Lymphoproliferative Disorders

(1)

Lymphoproliferative

Disorders

(2)

Learning outcomes Learning outcomes

Lymphocyte Ontogeny: know types Lymphocyte Ontogeny: know types and origin of lymphocytes

and origin of lymphocytes

Function of lymphocytesFunction of lymphocytes

Lyphoprloifertive DisordersLyphoprloifertive Disorders

Acute vs ChronicAcute vs Chronic

(3)

(4)

Definition of Lymphocyte

Lymphocytes:Lymphocytes: defending the body against disease. defending the body against disease.

Lymphocytes are responsible for Lymphocytes are responsible for immuneimmune responses. responses.

B cellsB cells and T cellsand T cells..

The B cells make antibodies that attack bacteria and The B cells make antibodies that attack bacteria and

toxins toxins..

T cells attack body cells themselves when they have been T cells attack body cells themselves when they have been

taken over by viruses or have become cancerous. taken over by viruses or have become cancerous.

Lymphocytes secrete products (lymphokinesLymphocytes secrete products (lymphokines) that modulate ) that modulate

the functional activities of many other types of cells and are the functional activities of many other types of cells and are often present at sites of

(5)

Lymphocytes

B Cells.B Cells.

Bone marrow.Bone marrow.

Mature B cells migrate to Mature B cells migrate to

secondary lymphoid organs secondary lymphoid organs (nodes).

(nodes).

Proliferate/ gene Proliferate/ gene

rearrangement in germinal rearrangement in germinal centres.

centres.

Memory or plasma cells Memory or plasma cells

T CellsT Cells

Marrow Marrow –– CirculationCirculation-

-Thymus. Thymus.

T Cell receptors are T Cell receptors are

specific for one antigen specific for one antigen –– gene rearrangement.

gene rearrangement.

Auto reactive T cells are Auto reactive T cells are

removed. removed.

CD4 cells help B cellsCD4 cells help B cells

CD8 cells kill virally CD8 cells kill virally

infected cells. infected cells.

(6)

(7)

(8)

(9)

(10)

(11)

Lymphoproliferative Disorders Lymphoproliferative Disorders

Peripheral blood lymphocytosisPeripheral blood lymphocytosis

Normal Value 1.5Normal Value 1.5--3.5 x 103.5 x 1099/l/l

ReactiveReactive ¾ ¾ InfectionInfection • • ViralViral •

• EBV (Infectious Mononucleosis)EBV (Infectious Mononucleosis) • • TBTB • • PertussisPertussis • • BrucellosisBrucellosis • • Maliganat Maliganat • • ChronicChronic • • AcuteAcute

(12)

Which of the following is true?

1. Most of the lymphocytes in the peripheral 1. Most of the lymphocytes in the peripheral

blood are B cells. blood are B cells.

blood are T cells. Y blood are T cells. Y

blood are NK cells. blood are NK cells.

4. T cells produce immunoglobulin.4. T cells produce immunoglobulin.

(13)

For every stage of lymphocyte

development,

there is a corresponding lymphoid

neoplasm

i.E Differentiation block: the cells don

i.E Differentiation block: the cells don’’t t grow up!

(14)

(15)

(16)

Bone Marrow

Stem Cell Pro-B Cell Pre-B Cell Immature-B Cell Naïve-B Cell Mature-B Cell

B Cell Development

µ

Surrogate Light Chain of Pre-BCR

Ig IgM

Pan B Cell Antigens CD19, CD20 CD38

CD22, CD23, CD40 Ig gene rearrangement: -ive and +ive selection

Somatic Hypermutation CLL, Myeloma, Waldenstroms DHJH Periphery Antigen-Independent Antigen-Dependent VHDHJH VLJL Y II II Igα/Igß Y _Y IgM Y Y II II IgD IgM II IIIIIIII _IIY Burkitt’s Precursor B-ALL

(17)

Acute Lymphoblastic

leukemia: ALL

10% of all 10% of all leukemiasleukemias

85% of childhood 85% of childhood leukemia

leukemia

Commonest 2Commonest 2--10 years10 years

(18)

We donWe don’’t knowt know

Chemicals/toxinsChemicals/toxins RadiationRadiation VirusesViruses

Genetics and congenital factorsGenetics and congenital factors

Aetiology

(19)

Poor prognostic factors in ALL Age Sex WCC @ DX. CNS disease Immunophenotype Cytogenetics <1 or >10yrs Male > 50x109_/l Blasts in CSF

(20)

Acute Lymphoblastic Leukaemia

(21)

Abnormalities seen in at least 90 %of cases Karyotype is of major prognostic significance Used in planning Treatment t(9:22), t(1:19), t(4:11), t(8:14)

(22)

ALL

Symptoms.Symptoms. VagueVague

Sore throatSore throat

FatigueFatigue

Bone painBone pain

InfectionInfection

SignsSigns

Bone marrow Bone marrow

failure failure PalePale BleedingBleeding InfectionInfection LymphadenopathyLymphadenopathy

(23)

Childhood ALL

Most Children are cured with Most Children are cured with chemotherapy!

chemotherapy!

Disease has a predeliction for CNS.Disease has a predeliction for CNS.

(24)

(25)

ALL in Adults

Very few long term cures compared Very few long term cures compared to children

(26)

Which of the following is true?

1. Acute lymphoblastic leukaemia occurs mostly 1. Acute lymphoblastic leukaemia occurs mostly

in adults. in adults.

2. Acute lymphoblastic leukaemia occurs montly 2. Acute lymphoblastic leukaemia occurs montly

in children.Y in children.Y

3. Most children with acute lymphoblastic 3. Most children with acute lymphoblastic

leukaemia die from their disease. leukaemia die from their disease.

4. Stem clee transplantation is never indicated as 4. Stem clee transplantation is never indicated as

treatment for acute lymphoblastic leukaemia. treatment for acute lymphoblastic leukaemia.

5. Bone pain is never a presenting feature of 5. Bone pain is never a presenting feature of

acute lymphoblastic leukaemia acute lymphoblastic leukaemia

(27)

Chronic Lymphoproliferative

diseases

Chronic |Lymphocytic Chronic |Lymphocytic

Leukemia Leukemia

Hodgkin diseaseHodgkin disease

Non Hodgkin LymphomaNon Hodgkin Lymphoma

Multiple MyelomaMultiple Myeloma

B CellB Cell EBV??EBV?? B or T CellB or T Cell

(28)

Chronic Lymphoproliferative Chronic Lymphoproliferative diseases diseases CLL CLL Adults/hypogammaglob Adults/hypogammaglob ulinemia ulinemia HDHD NHL /AdultsNHL /Adults

M Myeloma/ AdultsM Myeloma/ Adults

Progressive Progressive

disease/infection

Young/curable in mostYoung/curable in most

LymphadenopathyLymphadenopathy IncurableIncurable LymphadenopathyLymphadenopathy

Incurable/ bony lesionsIncurable/ bony lesions

(29)

Hodgkins

(30)

Chronic Lymphoproliferative

diseases

Majority have acquired Majority have acquired

cytogenetic/molecular lesions

(31)

Lymphoma Classification

B cell

Precursor B cell neoplasm

Precursor B lymphoblastic leukemia/lymphoma (precursor B cell acute lymphoblastic leukemia)

Mature (peripheral) B cell neoplasms

B cell chronic lymphocytic leukemia/small lymphocytic lymphoma B cell prolymphocytic leukemia

Lymphoplasmacytic lymphoma

Splenic marginal zone B cell lymphoma (± villous lymphocytes) Hairy cell leukemia

Plasma cell myeloma/plasmacytoma

Extranodal marginal zone B cell lymphoma of MALT type Mantle cell lymphoma

Follicular lymphoma

Nodal marginal zone B cell lymphoma (± monocytoid B cells) Diffuse large B cell lymphoma

Burkitt's lymphoma/Burkitt cell leukemia

T cell

Precursor T cell neoplasm

Precursor T lymphoblastic lymphoma/leukemia (precursor T cell acute lymphoblastic leukemia)

Mature (peripheral) T cell neoplasms

T cell prolymphocytic leukemia T cell granular lymphocytic leukemia Aggressive NK cell leukemia

Adult T cell lymphoma/leukemia (HTLV-I+) Extranodal NK/T cell lymphoma, nasal type Enteropathy-type T cell lymphoma

Hepatosplenic T cell lymphoma

Subcutaneous panniculitis-like T cell lymphoma Mycosis fungoides/Sézary syndrome

Anaplastic large cell lymphoma, primary cutaneous type Peripheral T cell lymphoma, not otherwise specified (NOS) Angioimmunoblastic T cell lymphoma

(32)

Which of the following is true?

1. Chronic Lymphocytic leukaemia is a T cell 1. Chronic Lymphocytic leukaemia is a T cell

disease. disease.

2. In chronic lymphocytic leukaemia the 2. In chronic lymphocytic leukaemia the

lymphocyte count in the blood is normal. lymphocyte count in the blood is normal.

3. Chronic lymphocytic leukaemia occurs mainly 3. Chronic lymphocytic leukaemia occurs mainly

in children in children

immunoglobulin levels are usually normal. immunoglobulin levels are usually normal.

immunoglobulin levels are usually decreased. Y immunoglobulin levels are usually decreased. Y

(33)

Learning outcomes Learning outcomes

Lymphocyte Ontogeny: know types Lymphocyte Ontogeny: know types and origin of lymphocytes

and origin of lymphocytes

Function of lymphocytesFunction of lymphocytes

Lyphoprloifertive DisordersLyphoprloifertive Disorders

Acute vs ChronicAcute vs Chronic

(34)

(35)

Acute vs. Chronic leukemia

•

• Acute Acute leukemiasleukemias::

_{young, immature,}_{young, immature,}_blast_blast_cells_cells

–

– more more fulminantfulminant presentationpresentation –

(36)

Acute vs. Chronic leukemia

Chronic _Chronicleukemias_leukemias:_:

–

– accumulation of mature, accumulation of mature, differentiated differentiated cellscells –

– often subclinical or incidental presentationoften subclinical or incidental presentation –

– in general, more indolent coursein general, more indolent course

Frequently splenomegaly_{Frequently splenomegaly}

–

(37)

leukemia

vs

lymphoma

Reasonably straightforward:

•

• leukemia = increased WBC in blood and leukemia = increased WBC in blood and marrow

marrow –

– leukemiasleukemias can be myeloid or lymphoid:can be myeloid or lymphoid: •

• lymphocytosis, lymphocytosis, neutrophilianeutrophilia, blasts of either , blasts of either

origin

•

• lymphoma is always of a lymphoid originlymphoma is always of a lymphoid origin

–

– B cell lymphoma (85%)B cell lymphoma (85%) –

(38)

leukemia

vs

Lymphoma

most lymphoid diseases can enter a

leukemic phase if advanced

enough

high high tumortumor burden, spills out into bloodburden, spills out into blood BUT

BUT

myeloid diseases very rarely present inmyeloid diseases very rarely present in lymph nodes

(39)

Lymphoma Classification

complicated, getting worsecomplicated, getting worse

–

– now able to distinguish subtle differences in now able to distinguish subtle differences in cells better than ever before

cells better than ever before

–

– broadly,broadly,

Hodgkin

(40)

leukemia

vs

Lymphoma

other common example:

chronic lymphocytic leukemia

and

small lymphocytic lymphoma

the two best examples:

called leukemia

called leukemia vsvs lymphoma depending on lymphoma depending on mode of presentation

(41)

leukemia

vs

Lymphoma

A few specific entities can present as A few specific entities can present as either either lymphoblastic lymphoma lymphoblastic lymphoma and and

acute lymphoblastic leukemia

are the same disease, but named

depending on mode of presentation

–

(42)

leukemia

vs

Lymphoma

leukemia presents in blood and marrowleukemia presents in blood and marrow

lymphoma most often presents primarily lymphoma most often presents primarily with lymphadenopathy

with lymphadenopathy

however: one caveat

(43)

leukemia

vs

Lymphoma

•

• lymphoma of two general types:lymphoma of two general types:

–

– HodgkinHodgkin’’s lymphomas lymphoma

•

•B cell originB cell origin •

•ReedReed--Sternberg cellsSternberg cells

–

– NonNon--HodgkinHodgkin’’s lymphomas lymphoma

•

•all othersall others •

(44)

Leukaemia Acute Myeloid (AML) 46% Lymphoblastic (ALL) 11% Myeloid (CML) 14% Lymphocytic (CLL) 29% Chronic

(45)

Acute vs. Chronic leukemia

•

• leukemiasleukemias are classified according to cell of are classified according to cell of origin:

origin:

–

– lymphoid cellslymphoid cells •

•ALL ALL -- lymphoblastslymphoblasts •

•CLL CLL –– mature appearing lymphocytesmature appearing lymphocytes –

– myeloid cellsmyeloid cells •

•AML AML –– myeloblastsmyeloblasts •

(46)

Acute vs. Chronic leukemia

•

• Acute leukemia = blasts in marrow and often Acute leukemia = blasts in marrow and often blood

blood

Chronic leukemia = mature appearing cells _{Chronic leukemia = mature appearing cells}

in marrow and blood

(47)

Lymphoma Classification

Newer classification: REAL, WHONewer classification: REAL, WHO •

• Take into accountTake into account

–

– cell type (B vs. T)cell type (B vs. T) –

– disease biologydisease biology –

– immunophenotypeimmunophenotype

(48)

Lymphoma Classification

Old classification: Working FormulationOld classification: Working Formulation •

• Classified according to clinical behaviourClassified according to clinical behaviour

Low GradeLow Grade

Intermediate GradeIntermediate Grade

(49)

Staging

Ann

Arbor

staging system 1974

I I —— Involvement of single lymph node region (I) or of single Involvement of single lymph node region (I) or of single

extralymphatic

extralymphatic organ or site (organ or site (IeIe) )

II —II — Involvement of 2 or more lymph node regions on the same Involvement of 2 or more lymph node regions on the same

side of the diaphragm alone (II) or with involvement of limited, side of the diaphragm alone (II) or with involvement of limited, contiguous

contiguous extralymphaticextralymphatic organ or tissue (organ or tissue (IIeIIe) )

III III —— Involvement of lymph node regions on both sides of the Involvement of lymph node regions on both sides of the

diaphragm (III) which may include the spleen (

diaphragm (III) which may include the spleen (IIIsIIIs) or limited, ) or limited, contiguous

contiguous extralymphaticextralymphatic organ or site (organ or site (IIIeIIIe) or both () or both (IIIesIIIes) )

IV IV —— Diffuse or disseminated foci of involvement of one or Diffuse or disseminated foci of involvement of one or

more

more extralymphaticextralymphatic organs or tissues, with or without organs or tissues, with or without associated lymphatic involvement

(50)

Chance Chance Chance Genetic Modifiers MHC/Immune Sx. Carcinogen metabolism DNA Repair

Inherited mutated alleles

Chance Environmental exposures Genotoxic Ionizing Radiation Solvents Proliferative Stress Infection Toxins Diet Transforming viruses Acquired Modifiers Diet Infection Immunosuppression dominant clone Stem cells Mutations Etiology Leukaemia Greaves, Lancet

(51)

Presentation

Acute leukemia is always serious and life threatening

Anemia: Pallor, lethargy, dyspnoea

Leucopenia: Infection - mouth, skin, perianal region

Thrombocytopenia: -bruising, menorrhagia, gum bleeding

Hepatosplenomegaly is common

(52)

Differential Diagnosis

Lymphadenopathy Infectious mono. or other viral infections, Lymphoma,

Hepatosplenomegaly Myelo or Lymphoproliferative disorders

Autoimmune, Metabolic, storage disorders

Pancytopenia Aplastic anemia, Drug related, Hypersplenism, Myelodysplasia

(53)

Investigations: General

FBC: Usually shows ↓ HB and platelets (maybe <20) WCC can vary <1.0 - > 200 x 109_/l,

Abnormal differential, Film: Blasts

Coag. Screening: Maybe abnormal

Chemistry: LDH reflects tumor burden,

renal failure, hyperuricemia

Others: Chest x-ray, USD, Virology, LP, Blood C/S

Initial evaluations are not only directed towards diagnosis but to initiate supportive measures for patients with advanced disease

(54)

Investigations: Specific

• Morphology

• Immunophenotype • Cytogenetics

(55)

HLA-DR CD34 TdT CD7 CD3 CD19 CD22 CD13 CD33

T-ALL _B-ALL _AML

Immunophenotyping: Flowcytometery

Stem cell compartment

(56)

Treatment

Supportive Care

• Red cell transfusion for anaemia

• Platelets transfusion for thrombocytopenia • Vigorous treatment of infection

• Social and psychological support

(57)

Principles of therapy in ALL

•Remission induction

•Consolidation

•CNS prophylaxis

•Allogeneic BMT for high risk groups

(58)

Treatment Outcome

The most important factor to influence

treatment outcome is AGE

Continuous decline in CR from 95% in Continuous decline in CR from 95% in

children to 40

children to 40--60% in pts older than 6060% in pts older than 60

CytogeneticsCytogenetics

Overall CR in adults: 75% (63Overall CR in adults: 75% (63--86)86)

(59)

Childhood ALL

(60)

Chronic Lymphocytic leukemia

Commonest leukemia in the western worldCommonest leukemia in the western world

Clonal proliferation of the BClonal proliferation of the B--LymphocytesLymphocytes

Disease of the elderlyDisease of the elderly

Younger patients now seenYounger patients now seen

M:F ratio, 2:1M:F ratio, 2:1

CLL is highly variable disorderCLL is highly variable disorder

75% cases, diagnosis by chance on a routine blood 75% cases, diagnosis by chance on a routine blood

test

(61)

Aetiology

Cause unknownCause unknown

Not associated with radiation or exposure to Not associated with radiation or exposure to

occupational hazards

Among the leukemias, CLL has the strongest Among the leukemias, CLL has the strongest

tendency for familial incidence

(62)

Clinical Findings

Asymptomatic: incidental findingAsymptomatic: incidental finding

Anaemia & thrombocytopeniaAnaemia & thrombocytopenia

InfectionsInfections

Weight loss, Night sweats, Fever (B Symptoms)Weight loss, Night sweats, Fever (B Symptoms)

LymphadenopathyLymphadenopathy

SplenomegalySplenomegaly

(63)

Binet system

A: <3 lymphoid sites involved, Hb>10, Plts> A: <3 lymphoid sites involved, Hb>10, Plts>

100

B: >3 lymphoid sites, Hb>10, Plts>100B: >3 lymphoid sites, Hb>10, Plts>100

C: Hb< 10, Plts <100, independent of lymph C: Hb< 10, Plts <100, independent of lymph

site involvement

(64)

Prognosis

Late stage patients have usually progressive Late stage patients have usually progressive

disease

Highly Variable for early stage patientsHighly Variable for early stage patients

Significant subset of early stage eventually Significant subset of early stage eventually

progress

Refractory to treatmentRefractory to treatment

Infectious ComplicationsInfectious Complications

(65)

Treatment

Watchful waiting Watchful waiting ““ First do no harmFirst do no harm””

Single agentsSingle agents

Alkylators: Chlorambucil, CyclophosphamideAlkylators: Chlorambucil, Cyclophosphamide

Purine analogues: FludarabinePurine analogues: Fludarabine

Monoclonal antibodiesMonoclonal antibodies

Rituximab (Anti Rituximab (Anti –– CD20 antibody)CD20 antibody)

Campath (Anti Campath (Anti –– CD52 antibody)CD52 antibody)

Combination ChemoimmunotherapyCombination Chemoimmunotherapy

FCRFCR

(66)

Hodgkin

’

_’

s disease

_{s disease}

Incidence: 70/million pop

Peak Incidence: 20

Peak Incidence: 20--29 years29 years M>F: 1.4

M>F: 1.4

Ethnic: 90% Caucasians

Association with EB virus (NS)

(67)

Clinical features: HD

Mass: neck, groin (Mass: neck, groin (axillaaxilla))

Cough, shortness of breathCough, shortness of breath

B symptoms: B symptoms:

Wt loss>10%, night sweats, pyrexia >38Wt loss>10%, night sweats, pyrexia >38

PruritusPruritus

Alcohol induced painAlcohol induced pain

Bone pain due to bone destructionBone pain due to bone destruction

(68)

Investigations: HD

FBC and ESRFBC and ESR

U&E, LFT, U&E, LFT, urateurate, LDH, LDH

ββ2m and CRP2m and CRP

CC--TscanTscan thorax and abdomenthorax and abdomen

BMA and trephine (III and IV)BMA and trephine (III and IV)

ECHOECHO

(69)

Management: HD (1)

Stage I and IIAStage I and IIA

Involved field radiotherapyInvolved field radiotherapy

(70)

Management: HD (2)

Stage IIB, III, IVStage IIB, III, IV

Gold standard therapyGold standard therapy--ABVD ABVD

AnthracyclineAnthracycline (doxorubicin)(doxorubicin)

BleomycinBleomycin VinblastineVinblastine DacarbazineDacarbazine

66--8 cycles at 28 day intervals8 cycles at 28 day intervals

Escalated BEACOPP in high risk patientsEscalated BEACOPP in high risk patients

(71)

Relapsed/refractory HD

PBSCT is treatment of choicePBSCT is treatment of choice

Salvage rate 50Salvage rate 50--60%60%

Salvage / priming chemotherapySalvage / priming chemotherapy

ESHAP, IEV, VAPECESHAP, IEV, VAPEC--BB

BEAM conditioningBEAM conditioning

(72)

Low grade lymphoma

Incidence: 30Incidence: 30--50/million 50/million increasing by 4% increasing by 4%

annually

Peak age: Peak age: 5050--60 years60 years

M>F: M>F: 11--5 : 1 5 : 1

Geographical/ethnic variationGeographical/ethnic variation

Pesticide use, hair dyesPesticide use, hair dyes

(73)

Clinical features:

LG

-

_-

NHL

_NHL

Mass: cervical, Mass: cervical, axillaaxilla, inguinal, inguinal

Bone marrow failureBone marrow failure

BB--symptomssymptoms

Abdominal distensionAbdominal distension

Odd presentationsOdd presentations

(74)

Investigations: LG

-

_-

NHL

_NHL

FBC and filmFBC and film

ImmunophenotypeImmunophenotype

BMAspBMAsp and and TxTx

Biochemistry, Biochemistry, urateurate, LDH, LDH

ImmunoglobulinsImmunoglobulins

(75)

Management: FCCL

Incurable: Incurable: conventional rxconventional rx

Median OS:Median OS: 88--10 years10 years

Median OS:Median OS: 3 years3 years

after one relapse

Stage III/IV disease in >80%Stage III/IV disease in >80%

(76)

Management: FCCL

Stage I (molecular staging)Stage I (molecular staging)

Local DXTLocal DXT

Other stagesOther stages

Watch and waitWatch and wait

CVP if concern about bulky diseaseCVP if concern about bulky disease

RituximabRituximab

CHOP CHOP

‘

(77)

Management: FCCL

Patient <60Patient <60

Allogeneic transplantAllogeneic transplant

Conventional Conventional vsvs NSTNST

AutologousAutologous PBSCTPBSCT

Early versus late harvestEarly versus late harvest

Avoid ChlorambucilAvoid Chlorambucil

Role of Role of RituximabRituximab

(78)

Management: LG

-

_-

NHL

_NHL

SLL (CLL) and LPLSLL (CLL) and LPL ChlorambucilChlorambucil FludarabineFludarabine

Fludarabine combination (FCR)Fludarabine combination (FCR)

HyperviscosityHyperviscosity

(79)

Unanswered questions

Role of transplantationRole of transplantation

Intensification of treatmentIntensification of treatment

Many previous reMany previous re--incarnations!incarnations!

RituximabRituximab at presentationat presentation

(80)

High

-

_-

grade NHL

_{grade NHL}

Incidence: 50%Incidence: 50%

All age groups, but increases with ageAll age groups, but increases with age

(81)

Clinical features: HG

-

_-

NHL

_NHL

Present with massPresent with mass

Atypical presentations occurAtypical presentations occur

Marrow involvement is rareMarrow involvement is rare

(82)

(83)

Management: DLCL

Gold standard therapy:Gold standard therapy:

CHOP: CHOP: 40% cure rate40% cure rate

Gela trial >65 yearsGela trial >65 years

RR--CHOP: CHOP: CR of 76% (CR of 76% (vsvs 63%)63%)

Stage I (reduced chemo+DXT)Stage I (reduced chemo+DXT)

Salvage treatmentSalvage treatment

(84)

Mantle cell lymphoma

55--10% of NHL10% of NHL

Middle aged to elderly malesMiddle aged to elderly males

Stage IVB diseaseStage IVB disease

Combines worse features of LG and HGCombines worse features of LG and HG--NHL NHL

Median OS is 3 yearsMedian OS is 3 years

Treat with hyperTreat with hyper--CVAD or FCRCVAD or FCR

(85)

Leukaemic

type

_type

-

_-

NHL

_NHL

Rare, <5% of lymphomasRare, <5% of lymphomas

Acute Lymphoblastic lymphoma/BurkittsAcute Lymphoblastic lymphoma/Burkitts

Explosive presentationExplosive presentation

Acute abdomen Acute abdomen

Rapid onset dyspnoea/Rapid onset dyspnoea/MediastinalMediastinal MassMass

Common in young peopleCommon in young people

Burkitts often associated with HIVBurkitts often associated with HIV

(86)

Management:

MultiMulti--agent chemotherapyagent chemotherapy

CODOXCODOX--M / IVACM / IVAC

UKALL XIIUKALL XII

HyperCVADHyperCVAD

CNS prophylaxisCNS prophylaxis

InIn--patient treatment: 4 monthspatient treatment: 4 months

(87)

Multiple

Myeloma

_Myeloma

Terminally differentiated B cells_{Terminally differentiated B cells}

Malignant plasma cells increasingly infiltrate the bone _{Malignant plasma cells increasingly infiltrate the bone}

marrow and produce a monoclonal immunoglobulin Ig (M

protein or a Ig chain)

Incidence _Incidence-_- Accounts for more than 10% of all _{Accounts for more than 10% of all}

haematological malignancies

_{Increase in incidence at the rate of 2% per annum for}_{Increase in incidence at the rate of 2% per annum for}

Europe

Incurable_Incurable: 3_{: 3}-_-4 year survival with routine therapy_{4 year survival with routine therapy}

(88)

Investigations

FBCFBC U+E, CaU+E, Ca SPEPSPEP

UPEP (Bence Jones Proteins)UPEP (Bence Jones Proteins)

Serum Free Light chainsSerum Free Light chains

Skeletal SurveySkeletal Survey

(89)

What Causes

Myeloma

_Myeloma

?

_?

Decline in the immune system_{Decline in the immune system}

_{Increases with age, 40% of patients around 60 yrs}_{Increases with age, 40% of patients around 60 yrs}

Genetic factors_{Genetic factors}

_{Higher incidence in African Americans}_{Higher incidence in African Americans}

Occupational exposures_{Occupational exposures}

_{Agriculture, petrochemical, rubber & paint}_{Agriculture, petrochemical, rubber & paint}

industries

(90)