Table III.

Evolution of Therapy for Pediatric Hodgkin Lymphoma

Treatment Modality	Decade					Historic Treatment Modalities Used in Contemporary Therapy
	1960	1970	1980	1990	Post-2000
Chemotherapy/Agents	Introduction of MOPP - first non-cross-resistant chemotherapy combination	Introduction of alternative non-cross resistant ABVD combination Introduction of MOPP derivative COPP, substituting cyclophosphamide for more toxic mechlorethamine.	Use of regimens alternating MOPP and ABVD (or derivatives) to reduce exposure to agents with dose-related toxicity	Introduction of risk-adapted regimens Use of etoposide as alternative to alkylating agents to reduce gonadal toxicity and enhance antitumor activity	Use of risk-adapted and response-based regimens Combination chemotherapy without alkylators for localized/favorable disease Combination chemotherapy with alkylators for advanced/unfavorable disease Introduction of alternate non-cross-resistant regimens for slow responders	Nitrogen mustard Vincristine (Oncovin) Prednisone Procarbazine Doxorubicin Bleomycin Vinblastine Dacarbazine Etoposide
Dose-Intensity/Duration	Standard treatment with 2 cycles beyond remission	6 to 12 cycles	4 to 6 to cycles based on presenting features	Introduction of abbreviated dose-dense chemotherapy 2 to 4 cycles for favorable/localized 4 to 6 cycles for unfavorable/advanced Duration (# cycles) based on early response		Risk-based, response-based Dose-dense regimens
Radiation Therapy	Definition of tumoricidal dose (35–40 Gy) and standard treatment fields of contiguous lymph nodes Extended treatment fields	Extended treatment fields Radiation therapy (35–40 Gy)as single modality favored for skeletally mature children with localized disease Low-dose (15–25.5 Gy) irradiation used with combination chemotherapy		Abandonment of high-dose radiation therapy alone. Low-dose (15–25.5 Gy) involved-field applied in conjunction with chemotherapy	Low-dose (15–25.5 Gy) involved-field targeting to involved (targeted) nodes Response-based No irradiation if early complete response in selected cases	Low-dose (15–25.5 Gy) involved-field to Involved (targeted) nodes
Staging		Laparotomy staging with splenectomy	Laparotomy staging with splenectomy limited to those with localized clinical staging.	Clinical staging with computed tomography and functional imaging (gallium).	Clinical staging with computed tomography and functional imaging (positron emission tomography).	Routine clinical staging with anatomic (CT) and functional imaging (PET) Surgical biopsy of equivocal staging findings only if results significantly impact treatment assignment

ABVD - Doxorubicin (Adriamycin), Bleomycin, Vinblastine, Dacarbazine; MOPP – Mechlorethamine, Vincristine (Oncovin), Procarbazine, Prednisone