i3 Health is pleased to make the Clinician's Resource Guide from this activity available for use as a nonaccredited self-study or teaching resource.

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Clinical Tools and Resources for
Self-Study and Patient Education
HODGKIN LYMPHOMA
REFERENCE GUIDE
The clinical tools and resources contained herein are provided as educational adjuncts to the
CME/CE-certified online activity Challenges and Opportunities in Hodgkin Lymphoma. To
access the activity and earn CME/CE credit, visit:
https://www.i3Health.com/Hodgkin-Lymphoma
CONTENTS
I: Types of Classical Hodgkin Lymphoma (cHL)............................................................... 2
II: Hodgkin Lymphoma Staging ....................................................................................... 3
III: International Prognostic Score.................................................................................... 4
IV: Deauville Criteria ........................................................................................................ 5
V: cHL: Refractory Disease (Second-Line Therapy).......................................................... 6
VI: cHL: Suspected Relapse ............................................................................................. 7
VII: Generic and Brand Names of HL Agents .................................................................. 8
VIII: Systemic Therapy Options: Relapsed/Refractory cHL ............................................ 10
IX: Therapeutic Options Depending on Treatment Outcome....................................... 11
X: Checkpoint Inhibitors and Guidelines for Use........................................................... 12
XI: Patient Education on Adverse Events....................................................................... 13

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I: TYPES OF CLASSICAL HODGKIN LYMPHOMA (CHL)
Type Description
Nodular sclerosing
• Most common type of Hodgkin lymphoma
• Usually found in early stage when lymph nodes in neck become
enlarged
Mixed cellularity
• Often affects a few groups of lymph nodes
• Contains a mixture of different types of lymphocytes and other blood
cells
Lymphocyte rich
• Very small
• Many lymphocytes but very few Reed-Sternberg cells seen under
microscope
Lymphocyte depleted
• Very rare
• Lymph nodes contain a lot of fibrous tissue with few Reed-Sternberg
cells
• Alternately, fibrous tissue could contain a lymphocyte called reticular
lymphocyte and many Reed-Sternberg cells
Cancer Research UK (2018). Hodgkin lymphoma. Available at: https://www.cancerresearchuk.org/about-cancer/hodgkin-
lymphoma/types

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II: HODGKIN LYMPHOMA STAGING
Stage Criteria
Stage I
• Involvement of a single lymph node region or
• Localized involvement of a single extralymphatic organ or site
Stage II
• Involvement of ≥2 lymph node regions on the same side of the diaphragm or
• Localized involvement of a single associated extralymphatic organ or site and its
regional lymph node(s)
• May or may not include involvement of other lymph node regions on the same
side of the diaphragm
Stage III
• Involvement of lymph node regions on both sides of the diaphragm, possibly also
accompanied by localized involvement of an associated extralymphatic organ or
site via involvement of the spleen or by both
Stage IV
• Disseminated (multifocal) involvement of one or more extralymphatic organs, with
or without associated lymph node involvement, or
• Isolated extralymphatic organ involvement with distant (nonregional) nodal
involvement
National Comprehensive Cancer Network (2018). Clinical Practice Guidelines in Oncology: Hodgkin lymphoma. Version
3.2018. Available at: https://www.nccn.org

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III: INTERNATIONAL PROGNOSTIC SCORE
International Prognostic Score: 1 Point per Factor (Advanced Disease)
• Albumin <4 g/dL
• Hemoglobin <10.5 g/dL
• Male
• Age ≥45 years
• Stage IV disease
• Leukocytosis (white blood cell count ≥15,000/mm3
)
• Lymphocytopenia (lymphocyte count <8% of white blood cell count and/or lymphocyte
count <600/mm3
)
National Comprehensive Cancer Network (2018). Clinical Practice Guidelines in Oncology: Hodgkin lymphoma. Version
3.2018. Available at: https://www.nccn.org

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IV: DEAUVILLE CRITERIA
Deauville Criteria: PET 5-Point Scale
Score PET/CT scan result
1 No uptake
2 Uptake not higher than mediastinum
3 Uptake higher than mediastinum but not higher than liver
4 Uptake moderately higher than liver
5 Uptake markedly higher than liver and/or new lesions
X New areas of uptake unlikely to be related to lymphoma
PET = positron emission tomography; CT = computed tomography.
National Comprehensive Cancer Network (2018). Clinical Practice Guidelines in Oncology: Hodgkin lymphoma. Version
3.2018. Version Available at: https://www.nccn.org

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V: CHL: REFRACTORY DISEASE (SECOND-LINE THERAPY)
Deauville
Score
Additional Therapy Maintenance Therapy
1-3
• High-dose therapy and autologous
stem cell rescue (HDT/ASCR) ± RT
(category 1)
• If HDT/ASCR is contraindicated:
observe ± RT
• Observe
• Brentuximab vedotin for 1 year for
patients at high risk of relapse
4
• HDT/ASCR ± RT
• RT
• Subsequent systemic therapy ± RT
• Brentuximab vedotin for 1 year for
patients at high risk of relapse
5
• RT
• Subsequent systemic therapy ± RT
• Autologous or allogeneic stem cell
transplant if patient responds to
secondary therapy
RT = radiotherapy.
National Comprehensive Cancer Network (2018). Clinical Practice Guidelines in Oncology: Hodgkin lymphoma. Version
3.2018. Available at: https://www.nccn.org

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VI: CHL: SUSPECTED RELAPSE
ISRT = involved site radiation therapy.
National Comprehensive Cancer Network (2018). Clinical Practice Guidelines in Oncology: Hodgkin lymphoma. Version
3.2018. Available at: https://www.nccn.org

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VII: GENERIC AND BRAND NAMES OF HL AGENTS
Generic Name Brand Name(s)
Bendamustine BendekaÒ
Bleomycin BlenoxaneÒ
Brentuximab vedotin AdcectrisÒ
Carboplatin ParaplatinÒ
Carmustine BiCNUÒ
Cisplatin PlatinolÒ
Cyclophosphamide CytoxanÒ
Cytarabine Cytosar-UÒ
, DepoCytÒ
Dexamethasone DecadronÒ
Doxorubicin AdriamycinÒ
, RubexÒ
Etoposide EtopophosÒ
, VePesidÒ
ToposarÒ
Everolimus AfinitorÒ
, Afinitor DisperzÒ
, ZortressÒ
Gemcitabine GemzarÒ
Ifosfamide IfexÒ
Lenalidomide RevlimidÒ
Liposomal doxorubicin DoxilÒ
Mechlorethamine MustargenÒ
Melphalan AlkeranÒ
Mesna MesnexÒ
Methylprednisolone Depo-MedrolÒ
, Solu-MedrolÒ
Mitoxantrone NovantroneÒ
Nivolumab OpdivoÒ
Pembrolizumab KeytrudaÒ
Prednisone DeltasoneÒ
, RayosÒ
, Prednisone IntensolÒ

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Generic Name Brand Name(s)
Procarbazine MatulaneÒ
Rituximab RituxanÒ
Vinblastine VelbanÒ
Vincristine MarqiboÒ
, Vincasar PFSÒ
Vinorelbine NavelbineÒ

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VIII: SYSTEMIC THERAPY OPTIONS: RELAPSED/REFRACTORY CHL
Treatments Subsequent Systemic Therapy Options
• Brentuximab vedotin, alone or in combination
with one of the second-line regimens below:
o DHAP (dexamethasone/high-dose
cytarabine/ cisplatin)
o ESHAP (etoposide/ methylprednisolone/
high-dose cytarabine/ cisplatin)
o Bendamustine/ gemcitabine/vinorelbine
o GVD (gemcitabine/ vinorelbine/liposomal
doxorubicin)
o ICE (ifosfamide/ carboplatin/etoposide)
o IGEV (ifosfamide/ gemcitabine/vinorelbine)
• Bendamustine
• C-MOPP
(cyclophosphamide/vincristine/procarbazine
/prednisone)
• Everolimus
• GCD (gemcitabine/ carboplatin/
dexamethasone)
• Lenalidomide
• MINE (mesna/ifosfamide/
mitoxantrone/etoposide)
• Mini-BEAM (carmustine/etoposide/
cytarabine/melphalan)
• Nivolumab
• Pembrolizumab
National Comprehensive Cancer Network (2018). Clinical Practice Guidelines in Oncology: Hodgkin lymphoma. Version
3.2018. Available at: https://www.nccn.org

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IX: THERAPEUTIC OPTIONS DEPENDING ON TREATMENT OUTCOME
Protocol After Second-Line Treatment
Treatment working well
• Stem cell transplant
• Radiotherapy if unable to have stem cell transplant
• Observation: “watch and wait”
Treatment working less than
desired
• Stem cell transplant
• Radiotherapy if unable to have stem cell transplant
• Chemo regimen not used previously, possibly with added
radiotherapy
Treatment working poorly
• Radiotherapy
• Chemo regimen not used previously, possibly with added
radiotherapy
*Patients receiving a transplant should not be administered chemotherapy with mechlorethamine, procarbazine, carmustine,
or melphalan, as these drugs may result in a poor collection of stem cells. Radiation therapy may be administered with the
transplant. TLI (total lymphoid irradiation) is radiation given to all lymphatic tissue.
National Comprehensive Cancer Network (2018). Clinical Practice Guidelines in Oncology: Hodgkin lymphoma. Version
3.2018. Available at: http://www.nccn.org

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X: CHECKPOINT INHIBITORS AND GUIDELINES FOR USE
Checkpoint Inhibitors (CPI)
Nivolumab
Indicated for the treatment of adult patients with cHL that has
relapsed or progressed after
• Autologous HSCT and brentuximab vedotin or
• ≥3 lines of systemic therapy, one of which is autologous HSCT
Pembrolizumab
Indicated for the treatment of adult and pediatric patients with
• Refractory cHL or
• Relapse after ≥3 prior lines of therapy
Guidelines for CPI Use
General Indications for Use
• Patients with refractory cHL who are transplant-ineligible based
on comorbidity or failure of first salvage chemotherapy
• Patients who have relapsed after autologous HSCT ±
brentuximab vedotin
Recommendations
Following Allogeneic
Transplant
• Patients can receive either nivolumab or pembrolizumab
• Caution is advised due to increased risk of GVHD and other
immunological complications
HSCT = hematopoietic stem cell transplantation; GVHD = graft-versus-host disease.
National Comprehensive Cancer Network (2018). Clinical Practice Guidelines in Oncology: Hodgkin lymphoma. Version
3.2018. Available at: https://www.nccn.org

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XI: PATIENT EDUCATION ON ADVERSE EVENTS
Neutropenia Scale
Mild ANC <1,500 cells/mm3
Moderate ANC <1,000 cells/mm3
Severe ANC <500 cells/mm3
ANC = absolute neutrophil count.
Neutropenia
Signs/symptoms
• Fever ³100.5°F
• Chills or sweating
• Sore throat, sores in the mouth, or toothache
• Abdominal pain
• Pain near the anus
• Frequent, painful, or burning urination
• Diarrhea or sores around the anus
• Cough or shortness of breath
• Any redness, swelling, or pain (especially around a cut, wound, or catheter)
• Unusual vaginal discharge or itching
Causes
• Some types of chemotherapy
• Cancers that directly affect bone marrow
• Cancer that has spread
• Radiation therapy to several parts of the body or to bones in the pelvis,
legs, chest, or abdomen
• Factors increasing neutropenia risk:
o Age ≥70
o Lowered immune system from other causes, such as HIV infection or
organ transplant
Treatment
• Antibiotics
• Hospitalization
Lustberg M (2012). Management of neutropenia in cancer patients. Clin Adv Hematol Oncol, 10(12):825-826.
American Society of Clinical Oncology (2018). Neutropenia. Available at: https://www.cancer.net/navigating-cancer-
care/side-effects/neutropenia

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Thrombocytopenia
Signs/symptoms • Prolonged bleeding, especially from minor cuts
• Bleeding from mouth or nose, especially nosebleeds or bleeding when
brushing teeth
• Purpura (bruising of the skin)
• Petechiae (small red or purple dots on skin)
• Blood in urine or stool
• Headaches/neurological symptoms (rare)
Causes • Cancer types, such as lymphoma, which destroy blood stem cells and
damage bone marrow
• Chemotherapy
Treatment • Corticosteroids
• Immunoglobulins/rituximab
• Splenectomy
National Heart, Lung, and Blood Institute (2018). Thrombocytopenia. Available at: https://www.nhlbi.nih.gov/health-
topics/thrombocytopenia