MD2B - Pediatric Oncology: Hodgkin's Lymphoma

Overview

Hodgkin lymphoma, also known as Hodgkin disease, is a cancer that originates in the lymphatic system. This system consists of organs that produce, store, and transport white blood cells to sites of infection throughout the body. Since lymphatic tissue is distributed across the body, Hodgkin lymphoma can develop and spread to almost any site. The disease follows a bimodal age distribution, with one peak in young adults and a second in the elderly. It accounts for 7% of childhood cancers and is the most common cancer in adolescents aged 15-19, where it is more prevalent in males than females. Under the microscope, Hodgkin lymphoma is identified by the presence of characteristic "owl-eyed" Reed-Sternberg multinucleated giant cells surrounded by inflammatory cells. The Epstein-Barr Virus (EBV) is associated with 20% of pediatric Hodgkin cases.

Symptoms

Hodgkin lymphoma can present in various ways. Most commonly, patients exhibit painless swollen lymph nodes in the neck, under the arms, or in the groin. The liver and spleen, being lymphatic organs, may also be enlarged. Children may experience nonspecific systemic symptoms such as fatigue and loss of appetite. The "classic" symptoms—fever, night sweats, unexplained weight loss, and pruritus (itchy skin)—occur in only 20% of children but hold significant prognostic and staging value when present. Other conditions that can present with similar symptoms include other cancers, infections, lymphatic disorders, and lupus.

Diagnosis

A careful history and physical exam are the first steps in evaluating a child for Hodgkin lymphoma. Parents should be asked about the child's previous health history, family history of cancer or lymphatic diseases, and any recent changes in the child's health. During the physical exam, all lymph nodes should be palpated and measured with particular attention given to the tonsils, liver, and spleen. Enlarged lymph nodes are typically painless, firm and rubbery in texture. Any pulmonary or neurological changes should also be noted, as they may indicate disease spread to other parts of the body.

Lab studies

• CBC (complete blood count) with differential: A blood sample is taken to assess the number and shape of various blood cells, including red blood cells, white blood cells, and platelets.
• Chemistry panel: A blood sample is analyzed to evaluate kidney and liver function and to measure levels of salt, enzymes, and other chemicals in the blood.
• ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein): These blood tests detect the presence of inflammation.

Imaging studies

• Chest X-ray and chest CT scan: A chest radiograph provides important information about structures in the chest, including the lungs and airways. Two-thirds of children with Hodgkin lymphoma present with a mass in the mediastinum.
• Abdominal and pelvic CT scans: These diagnostic imaging tests are used to assess the extent of disease spread in the abdominal and pelvic regions.
• PET (positron emission tomography): These diagnostic imaging tests evaluate glucose uptake in the body and can help to identify areas where cancer is present.

Lymph node biopsy

A tissue sample from an enlarged lymph node is the preferred method for diagnosing Hodgkin lymphoma. A definitive diagnosis is confirmed by the presence of classic multinucleated Reed-Sternberg cells under the microscope. Subclassification of the disease is possible based on the identification of specific cell types within the sample.

Staging and Prognostic Factors

Stage I: Involvement of a single lymph node region or direct extension from that node to an adjacent extralymphatic region.

Stage II: Involvement of two or more lymph node regions on the same side of the diaphragm, or extension from any one of these lymph nodes to an extralymphatic adjacent organ.

Stage III: Involvement of lymph node regions on both sides of the diaphragm, or extension to an adjacent extralymphatic organ or to the spleen.

Stage IV: Noncontinuous involvement of one or more organs.

Several factors contribute to prognosis, including extensive disease, the presence of "B symptoms" (fever, night sweats, weight loss, and itchy skin), elevated erythrocyte sedimentation rate, male sex, and a poor initial response to treatment- all of which are associated with a worse prognosis. Overall, however, prognosis is generally excellent, with up to 95% of patients achieving cure. Thus, treatment is administered with the dual goals of eradicating the disease and minimizing long-term toxicity.

Treatment

Multidrug chemotherapy and low-dose radiation therapy are administered concurrently to maximize treatment efficacy. The side effects of radiation therapy depend on the total dose delivered and the specific areas of the body irradiated. Potential toxicities include skin reddening, hair thinning, taste changes, and gastrointestinal discomfort. Long-term effects of radiation may include delayed bone growth, short stature, pulmonary dysfunction, cardiac complications, endocrine abnormalities, and the development of secondary malignancies within the radiation field. Chemotherapy side effects may include nausea, vomiting, and increased susceptibility to infection. Long-term side effects, such as cardiac and pulmonary complications, vary depending on the specific drugs used.

Specific regimens typically vary based on risk level. A patient’s risk level depends on disease stage and the presence or absence of tumor bulk.

Low-risk: Chemotherapy plus low dose radiation therapy. There are several chemotherapy regimens available including VAMP (vinblastine, doxorubicin, methotrexate, prednisone) and ABVE (doxorubicin, bleomycin, vinblastine, etoposide).

Intermediate-risk: Typically treated with more aggressive chemotherapy regimens, such as COPP (cyclophosphamide, vincristine, procarbazine, prednisone) and low-dose radiation therapy.

High-risk: Intensified therapy is recommended. One treatment approach includes the use of brentuximab vedotin, doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide (Bv-AVE-PC), followed by radiation therapy.