Non-Hodgkin lymphoma

Short description: Type of cancer of lymph nodes

Non-Hodgkin lymphoma

Other names| Non-Hodgkin disease
Micrograph of mantle cell lymphoma, a type of non-Hodgkin lymphoma. Terminal ileum. H&E stain.
Specialty| Hematology and oncology
Symptoms| Enlarged lymph nodes, fever, night sweats, weight loss, tiredness, itching[1]
Usual onset| 65–75 years old[2]
Risk factors| Poor immune function, autoimmune diseases, Helicobacter pylori infection, hepatitis C, obesity, Epstein-Barr virus infection[1][3]
Diagnostic method| Bone marrow or lymph node biopsy[1]
Treatment| Chemotherapy, radiation, immunotherapy, targeted therapy, stem cell transplantation, surgery, watchful waiting[1]
Prognosis| Five-year survival rate 71% (USA)[2]
Frequency| 4.3 million (affected during 2015)[4]
Deaths| 231,400 (2015)[5]

Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of blood cancers that includes all types of lymphomas except Hodgkin lymphomas.[1] Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and tiredness.[1] Other symptoms may include bone pain, chest pain, or itchiness.[1] Some forms are slow-growing while others are fast-growing.[1] Unlike Hodgkin lymphoma, which often spreads in an orderly pattern between nearby lymph nodes, NHL can involve multiple parts of the body and may not follow a predictable spread.[6]

## Contents

* 1 Signs and symptoms
* 2 Diagnosis
* 3 Causes
* 3.1 Familial component
* 3.2 HIV/AIDS
* 4 Treatment
* 4.1 Chemotherapy
* 4.2 Treatment complications
* 4.3 Other
* 5 Prognosis
* 6 Epidemiology
* 6.1 Australia
* 6.2 Canada
* 6.3 United Kingdom
* 6.4 United States
* 7 History
* 8 References
* 9 External links

## Signs and symptoms

The signs and symptoms of non-Hodgkin lymphoma vary depending upon its location within the body. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and tiredness. Other symptoms may include bone pain, chest pain, or itchiness. Some forms are slow growing, while others are fast growing.[1] Enlarged lymph nodes may cause lumps to be felt under the skin when they are close to the surface of the body. Lymphomas in the skin may also result in lumps, which are commonly itchy, red, or purple. Lymphomas in the brain can cause weakness, seizures, problems with thinking, and personality changes.[7]

While an association between non-Hodgkin lymphoma and endometriosis has been described,[8] these associations are tentative.[9]

## Diagnosis

Tests for non-Hodgkin lymphoma include;

* Complete blood count (CBC).
* Blood chemistry studies.
* Hepatitis B and hepatitis C test.
* HIV test.
* CT scan (CAT scan).
* PET scan (positron emission tomography scan).
* Bone marrow aspiration and biopsy.

If cancer is found, the following tests may be done to study the cancer cells:

* Immunohistochemistry.
* Cytogenetic analysis.
* Immunophenotyping.

Other tests and procedures may be done depending on the signs and symptoms seen and where the cancer forms in the body.[10][11]

## Causes

Lymphomas are types of cancer that develop from lymphocytes, a type of white blood cell.[2] Risk factors include poor immune function, autoimmune diseases, Helicobacter pylori infection, hepatitis C, obesity, and Epstein–Barr virus infection.[1][3] The World Health Organization classifies lymphomas into five major groups, including one for Hodgkin lymphoma.[12] Within the four groups for NHL are over 60 specific types of lymphoma.[13][14] Diagnosis is by examination of a bone marrow or lymph node biopsy.[1] Medical imaging is done to help with cancer staging.[1]

The many different forms of lymphoma probably have different causes. These possible causes and associations with at least some forms of NHL include:

* Infectious agents:
* Epstein–Barr virus: associated with Burkitt's lymphoma, follicular dendritic cell sarcoma, extranodal NK-T-cell lymphoma and diffuse large B-cell lymphoma.[15]
* Human T-cell leukemia virus: associated with adult T-cell lymphoma.
* Helicobacter pylori: associated with gastric lymphoma.
* HHV-8: associated with primary effusion lymphoma, multicentric Castleman disease.
* Hepatitis C virus: associated with splenic marginal zone lymphoma, lymphoplasmacytic lymphoma and diffuse large B-cell lymphoma.[16]
* HIV infection.[17]
* Some chemicals, like polychlorinated biphenyls (PCBs),[18][19][20] diphenylhydantoin, dioxins, and phenoxy herbicides.
* Autoimmune diseases, like Sjögren syndrome, celiac disease, rheumatoid arthritis, and systemic lupus erythematosus.[21][22]
* Bone trauma and microfractures associated with diffuse large B-cell lymphoma originating in bone marrow.[23][24]
* Implants, made from hard metals or silicone, associated with anaplastic large cell lymphoma.[25][26]

### Familial component

Familial lymphoid cancer is rare. The familial risk of lymphoma is elevated for multiple lymphoma subtypes, suggesting a shared genetic cause. However, a family history of a specific subtype is most strongly associated with risk for that subtype, indicating that these genetic factors are subtype specific. Genome-wide association studies have successfully identified 67 single-nucleotide polymorphisms from 41 loci, most of which are subtype specific.[27]

### HIV/AIDS

The Centers for Disease Control and Prevention (CDC) included certain types of non-Hodgkin lymphoma as AIDS-defining cancers in 1987.[28] Immune suppression rather than HIV itself is implicated in the pathogenesis of this malignancy, with a clear correlation between the degree of immune suppression and the risk of developing NHL. Additionally, other retroviruses, such as HTLV, may be spread by the same mechanisms that spread HIV, leading to an increased rate of co-infection.[29] The natural history of HIV infection has greatly changed over time. As a consequence, rates of non-Hodgkin lymphoma (NHL) in people infected with HIV has significantly declined in recent years.[17]

## Treatment

Treatment depends on whether the lymphoma is slow or fast growing and if it is in one area or many areas.[1] Treatments may include chemotherapy, radiation, immunotherapy, targeted therapy, stem-cell transplantation, surgery, or watchful waiting.[1] If the blood becomes overly thick due to high numbers of antibodies, plasmapheresis may be used.[1] Radiation and some chemotherapy, however, increase the risk of other cancers, heart disease, or nerve problems over the subsequent decades.[1]

The traditional treatment of NHL includes chemotherapy, radiotherapy, and stem-cell transplants.[30][31] There have also been developments in immunotherapy used in the treatment of NHL.[32]

### Chemotherapy

The most common chemotherapy used for B-cell non-Hodgkin lymphoma is R-CHOP, which is a regimen of four drugs (cyclophosphamide, doxorubicin, vincristine, and prednisone) plus rituximab.[33]

R-CHP with polatuzumab vedotin, an antibody-drug conjugate, was included as a category 1 preferred regimen for first-line DLBCL by the National Comprehensive Cancer Network in 2023.[34]

### Treatment complications

If participants receive stem-cell transplants, they can develop a graft-versus-host disease. When compared with placebo for treating immune mediated inflammation post transplantation and in autoimmunity, mesenchymal stromal cells (MSCs) may reduce the all-cause mortality if they are used for a therapeutic reason.[35] Moreover, the therapeutic use of MSCs may increase the complete response of acute and chronic GvHD, but the evidence is very uncertain.[35] The evidence suggests that MSCs for prophylactic reason result in little to no difference in the all-cause mortality, in the relapse of malignant diseases, and in the incidence of acute GvHD.[35] The evidence suggests that MSCs for prophylactic reason reduce the incidence of chronic GvHD.[35]

Platelet transfusions may be necessary for those who receive chemotherapy or undergo a stem cell transplantation due to the higher risk for bleeding. When comparing therapeutic/non-prophylactic platelet transfusions to prophylactic platelet transfusions there is little to no difference in the mortality secondary to bleeding and they may result in a slight reduction in the number of days on which a significant bleeding event occurred.[36] The evidence suggests that therapeutic platelet transfusions result in a large increase in the number of people with at least one significant bleeding event and they likely result in a large reduction in the number of platelet transfusions.[36][37]

### Other

It is unclear if including aerobic physical exercise, in addition to the standard treatment for adult patients with haematological malignancies, is effective at reducing anxiety and serious adverse effects.[38] Aerobic physical exercises may result in little to no difference in the mortality, in the quality of life and in the physical functioning.[38] These exercises may result in a slight reduction in depression and most likely reduce fatigue.[38]

## Prognosis

Prognosis depends on the subtype, the staging, a person's age, and other factors. Across all subtypes, 5-year survival for NHL is 71–74%.[39][40][41]

## Epidemiology

Globally, as of 2010, there were 210,000 deaths, up from 143,000 in 1990.[42]

In 2015, about 4.3 million people had non-Hodgkin lymphoma, and 231,400 (5.4%) died.[4][5] In the United States, 2.1% of people are affected at some point in their life.[2] The most common age of diagnosis is between 65 and 75 years old.[2] The five-year survival rate in the United States is 71%.[2]

Rates of non-Hodgkin lymphoma increase steadily with age.[21] Up to 45 years NHL is more common among males than females.[43]

### Australia

Around 6600 people are diagnosed with non-Hodgkin lymphoma in Australia each year.[44]

### Canada

In Canada NHL is the fifth most common cancer in males and sixth most common cancer in females. The lifetime probability of developing a lymphoid cancer is 1 in 44 for males, and 1 in 51 for females.[45]

### United Kingdom

On average, according to data for the 2014–2016 period, around 13,900 people are diagnosed with NHL yearly. It is the sixth most common cancer in the UK, and is the eleventh most common cause of cancer death accounting for around 4,900 deaths per year.[46]

### United States

Age adjusted data from 2012 to 2016 shows about 19.6 cases of NHL per 100,000 adults per year, 5.6 deaths per 100,000 adults per year, and around 694,704 people living with non-Hodgkin lymphoma. About 2.2 percent of men and women will be diagnosed with NHL at some point during their lifetime.[47]

The American Cancer Society lists non-Hodgkin lymphoma as one of the most common cancers in the United States, accounting for about 4% of all cancers.[48]

## History

## References

1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 "Adult Non-Hodgkin Lymphoma Treatment (PDQ®)–Patient Version". 3 August 2016. http://www.cancer.gov/types/lymphoma/patient/adult-nhl-treatment-pdq#section/all.
2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 "SEER Stat Fact Sheets: Non-Hodgkin Lymphoma". April 2016. http://seer.cancer.gov/statfacts/html/nhl.html.
3. ↑ 3.0 3.1 World Cancer Report 2014. World Health Organization. 2014. pp. Chapter 2.4, 2.6. ISBN 978-92-832-0429-9.
4. ↑ 4.0 4.1 "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet 388 (10053): 1545–1602. 8 October 2016. doi:10.1016/S0140-6736(16)31678-6. PMID 27733282.
5. ↑ 5.0 5.1 "Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet 388 (10053): 1459–1544. 8 October 2016. doi:10.1016/s0140-6736(16)31012-1. PMID 27733281.
6. ↑ "B–NHL Cases in a Tertiary Pediatric Hematology—Oncology Department: A 20-Year Retrospective Cohort Study". Life 14 (5): 633. May 2024. doi:10.3390/life14050633. PMID 38792653. Bibcode: 2024Life...14..633K.
7. ↑ "Non-Hodgkin Lymphoma". https://medlineplus.gov/ency/article/000581.htm.
8. ↑ "[Women with endometriosis: are they different from others?]" (in fr). Gynécologie, Obstétrique & Fertilité 33 (4): 239–46. April 2005. doi:10.1016/j.gyobfe.2005.03.010. PMID 15894210.
9. ↑ "Association between endometriosis and cancer: a comprehensive review and a critical analysis of clinical and epidemiological evidence". Gynecologic Oncology 101 (2): 331–41. May 2006. doi:10.1016/j.ygyno.2005.11.033. PMID 16473398.
10. ↑ "Non-Hodgkin Lymphoma Treatment - NCI". 24 November 2023. https://www.cancer.gov/types/lymphoma/patient/adult-nhl-treatment-pdq#:~:text=and treatment options.-,Non-Hodgkin lymphoma is a disease in which malignant (cancer,body from infection and disease.
11. ↑ "Non-Hodgkin lymphoma - Diagnosis". 23 October 2017. https://www.nhs.uk/conditions/non-hodgkin-lymphoma/diagnosis/.
12. ↑ "Adult Non-Hodgkin Lymphoma Treatment (PDQ®)–Health Professional Version". 1 June 2016. http://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq#section/all.
13. ↑ "Different types of non Hodgkin lymphoma". http://www.cancerresearchuk.org/about-cancer/type/non-hodgkins-lymphoma/about/types/the-most-common-types-of-non-hodgkins-lymphoma.
14. ↑ Bope, Edward T.; Kellerman, Rick D. (2015) (in en). Conn's Current Therapy 2016. Elsevier Health Sciences. p. 878. ISBN 978-0-323-35535-3. https://books.google.com/books?id=_x_mCgAAQBAJ&pg=PT914.
15. ↑ "Spectrum of Epstein-Barr virus-related diseases: A pictorial review". Japanese Journal of Radiology 27 (1): 4–19. 2009. doi:10.1007/s11604-008-0291-2. PMID 19373526.
16. ↑ "Hepatitis C-associated B-cell non-Hodgkin lymphomas. Epidemiology, molecular signature and clinical management". Journal of Hepatology 59 (1): 169–177. 2013. doi:10.1016/j.jhep.2013.03.018. PMID 23542089.
17. ↑ 17.0 17.1 "Non-AIDS-defining cancers among HIV-infected people". European Review for Medical and Pharmacological Sciences 16 (10): 1377–88. October 2012. PMID 23104654.
18. ↑ "Current Status of the Epidemiologic Evidence Linking Polychlorinated Biphenyls and Non-Hodgkin Lymphoma, and the Role of Immune Dysregulation". Environmental Health Perspectives 120 (8): 1067–75. 2012. doi:10.1289/ehp.1104652. PMID 22552995. Bibcode: 2012EnvHP.120.1067K.
19. ↑ "Polychlorinated biphenyls and cancer: an epidemiological assessment". J. Environ. Sci. Health C 31 (2): 99–144. 2013. doi:10.1080/10590501.2013.782174. PMID 23672403. Bibcode: 2013JESHC..31...99Z.
20. ↑ "Carcinogenicity of polychlorinated biphenyls and polybrominated biphenyls". Lancet Oncology 14 (4): 287–288. 2013. doi:10.1016/s1470-2045(13)70104-9. PMID 23499544. http://prodinra.inra.fr/ft/25BCE4BA-5EA4-4AA1-A446-23A01442B32E. Retrieved 8 November 2019.
21. ↑ 21.0 21.1 Cancer and its Management (7th ed.). Wiley-Blackwell. 2015. ISBN 978-1-118-46871-5.
22. ↑ Arnold S Freedman; Lee M Nadler (2000). "Chapter 130: Non–Hodgkin's Lymphomas". Holland-Frei Cancer Medicine (5th ed.). Hamilton, Ont: B.C. Decker. ISBN 1-55009-113-1. https://www.ncbi.nlm.nih.gov/books/NBK20925/.
23. ↑ Subik, M. Kristina; Herr, Megan; Hutchison, Robert E.; Kelly, Jennifer; Tyler, Wakenda; Merzianu, Mihai; Burack, W. Richard (November 2014). "A Highly Curable Lymphoma Occurs Preferentially in the Proximal Tibia of Young Patients". Modern Pathology 27 (11): 1430–1437. doi:10.1038/modpathol.2014.51. ISSN 0893-3952. PMID 24743213.
24. ↑ Stein, M. E.; Lewis, D. C.; Gershuny, A. R.; Quigley, M. M.; Zaidan, J.; Danieli, N. Siegelmann; Whelan, J.; Subramanian, R. (April 2003). "Trauma as an etiologic factor of primary bone lymphoma: a report of 4 cases". Journal of B.U.ON. 8 (2): 163–166. ISSN 1107-0625. PMID 17472245.
25. ↑ Palraj, Bharath; Paturi, Anil; Stone, Ross G.; Alvarez, Harold; Sebenik, Matjaz; Perez, Maria T.; Bush, Larry M. (2010-11-01). "Soft Tissue Anaplastic Large T-Cell Lymphoma Associated with a Metallic Orthopedic Implant: Case Report and Review of the Current Literature" (in en). The Journal of Foot and Ankle Surgery 49 (6): 561–564. doi:10.1053/j.jfas.2010.08.009. ISSN 1067-2516. PMID 20870426. https://www.jfas.org/article/S1067-2516(10)00326-1/abstract.
26. ↑ Popplewell, Leslie; Chang, Karen; Olevsky, Olga; Nademanee, A.; Forman, Stephen (2004-11-16). "Primary Anaplastic Large Cell Lymphoma of the Breast Occurring in Patients with Silicone Breast Implants." (in en). Blood 104 (11): 4563. doi:10.1182/blood.V104.11.4563.4563. ISSN 0006-4971. https://ashpublications.org/blood/article/104/11/4563/56021/Primary-Anaplastic-Large-Cell-Lymphoma-of-the.
27. ↑ "Familial predisposition and genetic risk factors for lymphoma". Blood 126 (20): 2265–73. November 2015. doi:10.1182/blood-2015-04-537498. PMID 26405224.
28. ↑ Centers for Disease Control (CDC) (August 1987). "Revision of the CDC surveillance case definition for acquired immunodeficiency syndrome. Council of State and Territorial Epidemiologists; AIDS Program, Center for Infectious Diseases". MMWR Supplements 36 (1): 1S–15S. PMID 3039334. https://www.cdc.gov/mmwr/pdf/other/mmsu3601.pdf.
29. ↑ "HIV-related lymphoma". HIV Therapy 4 (6): 649–659. 2010. doi:10.2217/hiv.10.54. ISSN 1758-4310.
30. ↑ "Non-Hodgkin lymphoma". Cancer Council Australia. 22 March 2019. https://www.cancer.org.au/about-cancer/types-of-cancer/lymphoma/non-hodgkin-lymphoma.html.
31. ↑ "Non-Hodgkin Lymphoma Treatment". American Cancer Society. 2019. https://www.cancer.org/cancer/non-hodgkin-lymphoma/about/new-research.html.
32. ↑ "Immunotherapy for Non-Hodgkin Lymphoma". American Cancer Society. 2019. https://www.cancer.org/cancer/non-hodgkin-lymphoma/treating/immunotherapy.html.
33. ↑ "Treating B-Cell Non-Hodgkin Lymphoma". American Cancer Society. 2019. https://www.cancer.org/cancer/non-hodgkin-lymphoma/treating/b-cell-lymphoma.html.
34. ↑ "With hard-fought Polivy approval, Roche looks to shake up decades of established practice in lymphoma". Fierce Pharma. https://www.fiercepharma.com/pharma/roche-wins-hard-fought-fda-approval-polivy-changing-20-years-lymphoma-practice.
35. ↑ 35.0 35.1 35.2 35.3 "Mesenchymal stromal cells as treatment or prophylaxis for acute or chronic graft-versus-host disease in haematopoietic stem cell transplant (HSCT) recipients with a haematological condition". The Cochrane Database of Systematic Reviews 1 (1). January 2019. doi:10.1002/14651858.CD009768.pub2. PMID 30697701.
36. ↑ 36.0 36.1 "Prophylactic platelet transfusion for prevention of bleeding in patients with haematological disorders after chemotherapy and stem cell transplantation". The Cochrane Database of Systematic Reviews (5). May 2012. doi:10.1002/14651858.CD004269.pub3. PMID 22592695.
37. ↑ "Comparison of different platelet count thresholds to guide administration of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation". The Cochrane Database of Systematic Reviews 2015 (11). November 2015. doi:10.1002/14651858.CD010983.pub2. PMID 26576687.
38. ↑ 38.0 38.1 38.2 "Aerobic physical exercise for adult patients with haematological malignancies". The Cochrane Database of Systematic Reviews 1 (1). January 2019. doi:10.1002/14651858.CD009075.pub3. PMID 30702150.
39. ↑ "Survival Rates and Factors That Affect Prognosis (Outlook) for Non-Hodgkin Lymphoma". https://www.cancer.org/cancer/types/non-hodgkin-lymphoma/detection-diagnosis-staging/factors-prognosis.html.
40. ↑ "Prognosis and survival for non-Hodgkin lymphoma". October 2023. https://cancer.ca/en/cancer-information/cancer-types/non-hodgkin-lymphoma/prognosis-and-survival.
41. ↑ "Non-Hodgkin Lymphoma Treatment - NCI". 24 November 2023. https://www.cancer.gov/types/lymphoma/patient/adult-nhl-treatment-pdq#_158.
42. ↑ "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010.". Lancet 380 (9859): 2095–128. 15 December 2012. doi:10.1016/S0140-6736(12)61728-0. PMID 23245604. PMC 10790329. https://zenodo.org/record/2557786.
43. ↑ Patte, Catherine; Bleyer, Archie; Cairo, Mitchell S. (2007). "Non-Hodgkin Lymphoma". Cancer in Adolescents and Young Adults (Pediatric Oncology). Springer. p. 129. doi:10.1007/978-3-540-68152-6_9. ISBN 978-3-540-40842-0.
44. ↑ "What is non-Hodgkin lymphoma?". 2023. https://www.leukaemia.org.au/blood-cancer/lymphoma/non-hodgkin-lymphoma/.
45. ↑ "Canadian Cancer Statistics". http://www.cancer.ca/en/cancer-information/cancer-101/canadian-cancer-statistics-publication/?region=on.
46. ↑ "Non-hodgkin lymphoma statistics". 14 May 2015. http://www.cancerresearchuk.org/cancer-info/cancerstats/types/nhl/.
47. ↑ "Cancer Stat Facts: Non-Hodgkin Lymphoma". National Cancer Institute: Surveillance, Epidemiology, and End Results (SEER) Program. https://seer.cancer.gov/statfacts/html/nhl.html.
48. ↑ "Key Statistics for Non-Hodgkin Lymphoma". https://www.cancer.org/cancer/non-hodgkin-lymphoma/about/key-statistics.html.

## External links

* Non-Hodgkin Lymphoma at American Cancer Society
* Non-Hodgkins Lymphoma from Cancer.net (American Society of Clinical Oncology)

Classification|

* ICD-10: C82-C85
* ICD-9-CM: 200, 202
* ICD-O: 9591/3
* OMIM: 605027
* MeSH: D008228
* DiseasesDB: 9065

|

External resources|

* MedlinePlus: 000581
* eMedicine: med/1363 ped/1343

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