Hodgkin's lymphoma natural history, complications and prognosis
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sowminya Arikapudi, M.B,B.S. [2] Mohsen Basiri M.D.
Overview
Hodgkin's lymphoma has a bimodal age distribution and both children and adult may be affected. The early peak occurs in the middle-to-late 20s and the second peak after age 50 years. Treatment outcomes of Hodgkin’s lymphoma are excellent and five-year survival rates are more than 80%. Owing to modern therapies, the natural history of untreated Hodgkin’s lymphoma is actually difficult to determine. Survivors are at risk for relapse, second primary malignancies, cardiovascular complications and other treatment-related toxicities. Prognosis is based on the stage of the disease and other prognostic factors. The early stage of the Hodgkin's lymphoma is associated with the most favorable prognosis. The 5-year survival rate of patients with Hodgkin's lymphoma varies with the stage of the disease.
Natural History
- Hodgkin's lymphoma has a bimodal age distribution and both children and adult may be affected. The most common symptom of classic Hodgkin's lymphoma includes painless localized peripheral lymphadenopathy.
- Owing to modern therapies, the natural history of untreated Hodgkin’s lymphoma is actually difficult to determine.
- If left untreated, Hodgkin's lymphoma develop complications depend on site and size of mass, including breathing problem, hypoxemia, chest pain, significant weight loss, and a tracheoesophageal fistula and eventually significant decrease in the overall survival.[1]
Complications
- The main complications of Hodgkin lymphoma are due to side effects of chemotherapy and/or radiotherapy, table below provides these general side effects:
| Complications of Chemotherapy[2] | Complications of Radiotherapy[2] |
| Skin reactions | Skin changes |
| Nausea and vomiting | Nausea and vomiting |
| Sore throat and painful swallowing | Sore mouth |
| Taste changes | Loss of appetite |
| Fatigue | Fatigue |
| Diarrhea | Diarrhea |
| Bone marrow suppression | Bone marrow suppression |
| Dental cavities | Constipation |
| Thyroid problems | Hair loss |
| Fertility problems | Cystitis |
| Heart and lung problems | Muscle and joint pain |
| Second cancers | Second cancers |
| Pain at the injection site | |
| Inflammation of the vein | |
| Allergic reactions | |
| Organ damage | |
| Fluid retention |
- Leading complications which cause of death in Hodgkin lymphoma survivors are second primary malignancies and cardiovascular toxicities. Cardiovascular complications of radiation therapy (RT) include pericarditis, myocardial ischemia or infarction, cardiomyopathy, heart failure, valvular abnormalities, or conduction abnormalities. [3][4]
- Breast, lung, and colon cancer are the majority of second cancers in Hodgkin’s lymphoma survivors. [5]
- Leukemia and non-Hodgkin lymphoma (NHL) are less common. Most leukemias that occur after the treatment are acute myeloid leukemia (AML) related to alkylating agent exposure. [6]
- The relative risk of non-Hodgkin lymphoma increases among Hodgkin lymphoma survivors, and this rise increases with follow-up time. [7] [8]
Prognosis
Prognostic factors for early (Stage I and II) Hodgkin's lymphoma[9]
- Hodgkin's lymphoma are divided into favorable and unfavorable groups based on prognostic factors.
- Early favorable Hodgkin's lymphoma
- Early favorable Hodgkin's lymphoma means that no factors listed below are present.
- Early unfavorable Hodgkin's lymphoma
- Early unfavorable Hodgkin's lymphoma means that one or more of the following factors are present:
- Bulky disease
- Larger than one-third the width of the chest
- At least 10 cm in its greatest dimension in areas other than the chest
- Presence of extra nodal disease (in areas other than the lymph nodes)
- 3 or more areas of lymph node involvement
- Erythrocyte sedimentation rate (ESR) of 50 mm/h or higher
- Mixed cellularity Hodgkin's lymphoma
- Presence of B symptoms
- Unexplained fever over 38°C
- Drenching night sweats
- Unexplained weight loss – loss of more than 10% of original body weight within the last 6 months
Prognostic factors in advanced (stage III and IV) Hodgkin's lymphoma[10]
- The International Prognostic Factors Project (IPFP) has developed an international prognostic score (IPS) based on 7 adverse factors for advanced (stage III and IV) Hodgkin's lymphoma. The factors that are present are combined to give a single score between 0 and 7.
- Advanced favorable Hodgkin's lymphoma
- Advanced favorable Hodgkin's lymphoma means that 0 to 3 factors listed below are present.
- Advanced unfavorable Hodgkin's lymphoma
- Advanced unfavorable Hodgkin's lymphoma means that 4 or more of the following factors are present:
- Stage IV disease
- Age 45 years or older
- Male sex
- Albumin level less than 4.0 g/dL
- Hemoglobin level less than 10.5 g/dL
- White blood cell (WBC) count at least 15,000/mm3
- Lymphocyte count less than 600/mm3 or less than 8% of the total WBC count
5-Year Survival
- Between 2004 and 2010, the 5-year relative survival of patients with Hodgkin's lymphoma was 87.7%.[11]
- When stratified by age, the 5-year relative survival of patients with Hodgkin's lymphoma was 90.5% and 52.8% for patients <65 and ≥ 65 years of age respectively.[11]
- The survival of patients with Hodgkin's lymphoma varies with the stage of the disease. Shown below is a table depicting the 5-year relative survival by the stage of Hodgkin's lymphoma:[11]
| Stage | 5-year relative survival (%), (2004-2010) |
| All stages | 85.3% |
| Localized | 90.8% |
| Regional | 92.1% |
| Distant | 76.2% |
| Unstaged | 80.7% |
- The survival of patients with Hodgkin's lymphoma also varies with the subtype of Hodgkin's lymphoma. Shown below is the 5-year relative survival by the subtype of Hodgkin's lymphoma:[11]
- Classical Hodgkin's lymphoma: 84.8%
- Lymphocyte-rich: 87.1%
- Mixed cellularity: 80%
- Lymphocyte-depleted: 56.6%
- Nodular sclerosis: 89.4%
- Classical Hodgkin's lymphoma not otherwise specified: 75.2%
- Nodular lymphocyte predominant Hodgkin's lymphoma: 95.3%
- Classical Hodgkin's lymphoma: 84.8%
- Shown below is an image depicting the 5-year conditional relative survival (probability of surviving in the next 5-years given the cohort has already survived 0, 1, 3 years) between 1998 and 2010 of Hodgkin's lymphoma by stage at diagnosis according to SEER. These graphs are adapted from SEER: The Surveillance, Epidemiology, and End Results Program of the National Cancer Institute.[11]
References
- ↑ Greco, Ralph S. (1974). "Hodgkin Disease in Connecticut From 1935 to 1962". Archives of Internal Medicine. 134 (6): 1039. doi:10.1001/archinte.1974.00320240073007. ISSN 0003-9926.
- ↑ 2.0 2.1 Hodgkin-lymphoma. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/hodgkin-lymphoma/treatment/?region=ab Accessed on September 10, 2015
- ↑ Shira L. Galper, James B. Yu, Peter M. Mauch, Jon F. Strasser, Barbara Silver, Ann Lacasce, Karen J. Marcus, Mary Ann Stevenson, Ming Hui Chen & Andrea K. Ng (2011). "Clinically significant cardiac disease in patients with Hodgkin lymphoma treated with mediastinal irradiation". Blood. 117 (2): 412–418. doi:10.1182/blood-2010-06-291328. PMID 20858859. Unknown parameter
|month=ignored (help) - ↑ Andrea K. Ng, Ann LaCasce & Lois B. Travis (2011). "Long-term complications of lymphoma and its treatment". Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 29 (14): 1885–1892. doi:10.1200/JCO.2010.32.8427. PMID 21483015. Unknown parameter
|month=ignored (help) - ↑ Michael Schaapveld, Berthe M. P. Aleman, Anna M. van Eggermond, Cecile P. M. Janus, Augustinus D. G. Krol, Richard W. M. van der Maazen, Judith Roesink, John M. M. Raemaekers, Jan Paul de Boer, Josee M. Zijlstra, Gustaaf W. van Imhoff, Eefke J. Petersen, Philip M. P. Poortmans, Max Beijert, Marnix L. Lybeert, Ina Mulder, Otto Visser, Marieke W. J. Louwman, Inge M. Krul, Pieternella J. Lugtenburg & Flora E. van Leeuwen (2015). "Second Cancer Risk Up to 40 Years after Treatment for Hodgkin's Lymphoma". The New England journal of medicine. 373 (26): 2499–2511. doi:10.1056/NEJMoa1505949. PMID 26699166. Unknown parameter
|month=ignored (help) - ↑ J. M. Kaldor, N. E. Day, E. A. Clarke, F. E. Van Leeuwen, M. Henry-Amar, M. V. Fiorentino, J. Bell, D. Pedersen, P. Band & D. Assouline (1990). "Leukemia following Hodgkin's disease". The New England journal of medicine. 322 (1): 7–13. doi:10.1056/NEJM199001043220102. PMID 2403650. Unknown parameter
|month=ignored (help) - ↑ M. Henry-Amar (1992). "Second cancer after the treatment for Hodgkin's disease: a report from the International Database on Hodgkin's Disease". Annals of oncology : official journal of the European Society for Medical Oncology. 3 Suppl 4: 117–128. PMID 1450072. Unknown parameter
|month=ignored (help) - ↑ F. E. van Leeuwen, W. J. Klokman, M. B. Veer, A. Hagenbeek, A. D. Krol, U. A. Vetter, M. Schaapveld, P. van Heerde, J. M. Burgers, R. Somers & B. M. Aleman (2000). "Long-term risk of second malignancy in survivors of Hodgkin's disease treated during adolescence or young adulthood". Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 18 (3): 487–497. doi:10.1200/JCO.2000.18.3.487. PMID 10653864. Unknown parameter
|month=ignored (help) - ↑ Hodgkin-lymphoma. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/hodgkin-lymphoma/diagnosis/?region=ab Accessed on September 16, 2015
- ↑ Hodgkin-lymphoma. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/hodgkin-lymphoma/diagnosis/?region=ab Accessed on September 16, 2015
- ↑ 11.0 11.1 11.2 11.3 11.4 Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.