eMedicine Specialties > Hematology > Stem Cells and Disorders

Hodgkin Disease: Follow-up

Author: Scott K Dessain, MD, PhD, Associate Professor, Lankenau Institute for Medical Research
Coauthor(s): James L Spears, MD, Consulting Staff, Bux-Mont Hematology Oncology Medical Associates; Athanassios Argiris, MD, Professor, Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine
Contributor Information and Disclosures

Updated: Oct 4, 2009

Follow-up

Further Outpatient Care

Follow-up for the patient in complete remission

NCCN and ESMO both provide recommendations for the long-term follow-up of treated patients with Hodgkin disease (Hodgkin's lymphoma).12,13

  • Most relapses occur in the first 3 years after therapy. Follow-up visits are recommended every 2-4 months for the first 1-2 years and every 3-6 months for the next 3-5 years.
  • Follow-up examinations include the following:
    • History and physical examination
    • CBC counts and chemistry panel, including LDH, ESR, glucose, and lipid levels
    • Thyroid-stimulating hormone (TSH) levels (at least annually if the patient has had neck XRT)
    • Chest x-ray or CT scans of the chest every 6-12 months in the first 2-5 years. Abdominal and pelvic CT scans may be added every 6-12 months in the first 2-3 years, especially if the disease had originally occurred below the diaphragm. 
    • PET scans obtained for surveillance following CR is specifically not encouraged by the NCCN due to the possibility that false-positive results may occur.
    • Spiral chest CT scans may be appropriate annually, starting 5 years after therapy to screen patients at increased risk for lung cancer.
  • Female patients with a history of chest irradiation should be screened annually with mammography, starting at age 40 years or 5-8 years following the XRT. 
  • Vaccinations against pneumococcus (especially in patients who have had splenectomy), Haemophilus influenzae, meningococcus, and influenza (annually, especially in patients who have received bleomycin or chest XRT), should be maintained.

Complications

Late complications of therapy in Hodgkin disease (Hodgkin's lymphoma) survivors

Survivors of Hodgkin disease (Hodgkin's lymphoma) may have long-term sequelae from their therapy.35 With the current widespread use of nonleukemogenic chemotherapy (ABVD) and the use of smaller radiation fields and doses, the rate of treatment-related deaths is expected to decrease.

  • Cardiac disease
    • Mantle radiotherapy increases the risk the risk of coronary artery disease, chronic pericarditis, pancarditis, valvular heart disease, and defects in the conduction system.36,37
    • Patients with history of mediastinal radiation have a 3-fold increase in their risk of cardiac death.
    • A study of patients who had previously undergone mediastinal irradiation for Hodgkin disease (Hodgkin's lymphoma) but who had no clinical evidence of heart disease demonstrated a significant incidence of silent coronary artery obstruction and previous ventricular damage.38 Based on these results, it is reasonable to initiate functional screening 5 years after XRT in patients with Hodgkin disease (Hodgkin's lymphoma).
  • Pulmonary disease
    • The ABVD regimen contains bleomycin, a drug associated with dose-related pulmonary toxicity, mainly interstitial pneumonitis, which may lead to fibrosis.
    • The addition of mantle irradiation enhances lung injury. Pulmonary symptomatology, such as cough or dyspnea upon exertion, is observed in 50% of patients, and declining pulmonary function parameters are observed in approximately one third of patients during ABVD chemotherapy, with or without XRT. This may lead to dose reductions or even discontinuation of bleomycin.
    • Baseline tests and follow-up evaluation with pulmonary function tests are recommended. The best parameter to follow is the carbon monoxide diffusion capacity.
    • Although acute toxicity is common, the incidence of severe long-term pulmonary toxicity is low. Fatal pulmonary toxicity has been reported in up to 2-3% of patients treated with the ABVD regimen.
  • Secondary cancers – Secondary leukemias and solid tumors are significant causes of morbidity and mortality for patients who have received early therapies, including the MOPP regimen and mantle XRT. With modern therapies that emphasize the widespread use of the ABVD and Stanford V regimens and the application of radiation to involved fields only, the incidence of secondary cancers is expected to be much lower.
    • Myelodysplastic syndromes (MDS)/acute leukemia
      • In the Stanford case series, the projected risk for developing MDS or acute leukemia over a follow-up period of 35 years was 2%, and the relative risk compared with matched controls was 38%. The MOPP regimen is associated with an approximately 5% incidence of MDS/leukemia. With the ABVD regimen, such risk is lower, less than 1%. 
      • MDS/AML is usually seen in the first 3-8 years following treatment for Hodgkin disease (Hodgkin's lymphoma); subsequently, the risk appears to decline. These findings are consistent with the biology of secondary leukemias following alkylator therapy. 
      • MDS/AML usually develops in the context of an MDS with cytogenetic abnormalities in chromosomes 5 and/or 7. Exposure to alkylating agents (eg, the mechlorethamine used in the MOPP regimen) has been implicated.
      • Exposure to epipodophyllotoxins (etoposide and teniposide) may also result in AML, which generally develops within 3 years and is associated with chromosomal abnormalities at band 11q23.
    • Breast cancer
      • Patients treated with mantle XRT when they are younger than 30 years are 19 times more likely to develop breast cancer. If women are exposed to chest XRT when they are younger than 15 years, this relative risk increases to 136.
      • MOPP chemotherapy also produces an increased risk for breast cancer when combined with XRT.
    • Other solid tumors
      • The most common secondary malignancy following treatment for Hodgkin disease (Hodgkin's lymphoma) is lung cancer. Both chemotherapy with alkylating agents and irradiation are associated with a 10-fold increased relative risk of lung cancer. Smoking can further increase the risk.
      • Patients in the Stanford case series were also found to have increased risks of developing melanoma, non-Hodgkin lymphoma, soft-tissue sarcoma, salivary gland cancers, pancreatic cancers, and thyroid cancers.
  • Infertility
    • MOPP chemotherapy causes permanent infertility in at least 80% of males and approximately 50% of females. Young females may maintain their ovarian function, and some studies suggest that this may be improved by the use of oral contraceptives.39 The escalated BEACOPP regimen is also likely to impair fertility.40
    • The ABVD and Stanford V regimens pose a lower risk of permanent sterility than regimens that contain an alkylating agent (eg, MOPP chemotherapy).41 The EORTC Lymphoma Group reported an 82% rate of recovery of fertility in male patients who were treated without alkylating agents. Male patients who are considering bearing children may consider sperm banking before initiating therapy.
  • Infectious complications
    • Patients who have undergone splenectomy are predisposed to bacterial sepsis secondary to encapsulated microorganisms (especially Streptococcus pneumoniae). Empiric antibiotic therapy should be instituted promptly in patients who have undergone splenectomy and present with fever. Pneumococcal vaccination before splenectomy and every 5-7 years thereafter is also recommended.
    • Influenza vaccination annually may help to reduce the incidence and/or complications of influenza in patients who have received bleomycin or chest XRT.
    • Herpes zoster usually appears in previously irradiated dermatomes, but this condition may also occur in patients who have not been irradiated.
  • Hypothyroidism – Elevation of thyroid stimulating hormone (TSH) occurs in one third of adult patients after neck/mediastinal XRT.
  • Lhermitte syndrome – Patients with this syndrome describe an electric shock sensation that radiates along the back and legs upon flexion of the neck. It can occur in approximately 15% of patients after mantle irradiation. Lhermitte syndrome is not associated with the development of radiation myelitis, and it does not require treatment. This syndrome may last for many months, but eventually, it resolves without long-term sequelae.
  • Psychosocial sequelae – Survivors of Hodgkin disease (Hodgkin's lymphoma) have an increased incidence of fatigue, psychiatric distress (anxiety, depression), employment problems, family issues, and sexual functioning problems, as compared with individuals without this disease or relative to survivors of acute leukemia.42,43

Patient Education

  • Before the initiation of HDC, patients with Hodgkin disease (Hodgkin's lymphoma) should be counseled about the risk of infertility, and sperm banking should be considered for males.
  • Patients should be counseled on health habits that may help reduce the risk of cancer and cardiovascular disease, including avoidance of smoking, control of lipids, and the use of sunscreen.
  • Female patients who have received chest XRT should be encouraged to perform regular breast self-examinations.
  • Patients should also be advised about the long-term risk of infection after undergoing splenectomy and the importance of calling their physician if they experience a fever.
  • Patients should understand the risk of psychosocial problems that may affect survivors of Hodgkin disease (Hodgkin's lymphoma). Consultations with social workers, psychologists, and psychiatrists may be helpful to manage some of these issues.

Miscellaneous

Medicolegal Pitfalls

  • Because Hodgkin disease (Hodgkin's lymphoma) is considered to be a curable malignancy, medicolegal problems may arise from failure to diagnose the disease in a timely manner, possibly attributable to the following factors:
    • The misinterpretation of B symptoms
    • A lack of follow-up for abnormal chest radiographs or physical examination findings
    • A missed pathologic diagnosis because a needle biopsy was obtained rather than an excisional lymph node biopsy
  • Treatment for Hodgkin disease (Hodgkin's lymphoma) seeks to balance the risk of treatment failure with the risk of treatment side effects. Medicolegal liability may therefore result from overtreatment of low-risk disease or undertreatment of high-risk disease.
  • Patients with refractory or relapsed Hodgkin disease (Hodgkin's lymphoma) should be promptly referred to centers capable of HDC with hematopoietic stem cell support.
  • In the case of survivors of Hodgkin disease (Hodgkin's lymphoma), problems may arise in the following scenarios:
    • Failure to identify secondary cancers in a timely manner
    • Failure to consider sepsis as a possible cause for fever in a splenectomized patient
    • Failure to diagnose and treat predictable complications of Hodgkin disease (Hodgkin's lymphoma) treatment, such as coronary artery, pulmonary, or thyroid disease
  • Failure to warn patients about potential complications of Hodgkin disease (Hodgkin's lymphoma) therapy, including the risk of cardiac disease, lung toxicity, and secondary cancers. Patients should also be apprised of the potential loss of fertility that may arise from MOPP chemotherapy, escalated BEACOPP chemotherapy, pelvic irradiation, or HDC, so that they may explore fertility-preserving options such as sperm banking, oral contraceptive use, or oophoropexy.
 
Acknowledgments

We are grateful to Virginia Kaklamani, MD, and Christine Wasilewski, MD, MPH, for help on prior versions.



More on Hodgkin Disease

Overview: Hodgkin Disease
Differential Diagnoses & Workup: Hodgkin Disease
Treatment & Medication: Hodgkin Disease
Follow-up: Hodgkin Disease
References
Further Reading
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Further Reading

Additional resources on Hodgkin Disease are available at Medscape’s Hodgkin Disease Resource Center.

Further Resources

Related eMedicine Topics

Clinical Trials

Clinical Guidelines

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Keywords

Hodgkin disease, Hodgkin's lymphoma, Hodgkin's disease, Hodgkin lymphoma, HD, malignant lymphoma, malignant lymphogranuloma, Reed-Sternberg cells, lymph cancer, Epstein-Barr virus, EBV, nodular sclerosis Hodgkin disease, NSHD, mixed-cellularity Hodgkin disease, MCHD, lymphocyte-depleted Hodgkin disease, LDHD, lymphocyte-depleted Hodgkin's disease, lymphocyte-rich Hodgkin disease, nodular Hodgkin disease, NHD, nodular lymphocyte-predominant Hodgkin disease, NLPHD, lymph node cancer

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Contributor Information and Disclosures

Author

Scott K Dessain, MD, PhD, Associate Professor, Lankenau Institute for Medical Research
Scott K Dessain, MD, PhD is a member of the following medical societies: American Society of Hematology
Disclosure: Nothing to disclose.

Coauthor(s)

James L Spears, MD, Consulting Staff, Bux-Mont Hematology Oncology Medical Associates
James L Spears, MD is a member of the following medical societies: American Society of Clinical Oncology
Disclosure: Nothing to disclose.

Athanassios Argiris, MD, Professor, Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine
Athanassios Argiris, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, and American Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Koyamangalath Krishnan, MD, FRCP, FACP, Paul Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine and Chief of Hematology-Oncology, Program Director, Hematology-Oncology Fellowship, James H Quillen College of Medicine at East Tennessee State University
Koyamangalath Krishnan, MD, FRCP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, and Royal College of Physicians
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Wendy Hu, MD, Consulting Staff, Department of Hematology/Oncology and Bone Marrow Transplantation, Huntington Memorial Medical Center
Wendy Hu, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Blood and Marrow Transplantation, American Society of Hematology, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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