Leukemia, Lymphoma

zizipasa's version from 2017-09-12 21:01



Question Answer
What's the first question you ask yourself when you're determining which leukemia you have?is it lymphoid or myeloid?
If it's lymphoid, what do you ask?are there precursors involved? if so, it's acute leukemia (B ALL or T ALL). If it's not a precursor, is it hodgkin's? If not, it's Non hodgkins
If it's myeloid, how do you determine which one?you have to determine if it's acute via >20% blasts or if you have certain translocations (15;17, 8;21, 16 inv :11q23)
Acute leukemias have _ blasts and ___ cells in peripheral blood. Compare to myelodysplastic and myeloproliferativeAML is hypercellular marrow and hypercellular peripheral blood. MPN is hypercellular marrow and blood. MDS has cytopenia in blood, bone marrow is hypercellular.
What is the characteristic process of MDS?ineffective hematopoiesis. A lot of hematopoiesis going on, but cells die in marrow. Less than 20% blasts and cytopenias
What diseases fall under the myeloproliferative neoplasms (MPN)?CML if BCR/ABl positive, if - it's either polycythemia vera, primary myelofibrosis, or essential thrombocytopenia
Polycythemia vera is characterized by-BCR/ABL, increased RBCs. Hypercellular marrow and hypercellular peripherally
Primary myelofibrosis is characterized byBCR/ABL negative, increased megakaryocytes/WBCs

Myeloproliferative Disorders

Question Answer
What are the myeloproliferative disorders?P vera, CML, Agnogenic myelofibrosis, essential thrombocytopenia, Paroxysmal nocturnal hemoglobinuria
What is erythrocytosis? What are the 3 types?elevated hematocrit. Relative is when you have decreased plasma volume, secondary is when you have too much EPO that causes increased RBC proliferation, and P Vera, which occurs via a clonal hematopoiesis
What is an appropriate EPO secretion?hypoxemia, sleep apnea, things that cause impaired O2 delivery or decreased O2 transport capacity
What mutation is associated with P Vera?jak2 mutation that upregulates it, yields increased hematopoiesis
What do you see clinically with P vera?headache/fullness of head, flushed face, puritis due to histamine release, hypertensive, thrombosis risk
Why are more RBCs bad?increased viscocity causes decreased O2 delivery
How do you treat P vera?phlebotomy
What causes CML?philadelphia chromosome translocation - recpiricol 9/22 translocation creates BCR/ABL region
What is ABL?oncogene that produces tyrosine kinase, upregulating myeloid production
Is CML acquired or inherited? How can you tell?it's AQCUIRED! It doesn't happen in stem cells, it happens in hematopoietic system
How do you treat CML?gleevac/imatinib, a tyrosine kinase inhibitor
What do you see clinically with angogenic myelofibrosis?extramedullary hematopoiesis due to clonal hematopoiesis/polyclonal fibroblast reaction in the marrow, leading to scarring and crowding out hematopoiesis. Anemia, painful spleen, teardrop erythrocytes
What do you see with essential thrombocytopenia?platelet clumps on peripheral smear b/c there's a lot of them
What do you see with paroxysmal nocturnal hemoglobinuria? what causes it?patient sleeps/hemolyzes and pees dark urine. Abnormality of red cell membrane that normally protects from complement mediated cell breakdown

Acute Leukemias

Question Answer
What are the acute myeloid leukemias?AML, APL
What are the favorable AML mutations?8, 21 and 16 inversion
What mutation causes APL?15/17, forming RARA.
How do you treat AML?7 + 3 cytarabine and donarubicine induction therapy and high dose cytarabine for consolidation or stem cell transplant if they can't take the cytarabine


Question Answer
What complication is feared with acute leukemias/chemotherapy?tumor lysis syndrome and infection risk
What are the acute leukemias?ALL, AML, APL
What leukemia does burkitt's fall under?Non hodgkin lymphoma, also ALL sometimes
Some ALL is ____, others can be ____Burkitt's lymphoma, Philadelphia chromosome +
What is the most common childhood cancer?ALL
What is characteristic on smear for AML?Auer Rods
What is general treatment for AML?7:3 induction/consolidation therapy for younger people, lower intensity drugs for older people
What are the unfavorable AML translocations?5 or 7 deletion, abnormal 3q, or 3 or more chromosome changes at the same time
What is APL?acute promyelocytic leukemia, a subset of AML
What is diagnostic of APL?FAGGOT cells - stuffed with auer rods
What mutation causes APL?T 15/17, yielding RARA
How does APL present?DIC at diagnosis, low fibrinogen b/c it's broken up b/c of DIC
How do you treat APL?ATRA - al trans retinoic acid

Lymphoid system

Question Answer
How do you distinguish between a benign and malignant process on histology?malignant lymphoma will have a lack of eosinophils/histiocytes, etc. Will be monotonous
How do you distinguish between a benign/malignant process on immunology?benign would have mixed B/t/NK cells, malignant would be ALL b cells or ALL t cells for example
What virus associations exist with hodgkin lymphoma? NHL?Late exposure to EBV for hodgkin, HIV for both
Hodgkin lymphoma is a cause of ___NHL
How do you stage lymphoma?Stage 1 - one nodal area, 2 - two or more areas on same side of diaphragm, 3 = involvement on both sides of diaphragm, 4 - diffuse disease outside of lymph
What is ann arbor/cotswold staging?A - no symptoms, B - fever, drenching night sweats, unexplained weight loss >10% - only need one of these to have "B" stage
What is diagnostic of Hodgkin lymphoma?reed sternberg cells
What do reed sternberg cells do?make a lot of cytokines, attract inflammatory cells, give you B symptoms. Make up a very small portion of the huge tumor mass
What are the most common Non hodgkin lymphomas?diffuse B cell and follicular lymphoma
Which has a younger "peak" - hodgkin's or non hodgkin?Hodgkin
What are the non hodgkin lymphomas/leukemias?DIffuse B cell, follicular, Burkitt's, CLL, Hairy cell, waldenstrom's macroglobulinemia, Plasma cell disorders (multiple myeloma) and amyloidoses.
What dictates the degree/grade of lymphoma with follicular lymphoma?the number of large cleaved cells that make up the tumor. The follicle is usually made up of small and large cleaved cells, and there are both in this cancer.
What mutation causes follicular lymphoma?BCL2/IgH translocation.
What is BCL2?it's anti apoptotic protein. B cells MAKE IMMUNOGLOBULINS, so that's what it thinks it's doing, but it's making BCL2
How do you treat follicular lymphoma?we treat for symptoms, but not for cure because cells are very difficult to kill
What cell/smear is characteristic of Chronic lymphocytic leukemia (CLL)?Smudge/basket cells.
How do you treat CLL?Ibrutinib - BTK inhibitor.
What happens with the immune system/cells in CLL?B cells express CD5, a T cell protein, which they shouldn't. It's associated with immune dysregulation - ITP, autoimmune hemolytic anemia, etc
What does the tumor look like in diffuse large B cell lymphoma?fleshy, monotonous mass of large B cells.
What associations exist with Diffuse B cell lymphoma?if you have cancer in waldeyer's ring in your neck, it's common to have gastric involvement. If you have cancer in testicles or marrow, we worry about meninges/CSF/brain
How do you treat diffuse large B cell lymphoma?CHOPr
What mutation causes burkitt's leukemia/lymphoma?C MYC/IgH translocation.
What does C MYC do? Which cancer is it associated iwth?burkitt's lymphoma, it makes cells stay in cell cycle.
What is easier to treat, Burkitt's or follicular, and why?Burkitt's - because chemo works well since they act on cells in cell cycle. Follicular is a disease where cells don't want to die.
What is distinctive of burkitt's on smear?starry sky, lipid filled vacuoles
Hairy cell leukemia is ___highly treatable
What causes waldenstrom's macroglobuilinemia? How do these patients present?serum hyperviscocity due to circulating IgM, usually due to lymphoblastic lymphoma. Hyperviscosity causes CNS/visual/organ issues.
What is MGUS? How does it differ from multiple myeloma?MGUS doesn't have CRAB symptoms (hypercalcemia, renal insufficiency, anemia, bony lesions). Multiple myeloma does
Why do you get bony lesions in multiple myeloma?Plasma cell proliferation stimulate osteoclasts
How do you treat multiple myeloma?high dose chemo with stem cell transplant, supportive measures for bone issues/immunodeficiency, bone fragility/pain
Why don't proteins get degraded in amyloidoses?beta pleated sheats in them make them harder to break down
How do you treat HOdgkin's disease?ABVD in the US. Adriamycin (doxorubicin), blemoycin, vinblastine, and decarbazine
What is the mechanism of action of adramiycin/doxorubicin?anthracycline. It gets into the DNA and interferes with replication, causing double strand breaks
Doxorubicin can also inhibit topoisomerase II, generate free radicals, and bind cell membrane --> change in fluidity and ion transport
What is the mechanism of action of bleomycin?binds heavy metals in pockets of DNA to produce reactive O2 species
What is the mechanism of action of vinblastine?it's a vinca alkaloid/spindle poison to kill cells
What is the mechanism of action of dacarbazine?alkalating agent, damages a lot of stuff
What are the different regimens to treat hodgkins in the US vs europe?in the US we use ABVD, europe uses stanford V, which adds topoisomerase and prednisone or BEACOPP
How do you treat non hodgkin lymphoma, generally?CHOPr - cyclophosphamide, hydroxydaunarubicine, oncovin, prednisone, rituximab
What is the mechanism of action of Cyclophosphamide?alkalating agent
What is the mechanism of oncovin?it's vincristine - a spindle poison
What is the mechanism of action of rituximab?monoclonal antibody that targets CD20 on B cells
How do you treat ALL?Vincristine, Dexamethasone, L asparaginase, Doxorubicine, and gleevac if PH+
How do you treat CML?Gleevac/imatinib
WHat is bortezomib?kills proteosome in cells, used to treat multiple Myeloma