The Feasibility of Introducing a Harmonised Treatment Regimen, Comparing Affordable Blood Tests and PET-CT Scans, to Improve Two-Year Survival Rates in Children, Adolescents and Young Adults with Hodgkin Lymphoma in South Africa

Abstract

Paediatric classical Hodgkin lymphoma (cHL) is highly curable using chemotherapy and radiotherapy. Prior to this study, no collaborative, prospective cHL studies had been performed in South Africa. The retrospective assessment informed the creation of the prospective harmonised guideline. We aimed to determine a baseline survival rate and prognostic factors; explore reasons for mortality in HIV-positive patients, assess the feasibility of introducing a harmonised treatment guideline, prospectively assess survival and analyse the prediction of chemosensitivity at interim assessment. In the retrospective analysis, multiple potential prognostic factors were analysed and survival rates calculated with Kaplan-Meier curves and Cox regression analysis. An initial survey was conducted of the clinical researchers before the launch of the prospective study, followed by a mid-study assessment. Two-year overall survival was calculated by Kaplan-Meier curves and computer-learning models were utilised to compare chemosensitivity based on interim PET-CT assessment with changes in haematological and non-specific markers of disease activity. The retrospective analysis accrued 294 patients, of whom 29 were HIV-positive. The 5-year overall survival was 84% in HIV-negative and 49% in HIV-positive patients. Advanced stage, HIV infection and treatment with regimens other than doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) were associated with lower survival rates. In HIV-positive patients, an AIDS-defining CD4 count and hypoalbuminaemia were associated with poorer prognosis. The pre-study assessment indicated that the majority of centres fulfilled all criteria to participate in the study. The mid-study assessment identified barriers to participation and methods to mitigate these challenges. Analysis of 132 prospectively accrued patients (19 HIV-positive, 113 HIV-negative) treated on a risk-stratified, response-adjusted treatment regimen resulted in higher survival rates of 93% in HIV-negative and 89% in HIV-positive patients. Changes in low-cost, widely available blood tests correctly predicted chemosensitivity, identifying patients who may not require radiotherapy. In conclusion, higher survival rates for paediatric cHL were documented following the introduction of a harmonised management guideline in South Africa. In settings that do not have access to PET-CT, changes in affordable blood tests may be used to substitute for xvi radiological interim assessment, although a format suitable for individual patients is yet to be developed for the clinical setting. This research marks the inaugural collaborative effort where patients from every South African paediatric oncology unit and the majority of private paediatric oncology practices, were afforded the opportunity to participate in a prospective study aimed at enhancing survival rates.