Case Studies in Leukemia and Lymphoma Flashcards
What are myelodysplastic syndromes (MDS)?
age related (~70 y/o) acquired genetic damage to hematopoietic cells which leads to ineffective erythropoiesis
How does MDS typically present?
anemia with macrocytosis
if the peripheral blood smear shows large cells with large nuclei and visible nucleoli, what are you looking at?
blasts
what study helps differentiate myeloid blasts from lymphoid blasts?
flow cytometry
if lab results show leukocytosis, anemia, and thrombocytopenia, what should you be thinking until proven otherwise?
bone marrow problem
how do you calculate an absolute neutrophil count?
WBC x (neutrophil % + Band %)
What is a severe neutropenia defined as?
an ANC < 500
If a patient has a neutropenic fever, how do you treat them?
need to get cultures but then start with empiric antibiotics
How do you treat AML?
admission for treatment: induction therapy (treat underlying disease)
What are empiric antibiotics?
Empiric coverage is targeted at gram negative organisms first
the first line of empiric antibiotics is used to provide coverage against what?
pseudomonas coverage
what are examples of first line empiric antibiotics?
cefepime, piperacillin-tazobactam, meropenem, and ceftazidine
Addition of MRSA coverage is often added if there is concern for what?
line infection, PNA, or soft tissue infection
what is an example of an antibiotic that offers MRSA coverage?
vancomycin
if fever persists after 48 hours after onset of antibiotic therapy, what is typically added?
fungal coverage
what are 2 examples of antibiotics that offer fungal coverage?
amphotericin B, voriconazole
what confirms the diagnosis of AML?
anything greater than 20% blasts in bone marrow
induction chemotherapy for AML is done where?
in the hospital- 10-14 day induction course based on AML subtype and genetic profile
What stain do you do to look for fungi?
silver stain
How can candida be identified? and how do you treat candida?
can be identified with silver stain; treat with voriconazole/ amphotericin B
what is consolidation chemo?
when you intensify chemo to make sure no cancer cells are left in the body
what is maintenance chemo?
for some cancers, longer term therapy to maintain remission and prevent relapse
What is acute lymphoblastic leukemia?
malignancy of T or B lymphoblast
how do you make the diagnosis of ALL?
if there is greater than 20% lymphoblasts on bone marrow biopsy
What coagulation studies resemble DIC?
increase PT/PTT, increased D-dimer, and decreased fibrinogen
if a peripheral smear shows circulating blasts with auer rods, what do you suspect?
acute promyelocytic leukemia
which translocation is consistent with acute promyelocytic leukemia?
t(15;17)
What occurs in acute promyelocytic leukemia?
the leukemic cells express tissue factor, which activates factor X; high levels of Annexin II receptors on APL cells convert plasminogen into plasmin
what two things are highly expressed by APL cells?
Tissue Factor and Annexin II
What are two treatment options for acute promyelocytic leukemia?
Immediate treatment!! ATO (arsenic trioxide) and ATRA (all trans retinoic acid)
What is a LAP score?
you are looking for alkaline phosphatase and you are staining the leukocytes with this special stain that will show up positive in cells that are reactive
what are reactive cells?
ones that are autoimmune, fighting infection, or just reactive to a stressful stimuli
what does a positive LAP score tell you?
leukemoid reaction
what does a low LAP score tell you?
neoplasm
how does a leukemoid reaction appear in a centrifuged sample?
there is only a mild increase in the buffy coat
how does leukemia appear in a centrifuged sample?
the buffy layer is huge
What is a common other finding present in the majority of patients with CML?
splenomegaly
What does the bone marrow look like in CML?
hypercellular bone marrow consisting of predominant mature granulocytes
what translocation is associated with CML?
t(9;22)
CML is a part of what broader category?
myeloproliferative neoplasms
besides the hypercellularity, what is another common finding of CML?
pseudo-gaucher cells
what are pseudo-gaucher cells?
macrophages that are cleaning up cellular debris in situations like CML where there is high rate of cell turnover in the marrow
what is the result of the t(9;22) translocation that occurs in CML?
the protein resulting from this rearranged gene is a “constitutively active” tyrosine kinase
What medication is used to treat CML?
Imatinib (Gleevec/Glivec)
what is imatinib’s mechanism of action?
it is a tyrosine kinase inhibitor- it goes in and blocks where that ATP binds
What is the gold standard for testing for CML?
BCR-ABL PCR
what defines successful treatment in CML cases?
hematologic response (white count normalizes) and a molecular response (negative BCR-ABL PCR)
why is monitoring CML so important?
CML can progress to an aggressive disease
what are the different phases of CML?
chronic phase–> accelerated phase–> blastic phase
in CML, what is the high white count predominated by?
mature granulocytes
What are the causes of lymphadenopathy you should think about?
Malignancy, infection, auto-immunity, miscellaneous, iatrogenic
when evaluating the lymph nodes, what are the risk factors for malignancy?
age older than 40 years, duration has been longer than a month, supraclavicular location
what are 3 things that when evaluating the lymph nodes would make you do a biopsy?
location was subclavian (aka supraclavicular), it was fixed “hard as a rock”, and the lymph node was greater than 4 cm
what can the fine needle aspiration be used for only?
non-hodgkin lymphoma
what is the gold standard biopsy?
excision/excisional biopsy
what is the only way to diagnose hodgkin-lymphoma
excision/excisional biopsy
what is a prime location for lymphoma?
around the appendix- there is lots of lymphoid tissue there
when the description of a biopsy is “sheet of cells or appears like a starry night/sky” what should you think of?
Burkitt Lymphoma
what translocation is associated with burkitt lymphoma?
t(8;14)
what does the t(8;14) involve?
MYC; it increases proliferation
what is one of the worst lymphoma translocations?
t(8;14)
Burkitt lymphoma has a high risk of what?
CNS lymphoma
how do you treat burkitt lymphoma with CNS involvement?
chemotherapy with intrathecal administration
if a patient is undergoing chemotherapy and then stops producing urine and their BMP reveals significant kidney injury, what should you suspect?
Tumor lysis syndrome
what is tumor lysis syndrome (and the specifics)?
significant electrolyte imbalance’ hyperkalemia, hyperuricemia, hyperphosphatemia, and hypocalcemia
How do you treat TLS?
aggressive IV fluids- urine output average of 100 cc/hr; treat prophylactically with allopurinol
what is allopurinol?
it is a xanthine oxidase inhibitor that prevents uric acid formation
how do you treat hyperkalemia?
elimination of K: furosemide; or temporizing: glucose/insulin, calcium gluconate, and albuterol
how do you treat hyperuricemia?
with rasburicase
what should you know before treating a patient with rasburicase?
if the patient has a G6PD deficiency- because rasburicase in those patients can cause hemolytic anemia
how do you treat hypocalcemia?
calcium gluconate
how do Burkitt lymphoma patients present?
with a huge mass generally
What is hodgkin lymphoma?
it is a neoplastic lymphoid proliferation with scattered B-derived reed-sternberg cells in an abundant backgroun of T lymphocytes, eosinophils, and other inflammatory cells- it is a VERY inflammatory state
what do Reed-Sternberg cells look like and what are they associated with?
they look like owl eyes; they are associated with hodgkin lymphoma
How is HL typically treated?
chemotherapy is very effective; typically 21 or 28 day cycle of chemo therapy
Hodgkin lymphoma typically present in 3 ways. What are they?
lymphadenopathy (but not always), B symptoms, incidentally found on CXR
If a peripheral blood smear shows 90% small lymphocytes and then flow cytometry shows monoclonal B cells, what should you diagnose it as?
CLL/SLL
how does CLL typically present?
it is usually asymptomatic- but they show LOTS of lymphocytes on their CBC
how do you diagnose CLL?
through peripheral blood- no need to biopsy the lymph node
if a patient has a history of CLL and then new symptoms present such as anemia and thrombocytopenia, what should you suspect?
richter’s transformation
what is richter’s transformation?
you get a low grade lymphoma like CLL that progresses to a high grade lymphoma, which are deadly
what is an example of a high grade lymphoma?
DLBCL
What are the symptoms of richter’s transformation?
increase fatigue and B symptoms
what is the treatment for richter’s transformation?
chemotherapy and RITUXIMAB
what is retuximab?
a monoclonal antibody- specifically a CD20 antibody
how does rituximab work?
it is an antibody against CD-20 cell receptors, and most of your lymphocytes have CD20 markers on them
Burkitt lymphoma, Hodgkin lymphoma, and CLL are all diagnosed in different ways- how is burkitt lymphoma diagnosed?
mass effect
Burkitt lymphoma, Hodgkin lymphoma, and CLL are all diagnosed in different ways-how is hodgkin lymphoma diagnosed?
constitutional symptoms (B symptoms)
Burkitt lymphoma, Hodgkin lymphoma, and CLL are all diagnosed in different ways- how is CLL diagnosed?
peripheral blood abnormalities
