Lymphoma: Diagnosis and Treatment

William D. Lewis; Seth Lilly; Kristin L. Jones

WILLIAM D. LEWIS, MD, SETH LILLY, PharmD, BCPS, AND KRISTIN L. JONES, PA-C

Am Fam Physician. 2020;101(1):34-41

Patient information: See related handout on lymphoma, written by the authors of this article.

Author disclosure: No relevant financial affiliations.

Article Sections

Lymphoma is a group of malignant neoplasms of lymphocytes with more than 90 subtypes. It is traditionally classified broadly as non-Hodgkin or Hodgkin lymphoma. Approximately 82,000 new U.S. patients are diagnosed with lymphoma annually. Any tobacco use and obesity are major modifiable risk factors, with genetic, infectious, and inflammatory etiologies also contributing. Lymphoma typically presents as painless adenopathy, with systemic symptoms of fever, unexplained weight loss, and night sweats occurring in more advanced stages of the disease. An open lymph node biopsy is preferred for diagnosis. The Lugano classification system incorporates symptoms and the extent of the disease as shown on positron emission tomography/computed tomography to stage lymphoma, which is then used to determine treatment. Chemotherapy treatment plans differ between the main subtypes of lymphoma. Non-Hodgkin lymphoma is treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with or without rituximab (R-CHOP), bendamustine, and lenalidomide. Hodgkin lymphoma is treated with combined chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), Stanford V (a chemotherapy regimen consisting of mechlorethamine, doxorubicin, vinblastine, vincristine, bleomycin, etoposide, and prednisone), or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) with radiotherapy. Subsequent chemotherapy toxicities include neuropathy, cardiotoxicity, and secondary cancers such as lung and breast, and should be considered in the shared decision-making process to select a treatment regimen. Once remission is achieved, patients need routine surveillance to monitor for complications and relapse, in addition to age-appropriate screenings recommended by the U.S. Preventive Services Task Force. Patients should receive a 13-valent pneumococcal conjugate vaccine followed by a 23-valent pneumococcal polysaccharide vaccine at least eight weeks later with additional age-appropriate vaccinations because lymphoma is an immunosuppressive condition. Household contacts should also be current with their immunizations.

Lymphoma represents a heterogeneous group of malignant neoplasms of lymphocytes, which can involve lymphatic tissue, bone marrow, or extranodal sites. The World Health Organization’s classification system identifies more than 90 different subtypes (Table 1).^1,2 The initial stratification is derived from B-cell, T-cell, or natural killer cell origin. Further classification of distinct lymphoma subtypes is beyond the scope of this article; however, they are ultimately each defined by morphology, immunopheno-type, genetic, molecular, and clinical features.^1,3 This article will focus on the types of lymphoma traditionally classified as non-Hodgkin or Hodgkin.

Clinical recommendation	Evidence rating	Comments
Open lymph node biopsy should be used to definitively diagnose lymphoma.^14,15	C	Expert opinion and clinical review articles
Positron emission tomography/computed tomography should be used to determine the staging of the lymphoma.¹⁹	C	Expert opinion and clinical review article
Patients with lymphoma should have intensive follow-up surveillance for the first two years following remission.⁴⁰	C	Expert opinion and clinical review article
A 13-valent pneumococcal conjugate vaccine (Prevnar 13), followed by a 23-valent pneumococcal polysaccharide vaccine (Pneumovax 23) at least eight weeks later and then again at least five years later, should be administered following lymphoma treatment.^44,45	C	Expert opinion and guidelines

Lymphoma subtype	Incidence per 100,000	Five-year survival
Hodgkin	2.8	85.7%
Non-Hodgkin B-cell lymphomas
Burkitt	0.4	64.1%
Diffuse large B cell	7.2	63.2%
Follicular	3.5	88.4%
Marginal zone	2.2	90.3%
Precursor B cell	1.5	68.9%
Non-Hodgkin T-cell and natural killer cell lymphomas
Mycosis fungoides	0.6	90.9%
Peripheral T-cell	1.2	58.4%

Epidemiology

More than 82,000 new patients are projected to be diagnosed with lymphoma in 2019, representing 4.7% of all new cancer cases in the United States. The current five-year survival rate for non-Hodgkin lymphoma is 72.0%, and for Hodgkin lymphoma it is 86.6%. Almost 21,000 people are projected to die from lymphoma in 2019, representing 3.5% of all cancer deaths. Incidence of non-Hodgkin lymphoma is higher in men and whites, and it increases with age. The median age of patients at diagnosis of non-Hodgkin lymphoma is 67 years, and the median age at death is 76. Hodgkin lymphoma is most commonly diagnosed at 20 to 34 years of age; however, the median age at death is 68 because of the higher survival rate among younger patients.^2,4

Risk Factors

Genetic, infectious, and inflammatory etiologies increase the risk of lymphoma. First-degree relatives of patients with non-Hodgkin lymphoma and Hodgkin lymphoma have a respective 1.7-fold and 3.1-fold increased risk of developing lymphoma. A family history of a specific subtype of lymphoma is associated with developing that same subtype.⁵ There are three main mechanisms through which infection increases lymphoma risk: direct transformation of lymphocytes, immunosuppression, and chronic antigenic stimulation⁶ (Table 2^6,7). Rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, dermatomyositis, and celiac disease are inflammatory conditions that increase the risk of lymphoma through disease-specific causes and the chronic use of immunosuppressive medications.⁸

Mechanism	Infection	Lymphoma type
Direct lymphocyte transformation	Epstein-Barr virus	Burkitt, non-Hodgkin, Hodgkin
Direct lymphocyte transformation	Human T-lymphotropic virus type 1	T-cell leukemia
Immunosuppression	HIV	Hodgkin, non-Hodgkin
Chronic antigenic stimulation	Helicobacter pylori Chlamydia psittaci Campylobacter jejuni Campylobacter coli Borrelia burgdorferi	Non-Hodgkin (mucosa-associated lymphoid tissue)
Chronic antigenic stimulation	Hepatitis C	Splenic marginal zone

Modifiable risk factors include current or former tobacco use⁹ and obesity (body mass index of 30 kg per m² or higher).¹⁰ Breast implants and long-term pesticide exposure have also been associated with non-Hodgkin lymphoma.^11–13

Clinical Presentation

Lymphoma commonly presents as painless adenopathy. Adenopathy can wax and wane over years in indolent presentations or involve rapidly progressive adenopathy in more aggressive subtypes. Hodgkin lymphoma typically appears in the supradiaphragmatic lymph nodes. Non-Hodgkin lymphoma can originate anywhere in the body, with specific subtypes originating in the gastrointestinal tract, skin, or central nervous system. Systemic symptoms of fever, unexplained weight loss, and night sweats occur in a subset of patients with more advanced disease. Lymphoma spreads to extranodal sites by direct invasion or by hematogenous spread to the spleen, liver, lungs, or bone marrow.^14,15 High-grade lymphomas can present as oncologic emergencies because of the structural compression from the enlarging tumor, including superior vena cava syndrome, malignant epidural spinal cord compression, or malignant pericardial effusion.¹⁶ Paraneoplastic syndromes are rare with lymphoma, occurring as paraneoplastic cerebellar degeneration in Hodgkin lymphoma and as dermatomyositis and polymyositis in Hodgkin and non-Hodgkin lymphomas.¹⁷

Diagnosis

The diagnosis of lymphoma is made using an open lymph node biopsy, based off morphology, immunohistochemistry, and flow cytometry.³ Although fine-needle aspiration and core needle biopsy are often part of the initial evaluation of any adenopathy, neither will provide adequate tissue for the diagnosis of lymphoma because of the need to verify Hodgkin lymphoma via the presence of Reed-Sternberg cells.^15,18

Staging

The Ann Arbor staging system was initially developed in 1971 for Hodgkin lymphoma, and was later adapted for non-Hodgkin lymphoma. The Lugano classification system further modified staging by incorporating positron emission tomography/computed tomography (PET-CT) results to determine the staging of the lymphoma (Table 3¹⁹). PET-CT is used for fluorodeoxyglucose-avid lymphoma subtypes, with symptoms alone being used for staging the remaining subtypes. The new staging system incorporates two symptom-based classifications: A (absence of symptoms) and B (presence of fever, weight loss, and night sweats) for Hodgkin lymphoma. A bone marrow biopsy is now recommended only for diffuse large B-cell lymphoma with a negative PET-CT result.¹⁹

Stage*	Description of disease from positron emission tomography/computed tomography results
I	Single nodal group or single extralymphatic lesion
II†	Multiple nodal groups on same side of diaphragm or with limited contiguous extralymphatic involvement
III	Multiple nodal groups on both sides of the diaphragm; may involve the spleen
IV	Noncontiguous extralymphatic involvement

Prognosis

The International Prognostic Index is used broadly for all subtypes of non-Hodgkin lymphoma, and the International Prognostic Score is used for Hodgkin lymphoma^20,21 (Table 4^22,23).

Non-Hodgkin	Hodgkin
International Prognostic Index	International Prognostic Score
Criteria	Criteria
Age > 60	Age > 45
Elevated serum lactate dehydrogenase	Male sex
Eastern Cooperative Oncology	Serum albumin concentration < 4.0 g per dL (40 g per L)
Group performance status ≥ 2*	Hemoglobin concentration < 10.5 g per dL (105 g per L)
Ann Arbor stage III or IV disease†	Hemoglobin concentration < 10.5 g per dL (105 g per L)
Extranodal sites > 1	Ann Arbor stage IV disease† Leukocytosis (≥ 15,000 μL [15 × 10⁹ white blood cells per L]) Lymphopenia (< 600 lymphocytes per μL [0.6 × 109 per L], or < 8% of total white blood cell count)
Total score____	Total score____
Five-year overall survival rate based on number of criteria from International Prognostic Index/Score
Score 0 or 1 = 73%	Score 0 = 89%
Score 2 = 51%	Score 1 = 90%
Score 3 = 43%	Score 2 = 81%
Score 4 or 5 = 26%	Score 3 = 78%
	Score 4 = 61%
	Score ≥ 5 = 56%

Treatment

Treatment of lymphoma consists of chemotherapy alone or in combination with radiotherapy.²⁴ Radiotherapy alone is not recommended.²⁵ Toxicity from radiotherapy can lead to serious long-term complications such as secondary cancers in the irradiated area, including breast or lung cancers.²⁵ Additionally, patients receiving chemotherapy can subsequently develop breast or lung cancers, melanoma, or acute myeloid leukemia.^26,27 Patients who are older than 60 years at diagnosis have worse outcomes, regardless of the staging. The National Comprehensive Cancer Network (NCCN) recommends avoiding certain chemotherapeutic agents in patients older than 60 years. The physician should focus on shared decision-making when discussing treatment options with all patients, but particularly for those older than 60 years, including whether the patient should pursue treatment.²⁵

The standard treatment for Hodgkin lymphoma is ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine [Velban], and dacarbazine), but other regimens such as the Stanford V (doxorubicin, vinblastine, mechlorethamine, etoposide [Toposar], vincristine, bleomycin, and prednisone) and escalated-BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine [Matulane], and prednisone) can be used.^24–28 Treatment for non-Hodgkin lymphoma varies depending on the histology, but often uses treatments such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with or without rituximab (Rituxan; R-CHOP), a monoclonal antibody specific for CD20-positive B lymphocytes.²⁹ Other medications such as bendamustine (Bendeka), an alkylating agent, and lenalidomide (Revlimid) are also used in many non-Hodgkin lymphoma treatments.^30,31 Common complications of these therapies are listed in Table 5.^{25–27,29–36}

Therapy	Regimen	Short-term complications	Long-term complications
Hodgkin lymphoma
ABVD	Doxorubicin (Adriamycin)	Nausea/vomiting Alopecia Neutropenia Neuropathy Bleomycin-induced pulmonary toxicity	Cardiotoxicity (heart failure) Neuropathy Pulmonary fibrosis Increased risk of myocardial infarction
	Bleomycin
	Vinblastine (Velban)
	Dacarbazine
Stanford V	Doxorubicin	Nausea/vomiting Fatigue Pulmonary toxicity Neuropathy	Neuropathy Pulmonary fibrosis Cardiotoxicity Rarely solid secondary malignancies of breast, lung, and skin
	Vinblastine
	Mechlorethamine
	Etoposide (Toposar)
	Vincristine
	Bleomycin
	Prednisone
Escalated-BEACOPP	Bleomycin	Anemia Leukopenia Thrombocytopenia Nausea/vomiting Infection Disulfiram reaction between ethanol and procarbazine	Acute myeloid leukemia Sterility/infertility
	Etoposide
	Doxorubicin (Adriamycin)
	Cyclophosphamide
	Vincristine (Oncovin)
	Procarbazine (Matulane)
	Prednisone
Non-Hodgkin lymphoma
CHOP	Cyclophosphamide	Heart failure Constipation Hyperglycemia Neuropathy	Cardiomyopathy Myelosuppression Neuropathy
	Doxorubicin
	(Hydroxydaunorubicin)
	Vincristine (Oncovin)
	Prednisone
R-CHOP	Rituximab (Rituxan) + CHOP	Reactivate hepatitis B infection	Progressive multifocal leukoencephalopathy

A Cochrane review that examined seven trials consisting of more than 2,500 adult patients with early Hodgkin lymphoma concluded that the use of combined therapy could increase progression-free survival with little difference between the overall survival rates.³² Short-term complications from radiotherapy include nausea, vomiting, headaches, fatigue, and dermatitis. Radiotherapy can also lead to long-term complications, including cardiac and pulmonary toxicity, hypothyroidism, or breast or lung cancers.^24–32 Radiotherapy can be avoided in patients with stage IA or IIA lymphoma without bulky disease²⁵ (Table 3¹⁹).

Interim Reassessment

PET-CT scans, and subsequent Deauville scoring (Table 6²¹), should be used to assess the response to chemotherapy in non-Hodgkin and Hodgkin lymphoma.^25,30,31,33 A score of 3 or less is considered complete remission in non-Hodgkin lymphoma and should conclude the current treatment course. A score of 4 or 5 is an indicator to consider escalating therapy.²⁵ Patients with Hodgkin lymphoma with a Deauville score of 1 or 2 have been shown to have similar progression and mortality outcomes between radiotherapy and no further treatment.³² Patients who receive a score of 3 or 4 should receive additional chemotherapy and/or radiotherapy, and a score of 5 indicates the need for a biopsy (excisional or core needle) in addition to chemotherapy and radiotherapy.²⁵ A positive biopsy should be considered refractory disease.²⁵

PET-CT finding	Score
No FDG uptake related to lymphoma	1
FDG uptake at lymphoma site is ≤ mediastinum FDG uptake	2
FDG uptake at lymphoma site is > mediastinum FDG uptake but < liver FDG uptake	3
FDG uptake at lymphoma site is > liver FDG uptake at any site	4
FDG uptake at lymphoma site is substantially > liver FDG uptake or new FDG uptake sites found	5

Relapse

Relapse rates for non-Hodgkin lymphoma are variable and based on the specific subtype. The most common subtype, diffuse large B-cell lymphoma, has a 40% lifetime relapse rate.³⁷ Lifetime relapse in Hodgkin lymphoma occurs in 10% to 15% of patients with early stage disease and 40% of patients with advanced stage disease.³⁸

Surveillance

Patients who have achieved remission need routine surveillance to monitor for complications and relapse, as well as age-appropriate screenings recommended by the U.S. Preventive Services Task Force.³⁹ Complications of lymphoma treatment include secondary malignancies (e.g., breast, lung, skin, colon), cardiac disease, infertility, and endocrine, neurologic, and psychiatric dysfunctions. Current NCCN guidelines outline specific monitoring parameters for follow-up and prevention of secondary disease²⁵ (Table 7^38–43). The extent and frequency of follow-up specifically depend on the histologic subtype of lymphoma. Patients should follow up with an oncologist every three to six months for the first two years, every six to 12 months until year 3, then annually thereafter. After five years of being cancer free, the patient can be transitioned to a primary care physician.⁴⁰

Cancer screening	Laboratory screening	Cardiac screening	Counseling	Immunizations
Breast: annual screening mammography starting at age 40; history of chest or axilla radiation: start eight to 10 years after treatment or at age 40, whichever comes first; consider annual breast magnetic resonance imaging if chest radiation was received between ages 10 and 30; consider referral to breast subspecialist to discuss possible chemoprevention	Complete blood count, fasting blood glucose, and comprehensive metabolic panel annually	Annual blood pressure screening, lifestyle modification, and treatment of obesity, hypertension, and tobacco use	Annual depression screening	Age-appropriate immunizations per the Centers for Disease Control and Prevention schedule, including annual influenza vaccine; resume live vaccines at least three months after completion of chemotherapy
Routine surveillance tests for cervical, colorectal, lung, and prostate cancers per the USPSTF guidelines	Lipid profile per the USPSTF guidelines	Consider stress test and/or echocardiography at 10-year intervals (frequency of testing based on findings and other associated risk factors)	Neurocognitive impairment screening for any patient who is high risk (e.g., history of brain radiation or intrathecal treatment)	PCV13 (Prevnar 13), followed by PPSV23 (Pneumovax 23) at least eight weeks later and again at least five years later
	Thyroid-stimulating hormone annually if neck irradiation	Carotid ultrasonography every 10 years if neck irradiation	Infertility: consider reproductive endocrinologist referral	Haemophilus influenzae type b: three doses following hematopoietic stem cell transplantation

If a patient is asymptomatic, routine surveillance imaging does not improve outcomes or provide a clinical benefit.^40,41 Surveillance imaging should be used in patients who have reported symptoms or who are at high risk of relapse in a place that would not be easily examined, and who would be candidates for treatment. However, NCCN imaging guidelines for lymphoma surveillance state that it is acceptable to perform chest radiography or CT of the chest every six to 12 months for the first two years and then yearly for the next three to five years posttreatment.⁴¹ Surveillance imaging with PET-CT scans following complete remission is not recommended.^40,41 Disease marker research is ongoing, examining minimal residual disease measurements, a polymerase chain reaction–based method that looks at identifying tumor-specific DNA sequences.⁴¹

Immunizations

All patients with lymphoma should receive pneumococcal vaccination initially with a 13-valent pneumococcal conjugate vaccine (Prevnar 13), followed at least eight weeks later by a 23-valent pneumococcal polysaccharide vaccine (PPSV23; Pneumovax 23) and then another PPSV23 at least five years later.⁴⁴ Patients receiving anti–B-cell antibodies should not receive annual influenza vaccination, and administration of live vaccines is contraindicated during chemotherapy. Routine vaccinations recommended by the Centers for Disease Control and Prevention (CDC) should resume, including any recommended inactivated or live vaccines three months after chemotherapy or six months after anti–B-cell antibody therapy.^43,45 Patients receiving a hematopoietic stem cell transplant should receive a series of three doses of Haemophilus influenzae type b vaccine starting six to 12 months after a successful transplant. Household contacts should receive appropriate CDC-recommended immunizations.⁴³

This article updates a previous article on this topic by Glass.^⁴⁶

Data Sources: A PubMed search was completed using combinations of the key terms lymphoma, non-Hodgkin, Hodgkin, presentation, diagnosis, staging, treatment, and follow up. The search included meta-analyses, randomized controlled trials, clinical trials, and reviews. Search dates: April 18, May 17, and May 31, 2018, and August 30, 2019. We also searched the Agency for Healthcare Research and Quality evidence reports, UpToDate, the Cochrane database, Essential Evidence Plus, the National Comprehensive Cancer Network, and the Surveillance, Epidemiology, and End Results database. Search dates: April 18, 2018, and August 30, 2019.

Research reported in this article was supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number 5U54GM104942-03. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375-2390.

National Institutes of Health, National Cancer Institute. Surveillance, epidemiology, and end results program cancer stat facts: non-Hodgkin lymphoma. Accessed September 30, 2019. https://seer.cancer.gov/csr/1975_2016/results_merged/sect_19_nhl.pdf

Campo E, Swerdlow SH, Harris NL, et al. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011;117(19):5019-5032.

National Institutes of Health, National Cancer Institute. Surveillance, epidemiology, and end results program cancer stat facts: Hodgkin lymphoma. Accessed September 30, 2019. https://seer.cancer.gov/statfacts/html/hodg.html

Cerhan JR, Slager SL. Familial predisposition and genetic risk factors for lymphoma. Blood. 2015;126(20):2265-2273.

Suarez F, Lecuit M. Infection-associated non-Hodgkin lymphomas. Clin Microbiol Infect. 2015;21(11):991-997.

Coghill AE, Hildesheim A. Epstein-Barr virus antibodies and the risk of associated malignancies: review of the literature. Am J Epidemiol. 2014;180(7):687-695.

Yadlapati S, Efthimiou P. Autoimmune/inflammatory arthritis associated lymphomas: who is at risk?. Biomed Res Int. 2016:8631061.

Sergentanis TN, Kanavidis P, Michelakos T, et al. Cigarette smoking and risk of lymphoma in adults: a comprehensive meta-analysis on Hodgkin and non-Hodgkin disease. Eur J Cancer Prev. 2013;22(2):131-150.

Lichtman MA. Obesity and the risk for a hematological malignancy: leukemia, lymphoma, or myeloma. Oncologist. 2010;15(10):1083-1101.

Gidengil CA, Predmore Z, Mattke S, et al. Breast implant-associated anaplastic large cell lymphoma: a systematic review. Plast Reconstr Surg. 2015;135(3):713-720.

Schinasi L, Leon ME. Non-Hodgkin lymphoma and occupational exposure to agricultural pesticide chemical groups and active ingredients: a systematic review and meta-analysis. Int J Environ Res Public Health. 2014;11(4):4449-4527.

U.S. Food & Drug Administration. Questions and answers about breast implant-associated anaplastic large cell lymphoma. Accessed September 14, 2019. https://www.fda.gov/medical-devices/breast-implants/questions-and-answers-about-breast-implant-associated-anaplastic-large-cell-lymphoma-bia-alcl

Ansell SM. Non-Hodgkin lymphoma: diagnosis and treatment. Mayo Clin Proc. 2015;90(8):1152-1163.

Ansell SM. Hodgkin lymphoma: diagnosis and treatment. Mayo Clin Proc. 2015;90(11):1574-1583.

Higdon ML, Atkinson CJ, Lawrence KV. Oncologic emergencies: recognition and initial management. Am Fam Physician. 2018;97(11):741-748. https://www.aafp.org/afp/2018/0601/p741.html

Graus F, Ariño H, Dalmau J. Paraneoplastic neurological syndromes in Hodgkin and non-Hodgkin lymphomas. Blood. 2014;123(21):3230-3238.

Gaddey HL, Riegel AM. Unexplained lymphadenopathy: evaluation and differential diagnosis. Am Fam Physician. 2016;94(11):896-903. https://www.aafp.org/afp/2016/1201/p896.html

Cheson BD, Fisher RI, Barrington SF, et al.; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Corsortium. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32(27):3059-3068.

Townsend W, Linch D. Hodgkin’s lymphoma in adults. Lancet. 2012;380(9844):836-847.

Armitage JO, Gascoyne RD, Lunning MA, et al. Non-Hodgkin lymphoma. Lancet. 2017;390(10091):298-310.

International Non-Hodgkin’s Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl JMed. 1993;329(14):987-994.

Hasenclever D, Diehl V. A prognostic score for advanced Hodgkin’s disease. International Prognostic Factors Project on Advanced Hodgkin’s Disease. N Engl J Med. 1998;339(21):1506-1514.

Torok JA, Wu Y, Chino J, et al. Chemotherapy or combined modality therapy for early-stage Hodgkin lymphoma. Anticancer Res. 2018;38(5):2875-2881.

National Comprehensive Cancer Network. NCCN guidelines & clinical resources. Hodgkin lymphoma guideline. Accessed May 15, 2018. https://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf

Edwards-Bennett SM, Jacks LM, Moskowitz CH, et al. Stanford V program for locally extensive and advanced Hodgkin lymphoma: the Memorial Sloan-Kettering Cancer Center experience. Ann Oncol. 2010;21(3):574-581.

Swerdlow AJ, Higgins CD, Smith P, et al. Second cancer risk after chemotherapy for Hodgkin’s lymphoma: a collaborative British cohort study. J Clin Oncol. 2011;29(31):4096-4104.

Filippi AR, Levis M, Parikh R, et al. Optimal therapy for early-stage Hodgkin’s lymphoma: risk adapting, response adapting, and role of radiotherapy. Curr Oncol Rep. 2017;19(5):34.

Pfreundschuh M, Trümper L, Osterborg A, et al.; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006;7(5):379-391.

National Comprehensive Cancer Network. NCCN guidelines & clinical resources. B-cell lymphomas guideline. Accessed June 16, 2018. https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf

National Comprehensive Cancer Network. NCCN guidelines & clinical resources. T-cell lymphoma. Accessed June 16, 2018. https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf

Blank O, von Tresckow B, Monsef I, et al. Chemotherapy alone versus chemotherapy plus radiotherapy for adults with early stage Hodgkin lymphoma. Cochrane Database Syst Rev. 2017(4):CD007110.

Van Heertum RL, Scarimbolo R, Wolodzko JG, et al. Lugano 2014 criteria for assessing FDG-PET/CT in lymphoma: an operational approach for clinical trials. Drug Des Devel Ther. 2017;11:1719-1728.

Radford J, Illidge T, Counsell N, et al. Results of a trial of PET-directed therapy for early-stage Hodgkin’s lymphoma. N Engl J Med. 2015;372(17):1598-1607.

van Nimwegen FA, Ntentas G, Darby SC, et al. Risk of heart failure in survivors of Hodgkin lymphoma: effects of cardiac exposure to radiation and anthracyclines. Blood. 2017;129(16):2257-2265.

Conway JL, Connors JM, Tyldesley S, et al. Secondary breast cancer risk by radiation volume in women with Hodgkin lymphoma. Int J Radiat Oncol Biol Phys. 2017;97(1):35-41.

Sarkozy C, Sehn LH. Management of relapsed/refractory DLBCL. Best Pract Res Clin Haematol. 2018;31(3):209-216.

Bröckelmann PJ, Goergen H, Kohnhorst C, et al. Late relapse of classical Hodgkin lymphoma: an analysis of the German Hodgkin study group HD7 to HD12 trials. J Clin Oncol. 2017;35(13):1444-1450.

U.S. Preventive Services Task Force. Published recommendations. Accessed February 13, 2019. https://www.uspreventiveservicestaskforce.org/BrowseRec/Index

Hiniker SM, Hoppe RT. Post-treatment surveillance imaging in lymphoma. Semin Oncol. 2017;44(5):310-322.

Cohen JB, Kurtz DM, Staton AD, et al. Next-generation surveillance strategies for patients with lymphoma. Future Oncol. 2015;11(13):1977-1991.

El-Galaly TC, Jakobsen LH, Hutchings M, et al. Routine imaging for diffuse large B-cell lymphoma in first complete remission does not improve post-treatment survival: a Danish-Swedish population-based study. J Clin Oncol. 2015;33(34):3993-3998.

Kroger AT, Duchin J, Vázquez M. General Best Practice Guidelines for Immunization. Best practices guidance of the Advisory Committee on Immunization Practices. Accessed February 2, 2019. https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/downloads/general-recs.pdf

Centers for Disease Control and Prevention. Adult immunization schedule: pneumococcal vaccine. Accessed February 2, 2019. https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html#note-pneumo

Rubin LG, Levin MJ, Ljungman P, et al.; Infectious Diseases Society of America. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host [published correction appears in Clin Infect Dis. 2014;59(1):144]. Clin Infect Dis. 2014;58(3):e44-e100.

Glass C. Role of the primary care physician in Hodgkin lymphoma. Am Fam Physician. 2008;78(5):615-622. https://www.aafp.org/afp/2008/0901/p615.html