Lymphoma - cancer

Lymphoma - cancer

1. Dr.Sana AL Aqqad

2. Learning Objectives
By the end of the session, you should be
able to:
1.What is Lymphoma?
2.Types of lymphoma? HL,NHL
3.Subtypes
4.Epidemiology
5.Stages of the disease
6.Sign and symptoms
7.Diagnosis
8.Treatment protocols
9.Side effects
10.Prognosis

4. Lymphoma: a cancer of blood cells (immune cells) called
lymphocytes.
Cancer of LNs /lymphatic system
May arise within single or multiple LNs
Arise from malignant transformationof lymphocytes
Cell of origin: B‐cell, T-cell
Lymphomas divided into 2 main types:
Hodgkin’s Lymphoma (HL) 15%
Non-Hodgkin’s Lymphoma (NHL) 85%

5. Hodgkin’s
Lymphoma

6. M > F (1.2:1)
Disease of the young(commonly)
Bimodal age of distribution
–First peak in 20s /30s
–Second peak > age 50 (less common)
Arise in single L.N or chain nodes:
HL appears to follow a predictable pattern of nodal
spread that is not seen with the NHLs
Spread to 1
st
anatomically contiguous nodes (orderly)
Typically from B-cell line

7. Most case curable (Cure rate 80-90%)
5-year overall survival for all stagesof HL is about 85%
Unknown aetiology:
Studies suggested an increased risk of H.L in patients:
Who have been infected with the Epstein-Barr’s virus
(EBV)40%
Immunosuppressed individuals(HIV)
Genetic factors
F.H
Pathophysiology
The malignant cell in
H.L is known as the
Reed–Sternberg cell (RSC)

9. WHO classification
Nodular Lymphocyte predominant NLPHL(5%)
Best prognosis. (cure 95%)
Express CD20 antigen. (Cellular marker CD 20 +ve)
More indolentin nature (Slow growing)
Classical HL (95%)
1.Nodular Sclerosis –good prognosis (most common type,
2/3 cases)
2.Mixed Cellularity -2
nd
most common type (15-30%)
3.Lymhocyte depleted (worst prognosis)-common HIV+
4.Lymphocyte rich HL -uncommon (good-excellent
prognosis)

10. STAGE DISCRIPTION
Stage IInvolve 1-lymphoid site (I) orsingle extranodal
site(IE)
Stage II2 ≥ lymphoid site either above or bellow
diaphragm (II) orlocalized involvement of an
contiguous extranodal organ/site(IIE)
Stage III2 ≥ lymphoid site above and bellow diaphragm
(III)orlocalized involvement of an
extralymphatic organ/site(IIIE)
Stage IVExtralymphoidtissue (B.M, liver)

12. Most patients present with a painless, rubbery, enlarged
lymph node (lymphadenopathy)
LN. abovediaphragm:
Cervical/supraclavicular, mediastinal, axillary L.Ns
LN. belowdiaphragm:
Mesenteric LNs, inguinal LNs.
L.Ns pain after alcohol
Asymptomatic
B-symptoms:
Fever (>38 C)
Excessive sweeting (night)
Loss of weight (>10% within 6 month)

13. 25% of patients present with the 3 B symptoms
Some pts. Present with B-symptoms before they discover
any LNs enlargement.
B-symptoms incidence increase in advance disease (50%)
B symptoms associated with poorer prognosis
Other symptoms:
Cough, SOB, itching (25%), flushing in face, fatigue,
weakness, pruritus.
Each stage is then divided into 2 categories A & B
A: Absence of B symptoms
B: Presence of B symptoms

14. Swollen lymph node/s
Symptoms (B symptoms)
LN biopsy : (excisional
biopsy) Reed Sternberg cell
(RSC) (Owl Eyes)
Immunohistochemistry
(IHC): Cell surface markers.
MRI
X-ray
CT Scan (chest, abdomen,
pelvis)
PET scan (staging role)
BM biopsy (advance
stage)
Lab. Tests (ESR,
CBC.LDH,LFT)

15. Prognosis:
Patients with early-stage disease (stages I to II) have a
90% to 95% cure rate
Those with advanced disease (stages III to IV) have only a
60% to 80% cure rate
Patients with Hodgkin lymphoma can be categorized into
4 prognostic groups:
1.Early favorable disease.
2.Early unfavorabledisease.
3.Advanced favorable disease.
4.Advanced unfavorable disease.
Unfavorable factorsin early stage:
Large mediastinalmass (bulky), high ESR≥50,
extranodal disease, or ≥3 nodal sites, B-symptoms.
Stage I & II

16. Unfavorable factorsin advanced stage
International Prognostic Score (IPS) for Advanced HL
Age ≥ 45
Gender Male
Serum Albumin <40g/dl
Haemoglobin <10.5g/dl
Stage 4
WBC ≥15,000 cells/mm3
(≥15x10
9
/l)
Lymphocytes
(Lymphocytopenia)
<600 cells/mm3
(<0.6x10
9
/l)

17. SCORES Overall survival at 5 years
0 90%
1 90%
2 81%
3 78%
4 61%
≥5 56%

18. Advanced-stage patients ≤ 3 poor prognostic factors
are considered to have favorable disease
Advanced-stage patients with ≥ 4 poor prognostic
factors are considered to have unfavorable disease
Therapy response:
Complete remission (90% of pts. will achieve it)
Partial remission
Resistance disease/ 5-10% refractory to initial regimen
Relapsed disease after complete/partial remission
(relapse rate can vary from 5% for early-stage disease
to 35% for advanced disease)

19. Treatment
options
Chemo-
therapy
Radio-
therapy
Bio-
therapy

20. Early disease
(Stage I & IIA)
Chemotherapy (2-4 cycles) +
radiotherapy
Early disease
(unfavourable)
Chemotherapy (4-6 cycles) +
radiotherapy
Advanced disease
Stage (III & IV) (IIB –
IV).
Chemotherapy(6-8 cycles) ±
radiotherapy (residual area, bulky)
Refractory/resistance
disease
Salvagechemotherapy(Treatment
given aftercancer not responded to
other treatments) (MOPP/ABVD) or
Stanford V or BEACOPP
Relapsed diseaseSalvage chemotherapyor high dose
chemotherapy with Stem cell support

21. ABVD
A: Adriamycin
(Doxorubicin)
B: Bleomycin
V: Vinblastin
D: Dacarbazine
MOPP
M: Mustin
(Mechlorethamine)
O: Oncovin (Vincristine)
P: Procarbazine
P: Prednisone

22. BEACOPP
B:bleomycin
E: etoposide
A: Adriamycin
C: cyclophosphamide
O: Oncovin (vincristine)
P:procarbazine
P: prednisone
Stanford V regimen
Adriamycin
Mustin
Oncovin
Adriamycin
Etoposide
Vinblastine
Bleomycin
Prednisone
(ABV/MOP)+E

23. ABVD is the preferred treatment compared with
MOPP
MOPP vs. ABVD: ABVD has been shown to have an
improved OS & lower risk of both short-and long-term
toxicities (myelosuppression, infertility, &2ndry leukemia)
ABVDstandard treatment in early disease
Stanford Vregimen is acceptable option
Safety precautions with ABVD:
Cardiac function EF (Adiamycin)
Pulmonary function test (bleomycin)
Patients receiving ABVD are at high risk for
neutropenia (Dacarbazine& vinblastine)increased
risk of infections.
Stage IIB (large mediastinal/extranodal) can treated as
advanced disease (some guidelines).

24. Advanced disease treatment:
ABVD (still treatment of choice).
Stanford-V
MOPP
ABVD was less toxic (leukemia, sterility,
myelosuppression) & provided similar/better
outcomes than MOPP it eventually replaced MOPP
as the standard regimen for advanced-stageHL.
More aggressive regimen: BEACOPP
Hybride-regimen MOPP/ABV (was superior to MOPP
but not ABVD)
BEACOPP superior to ABVD in high risk pts. (however,
more neutropenia, severe infection).
BEACOPPnot encouraged to be given to elderly.

25. Escalated-dose BEACOPPfor unfavourable disease, for
relapsed disease.
Escalated BEACOPP higher risk of neutropenia (37%vs.19%)
and leukaemia as compared to normal BEACOPP dose.
Patients who do not achieve a complete remission with the
initial regimen are considered to have primary refractory
disease Salvage chemotherapy or high dose
chemotherapy + autologous HSCT (hematopoietic stem cell
transplantation)
Patients who have an early relapse (<1 year) generally
respond poorly to standard-dose salvage chemotherapy 
(high dose chemotherapy + HSCT) or salvage
Late relapse (>1-year)same regimen, different regimen,
high dose chemotherapy+ HSCT
If relapse after HSCT Limited treatment Options

26. ABVD (repeated every 28 days)
Doxorubicin
(adriamycin)
25mg/m
2
IV Days 1 + 15
Bleomycin 10mg/m
2
IV Days 1 + 15
Vinblastine 6mg/m
2
IV Days 1 + 15
Dacarbazine375mg/m
2
IV Days 1 + 15

27. BEACOPP (Recycle: day 22.)
Bleomycin 10 mg/m
2
IV Day 8
Etoposide 100mg/m
2
IV Days 1-3
Adriamycin 25 mg/m
2
IV Days 1
cyclophosphamide650 mg/m
2
IV Days 1
Vincristine (Oncovin)2 mg/m
2
IV Days 8
Procarbazine 100mg/m
2
oral Days 1-7
Prednisolone 40mg/m
2
OralDays1-14

28. Escalated BEACOPP: (Recycle day 22)
Bleomycin 10 mg/m2 i.v.Day 8
Etoposide 200 mg/m2 i.v.Days 1–3
Adriamycin 35 mg/m2 i.v.Day 1
Cyclophosphamide 1250 mg/m2 i.v.Day 1
Oncovin 2 mg/m2, max. 2 mg i.v.Day 8
Procarbazine 100 mg/m2 p.o.Day 1–7
Prednisone 40 mg/m2 p.o.Day 1–14
Granulocyte-colony stimulating factor (G-CSF s.c.From
day 8 = Filgrastim(Neupogen®)

29. The more commonly used regimens for
relapsed/refractory HL include the platinum-based
regimens:
ESHAP(etoposide, methylprednisolone, high-
dose cytarabine, and cisplatin)
ASHAP(doxorubicin, solumedrol, high-dose
cytarabine, and cisplatin)
DHAP(cisplatin, cytarabine, and dexamethasone)
ifosfamide-containing regimen ICE(infused
ifosfamide, carboplatin, and etoposide)

30. NLPHL treatment :Nodular lymphocyte predominant:
Radiation (early stage without R.F) pts. Cannot tolerate chemo.
Or pt. choose to omit chemo., not affect survival).
Disadvantage of radiation alone high relapse rate (20-25%)
Rituximab alone (overexpress CD20) if localized
Dose: 375 mg/m2 weekly for 4 weeks
Treat with R-ABVD or R-CHOP (advance stage/standard) with
/without radiation.
Most pts. Receive chemo + radio (residual/bulky area)
Can be treated as other HL
If relapse new biopsy (exclude NHL)
Salvage
Follow –up for HL 
Every 3 months for 1
st
year, then every 6 months until the 4 year, then
once a year after that.
TSH function (yearly at least 5-years)

32. Short term S.E:
N, V, D
Loss of appetite
Hair loss (transient)
Fatigue
Neutropenia
(dacarbazine,
vinblastine)
Febrile neut.
Infections
Tumour Lysis
Syndrome (TLS)
Long term S.E
Gonadal dysfunction:
Infertility, Hypothyroidism
For men, even a single dose
ofnitrogen mustard
orchlorambucil can cause sterility,
so if fertility is a major
concern,ABVD may be the best
alternative)
Cardio-toxicity (5-10 y)
Pulmonary dysfunction.
2ndry Malignancy (↑3-fold).
MOPP, high dose E,
+radiotherapy, Chemo+HSCT,
alkylating agents

33. Non-Hodgkin’s
Lymphoma

34. Incidence NHL>HD
Males > females
Incidence increasing with age (occur in any age)
Commonly diagnosed at 60s(Median age of
presentation is 65-70 years)
5th most common cause of newly diagnosed cancer in
the U.S.
About 19,000 deaths each year in the U.S.
Lymphoma without of Reed‐Sternberg cell (RSC)
Extranodal involvement morecommon than HL
Cell of origin: B-cell-85% ; T-cell-15% (poor prognosis)

35. Proliferation of either malignant B or T lymphocytes
and their precursors
Un known aetiology
Risk increase with:
Genetics
Certain Infection:
EBVBurkitt’s lymphoma
H-pylori infection MALT lymphoma (mucosa
associated lymphoid tissue)
Immunodeficiency disorder (HIV)/ immunesuppressive
medications
Auto-immune disease: R.A, SLE
Hepatitis B,C
Occupational reason/environment: herbicide/pesticide

36. Same symptoms/stages as HL

37. ComparisonHL vs. NHL
Hodgkin’s LymphomaNon-Hodgkin’s Lymphoma
Incidence Less than NHL More than HL
Cell of origin-
(B or T cell)
B-cells B or T cells
Type of Cell RSC No characteristic cells
Age of
Occurrence
Commonly young adults Older adults
L.N spread Contagious (orderly) Sporadic
B-symptoms Common less common (>20% of
patients)
Extranodal Less common Morecommon
Cure Most
Some (based on score and type of
lymphoma –aggressive/not)

38. 1.Indolent (low-grade)
Slow-growing
Waxing & waning symptoms
25-40% of NHL (2
nd
common type)
Good prognosis (median survival 10 y)/long survival
Not curable
B-cells
Common among older adults (female slight more)
B-symptoms, bulky disease, extranodaluncommon
Can transform to aggressive form /unpredictable
eg: Follicular lymphoma (70%)

39. 2.Aggressive (high-grade)
Fast-growing
60-75% of NHL
Curein 30%-60% of patents
Short survival
B or T Cells
All ages, mostly 70s
Extranodalis common
eg: Diffuse large B-cell lymphoma (DLBCL)B-cell
neoplasm, mantle cell lymphoma, Richter syndrome.
Follicular and DLBCllymphoma as the most common
subtypes NHL

40. Highly aggressive lymphoma
Potentially curable
Progress very rapidly
Commonly metastasize to CNS
High risk of TLS(allopurinol, IV hydration, electrolytes)
Example 1: Burkitt’s lymphoma
50% pts. < 45 years (children, young adults)
Endemic form (malaria region)
<2% (rare) most common in African
Example 2: lymphoblastic lymphoma (ALL)
Treat as leukaemia

41. Classification Aggressive Indolent
Exemple DLBCL Follicular lymphoma
Cell types B or T cells B-cells
Presentation Rapid onset of
symptoms
Insidious onset
Naturalhistory
(growth rate)
Rapidly growing
(fatal if untreated)
Slow growing
(treatment not always required
at time of diagnosis)
Sensitivity to
Chemotherapy
(Cure)
Potentially curableResponses seen with
chemotherapy but rarely
curable

42. Indolent
Watch-and -wait (asymptomatic patients)
Median time to need treatment 3-5 years
20% will not need treatment for 10 years
If symptomatic:
Stage I & II : Teat with radiation therapy
Chemotherapy may be useful in high risk stage II
disease (bulky, multiple sites involvement)
Single agent therapy/Rituximab
Stage III &VI:
1.Oral therapy (alkylating agent +/-Prednisone)
Prednisolone + Cyclophosphamide

43. •Prednisolone + Chrolambucilno hair loss, little
nausea, minimum myelosuppression recommended
for older pts., comorbidities.
•Complete response occur more rapidly with combination
chemotherapy
2.IV chemotherapy:
•CVP: Cyclophosphamide+ Vincristine + Prednisone 
check baseline peripheral neuropathy
•CHOP: CVP+ Doxorubicine(if rapid response is more
necessary)check EF, baseline peripheral neuropathy
Note:
•Antiemetic, bowel regimen/stool softener (prevent
constipation).
•G-CSF prophylaxis for high risk patients (febrile
neutropenia).

44. 2.Immunotherapy
MoABagainst CD20
Rituximab (MabThera)
Dose: 375mg/m2 weekly for 4 wks.
Increase overall response
infusion related rxn(fever, chills, rigor( more
common), headache, fatigue during infusion.

45. Respiratory symptoms (bronchospasm), urticaria, pruritus,
angioedema, hypotension )Occur mostly within 30
minutes -2 hrs.
Particularly after 1
st
infusion (slow/interrupt infusion)
Premedication-30 minutes before infusion:
Paracetamol& 50mg Diphenhydramine
Infusion rate may take 4-5 hr
If tolerate 1
st
infusioninfused over 90 minutes
Hep.Btesting before MabThera(patients testing positive should
receive empiric antiviral therapy during chemotherapy treatment to
prevent hepatitis reactivation. )
FDA approve CVP + Rituximab as 1
st
line follicular
lymphoma (R-CVP).
R-CHOPacceptable option

46. 4.Purine analogs(Fludrabine)
Don’t cause N, V, hair loss
Associated with cumulative myelosuppressioninfection
risk
Can be used in refractory/relapseadvanced follicular
lymphoma
Can be used alone or with mitoxantrone&
dexamethasone
Impair stem cell collection not recommended for pts.
Candidate HSCT
4.Radiotherapy also can be used in relapse
5.Salvage
Multiple relapses can occur in Indolent form
Guidelines listed maintenance therapy Rituximab(every 2
months for 2 years) after 1
st
line therapy

47. Aggressive lymphoma
R-CHOP(6 cycles) +/-radiotherapy
The current standard for stage I & 2 3-6 cycle R-
CHOP + involved field radiation (IFR).
Stage III-IV & bulky stage II: 6-8 cycles R-CHOP
If refractory or relapseSalvage chemotherapy:
DHAP: dexamethasone, cytarabine, cisplatin
MINE: mesna, Ifosfamide, mitoxantrone, etoposide
ICE: Ifosfomide, carboplatin, etoposide
Combined with Rituximab followed by HSCT

48. Highly aggressive lymphoma,:
Regimen should include CNS prophylaxisintrathecal
methotrexate/ cytarabine.
R-CHOP may not enough intensive treatment
Best treatment:
(cyclophosphamide, vincristine, doxorubicin,
dexamethasone) or (high dose methotrexate &
cytarabine), CNS prophylaxis

49. CHOP (Recycle: day 22.)
cyclophosphamide750mg/m
2
IV Days 1
Doxorubicin 50mg/m
2
IV Days 1
Vincristine 2 mg/m
2
IV Days 1
Prednisone 100 mg/m
2
O Days 1 -5

50. THANKS

51. Tumour LysisSyndrome: (TLS)
Life threatening complicationof cancer therapy.
Common in lymphoma & acute leukaemia (most
frequently associate with aggressive NHL/ Burkittand ALL).
TLS occurs when tumour cells release their contents
into the bloodstream, either spontaneously or in
response to therapy, leading to metabolic
abnormalities (electrolytes abnormalities & renal
failure).
Can happen spontaneously or within 48-72 hrsafter
therapy (can 24 hr).
1.Metabolic abnormalities (ARF)
↑K, ↑U.A, ↑PO4, 2ndry ↓Ca
U.A crystals obstruction of renal tubules
Ca-PO4 crystals precipitation

53. 2.Cardiac arrhythmia ↑K, ↓Ca:ECG changes
↑K :Can lead to peak T wave, prolong PR interval, ……)
↓Ca: QT interval lengthen
3.Metabolic acidosis
Hyperkalaemia often first sign of this abnormality.
High risk ptsshould have lab monitoring: BUN, creatinine,
phosphate, uric acid, LDH, Calcium) prior therapy and 48-72
hrsafter treatment. (4-6 hrsdaily)
ECG monitoring
TLS Manifestations:
Hyperuricemiaappears 48-72 hours after chemotherapy
Hyperkalemia appears 6-72 hours after chemotherapy
Hyperphosphatemiaappears 24-48 hours after
chemotherapy
Hypocalcemia
Increased S.Crand decreased urine output

54. Start preventative strategies 24-48 hours prior to
treatment,
Identify patients who are at risk
Strategies for management :
1.Hyper-hydration
2.Urinary alkalinisation
3.Uricosuricagent
4.Correction of electrolytes abnormalities
5.Dialysis

55. To Control UA Allopurinol(xanthine oxidase
inhibitor): 600mg/d orally for prophylaxis, 600-900
mg/d for treatment
Will NOT decrease present levels of uric acid
Rasburicase (recombinant urateoxidaseConverts uric
acid to allantoin) , rapid onset of action.
For volume depletion and electrolytes disturbance :
Aggressive hydrationStart 24hr before chemo
Goal Fluid Rate: ~3L/m
2
/day (usually NS or D5W ½ NS),
continue for up to 72 hours after completion of
chemotherapy

56. For hyperkalaemia:
i.Discontinue all K
+
supplements, ACE-I, ARB,
aldosterone antagonist
ii.Loop diuretics + hydration
iii.Sodium polystyrene sulfonate(Kayexalate
®
)
iv.Calcium gluconate10% 100-200mg/kg by slow IV
infusion for life-threatening arrhythmias
v.Insulin 0.1U/kg IV) and D50 (2mL/kg) IV
vi.Sodium Bicarbonate 1-2 mEq/kg IV push) can be given
to induce influx of potassium into cells. However,
sodium bicarbonate and calcium should NOT be
administered through the same line
vii.Dialysis

57. For Hyperphosphatemia
i.Aluminum hydroxide, sevelamer, calcium carbonate
(only treat if Phos≥ 6 mg/dL)
For Hypocalcemia
i.IV calcium supplementation (only if symptomatic–ie.
Seizures, tetany)
Acute Renal Failure
i.Consider dialysis