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Non-Hodgkin Lymphoma: Causes, Symptoms & Treatment

Non-Hodgkin lymphoma is a diverse group of blood cancers affecting the lymphatic system. Abnormal lymphocytes multiply uncontrollably, leading to various clinical presentations.

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Things worth knowing about "Non-Hodgkin lymphoma"

Non-Hodgkin lymphoma is a diverse group of blood cancers affecting the lymphatic system. Abnormal lymphocytes multiply uncontrollably, leading to various clinical presentations.

What is Non-Hodgkin Lymphoma?

Non-Hodgkin lymphoma (NHL) refers to a large and diverse group of malignant cancers that originate in the lymphatic system. Unlike Hodgkin lymphoma, NHL lacks the characteristic Reed-Sternberg cells. The disease arises from malignant lymphocytes – white blood cells of the immune system – and can affect both B-lymphocytes and T-lymphocytes. NHL encompasses more than 60 distinct subtypes, which differ considerably in their behavior, treatment, and prognosis.

Causes and Risk Factors

The exact causes of Non-Hodgkin lymphoma are not fully understood in many cases. Several factors are known to increase the risk:

Immune deficiency: Congenital or acquired immunodeficiency (e.g., HIV infection, immunosuppressive therapy following organ transplantation)
Viral infections: Epstein-Barr virus (EBV), hepatitis C virus (HCV), or human T-lymphotropic virus (HTLV-1)
Autoimmune diseases: Such as rheumatoid arthritis or Sjogren syndrome
Chemical and radiation exposure: Exposure to pesticides, herbicides, or ionizing radiation
Age and sex: Risk increases with age; men are slightly more affected than women

Symptoms

Symptoms of Non-Hodgkin lymphoma can vary depending on the subtype and extent of the disease. Common signs include:

Painless swelling of the lymph nodes (e.g., in the neck, armpits, or groin)
B symptoms: Fever, night sweats, and unexplained weight loss
Fatigue and general weakness
Enlargement of the spleen or liver
Breathing difficulties or pressure in the chest when the mediastinum is involved
Abdominal pain or digestive issues when the abdomen is affected

Diagnosis

Diagnosing NHL requires a combination of investigative methods:

Physical examination: Palpation of lymph nodes and organs
Blood tests: Complete blood count, LDH levels, liver enzymes, and other laboratory parameters
Biopsy: Removal and histological examination of lymph node tissue – this is the decisive step for diagnosis and subtype classification
Imaging: Computed tomography (CT), positron emission tomography (PET-CT), or magnetic resonance imaging (MRI) to determine the extent of disease (staging)
Bone marrow biopsy: If bone marrow involvement is suspected

Classification and Staging

NHL is classified according to the Ann Arbor classification into four stages (I to IV), depending on how widely the disease has spread throughout the body. A further distinction is made between indolent (slow-growing) and aggressive (fast-growing) lymphomas.

Treatment

Treatment depends on the subtype, stage, and overall health of the patient. The main treatment options include:

Chemotherapy

Chemotherapy is frequently the cornerstone of NHL treatment. A widely used regimen is R-CHOP, which combines rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.

Immunotherapy and Monoclonal Antibodies

Rituximab is a monoclonal antibody that specifically targets the CD20 protein on B-lymphocytes, destroying these cells. It is used in many B-cell lymphomas.

Radiation Therapy

For locally confined disease or as consolidation after chemotherapy, radiation therapy may be applied.

Stem Cell Transplantation

For relapsed or refractory NHL, autologous or allogeneic stem cell transplantation may be considered.

Targeted Therapies and CAR T-Cell Therapy

Newer approaches include targeted therapies (e.g., BTK inhibitors such as ibrutinib) and the innovative CAR T-cell therapy, in which a patient's own T cells are genetically modified to specifically attack lymphoma cells.

Watchful Waiting

For indolent lymphomas without disease-related symptoms, an initial watch-and-wait approach may be justified.

Prognosis

Prognosis depends strongly on the subtype, stage, and response to therapy. Aggressive NHL often responds well to intensive chemotherapy and can be cured in many cases. Indolent NHL follows a chronic course and is frequently not curable, but can be controlled for many years. Modern treatment approaches have significantly improved survival rates.

References

Swerdlow SH et al. (eds.) - WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th edition. IARC Press, Lyon, 2017.
Cheson BD et al. - Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. Journal of Clinical Oncology. 2014;32(27):3059-3068.
National Cancer Institute (NCI) - Non-Hodgkin Lymphoma Treatment (PDQ). Available at: https://www.cancer.gov/types/lymphoma/patient/adult-nhl-treatment-pdq

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