This document provides an overview of Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). It discusses the definition, epidemiology, risk factors, signs/symptoms, diagnosis, classification, and treatment of HL. It also discusses the overview, epidemiology, etiology, classification, and treatment of several common subtypes of NHL, including follicular lymphoma, diffuse large B-cell lymphoma, and mantle cell lymphoma. Treatment options discussed include chemotherapy regimens like ABVD, R-CHOP, radiotherapy, immunotherapy with rituximab, and newer targeted therapies.
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Hodgkin Lymphoma and Non-Hodgkin Lymphoma Milestones
1. The lime green ribbon cancer milestones and
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. Follicular Lymphoma
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).
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
• Early adulthood (aged 20–39 years) (most often) or
late adulthood (aged 65 years and older) (less
often).
• Male Gender.
• Having a previous infection with the Epstein-Barr
virus in the teenage years or early childhood.
• Having a first-degree relative with HL.
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.
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(+)
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 subclassified into 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 fevers and weight
loss.
17. Treatment Overview of CHL
• Treatment duration dependent upon stage and
size
– Stage IA & IIA favorable
—ABVD x 2 cycles + 20 Gy involved 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 Gy ISRT
–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
• DOXOrubicin 25 mg /m² IV Days 1 & 15
• Bleomycin 10 units /m² IV Days 1 & 15
• VinBLAStine 6 mg /m² IV Days 1 & 15
• Dacarbazine 375 mg /m² IV Days 1 & 15
Repeated every 28 days
21. Supportive Care Issues with ABVD
Bleomycin pulmonary toxicity (BPT)
– Baseline pulmonary function tests
should be performed at baseline and
periodically during treatment
—More common in patients with
older age, co‐administration of
pulmonary irradiation and total doses
> 400 units
—BPT also associated with use of
growth factor support
22. Supportive Care Issues with ABVD
– Neutropenia is not an
indication for reduction in dose
intensity
— DOXOrubicin and vinblastine
should be adjusted according
to the liver function
— Bleomycin should be
adjusted according to the renal
functions
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
Brentuximab vedotin alone 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
27. Administration
• DO NOT administer as an IV push or bolus.
• Reconstitute each 50 mg vial with 10.5 mL of SWFI to
yield a single-use 5 mg/mL solution.
• Gently swirl the vial to aid dissolution; do not shake
after reconstitution
• Add to an infusion bag containing at least 100ml
volume to achieve a final concentration of 0.4-
1.8 mg/mL and use within 24 hours.
• Can be diluted into normal saline, 5% dextrose or
lactated ringer's injection.
• Infuse IV over 30 min.
28. Interactions
• CYP3A4 inducers ● CYP3A4 inhibitors
• CYP3A4 inducers (i.e. phenytoin, rifampin, dexamethasone, carbamazepine,phenobarbital, St.
↓ exposure to MMAE (up to 46%) ↑ metabolism of MMAE Caution; monitor for efficacy
• CYP3A4 inhibitors (i.e. ketoconazole, clarithromycin, ritonavir, fruit or juice from
grapefruit, Seville oranges or starfruit)
30. Nodular Lymphocyte‐Predominant HD
• No preferred chemotherapy regimen exists
• ABVD is often used based on data with CHL
• Consistently express the CD20 antigen ‐
• Rituximab can be considered as single‐agent
therapy or in combination with multidrug
chemotherapy regimens
32. Non-Hodgkin lymphomas (NHLs)
Tumors originating from
lymphoid tissues, mainly
of lymph nodes.
(originating in B-lymphocytes,
T-lymphocytes or natural killer
cells (NK))
33. Epidemiology
Incidence
• NHL occurs with increasing
frequency, with about 60.000
new cases annually in the
United States.
• According to The NCCN
guidelines In 2019, an
estimated 74,200 people will
be diagnosed with NHL and will
be approximately 19,790
deaths due to the disease.
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
Very aggressive
• Burkitt lymphoma
• Burkitt like lymphoma
37. Non-Hodgkin lymphomas (NHLs)
• Common subtypes of T-cell non-Hodgkin lymphoma
according to NCCN Guidelines and WHO criteria
Subtype
Indolent
Cutenous T-cell lymphoma (CTCL)
Aggressive
1- Peripheral T-cell lymphomas (PTCL)
2- Extranodal natural 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
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
• BR q28days x 6 cycles
B = bendamustine 90 mg/m² IV D1 and 2 R =
rituximab 375 mg/m² IV D1
• R-CHOP (Rituximab -cyclophosphamide,
doxorubicin, vincristine, and prednisone)
• R-CVP q21days 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
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 therapy is recommended for any patient who
is HBsAg or HBcAb positive and receiving anti-lymphoma therapy,
regardless of viral load or presence of clinical manifestation of HBV
reactivation.
• Entecavir is preferred over lamivudine due to concerns of resistance
• Monitor viral load via PCR
• Continue prophylaxis for up to 12 months after treatment
completed
49. Bendamustine
• Bendamustine is a mechlorethamine
derivative containing a purine-like
benzimidazole ring and is an alkylating agent.
Contraindications
• Patients with CrCl < 40ml/min
• moderate/severe hepatic impairment
• Sever infections
50. Preparation
• Bendamustine Injection: 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
minutes of reconstitution.
• CLL: 30 min infusion, NHL: 60 min infusion
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 (chlorambucil or
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
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, procarbazine and
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. Burkitt Lymphoma
65. Burkitt Lymphoma
• 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‐HyperCVAD alternating 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/m2 IV + doxorubicin 40mg/m2 IV
• Days 2–5: Cyclophosphamide 200mg/m2/day IV
• Days 1 and 3: Cytarabine 70mg intrathecally
• Days 1 and 8: Vincristine 1.5mg/m2 IV
• Day 10: Methotrexate 1,200mg/m2 IV over 1 hour, then 240mg/m2/hour
continuous IV infusion for the next 23 hours
• Day 11: Leucovorin 192mg/m2 IV 36 hours after initiation of MTX,
followed by leucovorin 12mg/m2 IV every 6 hours until MTX level <5 x10–
8 M
• Day 13: G-CSF 5µg/kg SC daily beginning 24 hours after initiation of
leucovorin until absolute granulocyte count ≥1 x 109/L
• Day 15: Methotrexate 12mg intrathecally
• Day 16: Leucovorin 15mg orally given 24 hours after intrathecal MTX, ±
• Day 1: Rituximab 375mg/m2 IV.
• Repeat cycle every 21 days for 3 cycles.
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 subq 3 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)
74. Peripheral T‐cell Lymphoma
• Arise from mature T‐cells of
post‐thymic origin
• 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 (+)