This trial proposes a therapy for pediatric Hodgkin lymphoma with the objective of achieving high levels of long lasting complete remission with less risk of late effects.
Patients of both genders, between 2 and 18 years, with newly diagnosed classical Hodgkin lymphoma are admitted.
Initial staging provides stratification in three groups: low, intermediate and high risk. An initial set of two chemotherapy courses is administered to all cases after which a new disease assessment is performed. According to disease response a final therapy group is assigned. Rapid early responders benefit from less chemotherapy. At the end of chemotherapy, radiotherapy is delivered only to patients who do not achieve a complete response. Thus therapy is tailored to initial extension and disease responsiveness. Complete responders at the end of chemotherapy do not receive radiotherapy. Those who are in partial remission receive low dose (30Gy) involved node radiotherapy. Stable or progressive disease at any moment is assumed as a trial failure and new therapeutic strategies are offered to patients off protocol.
Chemotherapy is based upon regimes with well known effectiveness in Hodgkin lymphoma. (i.e. ABVD: doxorubicin, bleomycin, vinblastine and dacarbazine and ESHAP: Etoposide, methyl prednisolone, citarabine and cisplatin). The schedules are delivered with low cumulative drug doses and avoiding the use of toxic alkylating agents. Risks of secondary leukemia and infertility are thus minimized. Doxorubicin and bleomycin do not achieve cumulative doses that may expose to significant risk of heart or lung damage. Radiotherapy reduction avoids late radiation sequels.
This clinical study proposes a therapeutic approach based on chemotherapy that do not sum up high cumulative toxic doses. Therapy is tailored according to initial risk assessment and disease responsiveness. Those who achieve a complete response to chemotherapy do not receive additional radiotherapy, thus avoiding further late effects.
Histopathological diagnosis of classical Hodgkin lymphoma.
Normal renal, hepatic, pulmonary and metabolic function standards.
Informed consent signed by patient and/or legal caretakers.
Lymphocyte predominant nodular Hodgkin lymphoma
Any form of immunodeficiency before diagnosis. (primary immunodeficiencies, trasplant recipients or immunosuppressive therapies of any kind including corticoid therapies during 28 days before diagnosis).
Pregnancy and breastfeeding period.
Sexually active female patients who do not accept an effective contraceptive method during therapy.
Parallel
No radiotherapy if CR at the end of chemotherapy.
RadiationAdapted chemotherapy without radiotherapy
Low risk with complete early response after two cycles of ABVD chemotherapy schedule. Only one more ABVD course is delivered.
DrugLow risk with complete early response after two cycles of ABVD chemotherapy schedule. Only one more ABVD course is delivered.
Low risk with partial remisssion after 4 cycles of ABVD chemotherapy schedule. Two ESHAP courses are delivered.
DrugLow risk with partial remission at early response assessment after two cycles of ABVD chemotherpay schedule. Two ABVD courses are delivered.
IN 30Gy RT in case of PR at the end of chemotherapy
RadiationLow risk with partial remisssion after 4 cycles of ABVD and 2 ESHAP courses: IN 30Gy RT
Intermediate risk with complete early response after two cycles of ABVD chemotherapy schedule. Three more ABVD courses are delivered.
DrugIntermediate risk with complete early response after two cycles of ABVD chemotherapy schedule. Three more ABVD courses are delivered.
Intermediate risk with partial remission after two cycles of ABVD chemotherapy schedule. Four more chemotherapy courses are delivered alternating ESHAP and ABVD.
DrugIntermediate risk with partial remission after two cycles of ABVD chemotherapy schedule. Four more chemotherapy courses are delivered alternating ESHAP and ABVD.
High risk with complete early response after 1 ABVD and 1 ESHAP courses. Four more chemotherapy courses are delivered alternating ESHAP and ABVD.
DrugHigh risk with complete early response after 1 ABVD and 1 ESHAP courses. Four more chemotherapy courses are delivered alternating ESHAP and ABVD.
High risk with partial remission after 1 ABVD and 1 ESHAP courses. Six more chemotherapy courses are delivered alternating ESHAP and ABVD.
DrugHigh risk with partial remission after 1 ABVD and 1 ESHAP courses. Six more chemotherapy courses are delivered alternating ESHAP and ABVD.
Low risk with partial remission at early response assessment after two cycles of ABVD chemotherpay schedule. Two ABVD courses are delivered.
DrugLow risk with partial remission at early response assessment after two cycles of ABVD chemotherpay schedule. Two ABVD courses are delivered.
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Treatment groupsSee each treatment group below.
Event-free Survival
Event free survival probability (event= relapse or death)
Overall Survival
Overall survival probability (event= death)
Acute, chronic or late toxic events
Number of patientsexperiencing treatment-related adverse effects and mortality according to CTCAE v4.0
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