Overview of Lymphomas

8/13/2019 Overview of Lymphomas

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Overview of Lymphomas

Jessica Hals, DO

June 16th2005


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Definition

Lymphomas are malignant transformations

of normal lymphoid cells which reside

predominantly in lymphoid tissues

They are divided into two major types:

Non-Hodgkins lymphoma (NHL)

Hodgkins Lymphoma


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Some Stats1

It is estimated that there will be 63,740 newcases of lymphoma diagnosed in 2005.

56,390 are expected to be NHL

19,200 of these pts are expected to die fromNHL

7,350 are expected to be HodgkinsLymphoma

1,410 of these pts are expected to die


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How to Diagnosis NHL

The initial evaluation must establish:

The precise histologic type of NHL

The extent and sites of disease

The performance status of the patient

All of this is important to establishprognosis and treatment


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Where to start

As always with the H&P:

Key points to obtain in your history:

Lymphadenopathy: more than 2/3 of ptwill present with peripheral adenopathy

Ask about waxing and waning of lymph nodes

As about the duration of lymphadenopathy


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The History Contd

B Symptoms:

Fever defined as T>38C

Weight loss defined by unexplained loss of

>10% of body wt over 6 mos

Night sweats defined by drenchingnight

sweats


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The Physical Exam

Exam all sites of potential involvementincluding:

Waldeyers ring (tonsils, base of tongue,

nasopharynx)

Std L.N. sites (cervical, inguinal, etc) Liver and spleen

Abdominal L.N. (mesenteric, retroperitoneal)

Others: occipital, preauricular, epitrochlear, etc.


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Unusual Sites/Presentations

10-35% will have primary extranodal NHLand about 50% will have extranodal diseaseduring their illness

Most common site of extranodal disease isthe GI tract followed by the skin

Symptoms from extranodal disease usuallyassoc with aggressive NHL


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Extranodal Sites Testicular NHL accounts for ~1% of NHL and 2% of

extranodal NHL. It is the most common malign.involving the testis in men over 60 y.o

NHL can present as solitary lesion of bone

Renal involvement occurs in 2-14% of pts

Rarer sites include: prostate, bladder, ovary, orbit,heart, breast, salivary gland, thyroid and adrenal

gland Examine skin carefully and bx any suspiciouslesions

NHL can account for poorly differentiatedcarcinoma of unknown primary


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Diagnostic tests

Lymph node biopsy

Preferably to have an entire intact lymphnode over FNA or core bx

This allows the pathologist to accuratelydetermine the pattern of involvement andallows for enough tissue for immunologicand molecular testing


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Tests Contd

Bone marrow bx

This is to determine stage

Controversial whether bilateral orunilateral bxs are required.

Most oncologists advocate bilateral

biopsy


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Lab tests

CBC

Serum chemistries

LDH Uric acid


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Imaging tests

CT chest/abd/pelvis

PET scan


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Staging3


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The FLIPI Score

The IPI was designed for aggressivelymphomas. Few Follicular lymphomas fellinto the high risk group based upon the IPI

and therefore its application to FL wasbeing questioned

Therefore the FLIPI has been proposed asa prognostic score for follicular lymphomas


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FLIPI

Five factors:

Age >60

Ann Arbor stage III or IV

Hb 4

LDH >ULN


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FLIPI Risk Groups

Low risk: 0-1 adverse factor (5 &10yrOS=91% & 71% respectively)

Intermediate Risk: 2 adverse factors(5&10yr OS=78% & 51% respectively)

High risk: 3 or more (5&10 yr OS=52%&36% respectively)


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Aggressive NHL3


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Historical tx of aggressive NHL

In 1972 Levitt, et al reported curability oflarge cell NHL with combination chemo2

In 1975 DeVita et al described curing ptsusing COPP (Cytoxan, adriamycin,vincristine, procarbazine and prednisone)2

During the 70s this regimen was simplifiedto the classic CHOP regimen we use today(Cytoxan, adriamycin, vincristine andprednisone)


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TX of Early Stage

A SWOG protocol randomized pts to either3 cycles of CHOP followed by involved fieldXRT vs. 8 cycles of CHOP alone3

This showed that pts had a better 5 yr. PFSand OS with combined therapy

76% vs. 67%, PFS respectively

82% vs. 74%, OS respectively


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Early Stage Contd

The GELA trial2

: A French group has investigated a moreintensive chemo regimen. They randomized ptsto either 3 cycles of CHOP with XRT vs. ACVBP(adriamycin, Cytoxan, vindesine, bleomycin,

prednisone followed with consolidation withifosfamide, VP-16 and AraC)

This new regimen did improve EFS and OS, butat significant toxicity


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Advanced Stage Tx

CHOP is still the most commonly usedregimen, and now with the addition ofrituximab

Several groups are investigating moreaggressive chemo regimens

Here are a few:


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The German group2

They divided pts into three groups: younggood px, young poor px, and elderly

They then randomized pts to one of fourarms:

Arm 1: CHOP 21 (traditional 21 day cycle) Arm 2: CHOP 14 (14 day cycle of CHOP)

Arm 3: CHOEP 21 (CHOP+VP-16 q 21 days)

Arm 4: CHOEP 14 (above q 14 days)


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The German Results

CHOEP 21 improved EFS, but CHOP 14 and

CHOEP 14 improved EFS, CR and OS over stdCHOP 21

The Germans now consider CHOEP 14 preferredchemo for young good px pt

Based on the results of the MInT tx in young good

px pts (CHOP-like chemo w/ Rituxan), they also willadd Rituxan to their chemo

They are also using this same regimen for youngpoor px pts


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The French Approach3

Study randomized pts to 3 cycles

CHOP +XRT vs. 3 cycles ACVBP

followed by consolidation.

EFS (82% vs. 74%), OS (90% vs. 81%)

were in favor of the chemo only arm

Ongoing study using above +Rituxan


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The North Americans

CHOP+Rituxan considered std of care

Trials are ongoing to improveoutcomes


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Indolent NHL

Follicular lymphoma is most commontype of indolent NHL

Majority of pts present w/ stage III/IVdisease with multiple enlarged LN thathave been present for a long time

Generally not considered curable


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Natural Hx of Indolent NHL

Can have long symptom free intervals

Several studies show no OS advantage toearly treatment vs. waiting until progression

or symptoms develop. Can go for years w/o needing tx. and obs

alone is a feasible approach. Mediansurvival for stage III/IV is 7-10 yrs


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Tx Early Stage I/II indolent NHL

For stage I/II XRT may be reasonable

sole tx


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Tx for advanced disease

Chemotherapy remains the mainstay of treatment.

Various regimens exist CVP, Fludarabine, FC, FCR, CVP-R

All appear to have same RR

Rituximab can be used alone or in combo w/ otherregimens

Radio-labeled monoclonal antibodies are also available forrefractory/relapsed disease (Bexxar and Zevalan)

Transplantation has been investigated for relapseddisease


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Summary of Tx Indolent NHL


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Tx summary Contd


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Marginal Zone Lymphomas (MZL)

3 main types:

Splenic

MALT lymphoma

Nodal

Can occur in GI tract, salivary glands,thyroid, orbit, conjunctiva, breast and lung

Surgery or XRT usually sufficient to treat


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Splenic lymphoma


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MALT lymphomas Extranodal lymphoma associated w/

mucosal tissue ~5% of NHL, 50% of these are gastric

Most are stage I/II at presentation

Gastric MALTomas assoc w/ H.pylori

infection. Tx w/ Abx causes regression oflymphoma in majority of cases

XRT or resection can be used for other sitesof MALToma


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Extra-nodal MZL

Are extremely rare

Usually indolent

Surgery can be used w/ or w/o XRT


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Tx Mantle Cell Lymphoma

CVP (Cytoxan, vincristine, prednisone)

Hyper-CVAD (mtx, adriamycin,Cytoxan, vincristine, dexamethasone,

AraC-C) w/ and w/o rituximab has alsobeen used.

Relapses are common even after BMT


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AID-related lymphomas

AIDS defining malignancies: Kaposis sarcoma, NHL, primary CNS

lymphoma, invasive cervical carcinoma

AIDS related NHL:

Primary CNS lymphoma (PCNSL)

Systemic NHL

1 effusion NHL


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HIV related NHL

Usually in pts w/ CD4 count


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PCNSL in HIV

Usually w/ CD4 counts


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TX PCNSL

No established std since it is relativelyrare and has a poor px

XRT w/ steroids can prolong survival

HAART can prolong survival

Chemotherapy can be used but isgenerally poorly tolerated


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Primary Effusion Lymphoma

Originates on serosal surfaces ofperitoneal, pericardial and pleuralcavities and joint spaces

Generally will have genetic materialfrom HHV-8 and EBV

CD4 count typically


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Hodgkins Disease

It is estimated that in 2005 there will

be 7350 new cases of HD

There will be an estimated 1410deaths from HD in 2005


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Clinical Presentation

Bimodal distribution: peak in 20s and asecond peak over age 50

Most will present with asymptomatic

lymphadenopathy often in the neck Can manifest as mediastinal mass on CXR.

If large enough can cause symptoms such ascough, retrosternal cp or SOB


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Systemic Symptoms

B symptoms similar to those seen with NHL often

are present: Fever: Pel Ebstein (fever recurring at variable intervals of

several days to weeks and lasts 1-2 wks before waning)

Night sweats

Weight loss

Fatigue

Pruritus: uncommon, but when present is usu. generalizedand can precede overt HD by mos. to a yr.


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Other possible Symptoms

ETOH induced pain

Skin lesions (ichthyosis, acrokeratosis (Bazexsyndrome), urticaria, erythema multiforme,erythema nodosum, necrotizing lesions,hyperpigmentation, and skin infiltration )

Nephrotic syndrome Hypercalcemia

Anemia

eosinophilia


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Diagnosis As always a good H&P is priceless

CT C/A/P

PET scan

BM Bx if pt has B symptoms, clinical stage II-IV,anemia, leukopenia or thrombocytopenia

CBC, LDH, CMP

Lymph node bx (again an entire intact LN ispreferable)


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Classification

WHO/REAL Classification: Nodular Lymphocyte Predominant (CD30-

/CD15-/pan-Bcell +) non-classical RS cells Classical Hodgkins lymphoma:

(CD30+/CD15+/CD45-/panB and panT antigennegative) Reed-Sternberg Cells

Lymphocyte-rich

Nodular sclerosis

Mixed cellularity

Lymphocyte depleted

Unclassifiable classical HD


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Nodular Sclerosis Classical HL

Most common subtype

Most common in women, adolescents andyoung adults

often will have a mediastinal mass, lowercervical, supraclavicular L.N. w/ and orderlypattern of spread

Good Px


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Lymphocyte depleted

Classical HL

Least common subtype

Older men and HIV infected pts

Less peripheral adenopathy, more

abdominal adenopathy.

HSM may be prominent

BM often involved


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Lymphocyte-rich Classical HL

Older patients usually

More frequently present w/ mediastinal

mass Late relapses less common, but more

fatal


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Nodular Lymphocyte Predominant

HL

Only 3-8% of HL

More common in adults (median age 34)

More often localized disease

More common in men Slowly progressive w/ very favorableoutcomes

Can progress to large B-cell NHL

St i


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Staging

Cotswold Staging


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Cotswold Staging


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Overview of Treatment

HD is highly curable even after relapse

Stage and prognostic factors will

determine high vs. low risk diseaseand will drive treatment choices


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International Prognostic Score

7 factors:

Albumin 15,000/mcl

Lymphocyte count


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5yr freedom from progression

No factors: 84%

1 factor: 77%

2 factors: 67%

3 factors: 60% 4 factors: 51%

>5 factors: 42%


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EORTC definitions

Adverse Px factors identified in CSI-II pts.Used to define tx for CSI-II HD

Defined as follows: Large mediastinal adenopathy

Age over 50

B symptoms >4 LN regions involved

B Symptoms + ESR>30 or ESR >50 w/o Bsymptoms


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Historical Tx HL

In 1964 the NCI developed a four drugregimen that cured 50% of pts.

Thus MOPP (mechlorethamine, vincristine,

procarbazine, prednisone) became std Significant toxicity and secondary

malignancies made it imperative to find alt.regimens


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The birth of ABVD

ABVD was originally developed forMOPP resistant disease

In a head to head trial, ABVD had

higher CR, PFS, and OS than MOPP It also had less short and long term

toxicity.


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Favorable Px Stage I-II

2-4 cycles ABVD (adriamycin, vinblastine,

bleomycin, dacarbazine) followed byinvolved field XRT to original L.N. regions

XRT alone to involved and uninvolved L.N.regions

Stanford V (adriamycin, mechlorethamine,vinblastine, prednisone, vincristine,bleomycin, VP-16) for 8wks w/ involved fieldXRT


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Favorable Px Contd

Ongoing trials are attempting to

identify newer regimens and

determine the optimal number of

chemotherapy cycles to administer to

obtain the lowest relapse rate and

improve overall survival


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Unfavorable Stage I-II

XRT alone not generally accepted due to

high rate of relapses

4-6 cycles ABVD followed by XRT to

involved sites Treat 2 cycles past maximum response as

assessed on imaging studies to max. 8 cycles


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Tx Stage III-IV HD 6-8 cycles of ABVD most common regimen

used Hybrid regimens tested, but not better than

ABVD

BEACOPP (bleomycin, VP-16, adriamycin,

Cytoxan, vincristine, procarbazine,prednisone) is alt. regimen

Stanford V for 12 wks followed by IFXRTalso being tested


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Relapsed/Refractory HL

Bx area of relapse to prove pt has truly

relapsed and not developed an

infection/other malignancy

If tx w/ XRT only can still salvage w/ chemo

If late (>12mo) relapse after chemo, canuse different regimen or autologous

transplant


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Summary Contd

HL is considered a highly curabledisease

The best regimen remains to be

determined Many salvage regimens exist including

BMT


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References

1. Jemal, Ahmedin DVM, PhD, etal. CancerStatistics, 2005.CA A Cancer Journal forClinicians:55;10-30. 2005

2. Armitage, James MD et al. TheTreatment of patients with aggressive NHL.Oncology: 19(4, supp1);1-34

3 Up to Date 2005

Documents

Overview of Lymphomas