Haem/Onc Flashcards

Question

Leukemoid reaction vs CML?

Answer 1

**_Leukemoid Reaction_** * High leukocyte alkaline phosphatase score * Toxic granulation (Dohle bodies) in the white cells * 'Left shift' of neutrophils i.e. increased neutrophils or 3 segments of the nucleus **_CML_** * Low leukocyte alkaline phosphatase score

Answer 2

* Myeloproliferative disorder caused by hyperplasia of abnormal megakaryocytes responsible for the production of platelets * Resultant release of platelet derived growth factor is thought to stimulate fibroblasts * Hematopoiesis develops in the liver and spleen **_Features_** * E.g. Elderly person with symptoms of anemia e.g. Fatigue (the most common presenting symptom) * Massive splenomegaly * Hypermetabolic symptoms: weight loss, night sweats etc **_Ix_** * Anemia * High WBC and platelet count early in the disease * 'Tear-drop' poikilocytes on blood film * Unobtainable bone marrow biopsy - 'dry tap' therefore trephine biopsy needed * High urate and LDH (reflect increased cell turnover)

Answer 3

30% progress to AML **_Presentation_** * Pancytopenia --\> anaemia, infection, bleeding **_Investigations_** * Serial blood counts --\> evidence of increasing bone marrow failure * Bone marrow shows increased cellularity **_Management_** * \< 5% blasts in the bone marrow --\> manage conservatively. * Raised WBC --\> gentle chemotherapy. * \< 60 years old --\> Intensive chemotherapy

Answer 4

Philadelphia chromosome * translocation between the long arm of chromosome 9 and 22 - t(9:22)(q34:q11). This results in part of the ABL proto-oncogene from chromosome 9 being fused with the BCR gene from chromosome 22. * The resulting BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of normal * Good prognostic sign in CML * Poor prognostic sign in AML + ALL

Answer 5

**_Presentation_** * Middle-age * Anemia, weight loss * Splenomegaly may be marked (lethargy, anorexia, abdominal discomfort – 75% palpable spleen) * Hepatomegaly and lymphadenopathy are uncommon * Spectrum of myeloid cells seen in peripheral blood * Reduced neutrophil alkaline phosphatase * May undergo blast transformation (AML in 80%, ALL in 20%) **_Diagnosis_** * Philadelphia is confirmatory * Peripheral blood film: (leukocytosis in all stages of differentiation within the myeloid linage) * Basophilia is important diagnostic marker especially when Philadelphia is absent * Monocytopenia * Bone-marrow hypercellularity with increased myloid-erythroid ratio **_Management_** * Hydroxyurea (also used in PRV, painful attacks in sicklers and as antiretroviral in HIV) * Interferon- a * Imatinib (inhibitor of tyrosine kinase) * Allogenic bone marrow transplant (optimum management)

Answer 6

* Most common form of acute leukemia in adults * May occur as a primary disease or following a secondary transformation of a myeloproliferative disorder (e.g CML, myelofibrosis) * **\> 30% blasts are almost diagnostic of AML** **_Presentation_ (pancytopenia)** * Early signs are vague and non-specific (influenza-like) * Persistent or frequent infections (due to low WBC) * Bruising and petechiae (due to low PLT) * Splenomegaly may occur but typically mild and asymptomatic. Lymph node swelling is rare

Answer 7

Combination of a myeloperoxidase or Sudan black stain and a non-specific esterase (NSE) stain will provide distinction of AML from ALL and in subclassification of AML in most cases

Answer 8

* M3 subtype of AML * Presents younger than other types of AML (25 yrs) * Classical presentation = rasied WCC, DIC or thrombocytopenia * Associated with t(15:17) translocation which causes fusion of the PML and RAR-a genes. * Good prognosis * Treated with the ATRA in addition to induction chemotherapy. * All-trans-retinoic acid - activates the RAR-a gene thus helps the WBCs to differentiate (i.e mature) but it will not eliminate the leukemia.

Answer 9

* \> 60 years * \> 20% blasts after first course of chemo * Cytogenics: deletions of chromosome 5 or 7

Answer 10

Chemo divided into two phases 1. **_Induction_** * All types (except M3) - cytarabine (ara-C) and an anthracycline (such as daunorubicin or idarubicin) * Regimen known as 7+3 - ara-C is given as a continuous IVI for 7 days while the anthracycline is given for 3 consecutive days as an IV push 2. **_Consolidation_** * *Further therapy needed to eliminate non-detectable disease and prevent relapse* * For good-prognosis leukemias [t(8;21), and t(15;17)], patients will typically undergo an additional 3–5 courses of intensive chemotherapy * For patients at high risk of relapse (e.g. those with high-risk cytogenetics, underlying MDS, or therapy-related AML), allogeneic stem cell transplantation is usually recommended

Answer 11

Caused by a monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells (99%) **_Features_** * Often none * Constitutional: anorexia, weight loss * Bleeding, infections * Lymphadenopathy more marked than CML **_Complications_** * Hypogammaglobulinemia leading to recurrent infections most common cause of death * Warm autoimmune hemolytic anemia in 10-15% of patients * Transformation to high-grade lymphoma (Richter's transformation) **_Poor Prognostic Factors_** * Male * Age \> 70 years * Lymphocyte count \> 50 * Prolymphocytes comprising \> 10% of blood lymphocytes * Lymphocyte doubling time \< 12 months * Raised LDH * CD38 expression positive

Answer 12

**_Ix_** * Immunophenotyping (flow cytmetry) * Immunophenotyping will demonstrate the cells to be B-cells (CD19 positive). CD5 and CD23 are also characteristically positive in CLL * Blood film: smear or smudge cells **_Mx_** * None early on * Chlorambucil to reduce lymphocyte count * Fludarabine * causes profound lymphopenia --\> increases the risk of opportunistic infections significantly, * Give co-trimoxazole or to use monthly nebulised pentamidine to prevent PCP pneumonia

Answer 13

* Progressive marrow failure: the development or worsening of anemia and/or thrombocytopenia * Massive (\>10 cm) or progressive lymphadenopathy * Massive (\>6 cm) or progressive splenomegaly * Progressive lymphocytosis: \> 50% raised over 2 months or lymphocyte doubling time \< 6 months * Systemic symptoms: weight loss \> 10% in previous 6 months, fever \>38ºc for \> 2 weeks, extreme fatigue, night sweats * Autoimmune cytopenias e.g. ITP

Answer 14

Rare malignant proliferation disorder of B cells lymphocytes Classified as a sub-type of chronic lymphoid leukemia Hairy cells = abnormal WBCs with hair-like projections of cytoplasm. **_Features_** * Pancytopenia (Monocytopenia is classical) * Splenomegaly * Skin vasculitis in 1/3 patients * 'Dry tap' despite bone marrow hypercellularity (also seen in myelofibrrosis) * Bone marrow biopsy migh show "fried egg appearance" * Tartrate resistant acid phosphotase (TRAP) stain positive **_Management_** * Chemotherapy is first-line: cladribine, pentostatin * Immunotherapy is second-line: rituximab, interferon- * Splenectomy sometimes required

Answer 15

Causes problems by crowding out normal cells in the bone marrow, and metastasising 2 peaks - 2-5 years, and old age * t(12:21) = most common translocation --\> good prognosis. * Philadelphia chromosome t(9:22) --\> bad prognosis. * t(4:11) is the most common in children under 12 months and portends a poor prognosis.

Answer 16

Presentation * Generalized weakness and fatigue, anaemia * Frequent or unexplained fever and infections * Weight loss and/or loss of appetite * Excessive and unexplained bruising; Petechiae due to thrombocytopenia * Bone pain, arthralgia. * Dyspnea due to lung infiltration. * Lymphandeopathy, hepatosplenomegaly. * Pitting edema in the lower limbs and/or abdomen

Answer 17

* Leukocytosis. * Blast cells are seen on blood smear in 90% of cases * Bone marrow biopsy is conclusive proof of ALL * LP to detect CNS involvement. * CXR: to look for mediastinal mass (common in ALL) * U&E to look for Tumor Lysis Syndrome. * Immunophenotyping, establish whether the "blast" cells origin is B or T lymphocytes * DNA testing; different mutations reflect prognosis. Terminal deoxynucleotide transferase (TdT) present in 95% of ALL

Answer 18

Good * Common ALL * Pre-B phenotype * Low initial WBC * FAB L1 type Bad * FAB L3 type * T or B cell surface markers * Philadelphia translocation, t(9;22) * Age \< 2 years or \> 10 years * Male Sex. * CNS involvement * High initial WBC (e.g. \> 100 \* 109/l) * Non-Caucasian

Answer 19

* Left-shifted granulocytic series and nucleated red blood cells) with pancytopaenia * Also defined when there are immature cells (e.g myelocytes, and nucleated red blood cells) seen on the peripheral blood film **_Associations_** * Increased Bone marrow turnover e.g. in severe hemolytic anemia (in which case the reticulocyte count would be high). * Myelofibrosis and Chronic Myeloid Leukaemia (where there would be splenomegaly, and the white cell and platelet count would usually be raised). * Bone marrow invasion. Often in bone marrow invasion the invading malignancy will already have been diagnosed previously. * Myeloma * Polycythaemia Rubra Vera * Osteopetrosis * Tuberculous infiltration of the bone marrow * Sarcoidosis

Answer 20

* Malignant proliferation of lymphocytes characterized by the presence of the Reed-Sternberg cell. * Bimodal age distributions being most common in the third and seventh decades. * Associated with EBV * 25% have constitutional symptoms (night sweats, weight loss, fever, pruritus and lethargy) **_Diagnosis_** * Hodgkin results in patchy bone marrow infiltration, an isolated bone marrow biopsy may yield non-specific results. * Bone marrow biopsy is more useful for staging of advanced disease. * Lymph node biopsy would be more likely to be positive, Reed-Sternberg cell is evident on microscopy

Answer 21

Ann-Arbor * I: single lymph node * II: 2 or more lymph nodes/regions on same side of diaphragm * III: nodes on both sides of diaphragm * IV: spread beyond lymph nodes Each stage may be subdivided into A or B * A = no systemic symptoms other than pruritus * B = weight loss \> 10% in last 6 months, fever \> 38c, night sweats (poor prognosis)

Answer 22

* Age = 45 years * Stage IV disease * Hemoglobin \< 10.5 g/dl * Lymphocyte count \< 600/μl or \< 8% * Male * Albumin \< 40 g/l * White blood count = 15,000/μl

Answer 23

**_IA/IIA_** * Radiation therapy AND chemotherapy. * The choice of treatment depends on the age, sex, bulk and the histological subtype of the disease. **_III, IVA or IVB_** * Combination chemotherapy alone **_Large mass in the chest (regardless of stage)_** * Treated with combined chemotherapy and radiation therap. * Chemo includes: Doxorubicin, Bleomycin, Vincristine, Cyclophosphamide and other cytotoxic drugs.

Answer 24

* Diverse group of lymphomas that include any kind of lymphoma except Hodgkin's lymphomas * Low-grade lymphoma is predominantly a disease of older people. * Most non-Hodgkin’s lymphomas are of B cell phenotype, though T cell tumours are recognised **_Presentation_** * Most present with advanced disease, bone marrow infiltration being almost invariable. * Extra-nodal presentation is more common than Hodgkin's disease. * Renal impairment in non-Hodgkin’s lymphomas usually occurs as a consequence of ureteric obstruction secondary to intra-abdominal or pelvic lymph node enlargement. * Anaemia, an elevated white cell count and/or thrombocytopaenia are suggestive of bone marrow infiltration.

Answer 25

* Lymph node biopsy is sufficient for a definitive diagnosis --\> immuno-phenotyping and cytogenetic/molecular analysis. * High-grade lymphomas are responsive to chemotherapy and potentially curable, * Low-grade lymphomas are incurable with conventional therapy. * Chemotherapy is the mainstay of treatment in most cases

Answer 26

High grade B cell neoplasm (NHL) Two forms * Endemic (African) form: typically involves maxilla or mandible * Sporadic form: abdominal (ileo-caecal) tumors are the most common form. More common in patients with HIV Associated with the c-myc gene translocation, usually t(8:14) EBV strongly implicated in African form but not so much sporadic Common cause of **Tumour Lysis Syndrome**

Answer 27

Occurs after the initiation of a chemotherapeutic. TLS tends to occur in patients with bulky, rapidly proliferating, treatment-responsive tumors **_Associations_** * Acute leukemia * High-grade non-Hodgkin’s lymphomas. * Pre-treatment raised LDH (levels of LDH correspond with tumor bulk) **_Manifestation_** (rapid 48-72 hours after initiation) * Hyperkalaemia * Hyperuricaemia * Hyperphosphataemia * Hypocalcaemia * Acute renal failure **_Management_** * Prevention is with good hydration before starting chemotherapy. * Hyperuricemia --\> urine alkalinisation and allopurinol * Osmotic diuretics are NOT first line therapy and may contribute to the precipitation of uric acid in the renal tubules. * Dietary modifications include restricting dietary potassium. * Further chemotherapy should be withheld until the patient has fully recovered

Answer 28

**_Viruses_** * EBV: Hodgkin's and Burkitt's lymphoma, nasopharyngeal carcinoma * HTLV-1 (Human T-lymphotropic virus Type I): Adult T-cell leukemia/lymphoma * HIV-1: High-grade B-cell lymphoma **_Bacteria_** * Helicobacter pylori: gastric lymphoma (MALT) **_Protozoa_** * Malaria: Burkitt's lymphoma

Answer 29

* Not used in first complete remission in most haematological malignancies - reserved for first relapse/second complete remission (high treatment related morbidity/mortality) * Transplants from matched sibling donors are used as first line therapy in certain circumstances, including CML * If no siblings, then imatinib to induce remission is first choice * **_Blood Products_** * *Irradiated blood* - patients receiving a bone marrow transplant, patients with previous purine analogue exposure and a diagnosis of Hodgkin’s disease * *CMV-negative blood* - atients who may need a bone marrow transplant in the future (CMV carriage increases transplant mortality

Answer 30

**_NAACCP_** * Neoplasia * Addison's * Allergy/Asthma * Collagen vascular diseases * Cholesterol emboli * Parasites

Answer 31

Results from the development of inhibitors against factor VIII. Occurs mainly in the elderly. Associations * Malignancy * Psoriasis * Pemphigus * Drugs: cephalosporins, penicillins Diagnosis * Bleeding tendencies * APTT: is prolonged (intrinsic pathway). * APTT doesn’t correct/will only correct slightly with the adding of normal plasma. * Bethesda titre can quantify the inhibitor. There is a 20% mortality rate from acquired factor VIII deficiency. Treat with recominant factor VIIa or factor VIII bypassing agent (latter is prothrombotic --\> MI/DIC)

Answer 32

**_Haemophilia A_** * X-linked; factor VIII (most common - 90%) **_Haemophilia B_** * X-linked; factor IX (more severe but less common) **_Haemophilia C_** * Autosomal; factor XI - not completely recessive, some heterozygotes show increased bleeding tendencies.

Answer 33

Associated with anti-factor VIII IgG antibodies and is idiopathic in the majority of cases. **_Associations_** * Autoimmune diseases: (Rheumatoid Arthritis or IBD) * Drugs such as phenytoin **_Mx_** * Sometimes replacement of factor VIII is all that is needed * Immunosupression with corticosteroids +/- steroid sparing agents such as cyclosporine may be required.

Answer 34

Most common inherited bleeding disorder. Mostly AD inheritence. Behaves like a platelet disorder. **_Types_** * Type 1 - partial reduction in vWF (80% of patients) * Type 2: abnormal form of vWF * Type 3: total lack of vWF (autosomal recessive) most severe **_Ix_** * PFA-100 has \>95% sensitivity to diagnose vWD * Prolonged bleeding time * Slightly prolonged APTT * Decreased factor VIII levels * Defective platelet aggregation with ristocetin **_Mx_** * TXA for mild bleeding * Desmopressin raises levels of vWF by inducing release of vWF from Weibel Palade bodies in endothelial cells. Used as prohyplaxis prior to procedures. * Factor VIII concentrate

Answer 35

* Promotes platelet adhesion to damaged endothelium * Carrier molecule for factor VIII

Answer 36

Severe * ITP * TT * DIC * Hematological malignancy **_Moderate_** * Heparin induced thrombocytopenia (HIT) * Drug-induced (e.g. quinine, diuretics, sulphonamides, aspirin, thiazides) * Alcohol and Vitamin B12 deficiency * Liver disease * Hypersplenism * Viral infection (EBV, HIV, hepatitis) * Pregnancy * SLE/antiphospholipid syndrome

Answer 37

Immune mediated reduction in the platelet count. Antibodies are directed against the glycoprotein IIb-IIIa or Ib complex. * **Acute** - mostly children - M=F. May follow infection/vaccination, self-limiting over 1-2 weeks. * **Chronic** - young/middle aged women, relapsing-remitting course. **_Ix_** * Antiplatelet autoantibodies (usually IgG) * Bone marrow aspiration shows megakaryocytes in the marrow. This should be carried out prior to the commencement of steroids in order to rule out leukemia **_Mx_** * Oral prednisolone (80% of patients respond) * Splenectomy if platelets \< 30 after 3 months of steroid therapy * IV immunoglobulins * Immunosuppressive drugs e.g. Cyclophosphamide

Answer 38

ITP in association with autoimmune haemolytic anaemia

Answer 39

Neurological features, renal failure, pyrexia and thrombocytopenia point towards a diagnosis of TTP - **difference from HUS = neuro signs and purpura.** * Abnormally large and sticky multimers of vWF cause platelets to clump within vessels * Autoantibody-mediated inhibition of the enzyme ADAMTS13, which normally cleaves the multimers into smaller units * Increased platelet adhesion --\> thrombi --\> decreased numbers of circulating platelets * Overlaps with hemolytic uraemic syndrome (HUS)

Answer 40

**_Features_** * Rare, typically adult females * Fever * Fluctuating neuro signs (microemboli) * Microangiopathic hemolytic anemia * Thrombocytopenia * Renal failure **_Causes_** * Post-infection e.g. Urinary, gastrointestinal * Pregnancy * Drugs: cyclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir * Tumors * SLE * HIV **_Management_** * No antibiotics - may worsen outcome * Plasma exchange is the treatment of choice * Steroids, immunosuppressants * Vincristine

Answer 41

* Cytotoxics * Antibiotics: trimethoprim, chloramphenicol * Anti-rheumatoid: gold, penicillamine * Carbimazole\* * Anti-epileptics: carbamazepine * Sulphonylureas: tolbutamide

Answer 42

Immune mediated (IgG) drug reaction. Usually takes about 5 days to manifest. **_Presentation_** * Bleeding is rare, more strongly associated with thrombosis (antibodies initiate platelet activation --\> clots) * Both venous and arterial thrombosis **_Dx (clinical)_** * Thrombocytopenia: PLT \< 100 or \<50% from the patient's baseline * The exclusion of other causes of thrombocytopenia * The resolution of thrombocytopenia after cessation of heparin * HIT antibodies can be demonstrated using lab tests and assays (HIPA, SRA) **_Management_** * Stop all forms of Heparin * Start alternative anticoagulant which do not cross-react with HIT antibodies, such as: **Danaparoid, Lepirudin, Argatroban**. * Oral anticoagulation with warfarin should NOT be initiated for longer-term protection from further events until substantial platelet count recovery has occurred * HIT patients who are switched to warfarin alone after the discontinuation of heparin may paradoxically have worsening thrombosis and develop venous limb gangrene and skin necrosis

Answer 43

* Target cells * Howell-Jolly bodies * Cabot's rings * Siderotic granules * Acanthocytes * Schizocytes

Answer 44

* Target cells * 'Pencil' poikilocytes * If combined with B12/folate deficiency a 'dimorphic' film * occurs with mixed microcytic and macrocytic cells

Answer 45

* **_G6PD_** = Heinz bodies * **_Myelofibrosis_** = 'Tear drop' poikilocytes * **_Intravascular Haemolysis_** = Schistocytes * **_Megaloblastic anaemia_** = Hypersegmented neutrophils

Answer 46

AD inheritence Types * HHT1: chromosome 9, associated with AVM (cerebral and pulmonary) * HHT2: chromosome 12. Features * Epistaxis * Telangiectasia develop on skin, mucous membranes and internal organs * Associated with pulmonary and other AV malformations in 10% * May present as iron-deficiency anemia secondary to bleeding in the GI tract or nasal mucosa

Answer 47

* Older men * Lymphoplasmacytoid malignancy characterized by the secretion of a **monoclonal IgM paraprotein** **_Features_** * Monoclonal IgM paraproteinemia * Systemic upset: weight loss, lethargy * Hyperviscosity syndrome e.g. Visual disturbance * Hepatosplenomegaly * Lymphadenopathy * Cryoglobulinemia e.g. Raynaud's * Raised ESR **_Mx_** * Monoclonal antibody rituximab, sometimes in combination with chemotherapeutic drugs such as chlorambucil, cyclophosphamide, or Vincristine or with thalidomide. * Steroids * Plasmaphoresis can be used to address the hyperviscosity

Answer 48

* Normal immune function * Normal beta-2 microglobulin levels * Lower level of paraproteinemia than myeloma (e.g. \< 30g/l IgG, or \< 20g/l IgA) * Stable level of paraproteinemia * No clinical features of myeloma (e.g. Lytic lesions on x-rays or renal disease)

Answer 49

**_Features_** * Usually asymptomatic * No bone pain or increased risk of infections * Around 10-30% of patients have a demyelinating neuropath * M protein level \< 30gm/l * No end-organ damage. **_Diagnostic Criteria_** * Serum paraprotein \<30 g/L AND * Clonal plasma cells \<10% on bone marrow biopsy AND * NO myeloma-related organ or tissue impairment

Answer 50

Oxidation of Fe²⁺ to Fe³⁺ by NADH methemoglobin reductase Results in tissue hypoxia as Fe³⁺cannot bind oxygen --\> dissociation curve moved to the left **_Causes_** * Congenital - Hb chain variants (HbM, HbH), deficiency of the enzyme * Acquired - drugs (sulphonamides, nitrates, dapsone, sodium nitroprusside, primaquine), chemicals (alanine dyes) **_Features_** * 'Chocolate' cyanosis * Dyspnoea, anxiety, headache * Severe - acidosis, arrhythmias, seizures, coma * Normal PO₂ but decreased sats **_Management_** * Ascorbic acid if enzyme deficiency * IV methylene blue

Answer 51

* Autosomal recessive * Aplastic anemia * Increased risk of AML * Neurological manifestation * Skeletal abnormalities * Skin pigmentation (café-au-lait spots)

Answer 52

Autossomal Recessive - HFE gene, chromosome 6 **_Typical Tests_** * Transferrin saturation \> 55% in men or \> 50% in women * Raised ferritin (e.g. \> 500 ug/l) and iron * Low TIBC **_Diagnostic Tests_** * Molecular genetic testing for the C282Y and H63D mutations * Liver biopsy: Perl's stain **_Monitoring Venesection_** * 'transferrin saturation should be kept below 50% and the serum ferritin concentration below 50 ug/l'

Answer 53

**_Presentation_** * Early symptoms include fatigue, erectile dysfunction and arthralgia (often of the hands) * 'Bronze' skin pigmentation * Diabetes Mellitus * Liver: stigmata of chronic liver disease, hepatomegaly, cirrhosis, hepatocellular deposition. * Cardiac failure (2nd to dilated cardiomyopathy) * Hypogonadism (2nd to cirrhosis and pituitary dysfunction - hypogonadotrophic hypogonadism) * Arthritis (especially of the hands) - joint X rays show chondrocalcinosis **_Complications_** * Reversible - cardiomyopathy, skin pigmentation * Irreversible - cirrhosis, DM, hypogonadism, arthropathy

Haem/Onc Flashcards

(85 cards)