Treatment of high-risk Hodgkin Lymphoma with a modified Stanford V regimen in the AHOPCA: substituting chemotherapy agents and hampered outcomes

Background: /Objectives: High-risk Hodgkin lymphoma (HRHL) in children is a curable with combined modality therapy. The AHOPCA is a consortium of cancer centers from Central America. In 2004, AHOPCA implemented a guideline with a short course of chemotherapy (mStanfordV), strict diagnostics and radiation guidelines, aimed at reducing abandonment and improving outcomes. Methods: Newly diagnosed children less than 18 years of age with high-risk HL (Ann Arbor stages: IIB, IIIB, IV) from AHOPCA centers were staged with chest X-ray, and ultrasound or CT. Therapy was a modified StanfordV (mStanfordV) substituting cyclophosphamide for mechlorethamine and involved field radiation. Results: Of 219 patients with HRHL, 181 patients were eligible and evaluable;146 (81%) were boys, 22% being less than 6 years; 43 were stage IIB, 84 IIIB and 54 IV. Thirty-one (17%) abandoned therapy, 28 (15%) progressed, 30 (17%) relapsed and 8 (4%) died of toxicity. Radiation guidelines were not followed. Five-year abandonment-sensitive event-free survival and overall survival (AS-EFS, AS-OS±SE) for the cohort were 46±4% and 56±4%; 5-year AS-OS for stages IIB, IIIB and IV was 76±7%, 59±7%, and 35±7% (p=0.0006). Conclusion: Despite instituting a short treatment guideline, it did not improve the abandonment rate (17%) and did not achieve the reported outcomes of StanfordV. The cyclophosphamide dose used to replace merchlorethamine was inadequate. Despite strict guidelines, the radiation therapy application was inaccuarate. Weekly chemotherapy may have adversely affected abandonment of therapy by increasing the burden of travel-time. Based on these results, AHOPCA established a new abandonment strategy and a new guideline.