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Delta Med - Haematology > Haematological Malignancies > Flashcards

Haematological Malignancies Flashcards

1
Q

What is the definition of leukaemia?

A
  • Circulating leukaemia cells in the peripheral blood

- Leukaemia cells in the bone marrow

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2
Q

Myelodysplasia

A
  • Insufficient production of mature blood cells

- +/- leukaemia cells in the peripheral blood/bone marrow

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3
Q

Myeloproliferative disorders

A

Excessive production of mature blood cells

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4
Q

Lymphomas

A

Lymphoid cancers in lymphoid containing tissues

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5
Q

Plasma cell dyscrasias

A
  • Increased plasma cells in BM
  • Paraprotein (monoclonal immunoglobulin - M band)
  • +/- end organ damage
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6
Q

Haematological malignancies associated with EBV infection:

A
  • Hodgkin lymphoma
  • Burkitt lymphoma
  • Post-transplant lymphoproliferative disorder
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7
Q

Haematological malignancies associated with HTLV-1 infection:

A
  • Acute t-lymphoblastic leukaemia/lymphoma
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8
Q

Haematological malignancies associated with HIV infection:

A
  • Cerebral DLCBL
  • Hodgkin lymphoma
  • Diffuse large B-cell lymphoma
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9
Q

Haematological malignancies associated with HHV-6 infection:

A

Primary effusion lymphoma

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10
Q

Environmental exposures assoc with increased risk of haematopoietic malignancies?

A

Chemotherapy:

  • Secondary/treatment related AML/MDS
    • etoposide
    • anthracyclines (doxorubicin etc.)
    • autologous SCT

Radiation:
- Secondary acute leukaemia/CML/myelodysplasia

Petrochemical/benzene
- multiple myeloma

Hair Dye
- follicular lymphoma

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11
Q

Familial haematological malignancies?

A

Cancer syndromes

  • Li fraumeni syndrome (p53)
  • Bloom syndrome (BLM gene, DNA helicase)

Identified mutations:

  • Acute leukaemia (RUNX1)
  • Myelodysplasia (GATA2)
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12
Q

What morphological, cytochemical and immunophenotyping characteristics are seen in AML?

A

Morphology:

  • acute leukaemia >20% blasts in blood or BM
  • blasts with auer rods - Myeloid leukaemia
  • Cytochemistry - myeloperoxidase positive

Immunophenotyping:
- myeloid antigens i.e. CD13, CD33

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13
Q

What is the strongest prognostic factor in AML?

A

Age >60 is the strongest adverse prognostic factor

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14
Q

What are the cytogenetic/molecular prognostic factors of AML?

A

Cytogenetics:
Good - t(15;17), inv(16), t(8;21)
Intermediate - normal, Y-
Poor - del7, del5q, inv(3), t(3;3), t(6;9), t(9:22), 11q23 abn, complex (>= 3 abnormalities)

Molecular (w. normal karyotype)

  • NPM1 - good
  • FLT3 - poor
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15
Q

What chemo is used in AML, and how many cycles?

A

Cytarabine, anthracycline (doxorubicin)

1x induction course, with 2x consolidation courses

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16
Q

How does age influence therapeutic strategy in AML?

A

Age > 60 - choose Rx based upon functional status. regardless, chemotherapy has not been shown to improve survival.

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17
Q

How does FLT3-ITD influence treatment in AML?

A

Consider allo BMT in 1st remission, if appropriate donor and patient.

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18
Q

What is the treatment strategy in relapsed AML?

A

Consider allo BMT - only curative therapy.

If appropriate donor, if appropriate patient

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19
Q

What are the options in treatment refractory AML?

A

Unclear if there is failure to reach CR2, or in relapses within 6 months of completing therapy.

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20
Q

How is the diagnosis of Acute lymphoblastic leukaemia made?

A

Morphology - >20% blasts on film with NO auer rods

Immunophenotyping:

  • lymphoid antigens:
    • either CD10 TdT
    • B-cell CD19/20
    • T-cell CD2/3/4/8
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21
Q

What are prognostic factors in ALL in Adults?

A

Adult ALL
- Poor t(9;22), with molecular Bcr-Abl also poor

(pediatric age group remains the strongest good prognostic factor)

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22
Q

What are treatment options in Acute Lymphoblastic Leukaemia?

A

Induction Chemotherapy:
No single therapy directly compared in trials.
Example = Hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone) alt with high dose MTX and cytarabine.

If Ph+ve, must use TKI (imatinib/dasatinib)

Maintenance chemotherapy:

  • consolidation as above
  • maintenance, no consensus

High risk disease - should consider Allo BMT - i.e. Ph+ALL in CR1 or in relapse.

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23
Q

What effect does minimal residual disease have upon prognosis?

A

In patients who achieve Molecular CR 4 months post Rx, vs those who do not, survival is significantly higher in those who are Ph- and did not undergo SCT post Cr1.

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24
Q

What AEs are associated with myeloablative chemo?

A

Gastro - mucositis, diarrhoea.
BM suppression - anaemia, thrombocytopenia, neutropenia
Hair loss

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25
Q 
What toxicity is associated with:
cytarabine
anthracycline
asparagine
vincristine
A

cytarabine - neurotoxicity
antrhacycline - cardiomyopathy
asparagine - liver toxicity
vincristine - neurotoxicity

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26
Q

What is the most effective therapy for acute adult leukaemia?

A

Allogeneic transplant

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27
Q

What is the mortality rate in allo SC transplant?

A

provides graft versus leukaemia effect.

up to 30% in MUD
10% in MRD

infection - bacterial, fungal/aspergillus, PCP, CMV, RSV
Acute GVHD - mortality >50%
Chornic GVHD

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28
Q

What is a complement mediated therapy in ALL?

A

rituximab - CD20+vs ALL - causes complement mediated lysis of CD20 B-cells.

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29
Q

What are T-cell mediated therapies in ALL?

A

1) blinotumomab - Bispecific T-cell engaging (BiTE) antibodies (CD19/CD3) - indicated in refractory/relapsed B-ALL
2) Chimeric antigen receptor 19-28z - modified T-cell infusions.

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30
Q

What are the two chronic leukaemias?

A

Chronic lymphocytic leukaemia - lymphoproliferative disorer

Chronic myeloid leukaemia - myleoproliferative disorder

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31
Q

What is the commonest haematologic malignancy and lymphoproliferative disorder?

A

Chronic lymphocytic leukaemia

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32
Q

What is the characteristic finding on a peripheral film in CLL?

A

Smear Cells

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33
Q

In what disease are smear cells seen?

A

chronic lymphocytic leukaemia

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34
Q

What is the characteristic immunophenotype seen on peripheral blood in CLL?

A

CD5+ CD19+ b-cells, displaying clonality

- lymphocytes kappa OR lambda light chain restricted

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35
Q

What clinical findings are associated in CLL?

A

lymphadenopathy
immune haemolysis (spherocytes)
thrombocytopenia
bone marrow failure

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36
Q

What are the prognostic factors (broadly) in CLL?

A

clinical stage
immunophenotypic
cytogenic
molecular

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37
Q

What are the clinical stages of CLL?

A

Stage I - lyphocytosis only
Stage II - lymphadenopathy
III - cytopenias (non-immune i.e. BM replacement more significant)

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38
Q

What are the cytogenetic prognostic factors in CLL?

A

> 90% have abnormal FISH

11q and 17p deletion - poor prognosis - rapid, therapy resistant

13q deletion - good prognosis

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39
Q

What is a poor molecular feature in CLL?

A

unmutated IgVH genes - assoc with advanced stage, adverse cytogenetics, therapy resistant

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40
Q

What is the significance of ZAP-70 in CLL?

A

Surrogate marker for IgH mutational status. Higher CD38+ ZAP-70 expression is associated with IgH unmutated.

  • earlier requirement for therapy
  • decreased response, PFS, OS to fludarabine based therapy
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41
Q

What resistance to therapy is a poor prognostic marker in CLL?

A

Fludarabine

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42
Q

What treatment is indicated in Asymptomatic CLL patients?

A

Watchful observation

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43
Q

What oral therapy is available to CLL patients?

A

chlorambucil

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44
Q

What are standard IV regimens in the treatment of CLL?

A

fludarabine/cyclophosphamide regimens

fludarabine/cyclophosphamide/rituximab (gold std)

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45
Q

What therapy can be used in CLL with p53 mutation?

A

alemtuzumab - anti CD52

SEs - neutropenia, CMV, PJP

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46
Q

What is the target of alemtuzumab? SEs?

A

alemtuzumab - anti CD52 - present on mature lymphocytes, but not on stem cells.
neutropenia, CMV, PJP

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47
Q

Indications for alemtuzumab?

A

CLL
Cutaneous t-cell lymphoma
t-cell lymphoma

48
Q

In what instances is a allo SCT indicated in CLL?

A

poor prognosis, in a patient who is suitable and has an appropriate donor

49
Q

What are the clinical features of myelodysplasia?

A

Bone marrow failure

  • anaemia
  • neutropenia
  • thrombocytopenia

+/- blasts in peripheral blood/BM

50
Q

What are the types of myelodysplasia? (7)

A

1) Refractory anaemia
2) Refractory anaemia w ringed sideroblasts
3) refractory anaemia with multilineage dysplasia
4) refractory anaemia with excess blasts 1 and 2 (1 peripheral blood monocytes

51
Q

What is the significance of 5q mutation in MDS

A

5q del syndrome

  • females
  • better prognosis
  • good response to lenalinomide
52
Q

What are prognostic factors in MDS?

A

Cytogenetics - poor if complex
Cytopenia - trilineage cytopenia with low plt count - poor
Bone marrow blasts >10% - poor
Transfusion requirements

Two prog systems - IPSS, WPSS
IPSS - cytogenetics, cytopenia, blast %
WPSS - type of MDS, chromosomal changes, transfusion requirements

53
Q

What are the treatment options in MDS?

A

Supportive care - transfusion (+ iron chelation with >20 units of RBCs)

Epigenetic therapy (clinical trials)

  • azacytadine
  • decitadine
  • lenolinamide

Chemotherapy
- Hi dose cheme as per AML

Allogeneic SCT

  • if poor prog (high risk IPSS, v. high risk WPSS)
  • suitable donor and recipient
54
Q

What are indolent non-hodkin lymphomas?

A 
CLL/SLL
Marginal zone lymphoma
 - MALT, nodal, splenic
Follicular Lymphoma
Mycosis fungoides
55
Q

What are aggressive NHL?

A 
Diffuse large B-cell lymphoma
Burkitt lymphoma
Precursor T-lymphoblastic
B-lymphoblastic
Mantle cell
56
Q

What is the rationale behind treatment of aggressive/non-aggressive NHL?

A

Always treat aggressive NHL.

Treat indolent NHL only if symptomatic or bulky, regardless of extent of disease.

57
Q

How is Lymphoma Diagnosed/staged?

A

Require tissue in all cases - Bx of Ln or Mass, BMAT

Staging is comprised of:

  • Ex
  • Biochem ?Inc LDH
  • Imaging - CT NCAP
  • PET scan (Hodgkin, DLBCL)
  • Bone marrow Bx
  • +/- LP
58
Q

What is the lymphoma staging system?

A

Ann Arbor:

  • stage I - single nodal group
  • stage II - >= nodal groups on same side of diaphragm
  • stage III - nodal groups on both sides of the diaphragm
  • stage IV - bone marrow/extranodal involvement

B - symptoms - poor prognosis, signify high disease burden

59
Q

What are the characteristic cells seen in Hodkin lymphoma?

A

reed sternberg cells

60
Q

What is the treatment of early stage disease in HL?

A

Stage I-II, non bulky, nil B Sx

are treated with abbreviated ABVD therapy - doxorubicin, bleomycin, vincristine, dacarbazine + involved field radiotherapy.

can achieve >80-90% DFS

61
Q

What is the treatment of extensive stage disease in HL?

A

Stage IIB, bulky, stage III-IV, B Sx

ABVD chemotherapy +/- involved field radiotherapy

Can use escalated dose BEACOPP: Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone

62
Q

What is the treatment of relapsed or primary refractory disease in HL?

A

Autologous SCT
Brentuximab - anti CD30
Allo SCT
PD-1 checkpoint inhibitor in trials.

63
Q

What is the prognostic index used for Extensive Stage HL?

A 
Hansen-Clever score:
Age >=45
Male Sex
HB 15
Lymph
64
Q

What are the features on histology of Follicular Lymphoma?

A

B-cell lymphoma - follicles on histology.

Note Grade III Dz is treated as DLBLC

65
Q

What is the prognostic index for Follicular lymphoma?

A

FLIPI index

  • nodal groups >4
  • LDH
  • Age >60
  • Stage III/IV
  • Hb
66
Q

What is the treatment for Follicular Lymhpoma?

A

In symptomatic disease:

  • no treatment
  • Radiotherapy - stage IA disease, which is uncommon, possibility of cure
  • Chemotherapy - fludarabine containing or R-CHOP
  • Auto SCT
67
Q

What is the maintenance thereapy for follicular lymphoma?

A

Rituximab up to 2 years post Rx of high risk FLIPI score follicular lymphoma.

68
Q

What is the histological characteristic of Diffuse Large B-cell lymphoma on histology?

A

diffuse effacement of LN on histology

69
Q

What is the prognostic scoring system for DLBCL?

A

International prognostic index

  • Age
  • ECOG 3-4
  • LDH
  • Extranodal sites
  • Stage III/IV
70
Q

What is the treatment of limited stage DLBCL?

A

6 cycles of R-CHOP = rituximab + cyclophosphamide, doxorubicin, vincristine, prednisone +/- IF radiotherapy

71
Q

What is the treatment of extensive stage DLBLC?

A

CHOP + Rituximab +/- IF radiotherapy - with 10-15% benefit

72
Q

What is the treatment of relapsed/refractory stage DLBLC?

A

Salvage high dose chemotherapy or Auto SCT

73
Q

What are the BCR-ABL positive myeloproliferative disorders?

A

Chronic Myeloid Leukaemia

74
Q

What are the BCR-ABL negative myeloproliferative disorders? (3)

A

Polycythemia vera
Essential thrombocythemia
Myelofibrosis

75
Q

What are 4 Myeloproliferative disorders?

A

Chronic myeloid leukaemia
Polycythemia
Essential thrombocytosis
Myelofibrosis

76
Q

What are the cells/features of Chronic myeloid leukaemia?

A
  • neutrophilia
  • basophils
  • immature myeloid cells
  • splenomegaly
77
Q

What are the cells/features of polycythemia

A

increased RBC + clots + headache + erythromelgia (painful peripheries)
(can be primary or secondary)

78
Q

Essential thrombocytosis

A

elevated platelets + clot + vascular disease

79
Q

Myelofibrosis

A

low blood counts
leukoerythroblastic film with tear drop red cells
splenomegaly, bone marrow failure

80
Q

What is the characteristic genetic mutation associated with CML?

A

t(9;22) - the philadelphia chromosome, causing a Bcr-Abl fusion protein

81
Q

What are the phases of CML? (3)

A

Chronic phase - 85%, best prognosis - 100

Accelerated phase - blasts 15-29%, blasts+PM >30%, basophils >20%, Plts 30% blasts, either myeloid or lyphoid

82
Q

What is the prognostic index for CML?

A 
SOKOL index:
Age
Spleen Size
Platelet count
Blast %
83
Q

What mutation is associated with BCR-ABL treatment resistance and poor prognosis?

A

T315I

84
Q

What is the target of therapy in CML, the names of the drugs used and the % of DFS achieved?

A

BCR-ABL
imatinib, dasatinib, nilotinib
>90% DFS

85
Q

When is allo SCT indicated in CML?

A

BCR-ABL therapy resistant mutation, primary resistant disease

86
Q

What gene mutations are associated with MPN signal transduction? (2)

A

JAK2 V617F and exon 12 mutations
- all PV, 60% ET, 65% PMF

MPLW515K/L in essential thrombocytopenia

87
Q

What are non signal transduction mutations associated in MPN?

A

Ca2+ binding ER chaperone - Calreticulin in Jak2V617 ET and MF - relatively good prognosis.

Epigenetic mods -TET2 EZH2 ASXL1
Cell metab IDH1/2
Protein stability CBL
Gene transcription IKZF1
RNA splicing factor SRSF2
88
Q

What is the primary cause of death in PV and ET?

A

morbidity and mortality is from thrombosis (AMI, stroke, PVD), and venous thrombosis in unusual sites - cerebral vv, budd chiari

89
Q

What treatment is indicated in esssential thrombocytosis?

A

Hydroxyurea:

- aim for plt

90
Q

When is hydroxyurea indicated in the treatment of PV?

A

With splenomegaly, thrombocytosis and or intolerant of phlebotomy, >50yo

91
Q

When is aspirin indicated in ET?

A

previous thrombotic event, age >60 - has 1/4 risk of recurrence

92
Q

When is primary prophylaxis indicated in PV or ET?

A

if able to tolerate ASA in PV

ET

93
Q

What are the goals of venesection in PV?

A

aim for Hct

94
Q

When is interferon alpha indicated in ET and PV?

A

ET - women of childbearing age

PV -

95
Q

What medication is used in the elderly with ET/PV?

A

chlorambucil

96
Q

What are adverse prognostic findings in Myelofibrosis?

A 
Age >65
BSx +ve
Hb 25
Blasts >1%
\+/- cytogenetics
Thrombocytopenia
97
Q

What constitutes supportive therapy in Myelofibrosis?

A

transfusion
palliative chemotherapy
+/- splenectomy/splenic irradiation

  • allogeneic transplant may be considered in appropriate patients
98
Q

What mutation is targeted in selective therapy for Myelofibrosis, and by what agent?

A

Jak2

Targeted by Jak1/2 inhibitor Ruxolitinib

improves splenomegaly/systemic symptoms, but no survival benefit over supportive Rx.

AEs: haematologic toxicity with anaemia and thrombocytopenia.

Does not eradicate the disease clone JAK2V617F

99
Q

What are the high risk mutations in PMF? (4)

A

ASXL1
EZH2
SRSF2
IDH1/2

100
Q

What is a low risk mutation in PMF?

A

CALR

101
Q

What are Clinical prognostic factors in PMF?

A

IPPSs
DIPPS
DIPPS-plus

102
Q

What are 3 significant plasma cell dyscrasias?

A

Monoclonal gammopathy of uncertain significance
Multiple myeloma
Amyloidosis

103
Q

What are the diagnostic features of MM?

A

> 10% malignant plasma cells on BMAT
Monoclonal Ig on serum/urine
- M band (suspicious if prot/albumin gap)
- IgG > IgA > IgM > IgD
- reduction in other immunoglobulins (immune paresis)

104
Q

What organs are involved typically in MM?

A

CRAB!

Calcium elevated
Renal impairment/failure
Anaemia
Bones - lytic lesions, significant osteopenia, spinal cord compression

105
Q

What is the prognostic index for MM?

A

International staging system
Stage I: B2 microglobulin =35
Stage II: not I or III
Stage III: B2 microglobulin >5.5

106
Q

What are poor prognosis cytogenetics in MM?

A 
complex karyotypes
del13
del17
t(4;14)
107
Q

What is oral disease modifying therapy in MM?

A

melphalan
dexamethasone
thalidomide

108
Q

What is IV disease modifying therapy in MM?

A

cyclophosphamide (esp if rapid response required/extensive disease)

109
Q

What are immune mod agents used in MM?

A

thalidomide

lenalinomide

110
Q

What is a small molecule inhibitor used in MM, and it’s target of action

A

Bortezomib
binds to 26S proteasome and inhibits.
30% have peripheral neuropathy.
also causes myelosupression and shingles

111
Q

What is coupled with auto SCT in MM?

A

high dose melphalan therapy has a mortality benefit.
Can do tandem auto-allo transplant in high risk patients
allow for high dose chemo to be given

112
Q

What is the pathology of primary systemic amyloidosis?

A

= MGUS with attitude
amyloidogenic monoclonal protein
(often very low level and undetectable on SPEP)
Serum free light chains elevated (kappa or lambda)

113
Q

What organs are involved in systemic amyloidosis?

A

Kidney - nephrotic syndrome/failure
Heart - cardiac amyloid - diastolic dysfunction, septal thickening, cause of death
GIT - vasculopathy and bleeding risk
Skin - amyloid plaques

114
Q

What is involved in the prognostic index for primary systemic amyloidosis?

A

Troponin

pro-BNP

115
Q

What is the therapy for Primary systemic amyloidosis?

A

po - melphalan, dexamethasone
immunomodulators - thalidomide, lenalinomide +/- auto SCT in select pats
Trials - anti-amyloid Ab

Delta Med - Haematology (3 decks)

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