Chronic Leukemia Flashcards by Iseoluwa Ojo

CHRONIC LEUKAEMIAS

(Rapidly or Slowly?) progressing malignancy that starts in blood- forming tissue and causes the production and accumulation of abnormal blood cells.

Slowly

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CHRONIC LEUKAEMIAS

Accumulated blood cells are ________ cells . cells in (early or late?) stages of myeloid or lymphoid cell production

matured white

Late

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CHRONIC LEUKAEMIAS

There are two main types: _________ and ________ , both of which primarily affect (children or adults?) .

chronic lymphocytic leukaemia (CLL) and chronic myeloid leukaemia (CML)

Adults

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CHRONIC LYMPHOCYTIC LEUKAEMIA (CLL)

____clonal disorder characterized by a progressive accumulation of __________ lymphocytes

Characterized by chronic persistent lympho_____.

Mono

functionally incompetent

cytosis

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CHRONIC LYMPHOCYTIC LEUKAEMIA (CLL)

In the case of CLL, B-cell CLL derives from the _____________ B cell.

They express CD___, CD__ and CD___ and have (elevated or reduced ?) levels of membrane immunoglobulins (IgM, IgD), CD79b & FMC7.

antigen- experienced

19; 5; 23

Reduced

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CHRONIC LYMPHOCYTIC LEUKAEMIA (CLL)

CLL cells are monoclonal because they _____________________

express only one form of light chain (lambda or kappa) on their cell surface.

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In CLL

All normal stages of lymphoid development are postulated to have a malignant counterpart.

T/F

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CHRONIC LYMPHOCYTIC LEUKAEMIA (CLL)
B cell CLL is characterized by a progressive accumulation within the marrow and blood of long-lived mature leukaemic lymphocytes due to:

stimulation of ______ by ______

due to reduced ______

not because of _______

growth by external signals

apoptosis

rapid production

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CHRONIC LYMPHOCYTIC LEUKAEMIA (CLL)
B cell CLL is characterized by a progressive accumulation within the marrow and blood of long-lived mature leukaemic lymphocytes due to:

•stimulation of growth by external signals e.g _____,_____ and ligands binding to ________, and

•due to reduced apoptosis felt to be largely mediated by overexpression of ___, a protein known to inhibit cellular apoptosis.

cytokines, chemokines; B cell receptors

bcl-2

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T-CLL is a common disease.

T/F

T-CLL is a rare disease, therefore Much less is known about

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_____ is the most common form of leukaemia in the western hemisphere

It makes up ___-__% of all leukaemias.

B-CLL

25-30

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The peak incidence of CLL is in the ___ decade of life.

The overall incidence is 20 per 100,000 in persons >___ years of age.

6th

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The male to female ratio of CLL is __:___

2:1.

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95% of CLL is of ___ cell origin.

___-CLL is a rare disease.

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CLL - Epidemiology

Overall median survival of patients is about ___-___ years.

10 to 20

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CLL - Epidemiology

Individual prognosis can be quite variable – _____ in some patients and life expectancy is not shortened, _____ in others and can progress rapidly and survival from diagnosis may be __-__ years.

indolent

aggressive

2-3

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CLL - Epidemiology

Mortality often due to:

•overwhelming _____ with marked ____ and ——-

•Overwhelming ______
•_______
•transformation to an aggressive ______, so called a _______

tumour burden; adenopathy and splenomegaly

infection

bleeding

Lymphoma; Richter’s transformation.

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CLL – Clinical features

Incidental finding on _____, where there is isolated _____ and the patient is asymptomatic.

If complaints are present, they are usually:____,_______, night sweats, fever and ________

CBC; lymphocytosis

weakness, easy fatigue

weight loss.

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CLL – Clinical features

• There may be frequent bacterial and viral infections because of ________.

•Patients with CLL may report ________ to _________ or _______

hypogammaglobulinemia

an exaggerated response

mosquito or other insect bites.

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CLL – Clinical features

On physical examination, (symmetrical or asymmetrical?) peripheral ______ is most frequent abnormal finding involving the neck, axillae and inguinal regions.

Nodes are usually (painful or painless?) .

symmetrical; lymphadenopathy

Painless

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CLL – Clinical features

_________ and ______ are variably present.

__________ and __________ are associated with CLL and can result in severe anaemia and thrombocytopenia.

Splenomegaly and hepatomegaly

Autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenic purpura (ITP)

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CLL – Clinical features

_____ occurs 10-25% of the time, while ___ is seen in 2% of patients.

AIHA; ITP

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CLL – Clinical features

________,______,_______, and _______ result from the immune dysregulation which occurs in CLL.

AIHA, ITP, hypogammaglobulinemia and an exaggerated response to mosquito bites

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Which occurs more in CLL patients

AIHA or ITP

AIHA

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Lymph gland involvement in CLL •may be _____ or ____, but generally it is ____________ •________ or ______ but not ______

subtle or spectacular ; only within nodes unsightly or uncomfortable; invasive

CLL – Laboratory findings Lymphocytosis: diagnosis of CLL requires evidence of lymphocytosis, at least ____ × 109/L, and lymphocytic infiltration in the ______ of at least ___%.

10 bone marrow 40

CLL – Laboratory findings With immunological methods, particularly the detection of monoclonal B-cell populations by _______, it is possible to diagnose the disease with lymphocyte counts below this threshold. (Absolute clonal B cell lymphocyte count >___ × 109/L)

light-chain restriction 5

CLL – Laboratory findings 30% of CLL patients have _______ or _______ secondary to an immune process or marrow infiltration.

anaemia or thrombocytopenia

CLL – Laboratory findings Morphologically, the lymphocytes in blood films are (small or large?) and show scanty cytoplasm and a characteristic pattern of ________, nucleolus is ______

Small nuclear chromatin clumping inconspicuous

Azurophil granules are seen on all normal T cells T/F

F Azurophil granules are seen only in a minority of normal T cells.

CLL – Laboratory findings The presence of ____/____ cells, literally _____, destroyed cells on a regular blood smear, is consistently seen with CLL

smudge/smear flattened

CLL cells morphologicallu indistinguishable from normal lymphocytes. T/F

CLL – Laboratory findings •Peripheral film usually shows ____cytic _____chromic anaemia in (early or later?) stages. •If AIHA is present, _____ and _____ can be seen on the blood smear. •Bone marrow: cellularity is ___eased and 30-99% of nucleated cells are (mature or immature?) lymphocytes.

normo; normo; later spherocytes and polychromasia incr; mature

CLL in blood counts of 50x109/l (or more) are often with symptoms T/F

F As cells are small, non-functional and largely “inert”, CLL in blood counts of 50x109/l (or more) are often without symptoms

CLL – Laboratory findings Immunophenotyping: CLL cells co-express CD___ and CD__.

19 ; 5

CLL – Laboratory findings CD19 is a __ cell marker, and CD5 is a __-cell marker.

B T

The expression of a T cell marker on a B cell is an example of _______

lineage infidelity

lineage infidelity is seen in only CLL T/F

F lineage infidelity that is seen not only in CLL but in AML and ALL as well.

CLL – Laboratory findings Immunophenotyping: CLL cells are also positive for CD___, negative for CD____ (or dim+), are either ________ or _______ restricted and have a dim level of expression of the immunoglobulin heavy chains IgM and IgD.

23 79b kappa or lambda light chain

Which is more normally, Bcell or Tcell

Tcell

The normal T-cell/B-cell ratio is reversed in CLL. T/F

Normally, T lymphocytes constitute approximately ____% of the total lymphoid population and B lymphocytes, ____% of the lymphoid cells.

80 20

In B-cell CLL, B cells account for nearly ____% of all lymphocytes.

Cytogenetics and molecular diagnostics are needed to make the diagnosis of CLL. T/F

F They are not

CLL – Laboratory findings Cytogenetics and molecular diagnostics are useful in _____________.

determining the survival of patients

CLL – Laboratory findings Cytogenetics and molecular diagnostics: In particular,___________, corresponding to a mutation in the _____ gene, is associated with a very short survival, as are ___________.

17p deletions; p53 11q deletions

CLL – Laboratory findings Cytogenetics and molecular diagnostics: Other markers of poor prognosis include the presence of the ____ mutation (with or without chromosome deletions), and an _________ gene.

p53 unmutated Vh

Vh corresponds to the _____ portion of the immunoglobulin _____ chain.

variable heavy

CLL – Diagnostic criteria •>__ x 109/L absolute blood lymphocytosis and cells morphologically _____ in appearance, sustained over at least a _____ period. •___% lymphocytes in a _________ bone marrow. •A monoclonal B-cell phenotype simultaneously showing CD__ positivity (dual positivity CD__, CD__-__ and CD___).

5; mature; 4 week 30; normocellular or hypercellular 5; 5; 19-20; 23

CLL – Differential Diagnosis _______ _______ _______ _______ ________ ________

B-PLL B cell prolymphocytic leukaemia T-PLL/CLL Hairy cell leukaemia (HCL) Non-Hodgkin’s lymphoma Mononucleosis and other viral infections Acute lymphoblastic leukaemias

CLL – Differential Diagnosis B-PLL – B cell prolymphocytic leukaemia: clonal disorder of B cells where 55% or more of cells have a _____ when examined morphologically. (More or less?) aggressive leukaemia.

nucleolus More

CLL – Differential Diagnosis T-PLL/CLL – may be indistinguishable from ____ or ____ morphologically. -_____distinguishes the T cell origin of this malignancy from its B cell counterpart. -(More or less?) aggressive leukaemia.

B-CLL or B-PLL Immunophenotyping More

CLL – Differential Diagnosis Hairy cell leukaemia (HCL) – also produces a clonal lymphocytosis but the lymphocytes have ________ . -Usually associated with more profound _______, and with marked ________.

hair-like projections pancytopenia splenomegaly

CLL – Differential Diagnosis Non-Hodgkin’s lymphoma with circulating lymphoma cells: -In ______ lymphoma and _____ lymphoma there may be circulating malignant lymphocytes. -____lymphoma with ___ lymphocytes (SLVL) (or splenic marginal zone lymphoma) may also present with a clonal lymphocytosis.

follicular; mantle cell Splenic; villous

CLL – Differential Diagnosis Mononucleosis and other viral infections: -Mononucleosis can cause ____,_____, and ______. - Usually it is an illness of ______, in whom CLL is quite (common or rare?) . -Unlike CLL, mononucleosis and other viral infections are _____ and the lymphocytosis _____________

lymphocytosis, splenomegaly and adenopathy younger adults;rare self-limited ; resolves spontaneously.

CLL – Differential Diagnosis Acute lymphoblastic leukaemias are usually very (difficultly or easily?) distinguished from CLL by their presentation and by the morphology of the _______.

easily blasts

Also, lymphocytes in mononucleosis are usually atypical. They are irregularly shaped, _______ size , and sometimes resemble ______.

medium to large monocytes

CLL – Staging (Rai) 0-_______: >___ x 10^9 in blood and >__% in bone marrow 1-stage 0 with ______ 2- stage 1 with _______ 3- stage 2 with _____ 4- stage 3 with ________

lymphocytosis; 15; 40 enlarge lymph node hepatomegaly, splenomegaly, or both Anaemia thrombocytopenia

CLL – Staging (Binet) Binet Staging classifies CLL according to the ____________ as well as presence of ________ or _______

number of lymphoid tissues that are involved low red blood cell count (anaemia) or low number of platelets (thrombocytopenia):

CLL – Staging (Binet) Binet Stage A patients have _______ areas of enlarged lymphoid tissue and _______ anaemia or thrombocytopenia. Binet Stage B patients have _______ areas of enlarged lymphoid tissue and ________ anaemia or thrombocytopenia. Binet Stage C patients _______ anaemia and/or thrombocytopenia

fewer than three ; do not have three or more ; do not have have

CLL – Secondary causes of anaemia eg iron def.,or AIHA or ITP must be treated after staging. T/F

F Before

CLL – Treatment and outcome The Rai staging system, developed in the 1980s, predicts ______ from the time of diagnosis and reflects the ____ of disease.

median survival burden

The Rai staging system aids in determining who should be treated. T/F

CLL – Treatment and outcome Indications for treatment: Unlike AML and ALL which are uniformly fatal shortly after diagnosis, CLL may have an indolent course. Thus, not all patients ______________. In fact, _____ patients, in particular, may die of another illness before they have any complications related to their CLL.

require therapy at diagnosis elderly

CLL – Treatment and outcome Decision to treat is guided by ______, the presence of _______, and ______ activity.

clinical staging symptoms disease

CLL – Treatment and outcome Evidence that treatment can improve outcome is only available for patients with Rai stage ________

III and IV

Patients in earlier stages of CLL (Rai 0-II, Binet A) are generally treated T/F

F Are generally not treated but monitored with a "watch and wait" strategy.

CLL – Treatment and outcome In early stages, treatment is necessary only if _____________ occur

symptoms associated with the disease

CLL – Treatment and outcome Some early stage patients will be treated if they have a lymphocyte doubling time of _______, which reflects (more or less ?) aggressive disease.

less than 6 months More

Indications for therapy in CLL: ________ ________ ____-related symptoms Markedly enlarged or ——— _____ Symptomatic ________ Blood lymphocyte count doubling time <________ _______ transformation _______ transformation

Anaemia; Thrombocytopenia Disease painful spleen; lymphadenopathy 6 months; Prolymphocytic; Richter

CLL – Treatment and outcome The main categories of treatment include: ____therapy _____therapy ___________ transplantation ___________ Intravenous ________

Chemo Immuno Allogeneic stem cell Glucocorticoids gammaglobulin

CLL – Treatment and outcome Chemotherapy: The ____ analog ,______ is the most active agent used to treat CLL. Other agents that are used are the alkylating agents, ______ and _____ •These drugs are given ___ or in ____ with ______ and/or with the ______

purine; fludarabine chlorambucil and cyclophosphamide. alone; combination; one another monoclonal antibodies

CLL – Treatment and outcome • Immunotherapy: _____, a monoclonal antibody targeting CD___, which has (weak or strong?) expression on CLL cells, has more recently been added to the treatment of CLL. Alemtuzumab, a monoclonal antibody against CD___, which is expressed on ___ lymphocytes, is also effective in CLL.

Rituximab 20; weak 53; all

CLL – Treatment and outcome Allogeneic stem cell transplantation: This intensive therapy is reserved for (younger or older ?) patients with aggressive disease that may be ______ or may have _____ after treatment with _____. It may cure up to ____% of patients but is associated with about a ____% chance of treatment related mortality, and a significant risk of ———— disease.

Younger resistant; relapsed; fludarabine 30-40; 20 graft versus host

CLL – Treatment and outcome Glucocorticoids (Prednisone) are used to treat ______ and _____

AIHA and ITP.

CLL – Treatment and outcome Intravenous gammaglobulin (pooled, multi-donor immunoglobulins) are used to reduce the rate of _____ in patients with _________ and __________.

infections hypogammaglobulinemia recurrent infections.

Allogeneic stem cell transplantation in CLL It offers the potential of the immune-mediated ____________ effect (adoptive immunotherapy).

graft-versus leukaemia

CLL – Late complications Richter Syndrome:___ % of patients with CLL will transform to an aggressive ___________, which is often (easy or difficult?) to treat.

1-10 large B cell lymphoma Difficult

CLL – Late complications Prolymphocytic transformation: may occur _______ in approximately _____% of patients with CLL.

terminally 10

CLL – Late complications Solid Tumour: CLL patients have a higher incidence of developing __________ (ie: GI, lung or any other organ) and also have a high risk of development of ____ cancers.

a second malignancy skin

Bacterial, viral and fungal infections are the 3rd most important cause of morbidity and mortality in CLL. T/F

F Thee most!

CHRONIC MYELOID LEUKAEMIA CML is a clonal disorder of _________________ cell.

a pluripotent stem

CHRONIC MYELOID LEUKAEMIA It is characterized by: ______ Extreme blood ______ and granulocytic _____ _____philia Thrombo_____ _____megaly

Anaemia granulocytosis; immaturity Baso cytosis; Spleno

CML Malignancy of the ________ cells with excessive proliferation of the _____ lineage (especially _______)

hematopoietic stem myeloid granulocytes

CML The diagnosis of CML is usually based on detection of the _______ chromosome, or ______ t(__;__), which is present in ___% of patients.

Philadelphia(Ph) translocation ; 9;22 95

CML Another 5% of patients with CML have complex or variant translocations involving ______ that have (different or the same?) end result, which is ___________________________________

additional chromosomes The same fusion of the BCR gene on chromosome 22 to the ABL gene on chromosome 9.

BCR -___________ gene on chromosome __ ABL- ________________ gene on chromosome __

breakpoint cluster region; 22 Abelson leukaemia virus; 9

CML The Philadelphia chromosome is found in cells from the _____,______,______,________ lineages, indicating that CML is a disease of the ______________________ -cell.

myeloid, erythroid, megakaryocytic, and B lymphoid pluripotent hematopoietic stem

Role of Ph. chromosome in pathogenesis of CML Genetic sequence on Chromsome _______ (__) are fused with sequences translocated from Chromosome __(__)

22 (bcr) 9 (abl)

Role of Ph. chromosome in pathogenesis of CML This fusion gene (___-___) codes for an abnormal protein with _____ activity ( ____ ). Which is involved in signal transduction and activates pathways within the affected cells leading to ________

BCR-ABL Tyrosine Kinase ; p210 malignant transformation.

Tyrosine kinases work by transferring a ___ group from ____ to intracellular proteins that regulate _______

phosphate ATP cell division.

The incidence of CML appears to be constant worldwide. T/F .

CML Epidemiology CML is rare below the age of _____ years But occurs at ____ decades of life, with a median age of onset of ___-___ years.

20 all 50–60

CML Epidemiology The incidence is slightly higher in (males or females?) than in (males or females?) .

Males Females

CML Epidemiology The risk of developing CML is slightly but significantly increased by exposure to ___________, as occurred in survivors of the _______ exploded in Japan in 1945, and in patients irradiated for ________ but, in general, almost all cases must be regarded as ‘ ______ ’ and no predisposing factors are identifiable.

high doses of irradiation atomic bombs ankylosing spondylitis sporadic

CML Epidemiology there is familial predisposition and definite association with HLA genotypes T/F

F In particular, there is no familial predisposition and no definite association with HLA genotypes has been recognized.

CML -clinical features The typical symptoms at presentation are: fatigue, anorexia, bleeding and weight loss. Signs are _______,_______(2%), _____ (16%), ______ (1% of males) About 20 - 40% of patients are ____ptomatic, and in these patients, the diagnosis is based solely on _________

splenomegaly, hepatomegaly purpura; priapism asym; an abnormal blood count.

CML -clinical features The most common abnormality on physical examination is _______, which is present in up to _____ of patients.

splenomegaly half

CML – Clinical features Natural Evolution of CML – CML Phases  _______ phase _______ phase ______ phase

Chronic Accelerated Blastic

CML – Clinical features Natural Evolution of CML – CML Phases  Chronic phase: usually presents in this phase, with progressive ______ and ________. The disease is (responsive or resistant ?) to cytotoxic therapy.

leukocytosis and splenomegaly responsive

CML – Clinical features Natural Evolution of CML – CML Phases  Accelerated phase: Symptoms are (better or worse?) , with night ____, ____ pain, splenomegaly is (more or less?) responsive to therapy. Peripheral blood shows increasing numbers of _____,_____, and _______. Disease is (easy or difficult?) to control. ____-___% blasts

Worse Night sweats, bone pain Less basophils, blasts and promyelocytes Difficult; 10-19

CML – Clinical features Natural Evolution of CML – CML Phases  Blastic phase: symptoms progress, _______ deposits (_______) appear >____% blasts in blood or bone marrow. Blast transformation may be lymphoid (___%) or myeloid (___%)

extramedullary; chloromas 20 15;85

CML – Laboratory findings Hematologic findings and Morphology: The white cell count is (elevated or depressed?) and the differential shows ______ neutrophils, bands, metamyelocytes, promyelocytes and myelocytes (precursors of the neutrophils). WBC >____ × 109/L The platelets are usually (elevated or depressed?)

Elevated ;mature 50 elevated

CML – Laboratory findings Hematologic findings and Morphology: Haemoglobin is often slightly (above or below?) normal. There is also ___ease in the number of basophils and sometimes of _____ in the peripheral blood. The bone marrow shows marked (myeloid or lymphoid?) hyperplasia.

Below incr; eosinophils myeloid

The biochemical changes seen in CML are specific T/F

F non-specific.

CML – Laboratory findings : Biochemical changes chronic phase serum uric acid is _____ but frequently ____. serum alkaline phosphatase is _____ or ____ LDH) is usually _____. Serum K+ may be spuriously _____ The serum vitamin B12 and B12 binding capacity are greatly ____eased

slightly raised ; normal normal or slightly raised. raised raised; incr

CML-biochemical changes Serum K+ may be spuriously raised due to ____________ from _______ or, less commonly, from ______ after the blood is drawn. The serum vitamin B12 and B12 binding capacity are greatly increased due to ______________.

leakage of intracellular potassium from platelets leucocytes raised levels of transcobalamin I

CML – Laboratory findings Immunophenotyping Is needed to make the diagnosis of CML. T/F

F Immunophenotyping Is not needed to make the diagnosis of CML.

CML Cytogenetics: The presence of the _______ is the sine qua non of this disease.

Philadelphia chromosome

CML - Treatment Supportive treatment •______ and ______ prior to starting cytotoxic therapy for prevention of ___ nephropathy (nucleic acid breakdown) •_____for bone pain or splenic pain •______________ may be used for palliation of massive splenomegaly

Hydration and allopurinol ; urate Analgesics Splenic irradiation

bone pain or splenic pain – these are more commonly seen in the _____________ phases of CML

accelerated and blast

CML - Treatment Specific treatment Choice of therapy depends on the ________,___________ and the availability of a matched bone marrow donor.

age of the patient, phase of disease

CML - Specific treatment Chronic phase •______(____) •_____therapy •_____ transplantation

Glivec (imatinib) chemo Stem cell

CML - Specific treatment Chronic phase Glivec (imatinib) inhibits the _______ of the ______. Produces clinical, haematological and cytogenetic remissions in a (low or high?) percentage of patients in the chronic phase.

tyrosine kinase activity BCR-ABL fusion protein High

First line drug in the management of chronic phase disease is ???

Imatinib

CML - specific Treatment Chemotherapy: Mention 5

Cytarabine Hydroxyurea Alpha- interferon Busulfan - α Homoharringtonine

Hydroxyurea : May be used in pregnancy carcinogenic T/F

T F( it’s not)

Alpha interferon will effectively ______ α Homoharringtonine Enhances ______ of CML cells.

lower the cell count. apoptosis

Interferon can used if BMT is planned. T/F With reason

F Interferon is not used if BMT is planned – worsens outcome.

CML- specific treatment Stem cell transplantation: Allogeneic SCT is a proven treatment for CML but due to its risks is usually reserved for ________. Although Better results are obtained in ____ than _______ or ____ phases.

imatinib failures chronic accelerated or acute

CML - Specific Treatment Blast phase Lymphoid: ____ and _____ will induce remissions in some patients ( back to ___ phase) ; remissions are of ___ duration Myeloid:______ and _____ , remissions are (easier or harder?) to induce than in de-novo AML.

vincristine and prednisone ; chronic; short cytosar and adriamycin; harder

CML - specific Treatment Accelerated phase Cytotoxic therapy used in _______, or ———— Combination of agents – add ——- to oral agent

higher doses; switch agents. cytosar

Imatinib is valuable in management of blastic transformation T/F

T Imatinib is valuable in management of blastic transformation but resistance usually occurs within a few weeks

Chronic Leukemia Flashcards

(123 cards)