Lymphoma

Lymphoma

1. The lime green ribbon cancer milestonesand
the management guidelines
Noha El Baghdady

2. Outline
Hodgkin Lymphoma
I.Definition
II.Epidemiology
III.Risk factors
IV.Signs & Symptoms
V.Diagnosis
VI.Classification
VII.Treatment
Non-Hodgkin Lymphoma
I.Overview
II.Epidemiology
III.Etiology
IV.Classification
V.FollicularLymphoma
VI.DLBCL
VII.Burkett lymphoma
VIII.Cutaneous cell lymphoma
IX.Peripheral T cell lymphoma

3. Lymphoma
•Lymphoma is a broad term
for cancer that begins in cells
of the lymph system.
•The two main types are:
1-Hodgkin lymphoma
2-Non-Hodgkin lymphoma
(NHL).

4. Lymphoma

5. Hodgkin Lymphoma(HL)

6. Hodgkin Lymphoma(HL)
•HL most frequently
presents in lymph node
groups above the
diaphragm and/or in
mediastinal lymph
nodes.

7. Epidemiology
•Uncommon malignancy
in adults.
•Estimated new cases
and deaths from HL in
the United States in
2019:
•New cases: 8,110.
•Deaths: 1,000.

8. Risk Factors
•Earlyadulthood(aged20–39years)(mostoften)or
lateadulthood(aged65yearsandolder)(less
often).
•MaleGender.
•HavingapreviousinfectionwiththeEpstein-Barr
virusintheteenageyearsorearlychildhood.
•Havingafirst-degreerelativewithHL.

9. Signs and Symptoms
•These and other signs and symptoms
may be caused by adult HL or by
other conditions
•Painless, swollen lymph nodes in the
neck, axilla, or inguinal area.
•Fever
•Night sweats.
•Unexplained Weight loss of 10% or
more of baseline weight in the
previous 6 months.
•Pruritus, especially after bathing
•Fatigue.

10. Diagnosis
Diagnostic evaluation of patients with lymphoma
may include the following:
•Biopsy (preferably excisional).
•History.
•Physical examination.
•Laboratory tests
•Radiographic examination
•HIV testing.
•Hepatitis B and C serology.

11. Hodgkin Lymphoma
The goal of treatment = CURE FOR ALL
PATIENTS.

12. Hodgkin Lymphoma
• Two main types of HL
1. Classical HL (CHL) –characterized by the presence of
Reed‐Sternberg cells
—CHL is divided into 4 subtypes:
–Nodular sclerosis—most common subtype (overall)
–Mixed cellularity—most common in HIV (+) patients
–Lymphocyte depleted—least common subtype
–Lymphocyte rich
2. Nodular lymphocyte‐predominant HL (NLPHL)
—Lacks Reed‐Sternberg cells
—Cells express CD20(+)

13. Hodgkin Lymphoma
Classical HL (CHL)

14. Treatment of CHL
•Newly diagnosed patients with CHL treated
according to the following categories
–Stage IA & IIA favorable
–Stage I & II unfavorable, non‐bulky disease
–Stage I & II unfavorable, bulky disease
–Stage III & IV

15. Favorable and Unfavorable disease
•NCCN unfavorable risk factors:
1-Bulky mediastinal or >10 cm
disease
2-B symptoms
3-ESR ≥50 OR ESR ≥30 with B
symptoms
4->3 nodal sites of disease.

16. B Symptoms
•All stages of adult HL can be subclassifiedinto A and B
categories:
“B for those with defined general symptoms (described
below) and A for those without B symptoms.”
The B symptoms
•Unexplained weight loss (more than 10% of body
weight in the 6 months before diagnosis).
•Unexplained fever with temperatures above 38°C.
•Drenching and recurrent night sweats.
The most-significant B symptoms are feversand weight
loss.

17. Treatment Overview of CHL
• Treatment duration dependent upon stage and
size
–Stage IA & IIA favorable
—ABVD x 2 cycles + 20 Gyinvolved site
radiotherapy (ISRT)
–Stage I & II unfavorable, non‐bulky disease
—ABVD x 4 –6 cycles ±ISRT
—ABVD alone or alternating with MOPP.

18. Treatment Overview of CHL
–Stage I & II unfavorable, bulky disease
—ABVD x 4 –6 cycles + 30 GyISRT
–Chemotherapy alone is not recommended
The difference between stage I & II bulky versus
non‐bulky is that in the non‐bulky group, patients
can receive chemotherapy alone if PET scan is
negative
–Stage III & IV
—ABVD x 6 cycles ±ISRT

19. Protocols
•ABVD (doxorubicin, bleomycin, vinblastine,
and dacarbazine)
•Stanford V (doxorubicin, vinblastine,
mechlorethamine, etoposide, vincristine,
bleomycin, and prednisone)
•Escalated BEACOPP (bleomycin, etoposide,
doxorubicin, cyclophosphamide, vincristine,
procarbazine, and prednisone)

20. ABVD Regimen
•DOXOrubicin25 mg /m² IV Days 1 & 15
•Bleomycin 10 units /m² IV Days 1 & 15
•VinBLAStine6 mg /m² IV Days 1 & 15
•Dacarbazine375 mg /m² IV Days 1 & 15
Repeated every 28 days

21. Supportive Care Issues with ABVD
Bleomycin pulmonary toxicity (BPT)
–Baselinepulmonaryfunctiontests
shouldbeperformedatbaselineand
periodicallyduringtreatment
—Morecommoninpatientswith
olderage,co‐administrationof
pulmonaryirradiationandtotaldoses
>400units
—BPTalsoassociatedwithuseof
growthfactorsupport

22. Supportive Care Issues with ABVD
–Neutropenia is not an
indication for reduction in dose
intensity
—DOXOrubicinand vinblastine
should be adjusted according
to the liver function
—Bleomycin should be
adjusted according to the renal
functions

23. Extravasations
Anthracycline extravasations are most severe
• Apply cold or warm compresses
–Coldfor anthracyclines
• Dexrazoxaneis indicated

24. Relapsed/Refractory CHL
Treatment goal = CURE
• Relapsed disease is broken down into the
following categories:
–Second line chemotherapy + autologous HSCT
–Second line chemotherapy only (HSCT
contraindicated)

25. Relapsed/Refractory CHL
• Chemotherapy regimens include any of the following, as none have
emerged as preferred regimens
Brentuximabvedotinalone or in combination with the second-line
regimens below
•DHAP (dexamethasone, cisplatin, high-dose cytarabine)
•ESHAP (etoposide, methylprednisolone, high-dose cytarabine,
cisplatin)
•Gemcitabine/bendamustine/vinorelbine
•GVD (gemcitabine, vinorelbine, liposomal doxorubicin)
•ICE (ifosfamide, carboplatin, etoposide)
•IGEV (ifosfamide, gemcitabine, vinorelbine)
Bendamustine
-Single agent therapy

26. Relapsed CHL
BrentuximabVedotin(Adcetris®)

27. Administration
•DONOTadministerasanIVpushorbolus.
•Reconstituteeach50mgvialwith10.5mLofSWFIto
yieldasingle-use5 mg/mLsolution.
•Gentlyswirlthevialtoaiddissolution;donotshake
afterreconstitution
•Addtoaninfusionbagcontainingat least 100ml
volumeto achieveafinalconcentrationof0.4-
1.8mg/mLandusewithin24hours.
•Canbedilutedintonormalsaline,5%dextrose or
lactatedringer's injection.
•InfuseIVover30min.

28. Interactions
•CYP3A4inducers ●CYP3A4inhibitors
•CYP3A4inducers (i.e.phenytoin, rifampin, dexamethasone, carbamazepine,phenobarbital,St.
↓exposuretoMMAE(upto 46%) ↑metabolismofMMAE Caution;monitorfor efficacy
•CYP3A4inhibitors (i.e.ketoconazole, clarithromycin, ritonavir,fruitor juicefrom
grapefruit,Seville orangesor starfruit)

29. Hodgkin Lymphoma
Nodular Lymphocyte‐Predominant
HD (NLPHD)

30. Nodular Lymphocyte‐Predominant HD
•No preferred chemotherapy regimen exists
•ABVD is often used based on data with CHL
•Consistently express the CD20antigen ‐
•Rituximabcan be considered as single‐agent
therapy or in combination with multidrug
chemotherapy regimens

31. Non-Hodgkin lymphomas (NHLs)

32. Non-Hodgkin lymphomas (NHLs)
Tumors originating from
lymphoid tissues, mainly
of lymph nodes.
(originating in B-lymphocytes,
T-lymphocytesor natural killer
cells (NK))

33. Epidemiology
Incidence
•NHLoccurswithincreasing
frequency,withabout60.000
newcasesannuallyinthe
UnitedStates.
•AccordingtoTheNCCN
guidelinesIn2019,an
estimated74,200peoplewill
bediagnosedwithNHLandwill
beapproximately19,790
deathsduetothedisease.

34. Etiology
1-Pathogens (Infections).
2-Immunodeficiency or
immune dysregulation.
3-Treatment related.
4-Environmental factors
(Toxins).
5-genetics (Chromosomal
translocations).

35. WHO / Revised European American Lymphoma
( REAL) Classification
B-cell lymphomas( 80% -85%) T-cell lymphomas (15% -20%)
•Diffuse large B-cell lymphoma
•Follicular lymphoma
•Chronic lymphocytic leukemia /small
lymphocytic lymphoma
•Mantle cell lymphoma
•Marginal zone B-cell lymphomas
•Burkittlymphoma
•Lymphoplasmacyticlymphoma
(Waldenstrommacroglobulinemia)
•Hairy cell leukemia
•Primary central nervous system (CNS)
lymphoma
•Precursor T-lymphoblastic
lymphoma/leukemia
•Peripheral T-cell lymphomas
•Cutaneous T-cell lymphomas (mycosis
fungoides, Sezarysyndrome, and others)
•Adult T-cell leukemia/lymphoma
•AngioimmunoblasticT-cell lymphoma
•Extranodalnatural killer/T-cell
lymphoma, nasal type
•Enteropathy-associated intestinal T-cell
lymphoma (EATL)
•Anaplastic large cell lymphoma (ALCL)
•Peripheral T-cell lymphoma, unspecified

36. Non-Hodgkin lymphomas (NHLs)
•Common subtypes of B-cell non-Hodgkin lymphoma
according to NCCN Guidelines and WHO criteria
Subtype
Indolent
•Follicular lymphoma
•Marginal zone B-cell lymphomas
Aggressive
1-Mantle cell lymphoma
2-Diffuse large B-cell lymphoma
3-primary mediastinal large B-cell lymphoma
4-Gray zone lymphoma
Veryaggressive
•Burkittlymphoma
•Burkittlike lymphoma

37. Non-Hodgkin lymphomas (NHLs)
•Common subtypes of T-cell non-Hodgkin lymphoma
according to NCCN Guidelines and WHO criteria
Subtype
Indolent
CutenousT-cell lymphoma(CTCL)
Aggressive
1-Peripheral T-cell lymphomas (PTCL)
2-Extranodalnatural killer/T-cell lymphoma

38. The treatment of non-Hodgkin lymphoma (NHL)
varies greatly, depending on the following factors
•Tumor stage
•Phenotype (B-cell, T-cell or natural killer (NK)
cell/null-cell)
•Histology (i.e:low, intermediate, or high-grade)
•Symptoms
•Performance status (PS)
•Patient age
•Comorbidities

39. 1-B-Cell NHL
A. Indolent
I. Follicular Lymphoma

40. Indolent or Low‐grade NHL: FL
• The most common indolent NHL & the second
most common NHL
•Accounts for ~22% of all newly diagnosed cases
•Median age of diagnosis: 60 years old
Goal of therapy = palliation
•Few patients achieve cure with therapy
regardless of stage
•Many patients go years without needing
treatment

41. Indolent or Low‐grade NHL: FL
Indications for treatment
•Autoimmune cytopenia, recurrent infections,
symptomatic disease, threatened end organ
function, cytopenia, bulky disease, steady
progression over 6 months or patient
preference

42. Stage I & II, non‐bulky (Grade 1 –2)
•Radiotherapy preferred
•Watch and wait may be appropriate in selected
cases.
When patient has indications for treatment (in
order of preference):
1. BR (Category 1)
2. R-CHOP (Category 1)
3. R-CVP (Category 1)
4. Rituximab x 4 weekly doses

43. Treatment Protocols
•BRq28days x 6 cycles
B = bendamustine90 mg/m² IV D1 and 2 R =
rituximab 375 mg/m² IV D1
•R-CHOP(Rituximab -cyclophosphamide,
doxorubicin,vincristine, and prednisone)
•R-CVPq21days x 6 cycles R = rituximab 375
mg/m² IV D1 C = cyclophosphamide 750
mg/m2 IV D1 V = vincristine 1.4 mg/m² IV D1
P = prednisone 100 mg PO D1-5

44. Rituximab

45. Preparation
Rituximab (IV)
•Dilute to a final concentration of 1-4
mg/mL in normal saline or D5W.
•To avoid foaming, gently invert the
bag to mix the solution.
•Do not admix with other drugs.
•Administer rituximab through a
dedicated line.
•Keep vials refrigerated; do not freeze.
Protect from light.

46. Administration
Infusion rates:
•Consider a slower infusion rate or split dosing where
bulky disease present or WBC > 25 x 10⁹/L.
First infusion:
•Initial rate of 50 mg/h, then escalate rate in 50 mg/h
increments every 30 minutes, to a maximum of 400
mg/h (about 4.25 hours in total).
Subsequent infusions:
•Initial rate of 100 mg/h, then escalate rate in 100
mg/h increments every 30 minutes, to a maximum
of 400 mg/h as tolerated (about 3.25 hours in total).
•Published data suggest that a 90 minute infusion
(20% of the dose in the first 30 min then the
remaining 80% over 60 min)

47. Practice Tips
Rituximab & Hepatitis B Reactivation
•Baseline hepatitis panel
•Due to the possibility of viral reactivation, hepatitis B surface
antigen (HBsAg) and hepatitis B core antibody (HBcAb) should
performed on all patients receiving rituximab or other anti-CD20
monoclonal antibodies.
•Prophylactic antiviral therapyis recommended for any patient who
is HBsAgor HBcAbpositive and receiving anti-lymphoma therapy,
regardless of viral load or presence of clinical manifestation of HBV
reactivation.
•Entecaviris preferred over lamivudine due to concerns of resistance
•Monitor viral load via PCR
•Continue prophylaxis for up to 12 months after treatment
completed

48. Bendamustine

49. Bendamustine
•Bendamustineis a mechlorethamine
derivative containing a purine-like
benzimidazolering and is analkylating agent.
Contraindications
•Patients with CrCl< 40ml/min
•moderate/severe hepatic impairment
•Sever infections

50. Preparation
•BendamustineInjection: 100 mg
•DO NOT administer as an IV push or
bolus.
•Dilute with 20 ml SWFI to a final
concentration of 0.2 -0.6 mg/mL in 500
mL infusion bag of 0.9% sodium
chloride or 2.5% dextrose/0.45%
sodium chloride.
•Reconstituted solution must be
transferred to infusion bag within 30
minutesof reconstitution.
•CLL: 30 min infusion, NHL: 60 min infusion

51. Interactions
•CYP1A2 inhibitors (e.g. ciprofloxacin)
•CYP1A2 inducers (e.g. omeprazole, smoking)

52. Stage II, Bulky ‐Stage III, IV (Grade 1or 2)
•Indicated for treatment
•Treatment Protocols:
1-BR
2-R-CHOP
3-R-CVP

53. Treatment Protocols
•Elderly patients unable to tolerate more aggressive
therapy:
1.Rituximab 375 mg/m² x 4 ---weekly doses
(preferred)
2. Single-agent alkylators(chlorambucilor
cyclophosphamide) +/-rituximab

54. Stage I ‐ IV (Grade 3A or 3B)
R-CHOP (cyclophosphamide, doxorubicin,
vincristine, and prednisone)
R-CHOP q21days (6-8 cycles)
-Rituximab 375 mg/m² D1
C = cyclophosphamide 750 mg/m² IV D1
H = doxorubicin 50 mg/m² IV D1
O = vincristine 1.4 mg/m² IV D1 (cap at 2mg)
P = prednisone 100 mg PO D1-5

55. First-line consolidation
D (Rituximab every 2 months x 2 years)
(Category 1)
•First-line consolidation / extended therapy for
advanced disease after frontline therapy
•If initially treated with single-agent rituximab,
consolidation with rituximab 375 mg/m² every 8
weeks for 4 doses

56. Relapsed FL
•After progressing from first line
therapy, some patients will still
benefit from observation.
•Indications for treatment include
symptomatic disease
•Progressive disease should be
histologically documented to
exclude transformation to DLBCL

57. 1-B-Cell NHL
B. Aggressive
I.Diffuse Large B‐cell Lymphoma

58. Diffuse Large B‐cell Lymphoma
•Most common lymphoid neoplasm in adults
•Approximately 30% of all NHLs diagnosed annually
• The goal of treatment = CURE
•Survival is months if left untreated
•Newly diagnosed patients treated according to
the following categories:
–Stage I & II, non‐bulky disease
–Stage I & II, bulky disease
–Stage III & IV disease

59. Treatment of DLBCL
• The standard first‐line therapy:
R-CHOP (cyclophosphamide, doxorubicin, vincristine, and
prednisone).
R-CHOP q21days
R = rituximab 375 mg/m² IV D1
C = cyclophosphamide 750 mg/m² IV D1
H = doxorubicin 50 mg/m² IV D1
O = vincristine 1.4 mg/m² IV D1 (cap at 2mg)
P = prednisone 100 mg PO D1-5
Doxorubicin may be given as continuous IV infusion (CIVI)
to decrease risk for cardiotoxicity

60. Treatment Overview of DLBCL
• Treatment duration dependent upon stage and
size
Stage I & II, non‐bulky disease
—R‐CHOP x 3 cycles + radiation therapy (RT)
Stage I & II, bulky disease
—R‐CHOP x 6 cycles ±RT
Stage III & IV disease
—R‐CHOP x 6 cycles ±RT
• No role for maintenance rituximab

61. DLBCL in the Elderly
Poor LVEF or frail
• R‐CEPP (Rituximab, cyclophosphamide, etoposide, procarbazineand
prednisone)
• R‐CDOP (R-CEOP = rituximab, cyclophosphamide, etoposide, vincristine and
prednisone)
• DA‐R‐EPOCH (Dose adjusted)(rituximab, etoposide, prednisone, vincristine,
cyclophosphamide and doxorubicin)
(doxorubicin maintained at base dose)
• R‐CEOP (rituximab, cyclophosphamide, etoposide, vincristine and
prednisone )
• R‐mini‐CHOP
Patients >80 years of age with co‐morbidities
• R‐mini‐CHOP
• R‐GCVP (rituximab, gemcitabine, cyclophosphamide, vincristine and
prednisolone. )

62. CNS Involvement in DLBLC
• Risk of CNS involvement is low
but possible
–Prophylaxis: IT MTX or
cytarabine
–Treatment: Systemic MTX +/‐
IT MTX or cytarabine

63. Relapsed DLBCL
• 40% of patients still experience early treatment failure
–Defined as refractory disease or relapse after
initial response to chemotherapy
—Particularly after treatment with R‐CHOP
• The goal of treatment = CURE
–Chemotherapy + autologous hematopoietic
stem cell transplant (HSCT)
–Chemotherapy alone
(Chemotherapy regimens include R‐Gem/Ox, B‐R,
lenalidomide+ rituximab)

64. 1-B-Cell NHL
C. Very Aggressive
I. BurkittLymphoma

65. BurkittLymphoma
• Extremely aggressive B‐cell lymphoma
–Fastest growing human tumor
–Patients will die within weeks if left
untreated
• Diagnosed in children and adults
–Uncommon in adults

66. Treatment Overview of BL
Goal of treatment = CURE
CHOP or R‐CHOP is NOT ADEQUATE TREATMENT
•The difference between low-risk disease and high-risk disease is the
number of chemotherapy cycles that can be given.
• Treatment options include:
–CALGB 10002 regimen
–CODOX‐M +/‐ rituximab x 3 cycles
–DA‐R‐EPOCH (minimum of 3 cycles, with 1 additional cycle after CR)
–R‐HyperCVADalternating with R‐Methotrexate/Ara‐C x 6 Cycles
All BL patient should receive intrathecal prophylaxis in addition to the specific
chemotherapy regimen

67. CODOX‐M +/‐ rituximab
•Day 1:Cyclophosphamide 800mg/m
2
IV + doxorubicin 40mg/m
2
IV
•Days 2–5:Cyclophosphamide 200mg/m
2
/day IV
•Days 1 and 3:Cytarabine70mg intrathecally
•Days 1 and 8:Vincristine 1.5mg/m
2
IV
•Day 10:Methotrexate 1,200mg/m
2
IV over 1 hour, then 240mg/m
2
/hour
continuous IV infusion for the next 23 hours
•Day 11:Leucovorin192mg/m
2
IV 36 hours after initiation of MTX,
followed by leucovorin12mg/m
2
IV every 6 hours until MTX level <5x10
–
8
M
•Day 13:G-CSF 5µg/kg SC daily beginning 24 hours after initiation of
leucovorinuntil absolute granulocyte count ≥1x10
9
/L
•Day 15:Methotrexate 12mg intrathecally
•Day 16:Leucovorin15mg orally given 24 hours after intrathecal MTX,±
•Day 1:Rituximab 375mg/m
2
IV.
•Repeat cycle every 21 days for 3 cycles.

68. Relapsed BL
• No definitive second‐line regimens exist
• Clinical trial preferred
• Limited data with:
–DA‐R‐EPOCH
–R‐IVAC
–R‐ICE
–R‐GDP

69. 2-T-Cell NHL
A-Cutaneous T-cell lymphoma

70. Cutaneous T‐cell Lymphoma
•Early‐stage disease –skin directed therapies
–Topical corticosteroids, topical chemotherapy,
local radiation or topical retinoids
•Systemic therapies reserved for advanced
stages or failure of multiple skin‐directed
therapies
•The administration of sequential, single-agent
chemotherapy is preferred over combination
regimens.

71. Alemtuzumab(Cambath®)
•Anti-CD52 monoclonal antibody
•Escalate to 30 mg IV or subq3 times per week
for up to 12 weeks (usually start with 3 mg for
dose 1, 10 mg for dose 2, 30 mg for dose 3.
•Toxicities: Cytopenias, infusion reactions,
infections (CMV), nausea, emesis, fatigue.

72. Supportive Care of CTCL
• Pruritis
–Topical moisturizers & emollients
–Systemic antihistamines, gabapentin
–Refractory symptoms: aprepitant, naloxone,
mirtazapine or SSRIs
• Infection prophylaxis (Staph aureus)

73. 2-T-Cell NHL
B-Peripheral T-cell lymphoma

74. Peripheral T‐cell Lymphoma
• Arise from mature T‐cells of
post‐thymicorigin
• Relatively uncommon –10% of
NHL cases
• Prognosis is poor compared to
B‐cell NHL
–Lower response rates and less
durable responses to standard
combination chemotherapy

75. Treatment: PTCL
• Anthracycline‐based chemotherapy is
backbone
–CHOP ±radiotherapy
–CHOEP‐21
–DA‐EPOCH
• Rituximab is not given –T‐cells are typically
not CD20 (+)

76. THANK YOU 