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    Childhood Hodgkin Lymphoma Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Treatment for Newly Diagnosed Children and Adolescents with Hodgkin Lymphoma

    Historical Overview of Treatment for Hodgkin Lymphoma

    Long-term survival has been achieved in children and adolescents with Hodgkin lymphoma using radiation, multiagent chemotherapy, and combined-modality therapy. In selected cases of localized lymphocyte-predominant Hodgkin lymphoma, complete surgical resection may be curative and obviate the need for cytotoxic therapy.

    Treatment options for children and adolescents with Hodgkin lymphoma include the following:

    1. Radiation therapy as a single modality.
      • Recognition of the excess adverse effects of high-dose radiation therapy on musculoskeletal development in children motivated investigations of multiagent chemotherapy alone or with lower radiation doses (15-25.5 Gy) to reduced treatment volumes (involved-fields) and multiagent chemotherapy. It also led to the abandonment of the use of radiation as a single modality and restriction of its use in contemporary trials.[1,2,3]
      • Recognition of the excess risk of cardiovascular disease and secondary carcinogenesis in adult survivors who were treated for Hodgkin lymphoma during childhood led to the restriction of radiation therapy as a single modality in contemporary trials.[4,5]
    2. Multiagent chemotherapy as a single modality.
      • The establishment of the noncross-resistant combinations of MOPP (mechlorethamine, vincristine [Oncovin], procarbazine, and prednisone) developed in the 1960s and ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, dacarbazine) developed in the 1970s made long-term survival possible for patients with advanced and unfavorable (e.g., bulky, symptomatic) Hodgkin lymphoma.[6,7] MOPP-related sequelae include a dose-related risk of infertility and secondary myelodysplasia and leukemia.[2,8] The use of MOPP-derivative regimens substituting less leukemogenic and gonadotoxic alkylating agents (e.g., cyclophosphamide) for mechlorethamine or restricting cumulative alkylating agent dose exposure reduces this risk.[9] ABVD-related sequelae include a dose-related risk of cardiopulmonary toxicity related to doxorubicin and bleomycin. The cumulative dose of these agents is proactively restricted in pediatric patients to reduce this risk.[10,11,12]
      • In an effort to reduce chemotherapy-related toxicity, hybrid regimens alternating MOPP and ABVD or derivative therapy were developed that utilized lower total cumulative doses of alkylators, doxorubicin, and bleomycin.[13,14]
      • Etoposide has been incorporated into treatment regimens as an effective alternative to alkylating agents in an effort to reduce gonadal toxicity and enhance antineoplastic activity.[15] Etoposide-related sequelae include an increased risk of secondary myelodysplasia and leukemia that appears to be rare when etoposide is used in restricted doses in pediatric Hodgkin lymphoma regimens.[16]
      • All of the agents in original MOPP and ABVD regimens continue to be used in contemporary pediatric treatment regimens. COPP (substituting cyclophosphamide for mechlorethamine) has almost uniformly replaced MOPP as the preferred alkylator regimen in most frontline trials.
    3. Radiation therapy and multiagent chemotherapy as a combined-modality therapy. Considerations for the use of multiagent chemotherapy alone versus combined-modality therapy include the following:
      • Treatment with noncross-resistant chemotherapy alone offers advantages for children managed in centers lacking radiation facilities and trained personnel, as well as diagnostic imaging modalities needed for clinical staging. This treatment option also avoids the potential long-term growth inhibition, organ dysfunction, and solid tumor induction associated with radiation.
      • Chemotherapy-alone treatment protocols usually prescribe higher cumulative doses of alkylating agent and anthracycline chemotherapy, which may produce acute- and late-treatment morbidity from myelosuppression, cardiac toxic effects, gonadal injury, and secondary leukemia.
      • In general, the use of combined chemotherapy and low-dose involved-field radiation therapy (LD-IFRT) broadens the spectrum of potential toxicities, while reducing the severity of individual drug-related or radiation-related toxicities. The results of prospective and controlled randomized trials indicate that combined modality therapy, compared with chemotherapy alone, produces a superior event-free survival (EFS). However, because of effective second-line therapy, overall survival (OS) has not differed among the groups studied.[17,18]
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