML - Auer rods (clusters of granules) on peripheral blood smears
Lymphadenopathy
Palpable lymph nodes - cervical, supraclavicular, axillary, inguinal
What they feel like
- soft, tender, mobile = infx/inflammation
- firm, rubbery, mobile, non-tender = lymphoma
- hard, fixed, non-tender = carcinoma
Localized Lymphadenopathy:
- Infection - bacterial or viral
- Lymphoma - Hodgkin/NHL
- Carcinoma (metastatic)
Generalized Lymphadenopapthy
- Infection - bacterial, viral, fungal
- Inflammatory - sarcoid, SLE
- Leukemia
- Lymphoma
What is Lymphoma?
CA of lymphoid tissues, malignant cell is the lymphocyte
Malignant lymphocytes accumulate in the lymph nodes, spleen, liver, and bone marrow
Malignant lymphocytes can also circulate in the blood and resemble leukemia
Lymphoma
Classification
Hodgkin’s Disease
- Relatively uncommon
- Primarily affects young adults
- High cure rates
Non-Hodgkin Lymphoma (NHL)
- Common
- Low grade typically affects older adults
- High grade (less common) affects kids, but responds better to chemo
- Wide variation in prognosis, tx success
Both have different subtypes depending on histology
Lymphoma
Signs and Symptoms
Ranges from asymptomatic to sudden, severe illness
Fatigue, weight loss, fever, night sweats
Lymphadenopathy (localized or generalized)
Enlarged liver and / or spleen
Skin lesions, pruritis
GI bleeding, obstruction - when lymphoma is near GI tract
Lymphocytosis
Lymphoma
Diagnosis
Detailed H&P
Labs: CBC, renal and liver ftn, coags, LDH, peripheral blood immunophenotyping (flow cytometry used in staging)
Imaging: CT, MRI, PET from head to toe to determine what is affected (usually more than one region)
Biopsy: lymph node (want entire node to accurately dx/stage) - surgical procedure; bone marrow, skin lesion, GI tract, liver depending on what is involved
Lymphoma
Staging
**Stages determine treatment **
- Stage I: 1 node group
- Stage II: > 1 node groups, same side of diaphragm
- Stage III: nodes on both sides of diaphragm
- Stage IV: marrow or other extranodal side
**Type (A - yes, B - no) determine prognosis **
- presence of fevers, night sweats, weight loss
Lymphoma
Treatment
Treatment approach varies depending on age of patient and specific type of lymphoma
- Surgery - to obtain tissue for diagnosis
- Chemo and Stem cell transplant (common)
- Radiation (uncommon)
Spectrum of Plasma Cell Disorders
General
MGUS – Smoldering Myeloma – Multiple Myeloma
Monoclonal gammopathy - excess production of gamma globulin protein (IgG) by a single clone of B cells/plasma cells
Plasma Cell Disorders
MGUS
Monoclonal Gammopathy of Underdetermined Significance
Common - occurs in 3% of people >70 y.o.
Plasma cells grow enough that you can monitor its antibody protein in the blood
Will see increased plasma cells on bone marrow biopsy, but no other clinical features of myeloma
Generally benign, but may progress to multiple myeloma (10-20% progress to myeloma, but can take more than 10 years)
No way to prevent the progression, so monitor closely
Plasma Cell Disorders
Multiple Myeloma
Etiology, epidemiology, clinical presentation
Malignant proliferation of plasma cells
10% of hematologic malignancies, MC >65y.o., MC AA
**Clinical Manifestations: **
-
Monoclonal protein:
- ppts into kidneys –> renal failure
- hyperviscosity which can lead to hypoperfusion
- amyloidosis
-
Lytic Bone Lesions: punched out appearance on x-rays because increased cell turnover
- Bone pain
- Pathologic fxs
- Hypercalcemia –> renal failure
- Anemia: because less EPO as kidneys fail, bone marrow replaced with plasma cells
- Infections: antibodies aren’t function so can’t fight infx
Plasma Cell Disorders
Multiple Myeloma
Treatment
Complete remission more common and durable
- Higher response rates to chemo - thalidomide as an angiogesis inhibitor
- Better are doing transplants
Treatment depends on age, etc.
Leukemia, Lymphoma, and Myeloma
vs.
MDS and MPN
Leukemia, Lymphoma, and Myeloma
- malignant transformation of mature blood cell or precursor
- accumulation of malignant cells result in clinical manifestations
- specific treatments - chemo - can reuslt in cure
MDS, MPN
- mutation in stem cell or early progenitor –> anything produced from these are malignant
- results in ineffective hematopoiesis (hypercellular, but dec production) or the overproduction of mature blood cells
- may transform to AML
- only curable with transplant
- generally are slower
MDS
Myelodisplastic Syndrome
Pathophysiology
- Heterogeneous group of malignant hematopoietic stem cell disorders
- Characterized by dysplastic and ineffective blood cell production
- Clonal process thought to develop from a single mutated stem cell –> any cell that arises from this is abnormal
Epidemiology/RF
- >65y.o.
- Benzene, radiation, tobacco, chemo, and genetic factors
Classification - dependent on molecular features in hopes to develop targeted therapies
Clinical Features
- anemia - transfusion dependent
- thrombocytopenia - nuisance to life threatening, transfusion dependent
- leukopenia - dysfunctional neutrophils –> infection
- transformation to secondary AML may occur after a few months, years, or not at all
**Diagnosis **
- Ineffective hematopoiesis - hypercellular marrow but low peripheral counts
- Dysplastic cells on smear and in bone marrow
- Cytogenetic abnormalities (FISH)
- Presence of circulating blasts, or increasing numbner of marrow blasts (<20% or AML)
Treatment: sucks - chemo, radiation, etc. Transplant only curative option
MPN
Patho, epidemiology
Myeloproliferative Neoplasms
Like MDS, MPN is a clonal process from a single mutation stem cell, but are characterized by excessive proliferation of mature blood cells
Median age 60 y.o, but more common in younger individuals
With tx survival for decades is possible
MPN
Specific entities
Common features
Complications
- polycythemia vera (p. vera)
- essential thrombocythemia (ET)
- chronic myeloid leukemia (CML)
- primary myelofibrosis (PMF)
Common features:
- chronic course
- over production of 1-3 blood cell lines
- marrow fibrosis, leading to splenomegaly
- PV, ET, PMF have JAK2 mutation - intracellular signaler that is more sensitive to GF
Complications
- clonal evolution, transformation to AML
- thrombosis - venous and arterial, unusual locations
- marrow fiborsis
MPN
Clinical features
Diagnosis
Treatment
Symptoms:
- disabling fatigue
- pruritis - p. vera
- splenomegaly
- hypermetabolic sx (wt loss, fever, night sweats)
- bone pain
- erythromelagia (burning sensation in hands/feet with erythema, pallar, or cyanosis, with palpable pulses)
- neurologic sxs
Diagnosis
- some diagnosed incidentally (CBC)
- others present with complications of dramatically elevated blood counts –> clotting
Treatment
- can’t prevent marrow fibrosis or transformation to AML
- PV and ET want to control counts to reduce symptoms and prevent thrombotic complications (phlebotomy adn hydroxyurea)
- CML - Gleevec
- PMF - JAK2 inhibitor
- transplant only curative therapy but limited use because of patient age
