A significant proportion of classic Hodgkin lymphoma recurrences represents clonally unrelated second primary lymphoma.
Diede A G van BladelWendy B C StevensLeonie I KroezeRuben Al de GroenFleur A de GrootJessica Lm van der Last-KempkesMadeleine R BerendsenJos RijntjesJeroen A C W LuijksIrina BonzheimEllen van der SpekWouter J PlattelJohannes PruijtSusan Dpwm de Jonge-PeetersGerjo A VeldersChantal LensenEsther R van BladelBirgit FedermannBrigiet HoevenaarsAgata PastorczakJutte van der Werff Ten BoschJoost S P VermaatPeet NooijenKonnie M HebedaFalko FendArjan DiepstraJ Han Jm van KriekenPatricia J T A GroenenMichiel van den BrandBlanca ScheijenPublished in: Blood advances (2023)
Despite high cure rates in classic Hodgkin lymphoma (cHL), relapses are observed. Whether relapsed cHL represents second primary lymphoma or an underlying T-cell lymphoma (TCL) mimicking cHL is under-investigated. To analyze the nature of cHL recurrences, in-depth clonality testing of immunoglobulin (IG) and T-cell receptor (TR) rearrangements was performed in paired cHL diagnosis and recurrences of 60 patients, supported by targeted mutation analysis of lymphoma-associated genes. Clonal IG rearrangements were detected by next-generation sequencing (NGS) in 69/120 (58%) diagnosis and recurrence samples. The clonal relationship could be established in 34 cases, identifying clonally related relapsed cHL in 24/34 patients (71%). Clonally unrelated cHL was observed in 10/34 patients (29%) as determined by IG-NGS clonality assessment, and confirmed by the identification of predominantly mutually exclusive gene mutations in the paired cHL samples. In recurrences of >2 years, ~60% of cHL patients for which the clonal relationship could be established showed a second primary cHL. Clonal TR gene rearrangements were identified in 14/125 samples (11%), and TCL-associated gene mutations were detected in 7/14 samples. Retrospective pathology review with integration of the molecular findings were consistent with an underlying TCL in 5 patients aged >50 years. This study shows that cHL recurrences, especially after 2 years, sometimes represent a new primary cHL or TCL mimicking cHL, as uncovered by NGS-based IG/TR clonality testing and gene mutation analysis. Given the significant therapeutic consequences, molecular testing of a presumed relapse in cHL is crucial for subsequent appropriate treatment strategies adapted to the specific lymphoma presentation.
Keyphrases
- end stage renal disease
- hodgkin lymphoma
- newly diagnosed
- chronic kidney disease
- peritoneal dialysis
- diffuse large b cell lymphoma
- acute myeloid leukemia
- prognostic factors
- patient reported outcomes
- gene expression
- genome wide
- cross sectional
- multiple myeloma
- transcription factor
- case report
- optical coherence tomography
- cell free