Pediatric Hodgkin Lymphoma Treatment & Management

Hodgkin lymphoma is one of the most curable malignancies of childhood and adolescence. Hodgkin lymphoma can be cured with radiation therapy, chemotherapy, or a combination of both. However, acute and late toxicities vary substantially according to the treatment modality used. Therefore, most modern pediatric treatment strategies focus on reducing late effects of therapy while maintaining excellent cure rates with risk-adapted chemotherapy alone or response-adjusted combined-modality regimens.^[7]

Placement of a peripheral or central venous catheter for chemotherapy and supportive care is suggested but not required. The decision to place a central venous catheter should be based on the intensity of the treatment, the level of supportive care anticipated, the state of the patient's peripheral venous access, and the patient's preference.

Staging laparotomy and splenectomy are no longer routinely performed in patients with Hodgkin lymphoma. In patients with suspicious lesions on imaging performed for staging, biopsy is sometimes necessary if the findings might alter the treatment regimen.

Children with Hodgkin lymphoma should be treated at a pediatric oncology center where pediatric oncologists, radiation therapists, and full ancillary services are available for children with malignancies. Initial evaluation, staging, and subsequent treatment of Hodgkin lymphoma (Hodgkin's lymphoma) can be performed on an outpatient basis. Admission is sometimes indicated for supportive medical care. Some clinical trials that treat pediatric patients with Hodgkin lymphoma accept patient enrollments well into the third decade of patient life.

Radiation therapy was the first curative modality used for Hodgkin lymphoma. However, the doses and fields used for the treatment of adult Hodgkin lymphoma causes profound musculoskeletal retardation, cardiac toxicity, and increased incidence of secondary malignancies in the radiation field (eg, breast cancer in female survivors).

Currently, radiation is used as an adjuvant treatment after chemotherapy. To reduce complications, risk-adapted or response-based, low-dose, involved-field, or extended-field radiation is given. In current trials, the use of nodal conformal radiation is being evaluated to further decrease the burden of radiation to other tissues.

Positron emission tomography (PET) scanning is becoming an important modality to guide involved-field radiation therapy in adult Hodgkin lymphoma,^[5] and its role in guiding involved-field radiation therapy in pediatrics is being explored.

Chemotherapy alone is effective and prevents radiation-associated treatment complications. This approach is recommended especially in centers where pediatric radiation therapy is not feasible but where chemotherapy can be reliably administered. However, in pediatric oncology centers with well-developed pediatric radiation programs, combined-modality therapy is preferred to avoid the high cumulative doses of alkylating agents, bleomycin, and anthracyclines used in chemotherapy-only protocols.

Although combined chemotherapy and radiation broadens the spectrum of potential toxicities, the incidence and severity of individual drug or radiation-related toxicities are generally reduced because of the lowered doses of each component.

Regimens that contain alkylating agents without anthracyclines include the following:

• Mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)
• Cyclophosphamide, vincristine, procarbazine, and prednisone (COPP)
• Cyclophosphamide, vincristine, methotrexate, and prednisone (COMP)
• Cyclophosphamide, vinblastine, procarbazine, and prednisone (CVPP)
• Chlorambucil, vinblastine, procarbazine, and prednisone (ChVPP)

Regimens that contain anthracyclines without alkylating agents include the following:

• Adriamycin (doxorubicin), bleomycin, vinblastine, and dacarbazine (ABVD)
• Doxorubicin, bleomycin, vincristine, and etoposide (ABVE)
• Vincristine (Oncovin), etoposide, prednisone, and doxorubicin (Adriamycin) (OEPA)
• Vincristine, doxorubicin (Adriamycin), methotrexate, and prednisone (VAMP)
• Vinblastine, bleomycin, etoposide, and prednisone (VBVP)

Regimens that contain alkylating agents and anthracyclines include the following:

• Adriamycin (doxorubicin), bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC)
• Bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP)
• Cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin (Adriamycin), bleomycin, and vinblastine (COPP/ABV)
• Vincristine, procarbazine, prednisone, and doxorubicin (Adriamycin) (OPPA)
• Doxorubicin (Adriamycin), vinblastine, nitrogen mustard, vincristine, bleomycin, etoposide, and prednisone (Stanford V)

Other combinations of chemotherapeutic agents, as well as novel therapies, have been studied and found effective in front-line and salvage therapy for Hodgkin lymphoma.^{[11, 12]}

Standard treatment regimens for pediatric Hodgkin lymphoma are as follows:

Treatment of Early or Favorable Disease

For early or favorable disease (stage IA or IIA with < 3 nodal sites), standard treatment includes 2-4 chemotherapy cycles without alkylators (ie, VAMP; etoposide, bleomycin, vinblastine, and prednisone [EBVP]; OEPA; or ABVE) plus low-dose, involved-field radiation of 15-30 Gy or 6 chemotherapy cycles (alternating COPP and ABVD or derivatives of these regimens) and no irradiation.

The use of very limited doses of chemotherapy (2-3 cycles) should be administered only as part of a clinical trial.

Treatment of Intermediate-Stage Disease

For intermediate-risk disease (stage IA, IIA, or IIA bulky disease with extension or ≥3 nodal sites), standard treatment includes 4-6 chemotherapy cycles (ie, OPPA and COPP, Stanford V) plus low-dose, involved-field radiation of 15-30 Gy or 6 chemotherapy cycles (alternating COPP and ABVD or their derivatives).

Alternatively, a dose-intense, hybrid regimen (eg, Stanford V, ABVE-PC, or BEACOPP) and no irradiation may be used.

Treatment of Advanced or Unfavorable Disease

For advanced or unfavorable disease (stages IIB, IIIB, or IV), one of the following 3 approaches is used:

• 6-8 chemotherapy cycles (OPPA and/or COPP, ABVE-PC, BEACOPP) plus low-dose involved-field radiation of 15-30 Gy
• Eliminating radiation therapy from the treatment of patients in this category has reduced event-free survival.^[13]

A variety of medications may be used to counter the toxicities of treatment, such as the following:

• Patients may benefit from antiemetics (eg, ondansetron, diphenhydramine [Benadryl])
• Pain relievers may include codeine and gabapentin (for neuropathic pain secondary to vinca alkaloids)
• To protect the gastric mucosa, patients receiving steroids may be given H2-blockers or proton-pump inhibitors
• Pneumocystis prophylaxis and granulocyte colony-stimulating factor are also considered.

Patients require regular monitoring to assess their response to therapy and to check for adverse effects of treatment. During periods of decreased blood cell counts due to bone marrow suppressive effects of treatment, neutropenic and thrombocytopenic precautions should be observed.

In patients who achieve remission, 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. Most relapses occur in the first 3 years after therapy.