The genomic and clinical consequences of replacing procarbazine with dacarbazine in escalated BEACOPP for Hodgkin lymphoma: a retrospective, observational study

作者：Anna Santarsieri, Emily Mitchell, My H. Pham, Rashesh Sanghvi, Janina Jablonski, Henry Lee-Six, Katherine Sturgess, Pauline Brice, Tobias Menne, Wendy Osborne, Thomas Creasey, Kirit M. Ardeshna, E. Joanna Baxter, Sarah Behan, Kaljit Bhuller, Stephen Booth, Nikesh D Chavda, Graham P. Collins, Dominic Culligan, Kate Cwynarski, Andrew Davies, Abigail Downing, David Dutton, Michelle Furtado, Eve Gallop‐Evans, Andrew Hodson, David Hopkins, Hannah Hsu, Sunil Iyengar, Stephen G. Jones, Mamatha Karanth, Kim Linton, Oliver Lomas, Nicolás Martínez‐Calle, Abhinav Mathur, Pam McKay, Sateesh Nagumantry, Elizabeth H. Phillips, Neil Phillips, John F. Rudge, Nimish K Shah, Gwyneth Stafford, Alex Sternberg, Rachel Trickey, Benjamin J. Uttenthal, Natasha Wetherall, Xiaoyin Zhang, Andrew McMillan, Nicholas Coleman, Michael R. Stratton, Elisa Laurenti, Peter Borchmann, Sven Borchmann, Peter J. Campbell, Raheleh Rahbari, George Follows · 发表于：The Lancet Oncology · 年份：2024 · DOI：10.1016/s1470-2045(24)00598-9 · 被引用次数：12 · 研究领域：Lymphoma Diagnosis and Treatment、CAR-T cell therapy research、Acute Lymphoblastic Leukemia research

BACKGROUND: Procarbazine-containing chemotherapy regimens are associated with cytopenias and infertility, suggesting stem-cell toxicity. When treating Hodgkin lymphoma, procarbazine in escalated-dose bleomycin-etoposide-doxorubicin-cyclophosphamide-vincristine-procarbazine-prednisolone (eBEACOPP) is increasingly replaced with dacarbazine (eBEACOPDac) to reduce toxicity. We aimed to investigate the impact of this drug substitution on the mutation burden in stem cells, patient survival, and toxicity. METHODS: In this two-part retrospective, observational study, we first compared mutational landscapes in haematopoietic stem and progenitor cells (HSPCs) from patients with advanced-stage Hodgkin lymphoma in remission for at least 6 months who had been treated with eBEACOPDac (eBEACOPDac cohort), eBEACOPP (real-world eBEACOPP cohort), or doxorubicin-bleomycin-vinblastine-dacarbazine (ABVD); in buccal DNA from five children of a female patient with classical Hodgkin lymphoma treated with eBEACOPP before conceiving the third child; in sperm DNA from a patient with mild oligospermia treated with eBEACOPP; and in caecal adenocarcinoma and healthy colon tissue from a survivor of Hodgkin lymphoma treated with chlorambucil-vinblastine-procarbazine-prednisolone. For the second part, we analysed efficacy and toxicity data from adult patients (aged >16 years) treated with first-line eBEACOPDac (eBEACOPDac cohort) at 25 centres across UK, Ireland, and France; efficacy was compared with the Ge...