Leukemias and Lymphomas Flashcards
what is leukemia
cancer of the bone marrow
what is primarily involved in leukemias
WBC - “leuk” for leukocytes
overgrowth of immature or abnormal cells leading to suppression of normal cells/cell growth
what are the classifications of leukemias
Myeloid vs. Lymphoid
acute vs. crhonic
what is the presentation of acute leukemias
all ages, more likely in kids
sudden onset
rapid course
symptoms present (bleeding, infections, anemia)
high % of blasts
variable WBC count
Anemia
thrombocytopenia
minimal lympadenopathy
minimal splenomegaly
goal of treatment is to cure (chemo, BMT)
what is the presentation of chronic Leukemias
older age of onset, less likely in kids
insidious onset
prolonged course
often asymptomatic
higher % of mature cells
increased WBC count
minimal anemia
minimal thrombocytopenia
lympadenopathy
splenomegaly
treatment goal is to slow disease progression, normalize cell counts - less often curative
what are the primary types of leukemia
Acute myeloid leukemia (AML)
Chronic Myeloid leukemia (CML)
Acute lymphocytic leukemia (ALL)
Chronic Lymphocytic Leukemia (CLL)
what is the epidemiology of AML
no significant predilection for gender or race
median age of diagnosis: 68
- rarely diagnosed under age 60
- makes up of 80% of acute leukemia in adults
what is the pathophysiology of AML
exact etiology unknown - many sporadic genetic mutations identified
environmental exposures increase risk
what environmental exposures increase risk for AML
Benzene exposure (fires, fuels, cigarette smoke, plastics/resins, dyes/detergents, pesticides)
Radiation exposure
Exposure to alkylating agents or topoisomerase inhibitors - antineoplastic agents
what is the presentation of AML
non specific symptoms less than 3 months in duration
fatigue (most common)
anorexia
weight loss
fever
weakness
dyspnea on exertion (DOE)
cough
HA
bone pain
unexplained infections
sweating (night sweats)
bruising/easy bleeding (epistaxis)
what is the diagnostic lab for for AML
variable WBC count - depends on disease stage (Blasts >20%)
Low neutrophil count
thrombocytopenia (low platelet count)
Anemia (decreased reticulocyte count - bone marrow failure)
what are the diagnostics for AML
Blasts >20% OR + genetic testing required for diagnosis
definitive dx with BM biopsy
what is the histological presentation of AML
AUER RODS- pathognomonic for AML if present - crystallized cytoplasmic inclusion granules
cytoplasmic granules on peroxidase stain
immature nuclei
what is the treatment of AML
Goal is complete remission
Induction treatment: combination chemotherapy
Post remission treatment: BMT is more effective
-preferred for anyone age <75 or who has an HLA compatible donor
-if patient is low risk can consider continuing cytarabine
what are the supportive treatment measures of AML
platelet transfusions
PRBC’s
Prophylaxis with neutropenia
Prompt broad-spectrum abx if febrile
what is the prognosis of AML
overall 5 year survival rate of 28.7%
what makes the prognosis for AML worse
Older age - tx toxicities, more likely to have resistant disease
prior hematologic disease (myelodysplastic syndromes)
prior environmental exposures (benzene, radiation, etc)
certain genetic profiles
shorter time between remission and relapse
What is the epidemiology of CML
15% of all cases of leukemias
more common M>F
no significant predilection for race
median age at diagnosis: 65
- rare under age 40
what is the pathophysiology of CML
not hereditary
exception radiation, not related to environmental exposure (peak dx 5-10 years after radiation)
90% secondary to chromosomal translocation: 9:22
Bcr-abl gene (PHILADELPHIA CHROMOSOME)
What does the Bcr-abl gene result in
hyperactive tyrosine kinase
also interferes with the JAK/STAT pathway to produce resistance to apoptosis
what is the presentation of CML
most patient identified on routine screenings
patients without healthcare may be symptomatic with non-specific symptoms: fatigue, weight loss, abd pain, blood clots, evidence of bleeding, bone pain
what is the physical exam findings for CML
splenomegaly
hepatomegaly
myphadenopathy
what are the laboratory findings for CML workup
primary leukocytosis
WBC > 50,000
presence of band cells/’left shift’
increased ANC/neutrophil %
often with thrombocytosis
+/- anemia (1/3 of pts)
what is the definitive diagnostic test for CML
BM biopsy - hypercellular marrow, preponderance of myeloid cells, large immature granulocytes
Genetic testing - t(9:22) on FISH/PCR
what is the treatment for CML
first line = tyrosine kinase inhibitors (TKIs) - imatinib (gleevec), dasatinib, hilotinib, bosutinib - chronic treatment: goal is complete cytogenic response after 12 months
BMT - considered curative, but TKIs superseded as first line
what is the prognosis of CML
all will predictably develop resistance/progression
accelerated phase: 70% 4 year survival rate
Blastic phase identified by >30% blasts
how are progressions of CML identified
leukocytosis resistant to treatment
worsening anemia
fever and B symptoms
increase number of blasts/basophils
What is the epidemiology of ALL
M = W
more common in hispanic and caucasian patients
median age at diagnosis: 17
most common malignancy in kids
what is the pathophysiology of ALL
drives from T or B cells:
- 75-85% B cell types; T cell type has worse prognosis
etiology unknown: several associated mutations
increased risk with exposure to radiation/chemicals/chemotherapy - risk less than AML
children with down syndrome have 20x increased risk for developing ALL
what is the presentation of ALL
similar to AML
Non-specific symptoms less than 3 months in duration: fever (most common), fatigue/lethargy, bone pain (more common than AML), anorexia, weight loss, weakness, dyspnea on exertion(DOE), cough, HA, unexplained infections, sweating, bruising/ easy bleeding
what is shown on the PE for ALL
Pallor, petechiae, ecchymosis are most common fdindings
hepatomegaly, splenomegaly and lymphadenopathy more common than AML
+/- anterior mediastinal mass (cough, dyspnea, orthopnea, stridor, cyanosis, dysphagia, edema, syncope, elevated ICP)
what are the laboratory findings for ALL
leukocyte count normal or evelated
90% of pts will have blasts
elevated # eosinophils
anemia
neutropenia
thrombocytopenia
what is the presentation of ALL
more likely to have other metabolic derangements
- elevated LDH - marker or ‘tumor burden’
- elevated serum uric acid - increase purine metabolism
-elevated BUN/creatinine/phosphorus - kidney involvement
- hypercalcemia - bone infiltration, parathyroid-hormone like proteins
what is the definitive diagnostic test for ALL
BMB
hypercellular marrow, preponderacne of lymphoblasts, large immature lymphocytes
what are adjunctive tests used for ALL diagnosis
imaging - pts should be screened with CXR - r/o anterior mediastinal mass
CSF analysis - looking for blasts in CSF, r/o lymphoblastic infiltration
what is responsible for the production and maturation of T-lymphocytes
thymus
what is the treatment of ALL
goal is remission
induction therapy: multi-agent chemotherapy
intensification/consolidation therapy: another round of same or different multi-agent chemotherapy
continuation therapy: lower dose treatment for additional 2-3 years, longer for boys then girls
+/- intrathecal chemotherapy - indicated if CNS involvement
what is the prognosis of ALL
better in kids than adults:98% remission in kids
- 90% 5 year survival rare, close to 90% cure rates, 50% 5 year survival rate in adults
what makes a poorer prognosis for ALL
primarily T cell ALL
increased age (>35, worse >60)
males
Leukocyte count <50
certain genetic profiles
longer time to response after initiation of treatment
what time period of remission of ALL typically indicates a cure
10 or more years of remission = cure
what is the CLL epidemiology
M>F
caucasians > other ethnicities
median age at diagnosis: 70
- 90% > 50 yo
what is the pathophysiology of CLL
malignancy of B lymphocytes
etiology unclear: risk increased with + FH of leukemia, lymphoma or myeloma - no specific genes identified
NOT associated with radation
what increases your risk factors for CLL
farmers
hairdressers
history of HCV infection
AGENT ORANGE EXPOSURE (Vietnam vets)**
what is the presentation of CLL
primarily identified by asymptomatic screening/incidental finding
non-specific symptoms: fatigue, lymphadenopathy, recurrent infections, fever, weight loss, night sweats, symptoms from anemia
what is the PE findings for CLL
80% have lymphadenopathy - non-tender, non-fixed (Mobile)
50% with splenomegaly or hepatomegaly
+/- bruising, petechiae/purpura
+/- pallor
what is the laboratory presentation of CLL
sustained lymphocytosis >20,000
lymphocytes on differential
CD19 and CD5 markers on flow cytometry
+/- hypogammaglobulinemia - reduced levels of circulating IgG, IgM and IgA
+/- anemia - normocytic, normochromic, normal Hct
platelet count usually normal
how are CLL definitively diagnosed
BM biopsy
- lymphocytic infiltration
- usually small, mature lymphocytes
- SMUDGE cells - ruptured CLL cells during slide preparation, presence of larger % Smudge cells - better prognosis
what is the classifications of CLL
staged based on Rai classification
Stage 0 - Stage IV
what is Stage 0 CLL
isolated lymphocytosis
what is stage I CLL
presence of lymphadenopathy
what is stage II CLL
spleno - or hepatomegaly
what is stage III CLL
presence of anemia
what is stage IV CLL
presence of thrombocytopenia
what is the treatment of CLL
very slowly progressive
first line treatment = observation
- chemo/chemoimmunotherapy offer no significant survival beneift
treatment if symptomatic- first line = bruton tyrosine kinase (BTK) inhibitors - ibrutinib, acalbrutinib
what is the prognosis of CLL
significantly improved with targeted therapy (BTK inhibitors)
- stage 0-1 = median survival of 10-15 years
- stage II - IV = 2 year survival of 90%
what are at risk for developing secondary malignancy with CLL
skin - annual derm exams
Breasts - annual mammograms
GU cancer - annual PAP
Prostate - annual PSA, DRE
Colon - colonoscopy every 5 years after age 50
what is non-hodgkin lymphoma
7th most common cancer (heterogenous group of lymphoproliferative malignancies)
originates in lymph system, lymphoid tissues
M>F
Caucasians > other ethnicities
Median age at dx: 76 (65-74)
what is the pathophysiology of non-hodgkin lymphoma
malignancy of lymphoid origin - B or T lymphocytes (85% B lymphocyte origin)
oncogene activation or tumor suppressor gene inactivation
what are the two types of non-hodgkin lymphoma
Burkitt lymphoma: t(8:14) - over expression of c-myc gene; leads to unchecked b-cell proliferation
Follicular lymphoma: t(14: 18) - bcl-2 over-expression; inhibition of apoptosis
what is the presentation of non-hodgkin lymphoma
primarily present with lymphadenopathy - one or multiple (usually painless, mobiles, rubery)
Often with B symptoms: fever, night sweats(drenching), weight loss
1/3 of pts have extranodal involvement (skin lesions, GI tract, bone marrow, GU tract, thyroid, CNS)
what is the laboratory findings of non-hodgkin lymphoma
normal lab workup - may see anemia, thrombocytopenia, lympocytosis if BM infiltration
no circulating abnormal lymphocytes or lymphocytosis
how is non-hodgkin lympoma definitively diagnosed
lymph node biopsy
what are the tests that non-hodgkin lymphoma is staged with
PET/CT neck, chest and pelvis
BMB
+/- lumbar puncture (r/o CNS infiltration)
what is the treatment of non-hodgkin lymphoma
mainstay is chemotherapy
Radiation therapy: possible stand alone treatment for some stage 1 and 2 disease
BMT often reserved for relapse that remains responsive to chemotherapy
what is the prognosis of Non-hodgkin lymphoma
median survival of 10-15 years
all eventually becomes refractory to chemotherapy - transition to more aggressive disease
what makes a worse prognosis with non-hodgkin lymphoma
age > 60
elevated serum LDH
stage III or IV
> 1 extranodal site
poor baseline functional status
what stage of non-hodgkin lymphoma is the most common presentation
stage 4: diffuse or disseminated involvement
What is Hodgkin lymphoma
M>F
no predilection for ethnicity
median age at diagnosis: 39.5
- ave age range 20-34
- more common in young adults (20)
- second peak > age 55
what is the pathophysiology of Hodgkin lymphoma
still a malignancy of lymphoid tissue - B-cell origin
genetics less implicated than non-Hodgkin lympoma - but +FH does increase risk
what are the risk factors of Hodgkin lymphoma
50% associated with Epstein Barr Virus (EBV)
associated with HIV and AIDS
What is the presentation of Hodgkin lympoma
similar to non-hodgkin lympoma:
lymphadenopathy, usually painless, mobile rubbery enlarged nodes
usually arises as single lymph node- contiguous spread - hematogenous spread
generalized pruritus with ETOH ingestion and bathing
what are the laboratory findings for Hodgkins lymphoma
presentation same as non-Hodgkin lympoma
often normal lab work-up
no circulating abnormal lymphocytes or lymphocytosis
what is the definative diagnosis for hodgkins lymphoma
lymph node biopsy
REED-STERNBERG cells on biopsy (owl eye appearance, symmetric bilobed nucleus)
what is the treatment of Hodgkin lymphoma
mainstay of treatment is chemotherapy
stage 1 or 2: short course + radiation
stage 3 or 4: full chemo cycle
BM transplant often reserved for relapse that remains responsive to chemo
what is the prognosis of hodgkin lymphoma
better than non-hodgkin lymphoma
75% of patients if 0-1 prognostic factors, 55% if 3+ prognostic factors
stage 1 and 2: 10 year survival rate 90%
Stage 3 and 4: 10 year survival rate of 50-60%
what are poor prognostic factors for hodgkin lymphoma
stage 4
age > 35
male gender
lymphocyte deplete
WBC count >15,000
Hgb <10
albumin < 4
what is multiple myeloma
Males equal to or greater than females
age > 40 (avg 65)
2x more likely in AA
most common primary bone malignancy
What is the pathophysiology of Multiple Myeloma
plasma cell tumor
what is the presentation of MM
many pts are asymptomatic
many identified incidentally via labs
if symptomatic, present with: bone pain(often first symptom - spine, chest, skull), spinal cord compression (numbness, weakness of legs), pathologic fracture (femoral neck or vertebrae)
what is the lab work up presentation of MM
anemia (characteristic rouleaux formation) - rarely plasma cells on peripheral smear
hypercalcemia (secondary to bone resorption)
renal insufficiency (elevated BUN/creatinine)
Proteinuria - BENCE JONES proteins on urine protein electrophoresis (UPEP) - pathognomonic
how is MM diagnosed
presence of paraproteins - plasma cells - produce immunoglobulins (antibodies): increase in monoclonal proteins on serum protein electrophoresis (SPEP) - characteristic “M spike”
Lytic lesions on imaging - “moth eaten” ,” punched out appearance”
what is the gold standard diagnostic test for MM
biopsy
>60% plasma cells
“fried egg appearance”
What is the treatment of MM
annual surveillance for myeloma ‘precursors’
Frank multiple myeloma - multi-agent chemotherapy +/- radiation for palliation of bone pain/prevention of fx, +/- stem cell transplant, +/- bisphosphonates, +/- immunotherapy, operative fixation of fx/impending fxs
what is the prognosis of MM
median overall survival: 7 years
lower risk genotypes + BM transplant: 10 years
What is Leukopenia
reduced leukocyte (WBC) count <4300
- neutropenia: ANC <2,000
- lymphopenia: absolute count <1,000
- monocytopenia: absolute count <100
- eosinopenia: aboslute count <50
what are the causes of Neutropenia
Drugs: chemotherapy, antiseizure meds, abx, gout meds, immunosuppressants, ETOH, thyroid meds
infections: viral, bacterial, malarial
Nutritional: B12 and folate deficiency
Genetic
Hematologic disease: leukemia, lymphomas, aplastic anemia, etc
Hypersplenism
Autoimmune disease: SLE
What are the causes of Lymphopenia
acute stressful illness: MI, Pneumonia, sepsis
Glucocorticoids
lymphoma
immunodeficiency syndromes
immunosuppressants
radiation
chronic illness
bone marrow failure
What are the causes of Monocytopenia
acute stressful illness
glucocorticoids
aplastic anemia
leukemia
chemotherapy
immunosuppressants
what are the causes of Eosinopenia
acute stressful illness
glucocorticoids
