A significant proportion of classic Hodgkin lymphoma recurrences represents clonally unrelated second primary lymphoma.
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van Bladel Diede A G, Stevens Wendy B C, Kroeze Leonie I, de Groen Ruben A L, de Groot Fleur A, van der Last-Kempkes Jessica L M, Berendsen Madeleine R, Rijntjes Jos, Luijks Jeroen A C W, Bonzheim Irina, van der Spek Ellen, Plattel Wouter J, Pruijt Johannes F M, de Jonge-Peeters Susan D P W M, Velders Gerjo A, Lensen Chantal, van Bladel Esther R, Federmann Birgit, Hoevenaars Brigiet M, Pastorczak Agata, van der Werff Ten Bosch Jutte, Vermaat Joost S P, Nooijen Peet T G A, Hebeda Konnie M, Fend Falko, Diepstra Arjan, van Krieken J Han J M, Groenen Patricia J T A, van den Brand Michiel, Scheijen Blanca
Аннотация
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 underinvestigated. To analyze the nature of cHL recurrences, in-depth clonality testing of immunoglobulin (Ig) and T-cell receptor (TCR) rearrangements was performed in paired cHL diagnoses and recurrences among 60 patients, supported by targeted mutation analysis of lymphoma-associated genes. Clonal Ig rearrangements were detected by next-generation sequencing (NGS) in 69 of 120 (58%) diagnoses and recurrence samples. The clonal relationship could be established in 34 cases, identifying clonally related relapsed cHL in 24 of 34 patients (71%). Clonally unrelated cHL was observed in 10 of 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 patients with cHL for whom the clonal relationship could be established showed a second primary cHL. Clonal TCR gene rearrangements were identified in 14 of 125 samples (11%), and TCL-associated gene mutations were detected in 7 of 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/TCR 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.