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273 Cards in this Set
- Front
- Back
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Hodgkin's lymphoma associated with what virus?
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EBV (50% of Hodgkins associated with it)
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Ratio of lymphocytes to Reed-Sternberg cells and prognosis?
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High ratio = good prognosis in Hodgkins lymphoma
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Hodgkin's vs. Non-Hodgkin's lymphoma:
Distinctive tumor cell? Extranodal involvement? Localized, single group of nodes? Constitutional symptoms? Viral associations? |
Distinctive tumor cell = Reed Sternberg cells in Hodgkin's
Extranodal involvement = Non-Hodgkin's Localized, single group of nodes? Hodgkin's Constitutional symptoms = Hodgkin's (B symptoms) Viral associations: EBV=Hodgkin's; HIV (and immunosuppression)= Non-Hodgkin's |
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Most common type of Hodgkin's lymphoma? Prognosis?
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Nodular sclerosing. Good prognosis (few RS cells, lots of lymphocytes)
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Types of Hodgkin's lymphoma? (4)
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Nodular sclerosing, mixed cellularity, lymphocyte predominant, lymphocyte depleted.
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Burkitt's lymphoma
Neoplasm of what cell type? Occurs in what age group? Genetics? Appearance? Associated with virus? |
Neoplasm of mature B cells
Occurs in young adults Genetics: t(8;14) (c-myc gene moves next to heavy-chain Ig gene) "Starry-sky" appearance Associated with EBV |
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Diffuse large B-cell lymphoma
Occurs in what age group? Neoplasm of what cell types? |
Most common NHL of adults
Usually mature B-cells (20% are T cell in origins) |
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Mantle cell lymphoma
Neoplasm of what cell type? Occurs in what age group? Genetics? Prognosis? |
Neoplasm of mature B cells
Occurs in older males t(11;14) Poor prognosis (Non-Hodgkin's lymphoma) |
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Follicular lymphoma
Occurs in what age group? Genetics? |
Adult
t(14;18) bcl-2 expression inhibits apoptosis (indolent course; difficult to cure) (Non-Hodgkin's B cell lymphoma) |
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Adult T-cell lymphoma associated with which virus? Symptoms?
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HTLV-1
Adults present with cutaneous lesions |
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Mycosis fungoides/Sezary syndrome
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Non-Hodgkin's (helper) T cell lymphoma
Adults present with cutaneous patches/nodules. |
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Which non-Hodgkin's lymphomas are neoplasms of mature B cells? T cells?
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B cells: Burkitt's, Diffuse large B-cell, Mantle cell, and Follicular lymphoma
T cells: Adult T cell lymphoma, Mycosis fungoides/Sezary syndrome |
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Destructive bone lesions
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Multiple myeloma (leads to hypercalcemia)
(Adult T-cell leukemia/lymphoma can also cause bone lesions) |
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Signs and symptoms of multiple myeloma
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hyperCalcemia, Renal insufficiency, Anemia, Bone/Back pain (CRAB)
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Monoclonal plasma cells, "fried egg" appearance, produces large amounts of IgG (most common) or IgA
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Multiple myeloma
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Most common primary tumor arising within bone in elderly (>40)
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Multiple myeloma
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Characterized by monoclonal immunoglobulin spike (M protein) on serum protein electrophoresis and Bence Jones protein in urine
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Multiple myeloma
(Bence Jones protein=Ig light chain in urine) |
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Leukemia vs. lymphoma
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Leukemia=lymphoid neoplasms with widespread involvement of bone marrow. Tumor cells usually found in peripheral blood.
Lymphoma=discrete tumor masses Presentations often blur definitions |
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Leukemias:
Which ones are lymphoid? Which are myeloid? |
Lymphoid:
Acute lymphoblastic leukemia/lymphoma (ALL) Small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia (CLL) Hairy cell leukemia Myeloid: Acute myelogenous leukemia (AML) Chronic myelogenous leukemia (CML) |
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Auer rods, increased circulating myeloblasts on peripheral smear
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Acute myelogenous leukemia (AML)
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Treatment for AML-M3?
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All trans retinoic acid (ATRA) therapy
(Acute promyelocytic leukemia is a subtype of AML in which there is a chromosomal translocation involving the retinoic acid receptor alpha (RARα or RARA) gene; forces cells to mature and become benign) |
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Acute vs. chronic leukemia
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Acute:
Blasts predominate Children/elderly Short & drastic course ALL & AML Chronic: More mature cells Midlife age range Longer, less devastating course CLL & CML |
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Leukemoid reaction vs. acute leukemia
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Both: Increased WBCs
Leukemoid: Left shift (bands), increased leukocyte alkaline phosphatase Acute Leukemia: Blasts, decreased leukocyte alkaline phosphatase |
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t(9;22)
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CML
Philadelphia chromosome; bcr-abl hybrid (constitutively active tyrosine kinase) |
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t(8;14)
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Burkitt's lymphoma (Non-Hodgkin's B-cell lymphoma)
c-myc activation |
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t(14;18)
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Follicular lymphoma (Non-Hodgkin's B-cell lymphoma)
bcl-2 activation |
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t(15;17)
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M3 type of AML (acute promyelocytic leukemia responds to all-trans retinoic acid)
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t(11;22)
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Ewing's sarcoma
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t(11;14)
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Mantle cell lymphoma
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What is Langerhans cell histiocytoses (histiocytosis X)? How can you identify it?
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Proliferative disorders of dendritic (Langerhans) cells from monocyte lineage. Birbeck granules ("tennis rackets"). Defective cells express S-100 and CD1a
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Birbeck granules
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Tennis racket shaped granules on EM seen in Langerhans cell histiocytoses
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What cells are elevated in polycythemia vera?
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RBCs, WBCs, Platelets
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JAK2 mutations
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Polycythemia vera, essential thrombocytosis, myelofibrosis
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Pathogenesis of polycythemia vera
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Abnormal clone of hematopoietic stem cells are increasingly sensitive to growth factors
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Essential thrombocytosis
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Elevated platelets (abnormal clone of megakaryocyte more sensitive to growth factors)
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Myelofibrosis
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Fibrotic obliteration of bone marrow
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CML clinical features
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Hepatosplenomegaly (not typically seen in myeloproliferative disorders; extramedullary hematopoiesis/infiltration), generalized painless lymphadenopathy
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CML treatment, mechanism of action, and major cause of resistance
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Imatinib (Gleevec)
Competitively binds to kinase binding site on bcr-abl Resistance if bcr-abl1 point mutations (drug can't bind bcr-abl) |
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How does bcr-abl1 lead to disease?
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abl (chr9) translocates to bcr (chr22) and the bcr-abl fusion protein is constituitively active tyrosine kinase. It causes constant myeloid cell production.
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What can CML, essential thrombocytosis, polycythemia vera, and primary myelofibosis evolve into?
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AML (and each other)
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Causes of large platelets (macrothrombocytopenia)
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Essential thrombcytosis, Bernard-Soulier disease, ITP
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What are the genetic causes of the 4 chronic myeloproliferative diseases?
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t(9:22) bcr-abl (Philadelphia chromosome): CML
JAK2 mutations: Polycythemia vera, essential thrombocytosis, primary myelofibrosis |
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Hydroxyurea
(mechanism, clinical use, toxicity) |
Mechanism: inhibits ribonucleotide reductase leading decreased DNA synthesis in S phase
Clinical use: Melanoma, CML, sickle cell (increase HbF) Toxicity: Bone marrow suppression, GI upset |
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Imatinib (Gleevec)
(mechanism, clinical use, toxicity) |
Mechanism: Philadelphia chromosome bcr-abl tyrosine kinase inhibitor
Use: CML, GI stromal tumors Toxicity: Fluid retention |
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Cisplatin, carboplatin
(mechanism, clinical use, toxicity) |
Mechanism: Cross-link DNA
Use: Testicular, bladder, ovary, lung carcinomas Toxicity: Nephrotoxic, acoustic nerve damage |
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Tamoxifen, raloxifene
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Mechanism: SERMs - receptor antagonists in breasts, agonists in bone; blocking binding of estrogen to estrogen receptor positive cells
Use: Breast cancer (or prevent osteoporosis) Toxicity: hot flashes, tamoxifen may increase risk of endometrial cancer (not raloxifene b/c it's an endometrial antagonist) |
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2 types of light chains
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Kappa and lambda
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What determines Ig class (IgG vs. IgA)?
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Heavy chain (i.e. gamma heavy chains are found in IgG)
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What are Bence-Jones proteins?
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Monoclonal light chains
Secreted after heavy chain expression is lost (i.e. multiple myeloma) instead of intact immunoglobulin. Found in urine. |
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What are M proteins? When might they be made? How are they detected?
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Monoclonal intact or incomplete immunoglubulins
Multiple myeloma, MGUS, Waldenstrom's macroglobulinemia, cryoglobulinemia, primary amyloidosis Detected as a discrete, dense band on electrophoresis or narrow peak on densitometer. (contrast with broad band/peak from excess polyclonal Ig from inflammation) |
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What is MGUS?
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Monoclonal gammopathy of undetermined significance
Production of M proteins without evidence of multiple myeloma or related diseases. Asymptommatic but may progress to multiple myeloma/related malignancy. Associated with t(11;14) and may be triggered by infection. More common in elderly |
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Neoplastic proliferation of a single clone of plasma cells in bone marrow (more than 10% of marrow). Plasma cells make monoclonal immunoglobulin (not IgM)
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Multiple myeloma
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Why do lytic bone lesions occur in multiple myeloma? What are the complications of these lesions?
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Myeloma cells release cytokines that activate osteoclasts
Leads to hypercalcemia, osteopenia, and pathologic fractures (compression fractures in spine can cause radiculopathy) |
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Lab findings in multiple myeloma?
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M proteins (most common: IgG > IgA > Bence Jones). Bence Jones proteins are found in urine and are hard to detect in blood. Rarely hypogammaglobulinemia.
Normocytic/chromic anemia (pallor) Plasma cells >10% of bone marrow |
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How can multiple myeloma cause renal insufficiency?
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Light chain cast nephropathy and hypercalcemia
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Cancer of class switched plasma cells?
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Multiple myeloma (never IgM)
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Cancer of IgM secreting plasma cells?
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Waldenstrom’s Macroglobulinemia
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Formal diagnosis of multiple myeloma?
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Evidence of Monoclonal plasma cell disorders + one or more of the following (CRAB=hyperCalcemia, renal failure, anemia, bone lesions)
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What can MGUS progress into?
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If IgM: Waldenstrom's
If other: Multiple myeloma |
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What do MGUS and smoldering myeloma have in common? What differentiates them?
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Both have NO end organ damage
MGUS has M protein <3g/dL AND <10% bone marrow plasma cells Smoldering myeloma has >3g/dL OR >10% bone marrow plasma cells (between MGUS and MM) |
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What factors worsen prognosis of multiple myeloma?
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Deletion of chr13 (FISH), increased plasma cell labeling index (PCLI), stage, amount of M protein, translocations
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How would you treat multiple myeloma in an older patient with comorbidities? In a young, healthy patient?
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Older: Melphalan-Prednisone (suppress marrow production of tumor cells) + Thalidomide (anti-angiogenic; birth defects)
Young: Transplant + Thalidomide/Lenalidomide + Steroids Bisphosphonates to decrease osteoclast activity (No cure) |
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Why does rouleaux occur in multiple myeloma?
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M proteins coat RBCs and neutralize negative charge
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How does multiple myeloma affect the kappa/lambda light chain ratio?
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Becomes 100% kappa or 100% lambda (clonal process; normal is 2:1)
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Multiclonal plasma cell proliferation, single bony (extramedullary) lesion, possibly M protein, NO bone marrow involvement
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Solitary Plasmacytoma
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Treatment for solitary plasmacytoma? Prognosis?
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Radiation (45% cured, 55% progress to multiple myeloma)
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IgM producing malignant plasma and/or B-cells, lymphoplasmacytoid cells, lymphadenopathy, hepatosplenomegaly
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Waldenstrom’s Macroglobulinemia (Lymphoplasmacytic Lymphoma)
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What are the consequences of having high levels of IgM in Waldenstrom’s Macroglobulinemia?
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Hyperviscosity symptoms b/c IgM forms huge pentamers
(headache, epistaxis, vision changes, hearing loss, parasthesias, seizures, somnolence) |
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Treatment for Waldenstrom’s Macroglobulinemia?
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Rituximab (anti-CD20) or Purine Nucleoside analogues or Alkylators
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What type of amyloid results from proliferative plasma cell disorders?
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AL (amyloid light chain)
Cardiomyopathy, nephropathy, macroglossia (AL is primary, i.e. not secondary to infection, and the most common) |
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Which amyloid is secondary to infection?
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AA (amyloid associated) = Non-Ig protein made in liver
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>20% plasma cells in peripheral blood
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Plasma cell leukemia
(Primary if diagnosed in leukemia phase, secondary if develops from multiple myeloma) |
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Plasma cell tumor in an extramedullary site and the absence of multiple myeloma
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Extramedullary plasmocytoma
(Called solitary plasmocytoma if arise in bone and extramedullary if arise in soft tissue. If multiple lesions, it's multiple myeloma) |
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Define myelodysplastic syndromes
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A group of diseases characterized by abnormal appearance of bone marrow and impaired formation of healthy blood cells
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What do patients with myelodysplastic syndrome usually present with?
What other abnormalities would be seen in bone marrow/chr analysis? |
1) Cytopenia (>95%, usually macrocytic-ish/megaloblastoid anemia; could also have infections, bleeding)
2) Monocytosis Would see hypercellular, dysplastic bone marrow. Multiple chromosomal abnormalities |
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What increases risk of developing myelodysplastic syndrome?
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1) Older (median age 65)
2) Prior chemotherapy (alkylators, topoisomerase II inhibitors) 3) Prior radiation |
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What are people with myelodysplastic syndrome at risk of developing?
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Can progress to AML ("preleukemia")
(Also infection, bleeding (despite mild thrombocytopenia), anemia from cytopenias) |
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What must be ruled out when diagnosing myelodysplastic syndrome?
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Folate/B12 deficiency (also HIV and certain medications like azathioprine)
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Condition in which most cells die in bone marrow. Dysplasia; cells released are dysfunctional (bleeding, infections, anemia)
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Myelodysplastic syndrome
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5q- syndrome
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Deletion of part chromosome 5 q arm that leads to myelodysplastic syndrome with refractory anemia.
Can progress to AML. Can be treated with Lenalidomide. Good prognosis |
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Prognosis of myelodysplastic syndrome depends on...
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# of blasts in marrow
How many blood counts are low Chromosome pattern Whether patient needs transfusions |
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Treatment of myelodysplastic syndrome
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Erythropoietin for anemia
Hypomethylating agents azacitidine and decitabine Lenalidomide for patients with del(5q) Stem cell transplant can be curative |
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Bone marrow failure syndrome, most common in elderly persons.
Risk of developing AML, but main problem is low blood counts despite hypercellular BM. |
Myelodysplatic syndrome
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Histiologic requirements to diagnose Hodgkin's lymphoma
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1) Reed-Sternberg cells of appropriate immunotype (these are the neoplastic cells of HL)
2) Appropriate reactive cell background (includes small lymphocytes, plasma cells, histiocytes, and eosinophils) |
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Treatment for for Hodgkin's lymphoma
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Radiation +/- chemo for early stages
ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) for advanced |
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bcl-2
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Inhibits apoptosis
Naive B cells are bcl-2 positive (immortal) but stop expressing it when exposed to antigen. bcl-2 stays on in Follicular lymphoma (immortal B cells) |
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Which B-cell lymphomas are pre/post/germinal center malignancies?
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Pre-germinal center: Mantle cell (poor prognosis); CLL/SLL
Germinal center: Diffuse Large B cell lymphoma, follicular lymphoma, Burkitt's lymphoma Post-germinal center: Marginal zone lymphoma |
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CD5+
Where originate in lymph node? Which malignancies? |
Pre-germinal center malignancy
CLL/SLL (CD23+) Mantle cell (CD23-) |
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CD10+
Where originate in lymph node? Which malignancies? |
Germinal center malignancy
Diffuse large B-cell lymphoma Follicular lymphoma Burkitt's lymphoma |
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CD5- and CD10-
Where originate in lymph node? Which malignancies? |
Post germinal center malignancy
Marginal cell lymphoma |
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For B cell non-Hodgkin's lymphomas, which are...
Indolent/incurable? Intermediate aggressive/possible cure? Highly aggressive/possible cure? Aggressive/incurable? |
Indolent/incurable = Follicular lymphoma (grades 1-2)
Intermediate aggressive/possible cure = Follicular lymphoma (grade 3), Diffuse large B cell lymphoma Highly aggressive/possible cure = Burkitt's lymphoma Aggressive/incurable = Mantle cell lymphoma (usually indolent don't respond to chemo b/c don't divide rapidly) |
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Match translocation to NHL type:
t(14;18) t(8;14) t(11:14) What is on chr14 that is translocated and which genes is it moved next to in each malignancy? |
chr14 has gene for Ig Heavy Chain (IHC) which is heavily transcribed. The gene it is juxtaposed to after translocation will be heavily transcribed too (oncogene)
t(14;18): Follicular (IHC beside bcl-2 oncogene so no apoptosis) t(8;14): Burkitt's (IHC beside c-myc on chr 8 which drives cell into cell cycle. This makes it more aggressive than just inhibiting apoptosis.) t(11:14): Mantle cell (IHC beside CCND1 which encodes cyclin D1; overproduction of cells) |
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Lymphocytosis, smudge cells, warm antibody hemolytic anemia (+Coomb's, increased indirect bili)
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CLL/SLL
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Pancytopenia, monocytopenia, few cells in BM (fibrosis), blood lakes in red pulp of spleen
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Hairy cell
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Treatment for Hodgkin's lymphoma
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Excision/radiation if early stages
ABVD if later stages (good prognosis, but more at risk for solid tumors later) |
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Histology of Hodgkin's lymphoma (3)
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1) Complete or partial destruction of LN architecture
2) Reed-Sternberg cells 3) Appropriate reactive cell background (eosinophils, plasma cells, lymphocytes) |
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Popcorn cells
CD20+, CD45+ |
Lymphocyte predominant HL
(not a classical HL; popcorn cells called LP cells too) |
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CD30+ and CD15+
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Hodgkin cell lymphoma (all subtypes have these CDs: Nodular sclerosing, mixed cellularity, lymphocyte depletion, lymphocyte-rich)
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What can follicular lymphoma (NHL) transform into?
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Diffuse Large B Cell Lymphoma
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HL vs. NHL
More common? Age affected? Mode of spread? Sites of involvement? |
More common? NHL (70% of all lymphomas, HL 30%)
Age affected? HL Young adult, NHL middle age/elderly Mode of spread? HL Contiguous, NHL noncontiguous (more disseminated/unpredictable) Sites of involvement? Both: Peripheral LNs and mediastinum; NHL can be found in mesenteric nodes, Waldeyer's ring, and extranodal sites (HL is not) |
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Follicular lymphoma (NHL)
Indolent/aggressive? CD? Place of origin in lymph node? Can transform to? Genetics? |
Indolent (grade 1-2)
CD10+ Germinal center origin DLBCL t(14:18) bcl-2 |
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Aggressive but incurable NHL, can have extranodal dz. (GI=lymphomatous polyposis)
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Mantle cell
t(11;14) |
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Mantle cell lymphoma
CD? Origin in lymph node? |
CD5+ (CD23-)
Pre-germinal center (NHL) |
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Germinal center NHL malignancies:
CD? 3 types? |
CD10+
DLBCL (bigger than macrophage nuc.) Follicular (smaller) Burkitt's |
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Marginal zone lymphoma
CD? Origin in lymph node? |
CD5-, CD10-
Post-germinal center malignancy |
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Most rapidly growing neoplasm, potential for tumor lysis syndrome with chemo, t(8;14)
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Burkitt's lymphoma
(c-myc) |
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T-cell lymphoma of the skin?
What is it called in the leukemia? |
Mycosis fungoides
If cells in blood, Sezary syndrome |
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Post germinal center NHLs
CD? Types? |
CD5-, CD10-
Marginal zone lymphoma Hairy cell lymphoma |
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Which T cell lymphomas have...
CD4? CD8? |
CD4: MF/Sezary, Adult T lymphocyte lymphoma
CD8: T cell large granular lymphoma (T-LGL) |
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Most common adult leukemia?
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CLL
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Does CLL have a better or worse prognosis with:
ZAP-70/CD38 +? Deletion of 17p? |
Worse for both
(17p has p53 gene) |
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Pancytopenia, monocytopenia, dry tap, splenomegally
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Hairy cell leukemia
(bone marrow hypocellular/fibrosed) |
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TRAP+
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Hairy cell leukemia
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Red pulp (spleen) infiltration (bloody lakes)
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Hairy cell leukemia
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Treatment for hairy cell leukemia?
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Pentostatin, (2-CDA) Cladribine
Very effective |
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Large Granular Lymphocyte Leukemia
Cell type? Indolent/aggressive? |
CD8 suppressor T cell
Indolent (Chronic lymphoproliferative disorder) |
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Which plasma cell disorders have...
No symptoms? Tumor bulk? Paraprotein? |
No symptoms: MGUS, SMM
Tumor bulk: MM, Macroglobulinemia (Walenstrom's), Plasmacytoma Paraprotein: Amyloid, neuropathy, LCDD, cryoglobulinemia |
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<3g M protein, <10% plasma cells, no anemia or bone lesions.
Normal calcium and kidney function Can it progress to MM? |
MGUS
1% chance/year to progress to MM |
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>3g M protein or >10% plasma cells, no anemia or bone lesions.
Normal calcium and kidney function What is it? Can it progress to MM? |
SMM
10% chance/year to progress to MM |
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Anemia, bone lesions,
high calcium or abnormal kidney function. >10% plasma cells, M protein spike |
Multiple myeloma
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Small/absent M protein spike, solitary monoclonal plasma cell mass
Can it progress to MM? |
Plasmacytoma
Osseous: 50% progress to MM Extraosseous: 15% progress to MM |
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Plasma cell neoplasm in which monoclonal immunoglobulin is deposited in various tissues, forming a beta-pleated sheet structure
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Primary amyloidosis
(bad prognosis) |
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Two major differences between multiple myeloma and Walenstrom's macroglobulinemia?
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Multiple myeloma: class switched plasma cells (all Ig's except IgM); lytic bone lesions
Walenstrom's macroglobulinemia: IgM; no bone lesions |
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What hematomalignancy presents with DIC in young patients?
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AML-M3 (acute promyelocytic leukemia)
(Other info: stuffed with Auer rods (Faggot cells), t(15;17), treat with ATRA) |
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Which has better prognosis: B-cell ALL or T-cell ALL?
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B-cell ALL
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"Preleukemia"
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Myelodysplastic syndrome
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Supportive care for myelodysplastic syndrome?
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1) Transfusions
2) Antimicrobials prn (not prophylactic) 3) Hematopoietic growth factors (erythropoietin, thrombopoietin stimulators, G-CSF/GM-CSF) MDS involves: 1) Bleeding, infections, complications of anemia (50%) 2) Death from other causes (25%) 3) Progress to AML (25%) |
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Imatinib
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Treatment for CML. Inhibits the constitutively active tyrosine kinase (bcr-abl)
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bcr-abl negative myeloproliferative neoplasms (3)
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Polycythemia vera, essential thrombocytosis, primary myelofibrosis
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Differential for essential thrombocytosis
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Reactive thrombocytosis (IDA, inflammation, splenectomy), other CMDs (PV, etc.)
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Treatment for essential thrombocytosis in low, high, indeterminate risk?
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Cytoreduction in high (optional for indeterminate)
Aspirin in high/low is optional but don't use in indeterminate until r/o vWD |
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What is relative polycythemia?
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Higher cell count due to less plasma (hematocrit is high). Cell mass (total amount of RBCs) is normal.
i.e. dehydration |
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Causes of polycythemia and their effect on plasma
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Secondary polycythemia: RBC mass increased, plasma volume normal, Hct high, EPO high (low O2 sat from COPD, etc.)
Polycythemia vera: RBC mass increased, plasma volume increased, Hct high or normal, EPO low/normal (normal O2 sat) (myeloproliferative disease) EPO secreting tumor: RBC mass increased, normal plasma, high EPO, normal O2 sat |
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Polycythemia vera findings
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1) Hyperviscosity: ischemia, thrombosis anywhere, Budd-Chiari syndrome, headaches
2) Hyperhistaminemia: (PV increases mast cells too which degranulate with temp change) post-bath pruritis, flushing 3) Hypervolumic: PV increases plasma too 4) Hyperuricemia: increased nucleated cell turn over increases uric acid (purine breakdown) 4 H's |
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Peripheral blood findings in myelofibrosis
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Dacrocytes, nucleated RBCs, left-shifted WBCs, leukoerythroblastic picture
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Hypercellular BM, reticulin or collagen fibrosis in BM, osteosclerosis
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Myelofibrosis
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Myeloproliferative neoplasm with worst prognosis
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Primary myelofibrosis
(palliative care: androgens or thalidomide or EPO for anemia, splenectomy or chemotherapy for splenomegaly) |
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Where does hematopoiesis occur at...
3 wga? 6 wga? 12 wga? 3rd trimester? |
Yolk sac
Liver Spleen Bone Marrow |
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About what percentage of a 70 year old's bone marrow is fat?
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70% fat
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What is primary lymphoid tissue? Secondary?
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Primary: Bone marrow + thymus (T cell maturation)
Secondary: Spleen + lymph nodes (maturation of immature lymphocytes in response to antigen; concentrates cells in one area so easier to activate with antigen) |
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Which organ can sequester large numbers of platelets?
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Spleen (severe splenomegally can cause thrombocytopenia)
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2 general ways to cause splenomegally
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1) Defective bone marrow (CML, myelofibrosis)
2) Infiltration of spleen with excess lymphocytes (reactive/malignant lymphocytosis) |
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Signs and symptoms of anemia
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1) Pale conjunctiva, palms, cold extremities
2) If chronic, kolionychia 3) Fatigue, headache, dyspnea 4) Tachycardia, flow murmur |
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Venous vs. arterial thrombosis
Which has fibrin>platelets? How do you prevent medically? |
Venous: fibrin>platelets, prevent with Coumadin
Arterial: platelets>fibrin, prevent with aspirin |
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Differential for microcytic anemia
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Thalassemia, Anemia of chronic dz., Iron deficiency, Lead, Sideroblastic
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Differential for normocytic anemia
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1) Acute hemorrhage
2) Hemolysis 3) Marrow dysfunction (i.e. aplastic anemia) 4) Renal failure (no EPO) |
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Differential for macrocytic anmeia
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1) Vit B12 deficiency
2) Folate deficiency 3) Drugs (esp. ones that interfere with DNA synthesis) 4) Liver dz. 5) Alcoholism 6) Hypothyroid |
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Which cytokines are responsible for differentiation of the following cells?
RBCs Platelets Monocytes and neutrophils |
Erythropoietin (kidney>>liver)
Thrombopoietin (liver) GM-CSF |
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How do you correct for EDTA causing pseudothrombocytopenia?
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Repeat CBC with sample collected in citrate. (EDTA is anticoagulant but in some people it causes clumping in vitro; platelet clumping=falsely high WBC count & low platelet count)
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Hereditary Hemorrhagic Telangiectasia (HHT)
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Autosomal dominant vascular bleeding disorder. Dilated/thin walled tortuous capillaries which rupture and cause telangiectasias (red spots/hemorrhage) on lips/tongue, skin, mucosa, lungs, brain, liver.
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Primary Hemostatic Response
What is created? Which receptors and factors are needed? |
Platelet plug
1) vWF binds exposed collagen and Gp1b-IX 2) Platelets aggregate: GpIIb/IIIa receptors linked by fibrinogen 3) Platelets release: ADP and TXA2 for more platelet aggregation |
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Secondary Hemostatic Response
What is created? Which receptors and factors are needed? |
Fibrin Plug
1)Tissue factor, phospholipid surface and Ca2+ 2) Activate coagulation cascade 3) Fibrin fills space between platelets |
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Most common congenital bleeding disorder
(Causes platelet type bleeding usually) |
Von Willebrand factor deficiency
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Large platelets that don't bind basement membrane. All aggregation patterns normal EXCEPT in ristocetin.
What disease? What defect? |
Bernard-Soulier
Gp1b-IX Abnormality |
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Which type of vWF deficiency can mimic hemophilia A?
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vWF type 2N (qualitatively abnormal vWF)
Decreased affinity for Factor VIII so can't "protect" it in blood. (normal distribution of HMWM and LMWM). Take history and look at binding activity to factor VIII. |
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Which types of vWF deficiency are quantitative/qualitative?
How should they be treated? |
Quantitiative: Types 1 & 3
Qualitative: Type 2 (decreased/abnormal HMW multimers; except type 2N) DDVAP for type 1 (stimulate more vWF production) Plasma derived vWF concentrations for types 2 & 3 |
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Platelets bind to basement membrane but not each other.
Which disease? What's abnormal? Would platelets aggregate in ristocetin? |
Glanzman's
GpIIb/IIIa receptor abnormality Platelets ONLY aggregate in ristocetin. |
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Ristocetin
What receptor does it work through? Will it cause aggregation in Bernard-Soulier or Glanzman's? |
Works via Gp1b
Gp1b is abnormal in B-S so ristocetin will NOT cause aggregation. Gp1b is normal in Glanzman's so ONLY ristocetin will cause aggregation. |
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Which drug can mimic Glanzmans?
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Abciximab
Both affect GpIIb/IIIa |
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Primary vs. Secondary hemostatic defects:
How do bleeding symptoms differ? Examples of primary/secondary? |
Primary: Mucocutaneous (petichiae, purpura, ecchymosis), GI/GU bleeds.
Examples: Platelet or vWF defects/deficiency. Vascular bleeding disorders (HHT, Ehlers-Danlos). Secondary: Soft tissue and joint bleeding, mucocutaneous. Often normal bleeding time but get rebleeding b/c no fibrin plug. Examples: clotting factor deficiencies. |
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How and when do you treat ITP?
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Treat when platelets <20K or <50K and bleeding.
Treat with 1) glucocorticoids 2) IVIG for severe thrombocytopenia 3) splenectomy if fail glucocorticoids Only give platelets if there is a life threatening (i.e. cranial) hemorrhage as they will just be destroyed by Ig/spleen |
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What could cause ITP?
What is the mechanism? What are symptoms? Course in children vs. adults? |
Immune/idiopathic thrombocytopenic purpura
Causes: infections, collagen vascular dz, lymphoproliferative dz., drug rxn, possibly autoimmune dz. Mechanism: Antibody mediated platelet destruction (spleen macrophages destroy labeled platelets) Symptoms: mucocutaneous and rarely intracerebral bleeds Kids have acute, self limiting course (often post infection); adults have chronic relapsing course |
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Hemolytic uremic syndrome/Thrombotic thrombocytopenic purpura
Lab findings? |
1) Severe thrombocytopenia
2) Microangiopathic anemia 3) Intravascular hemolysis 4) NORMAL coagulation studies 5) Renal disease 6) Normal to increased megakaryocytes 7) Schistocytes on PBS |
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ITP leads to hyperplasia of what cell?
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Megakaryocytes
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HUS/TTP vs. DIC
What do they have in common? What's different? |
Both: Intravascular hemolysis (schitocytes), microangiopathy with thrombosis, thrombocytopenia (use up platelets)
DIC: Uses up clotting factors! So prolonged PT/aPPT, + D-dimer, low fibrinogen (all these would be normal in HUS/TTP b/c don't activate clotting cascade) |
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Disorder platelet-endothelial cell
Platelet thrombi microvasculature Thrombocytopenia Microangiopathic hemolytic anemia Does not deplete clotting factors |
HUS/TTP
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HUS/TTP symptoms
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Fever
Neurologic abnormalities (TTP) Platelet type bleeding Renal failure Abdominal pain Diarrheal prodrome (enterotoxin associated) (HUS) |
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Causes of DIC
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Infections (sepsis), acute pancreatitis, neoplasms, massive tissue injury, obstetric (amniotic fluid embolism, retained dead fetus), nephrotic syndrome
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Vitamin K dependent factors
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II, VII, IX, X
Protein C, S |
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Warfarin prolongs aPTT or PT?
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PT
Inhibits entire extrinsic pathway (factor VII, also II, IX, X) |
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Factor VIII deficient, X-linked disease
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Hemophilia A
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Factor IX deficient, X-linked disease
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Hemophilia B
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Clotting factors:
Intrinsic pathway? Extrinsic pathway? Common? |
Intrinsic (aPTT): 12, 11, 9, 8
Extrinsic (PT): 7, (3=tissue factor) Common: 5, 10, 2, fibrinogen |
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What is a conditioning regimen? Why do you do it?
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Medications designed to wipe out a patient's bone marrow before BM transplant.
Do this for anti-leukemic effect and prevent patient's immune system from attacking the donor graft (give drugs to prevent graft vs. host disease) |
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What is mechanism of graft vs. host disease?
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Donor cytotoxic T cells attack host cells of different HLA type (especially liver, colon, skin)
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What is mechanism of glucocorticoids in treating GVHD?
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Stimulate production of apoptotic proteins in lymphocytes (used for lymphomas/leukemias too).
GVHD is caused by donor cytotoxic T cells attacking host. |
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What is a potential benefit of GVHD following BM transplant in cancer treatment?
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Some GVHD reaction can kill any remaining leukemic cells. Less likely to have relapses of the cancer.
However it is a balance as GVHD can kill the patient if the reaction is too much. |
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What is the most common inherited thrombophilia? What is the pathology?
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Factor V Leiden
Factor V is resistant to inactivation by protein C |
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Acquired thrombophilia causes
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Antiphospholipid syndrome
Estrogen (BCP, HRT) Malignancy Trauma/Ortho surgery Immobilization/obesity Age Smoking |
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Clinical and lab criteria to diagnose Antiphospholipid Antibody Syndrome
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Clinical: >1 fetal death (>10 weeks), >3 fetal death (<10 weeks), >1 premature birth
Lab: 1) Lupus anticoagulant (prolonged aPTT doesn't correct) 2) Anticardiolipin Ab Must have + labs on 2 tests 12 weeks apart |
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Conditions associated with reactive thrombocytosis?
Risk for thrombosis with reactive thrombocytosis? |
1) Infection (acute/chronic)
2) Chronic inflammatory disease 3) Malignancy 4) Splenectomy 5) IDA 6) Hemorrhage, hemolysis Low risk for thrombosis (clonal thrombocytosis has higher risk of thrombosis than reactive) |
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Deficiencies of which factors can prolong aPTT but never lead to bleeding problems?
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Factor 12, Prekallikrien, HMW kininogen
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What is hepcidin?
Would it be high/low in... iron deficiency anemia? anemia of chronic disease? |
Inhibits ferroportin so less iron is absorbed by intestines. (Ferroportin a transmembrane protein in enterocytes and other cells that transports iron from the inside to outside of cells)
Hepcidin would be... LOW in IDA (want to absorb iron) HIGH in ACD (have a lot of stored iron) |
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What is ferroportin? What inhibits it?
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Transmembrane protein in enterocytes and other cells that transports iron from the inside to outside of cells. Allows for absorption of iron.
Hepcidin inhibits it |
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What is transferrin?
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Plasma protein that carries iron in the blood
(Ferroportin allows iron to be absorbed from intestine and taken by transferrin) |
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Would the following be increased/decreased/normal in IDA?
Hepcidin? Ferroportin? Ferritin? Serum iron? TIBC? |
Hepcidin? Decreased (increases ferroportin)
Ferritin? Decreased Serum iron? Decreased TIBC? Increased |
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Would the following be increased/decreased/normal in ACD?
Hepcidin? Ferroportin? Ferritin? Serum iron? TIBC? |
Hepcidin? Increased (decreases ferroportin)
Ferritin? Increased Serum iron? Decreased TIBC? Decreased |
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Would the following be increased/decreased/normal in thalassemias?
Hepcidin? Ferroportin? Ferritin? Serum iron? TIBC? |
All normal (thals affect globin, not heme so don't alter iron)
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Pencil/cigar cells, hypochromia
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IDA
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Where are B12, folate, and iron absorbed?
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Iron: stomach/prox. small bowel
Folate: prox. small bowel B12: terminal ileum (bile salts absorbed here too!) |
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Which globin chains make up HbA, HbF, HbA2?
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HbA=alpha2 + beta2
HbF=alpha2 + gamma2 HbA2=alpha2 + delta2 |
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What would Hb electrophoresis look like for alpha and beta thalassemias?
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Alpha=normal
Beta=low HbA, high HbF & A2 |
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Peripheral smear of ACD
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Can have rouleaux (proteins coat RBCs) but otherwise normal (maybe microcytic)
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Causes of ACD
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1) Chronic infection (osteomyelitis)
2) Chronic immune disorders (lupus) 3) Chronic neoplastic disorders (Hodgkin's) When chronic inflammation, sequester iron so cannot be utilized by bacteria. Chronic inflam can also lead to increased serum protein/rouleaux |
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Normocytic anemia differential
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Acute hemorrhage
Hemolysis Aplastic bone marrow |
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Conditions you can see spherocytes on peripheral smear
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1) Hereditary spherocytosis
2) Autoimmune hemolytic anemia (warm antibodies) 3) Post transfusion |
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Lab differences between intravascular and extravascular hemolysis
Haptoglobin? Urine hemosiderin? Urine hemoglobin? Indirect bilirubin? Lactate Dehydrogenase (LDH)? |
Products of intravascular Hb spillage:
Haptoglobin: IV=very low, EV=little low or N Urine hemosiderin: IV=high, EV=N Urine hemoglobin: IV=high, EV=N Other: Indirect bilirubin: IV=high, EV=little high Lactate Dehydrogenase (LDH): IV=high, EV=little high (sign of cell turnover) |
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Causes of intrinsic hemolysis
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Membrane: hereditary spherocytosis/eliptocytosis
Enzyme: G6PD, nocturnal paroxysmal hemoglobinuria, pyruvate kinase Hemoglobin: thalassemias, sickle cell |
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Causes of megaloblastic, oval macrocytes?
Causes of non-megaloblastic macrocytes? |
Megaloblastic, oval macrocytes:
1) B12/folate def. 2) drugs (inhibit DNA synthesis 3) stem cell defect (MDS) Non-megaloblastic macrocytes: 1) Reticulocytosis 2) EtOH 3) Liver dz. 4) Hypothyroidism 5) Drugs, tobacco, age (without anemia) |
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Causes of decreased B12 absorption
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1) Achlorhidria (gastrectomy)
2) Decreased intrinsic factor (pernicious anemia has antibodies against parietal cells and intrinsic factor) 3) Pancreatic insufficiency (need trypsin to cleave B12 from R factor so it can bind intrinsic factor in duodenum) 4) Terminal ileum problem (bacterial overgrowth, celiac/Crohn's, resection) Differentiate with Schilling's test |
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What substances accumulate in B12 deficiency? Folate?
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Homocysteine and Methylmalonyl Co-A for B12
Only homocysteine for folate |
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Clinical manifestations of B12 deficiency?
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Atrophic glossitis, proprioception/motor/equilibrium defects, psychosis
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Most common cause of folate deficiency? Other causes
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Insufficient intake (smaller stores and greater need than B12)
Also increased need (pregnancy, hemolysis), impaired use (drugs), decreased absorption (celiac, anti-convulsants) |
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Hypersegmented neutrophils
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B12 or folate deficiency
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Difference between hemoglobinopathy and thalassemia
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Hemoglobinopathy: abnormal globin chains (i.e. sickle cell); qualitative
Thalassemia: decreased production of normal globin chains; quantitative |
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Symptom/sign of HbM (methemoglobin)
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Cyanosis
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Hemoglobin variants that can cause thalassemic phenotype
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HbE, Hb Lepore
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Hb H
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Tetramers of beta globin=HbH (shows up on electrophoresis)
Alpha thal with 3 alpha globin genes deleted (thalassemia intermedia) |
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Hb Bart's
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Tetramers of gamma globulin (shows up on electrophoresis)
Alpha thal with all 4 alpha globin genes deleted (fatal, hydrops fetalis) |
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Acute intermittent porphyria
Genetics? Precipitated by? Symptoms? Lab findings? |
Autosomal dominant (more common in women)
Can be precipitated by use of certain drugs Abdominal pain, fever, nausea, vomiting, constipation, peripheral neuropathy, paralysis, pysch symptoms (agitation, depression, paranoia, visual hallucinations) Labs: Leukocytosis, high porphyrobilogen |
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Treatment for beta thal major? intermedia? minor?
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Major (B0/B0 or B0/B+) RBC transfusions for severe anemia (iron chelation), H/Smegaly, prophylaxis for infections, bone marrow transplant
Intermedia (B+/B+ or B+/B0) occasional RBC transfusion for moderate anemia Minor (B0/B or B+/B) none needed |
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Mutation causing HbS
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Missense mutation at 6th aa (Glu>Val)
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HbC molecular pathology
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Missense mutation for 6th aa in beta globin (Glu>Lys)
Less severe than HbS, target cells, can promote sickling |
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HbE molecular pathology
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Missense mutation for 26th aa in beta globin (Glu>Lys)
Asymptomatic/mild microcytic anemia |
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What can be coinherited to decrease severity of sickle cell phenotype?
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1) Hereditary persistence of HbF (virtually asymptomatic)
2) Beta thalassemia |
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Consequences of high O2 affinity Hb
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Won't give up as much O2 in tissues-->perceive hypoxia-->increase EPO-->increase RBCs (may need phlebotomy)
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Frontal bossing, hepatoslenomegally (extramedullary hematopoiesis), profound anemia, weak bones (marrow expansion)
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Beta thal major
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What is the difference cause of anemia in thalassemias vs. sickle cell anemia?
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Thalassemia: unpaired chains precipitate and cause inclusions that are removed in spleen (extravascular hemolysis); inclusions also interfere with hematopoeisis (coinherited disorders that decrease unpaired chains decrease severity of disease)
Sickle cell: chronic intravascular hemolysis |
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Treatment for sickle cell
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1) Prophylactic penicillin
2) Hydroxyurea (reduce frequency of pain crises by increasing HbF) 3) |
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How do you get iron overload in beta thal major?
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1) Anemia causes increased EPO leading to more iron absorption. Hemolysis in beta thal is extravascular (spleen) so iron is recycled and accumulates.
2) Frequent transfusions Must iron chelate or else heart failure! |
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How do you prevent GVHD when giving blood product transfusions?
Who is at risk for GVHD? |
Irradiation to kill lymphocytes (cytotoxic T lymphocytes from donor attack host)
People without cellular immunity (but not HIV patients; HIV will kill the donor T cells) |
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What happens to plasma cell volume and RBC mass in pregnancy?
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Both increase
Plasma increases more than RBCs so get dilutional anemia (Hb>10.5 is normal in T3) |
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What is most common anemia in pregnancy in the world? What consequences for the fetus?
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IDA is most common (fetus has huge iron needs)
Low birth weight and preterm delivery risk increases |
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Do pregnant women with sickle cell anemia require transfusions?
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No, transfuse only if they have a pain crisis
Note: You would not transfuse to keep Hb high in sickle cell, but you would transfuse to keep Hb>10 in thalassemia (Induction increases risk of pain crisis. Need folate b/c higher cell turn over.) |
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Why is there leukocytosis in pregnancy/labor?
|
Demargination of WBCs (physiologic leukocytosis)
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What is an abnormal platelet count in pregnancy? What are 4 causes of low platelet count in pregnancy?
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<100K
1) Gestational (70-100K, resolves post-partum, no treatment) 2) ITP (<30K treat; monitor baby post-partum) 3) HELLP Syndrome (induce labor) 4) DIC (amniotic fluid embolism, retained dead fetus, placental abruption) |
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What is HELLP?
Signs/symptoms? Treatment? |
H=hemolysis, EL=elevated liver enzymes, LP=low platelets
Severe RUQ pain (liver can rupture) Induce labor ASAP Etiology unknown but occurs in 10% patients with preeclampsia (liver microinfarcts, hepatic congestion) |
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Pre-eclampsia
|
Nephrotic syndrome, HTN, edema (10% get HEELP)
(put patient in left lateral decubitus to increase renal perfusion) |
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Eclampsia
|
Tonic-clonic seizures on top of pre-eclampsia
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How does pregnancy affect elements of Vichow's Triad?
When is risk of thrombosis greatest? |
Hypercoaguability: decreased anticoags (protein S, ATIII), aquired APC-resistance, increase clotting factors (fibrinogen, F8)
Stasis: compress IVC Vessel wall damage: damage pelvic vessels peripartal Greatest risk is 3 mo post-partum |
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How do you prevent miscarriage in woman with anti-phospholipid antibody syndrome?
|
Prophylactic heparin + aspirin
(Don't give Warfarin b/c teratogen) |
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Malignancy in pregnancy: when should you treat with chemo?
|
Try to wait til 2nd trimester (organogenesis in 1st) for Hodgkins/NHL. Cannot delay treatment for acute leukemia.
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Which type of lymphocyte is usually most prevalent in blood? Which is the most common neoplasm?
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T cells usually 80% of lymphocytes
B cell neoplasms more common |
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Which leukemia/lymphoma can have warm autoimmune hemolytic anemia? What unusual cell type would you see?
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CLL/SLL (direct Coomb's positive)
AIHA causes spherocytes |
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Smudge cells on peripheral smear
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CLL/SLL
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Chronic lymphoproliferative disorders (in blood):
Which are B cell? T cell? |
B cell:
CLL Hairy cell Plasma cell prolif. disorders (MM, amyloidosis, Walenstrom, etc.) (Leukemic phase of HL/NHL) T cell: Large Granular Lymphocyte Leukemia Adult T cell leukemia Sezary syndrome (when mycosis fungoides cells get in blood) |
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Labs for CLL
|
Hypogammaglobulinemia (increased infections)
Warm AIHA (IgG) (leads to extravascular hemolysis: increase retics, LDH, indirect bilirubin) |
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Prognosis for CLL
|
1/3 indolent course
1/3 progress to aggressive course 1/3 present in aggressive phase (17p deletion, CD38 & ZAP-70 positive worsen prognosis) |
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Cells have fried egg appearance in spleen/BM. Treat with purine analogues (Cladribine, Pentostatin) for remission.
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Hairy cell leukemia
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Mycosis Fungoides extension into blood
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Sezary syndrome (atypical CD4+ helper T cells)
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Associated with HTLV-1 retrovirus. Hypercalcemia and lytic bone lesions.
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Adult T-cell leukemia/lymphoma
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T cell lymphomas
Which 2 are CD4 helper T cells? Which one is CD8? |
CD4: MF/Sezary, Adult T cell leukemia/lymphoma (ATLL)
CD8: T-LGL |
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Germinal center B cell malignancy, contiguous spread (usually starts in cervical node), bimodal age distribution
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Hodgkins lymphoma
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Clinical manifestations of Hodgkins
|
B symptoms (night sweats, fever, weight loss)
Pruritis Alcohol induced LN pain SVC syndrome (mediastinal mass compresses SVC) Painless LN enlargement (exp. neck/axilla) |
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Destruction of LN architecture (fibrosis), RS cells, reactive cell background
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Hodgkins lymphoma
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Neoplastic cell of nodular sclerosing HL
|
Lacunar RS cell (area of white clearing around nucleus)
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L&H cell
|
aka Popcorn cell
Lymphocyte predominant subtype of Hodgekins lymphoma |
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Non-classical Hodgkin's lymphoma; excellent prognosis but frequent relapses
|
Lymphocyte predominant (popcorn cells, aka L&H cells)
LPHL has CD20+, CD45+ Classical HL has CD15+, CD30+ |
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|
What is important in determining prognosis of Hodgkins lymphoma?
|
Stage
Stage 1= single LN 2=2 or more LNs on same side of diaphragm 3=LN on both sides of diaphragm 4=extra-lymphatic site (BM, liver, etc) Stage A=no symptoms Stage B=one of the B symptoms (fever, weight loss, night sweats) |
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ABVD treats what?
Complications? |
Chemo to treat Hodgkins lymphoma
Increased risk of leukemia later |
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|
Chronic lymphoproliferative disorder
|
Lymphoid neoplasm arising in BM or blood (not quite as defined as leukemia)
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|
HL vs. NHL
Which is more common? Which is more curable? |
NHL is 70% lymphomas
HL is more curable |
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CD5- and CD10- B cell lymphoma
|
Marginal cell and hairy cell
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Proliferation centers, CD5+ and CD23+ B cell malignancy
|
CLL/SLL
|
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|
Gastric H. pylori can cause which lymphoma?
|
B-MALT lymphoma
Extranodal Marginal Zone Lymphoma of mucosal associated tissue. Treat H. pylori and will probably resolve. |
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|
Lymphomatous polyposis (GI tract) can occur, CD5+, CD23-
|
Mantle cell
t(11;14) |
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|
Endemic form presents as mass in jaw in African children. Sporadic most commonly in abdomen
|
Burkitt's lymphoma
|
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|
TdT is usually a marker of
|
ALL (can be in AML sometimes)
|
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|
Age of onset of leukemias?
0-14? 15-39? 40-59? >60? |
0-14: ALL (B more common)
15-39: AML 40-59: AML, CML (differentiate by >30% blasts or Philadelphia chr) >60: CLL |
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|
Prognosis for NHL determined by what score?
|
IPI (high score=bad prognosis)
APLES Age >60 Performance status >1 LDH>1 Extranodal Stage 3 or 4 |
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|
What is untreated survival for the following? Prognosis with treatment?
Follicular NHL Diffuse Large B cell NHL Burkitt's |
Follicular: years, no curative treatment but indolent
DLBCL: weeks/months, good prognosis with treatment Burkitts: days/weeks, good prognosis with treatment |
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|
Cell types in the cortex of lymph node
|
B cells
Primary follicles: B cells not exposed to antigen (no germinal center) Secondary follicle: has germinal center with B cells that have been exposed to antigen and present antibodies to be "picked" T cells |
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|
Cell types in paracortex of lymph node
|
T cells
(region between cortex and medulla; increases in size during cellular immune response like TB/virus/fungi) |
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Cell types in medulla of lymph node
|
Cords=plasma cells
Sinuses=macrophages |
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|
Causes of follicular lymphoid hyperplasia
|
(B cell response)
Bacterial infection (except mycobacteria/brucella), toxoplasma gondii, CMV, HIV (not EBV, this infects B cells but T cells proliferate and respond) |
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Causes of paracortical lymphoid hyperplasia
|
EBV, dermatopathic lymphadenopathy, drug rxn (phenytoin), SLE, granulomatous lymphadenitis (mycobacteria, fungi)
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|
Cyclophosphamide
Mechanism of action? Toxicities? |
DNA cross links
Marrow, bladder, increased risk of MDS/leukemia (alkalator) |
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|
Doxorubicin
Mechanism of action? Toxicities? |
Topoisomerase II inhibitor, helicase inhibitor (like idorubicin)
Cardiac (dialated cardiomyopathy) Oropharynx Marrow |
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Bleomycin
Mechanism of action? Toxicities? |
Inhibit DNA synthesis
Pulmonary fibrosis |
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Vincristine
Mechanism of action? Toxicities? |
Tubulin
Marrow Neuropathy |
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|
Cytarabine
Mechanism of action? Toxicities? |
Inhibit DNA synthesis
Cerebellar (ataxia) Marrow |
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|
Idarubicin
Mechanism of action? Toxicities? |
Topoisomerase II inhibitor, helicase inhibitor (like doxorubicin)
Marrow Cardiac |
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|
Methotrexate
Mechanism of action? Toxicities? Mechanism of resistance? |
1) Transported into cells on folate transporter
2) Inhibits dihydrofolate reductase which is needed to make purines/pyrimidines Resistance: 1) Diminished uptake 2) Diminished foylpolyglutamate synthase 3) Elevated dihydrofolate reductase 4) Diminished affinity of target enzyme for methotrexate |
