Haematology Flashcards

Question

Chronic myelomonocytic leukaemia - features and treatment

Answer 1

MPN features * Leucocytosis , monocytosis >1 x 109/L for longer than 3 months (excluded a reactive cause) * Splenomegaly * Circulating immature myeloid cells * Absence of MPN driver mutations (JAK2 / BCR-ABL1) * Somatic mutations commonly encountered – TET2 , SRSF2, ASXL1 MDS features * Dysplasia of myeloid lineages Treatment * Supportive * Cytoreductive agents if proliferative – hydroxyurea * Hypomethylating agents – azacitidine

Answer 2

Heterogeneous group of clonal haematopoietic stem cell malignancies Significant morbidity > 60 years of age Associated with : 1. Bone marrow failure 2. Peripheral cytopenia(s) 3. Propensity for progression to acute myeloid leukaemia Diagnosis - Blood film: microcytic anaemia, dysplasia - BM biopsy: cellularity, morphology, blasts, cytogenetics

Answer 3

Cytogenetics Blast % Hemoglobin Platelets ANC

Answer 4

Supportive - transfusions Hb<80g/L, Platelets <10 or <20 if febrile - EPO, G-CSF Low risk - Luspatercept or sotatercept = fusion protein blocking TGF B thus allowing effective erythropoiesis through maturation High risk - Azacitidine = hypomethylating agent decreases inhibition of tumor supressor genes >> decreases transformation to AML and improves survival

Answer 5

1. FBE and blood film * Pancytopenia * Blasts in peripheral blood * Morphology 2. BM aspirate and trephine * percentage of blasts in the bone marrow * >20% of leucocytes * Blasts with Auer rods = myeloid leukaemia * Immunophenotyping of the blasts

Answer 6

Curative - 3 days of an anthracycline and 7 days of cytarabine >> allogenic stem cell - Unfit >70yo >> azacitidine an dvenetoclax (70% response, similar to 7+3) Targeted - Midosaturin = FLT3 inhibitor - Gilteritinib = more potent and specific FLT3 inhibitor for relapsed/ refractory Measurable residual disease defines response and outcomes Relapse = one of: 1. >5% blasts in BM 2. Reappearance of blasts in peripheral blood 3. Development of new extra medullary disease

Answer 7

Balanced chromosomal translocation t(15;17)(q24;q21) >> fusion of promyelocytic leukaemia (PML) and the retinoic acid receptor alpha (RARA) genes >> impairs myeloid differentiation High risk due to coagulopathy and DIC risk Treatment * Standard-risk vs High-risk (WBC ≥10) * all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) +/- chemotherapy (anthracycline), CR 96% * Differentiation syndrome is a potentially life-threatening complication of treatment

Answer 8

Diagnosis - film: pancytopenia + blasts - biopsy: >20% blasts with lymphoid antigens - extra medullary involvement common in B cell, T cell will have mediastinal mass Prognosis - excellent in children, worsens with age - Poor risk 1. BCR-ABL1 (9;22) 2. Ph-like 3. Early thymocyte precursor (ETP) phenotype 4. 11q23 5. Ikaros deletion

Answer 9

* Induction chemotherapy with a number of different regimens – ongoing trials * BCR-ABL inhibitor if Ph+ALL (e.g. imatinib, dasatinib) * Maintenance chemotherapy (up to 2 years) Allogeneic BMT - graft versus leukemia * Ph+ ALL in CR1 * MRD+ * Relapsed disease Targeted therapy - Bispecific t-cell engaging (BiTE) abs promote elimination of lymphoblasts by cytotoxic T cells - Bilnatumomab (CD19/CD3) - relapsed/ refractory - SE - neurotoxicity (ICANS), and cytokine release syndrome

Answer 10

FBE and blood film * Isolated lymphocytosis , > 5 x 109/L clonal B lymphocytes > 3 months * Cytopenias Immunophenotyping peripheral blood * CD5 + CD19 + clonal B cells Rai and Binet classification Low-risk * Stage 0 - lymphocytosis only Intermediate risk * Stage I - lymphocytosis * Stage II – lymphadenopathy at any site , hepatosplenomegaly High risk * Stage III – anaemia Hb < 10g/dL * Stage IV – thrombocytopenia * These cytopenias are non immune and due to bone marrow replacement

Answer 11

Good - 13 q deletion - IGHV gene mutation Poor - 11q deletion - 17p deletion - unmate

Answer 12

When 1. Autoimmune complications 2. Bone marrow failure – cytopenias 3. Lymphocyte doubling time–>50% 2 months OR doubled in<6months 4. Disease related symptoms Immunotherapy 1. Venetoclax * Inhibits BCL‐2, an anti‐apoptotic protein. BCL‐2 is over-expressed in CLL mediates tumour cell survival and has been associated with resistance to chemotherapeutics *can be combined with obinutuzumab 2. Ibrutinib * B-cell–receptor signaling has emerged as a driving factor for CLL tumor-cell survival * Downstream of the B-cell receptor and of critical importance to its function is a member of the Tec family of kinases, Bruton's tyrosine kinase (BTK) * Monotherapy in relapsed/refractory disease 3. Acalabrutinib

Answer 13

1. MGUS - protein <30, plasma cells <10%, no end-organ 2. Plasmacytomas - bone or soft tissue lesion with clonal plasma cells, none in bone marrow, and no end-organ 3. POEMS - polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes 4. Systemic AL amyloidosis - MGUS + deposition - Kidney, cardiac, GI, skin - Congo stain - Bortezomib based or autologous transplant 5. MM (detailed in another card)

Answer 14

Diagnosis = >10% plasma cells and one of the following: 1. Hypercalcemia 2. Renal insufficiency 3. Anaemia 4. Bone lesions 5. >60% plasma cells 6. Ratio >100 7. 2 or more lesions on MRI at least 5mm Prognosis - stage 2 = B2 micro globulin 3.5-5.5 and albumin <35 Treatment - autologous stem cell - induction/ alone for frail: dexamethasone + bortezomib + lenalidomide (VRD) - daratumumba + lenalidomide = gold standard

Answer 15

Rapidly enlarging mass - single or multiple sites >> diagnose via biopsy (excisional) Risk 1. Age >60yo 2. Ann arbor stage III or IV (extensive) 3. ECOG >2 4. Serum LDH 5. Extra nodal sites Treatment - R-CHOP +/- radiotherapy - refractory > high dose chemo + autologous stem cell transplant

Answer 16

Doubling time of 25hrs - very aggressive Endemic to Africa + PNG Histology - atypical lymphoid cells with high proliferation and apoptosis - starry-sky = large histiocytes with ingested apoptotic tumor cells on a background of basophilic tumor cells Diagnosis = translocation involving myc 1. Ig heavy chain 8;14 2. Kappa light chain 2;8 3. Lambda light chain 8;22 Multiagent chemo

Answer 17

Indolent Diagnosis - follicles composed of centrocytes and centroblasts - BCL2 overexpression - t(14;18) - IGH and BCL2 Prognosis 1. >4 nodal groups 2. LDH 3. Age >60 4. Extensive stage III/IV 5. Hb <120 Watch and wait unless symptomatic/ end-organ - obinutuzumab = glycoengineered anti CD20, greater B cell killing then rituximab + bendamustine or CHOP

Answer 18

Symptoms related to IgM 1. Acts an autoantibody – peripheral neuropathy 2. May precipitate out of the serum in cold temperatures – cryoglobulinemia 3. Pentamer – hyperviscosity syndrome 4. Can deposit as amorphous extracellular material in GIT – malabsorption Infiltration of haematopoietic tissue by neoplastic B cells 5. Cytopenias 6. Hepatosplenomegaly Diagnosis - IgM paraprotein + >10% small lymphocyte infiltrate in BM - MYD88 L256P in >90% of patients Plasma exchange for hyper viscosity syndrome

Answer 19

BRAF V600E Cladribine

Answer 20

95% b-cell lineage > CD20+ Associated with EBV Decrease immunosupression Rituximab followed by chemotherapy

Answer 21

multinucleated Reed-Sternberg cells CD30+ Early stage - non bulky >> ABVD + RT Advanced stage - IIB-IV, bulky, B symptoms >> ABVD +/- IFRT or escalated BEACOPP Refractory - salvage chemo - brentuximab (anti CD30) vedotin (anti-tubulin) - PD-1 inhibitors - Nivolumab

Answer 22

Autosomal dominant Definite requires 3: 1. Epistaxis 2. Telangiectases: multiple at characteristic sites (lips, oral cavity, fingers, nose) 3. visceral lesions: for example gastrointestinal telangiectasia, pulmonary, hepatic, cerebral or spinal AVM 4. first-degree relative

Answer 23

Answer = A For emergency/urgent splenectomy give the vaccine series 14 days after splenectomy 1. A pneumococcal protein‐conjugate vaccine (PCV13; Prevnar 13) that includes capsular polysaccharide antigens covalently linked to a nontoxic protein that is nearly identical to diphtheria toxin. 2. A pneumococcal polysaccharide vaccine (PPSV23; Pneumovax 23, Pnu‐Immune) that includes 23 purified capsular polysaccharide antigens The recommendation is to give the PCV13 first followed by the PPSV23 8 weeks later. If this is for an elective/planned splenectomy this can be completed 10‐12 weeks prior to surgery so that the last vaccination is given at least 14 days prior to the operation.

Answer 24

Answer = B Stem cells are recognised by CD34+. CD45 is found on all leukocyte groups. CD4 on monocytes and T helper cells, and CD24 on B lymphocytes and granulocytes.

Answer 25

B. Bortezomib Major side effect = painful glove-and-stocking neuropathy, usually after the first few cycles of therapy

Haematology Flashcards

(49 cards)