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A response-adjusted PET-based transplantation strategy in primary resistant and relapsed Hodgkin Lymphoma

Leukemia volume 27, pages 1419–1422 (2013)Cite this article

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Although the majority of patients with Hodgkin Lymphoma (HL) are cured by first-line therapy, there remains a group of 25–30% who either fail to achieve complete response (CR) with initial chemotherapy or who subsequently relapse. Increasing the intensity of primary treatment reduces this failure rate, but this must be balanced against greater toxicity and the debate surrounding the most appropriate first-line therapy continues.1 Autologous stem cell transplantation (ASCT) was established as the treatment of choice for relapsed HL in two randomised trials, resulting in long-term disease-free survival in 40–50% of those who achieved at least a partial response (PR) with first-line salvage.2, 3 However, for those patients who fail to achieve PR, those who relapse <12 months from the completion of initial treatment, those with extranodal disease at relapse, and those with primary resistant disease (less than CR, or progression within 3 months of completion of therapy) the prognosis is considerably worse.4, 5 More recently, the prognostic value of functional imaging in predicting outcomes of patients with recurrent or refractory HL has been evaluated.6, 7 Those with negative studies (metabolic CR, mCR) before ASCT had favourable outcomes (3–5 year progression-free survival (PFS) >70%). Those with chemosensitive disease but with residual metabolic activity, which occurred in 55–60% of those with PR by computerised tomography (CT) following first-line salvage, had only a 25–30% 3–5 year PFS. To improve the outcome after failure of primary therapy, alternative strategies are required for patients who fail to normalise functional imaging pre-ASCT.

Allogeneic hematopoietic stem cell transplantation is one possibility in these high-risk patients, although its use was previously limited by high procedure-related mortality. Reduced-intensity strategies have improved non-relapse-related mortality (NRM) rates,8, 9 allowing re-evaluation of a potential role in these patients.10, 11 We evaluated a fluorodeoxyglucose-positron emission tomography (FDG-PET)-directed transplant strategy using a more intensive conditioning protocol and report a retrospective analysis of mature data (median follow-up of 3.3 years) from this uniformly treated cohort. PET-CT scans were assessed in keeping with consensus recommendations incorporating visual analysis using a 5-point scale being applied in concurrent prospective lymphoma studies in the UK and subsequently ratified in the Deauville criteria, with a threshold of 4 or above considered positive.12, 13 Patients attaining mCR to first-line salvage received conventional consolidation with an autograft (carmustine (BCNU) 300 mg/m2 on day −6, etoposide 200 mg/m2 once daily and cytarabine 200 mg/m2 twice daily on days −5 to −2, and melphalan 140 mg/m2 on day −1 (BEAM)). Patients were considered for allogeneic transplantation if they failed to attain mCR to initial salvage, had at least stable disease following most recent salvage, and had an appropriate donor (fully HLA-matched sibling or 8–10/10 HLA-matched unrelated).

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Acknowledgements

This work was undertaken at University College London Hospitals/University College London, which received a proportion of funding from the Department of Health’s NIHR Biomedical Research Centres funding Scheme. The funding sources had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.

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Authors and Affiliations

  1. University College London Cancer Institute, London, UK

    K J Thomson, R Hough, D C Linch & K S Peggs

  2. Department of Haematology, University College London, University College London Hospitals NHS Trust, London, UK

    K J Thomson, I Kayani, K Ardeshna, E C Morris, R Hough, A Virchis, A H Goldstone, D C Linch & K S Peggs

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Correspondence to K S Peggs.

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Thomson, K., Kayani, I., Ardeshna, K. et al. A response-adjusted PET-based transplantation strategy in primary resistant and relapsed Hodgkin Lymphoma. Leukemia 27, 1419–1422 (2013). https://doi.org/10.1038/leu.2012.318

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