TY - JOUR
T1 - A significant proportion of classic Hodgkin lymphoma recurrences represents clonally unrelated second primary lymphoma
AU - van Bladel, Diede Ag
AU - Stevens, Wendy B C
AU - Kroeze, Leonie I
AU - de Groen, Ruben Al
AU - de Groot, Fleur A
AU - van der Last-Kempkes, Jessica Lm
AU - Berendsen, Madeleine R
AU - Rijntjes, Jos
AU - Luijks, Jeroen A C W
AU - Bonzheim, Irina
AU - van der Spek, Ellen
AU - Plattel, Wouter J
AU - Pruijt, Johannes
AU - de Jonge-Peeters, Susan Dpwm
AU - Velders, Gerjo A
AU - Lensen, Chantal
AU - van Bladel, Esther R
AU - Federmann, Birgit
AU - Hoevenaars, Brigiet
AU - Pastorczak, Agata
AU - van der Werff Ten Bosch, Jutte
AU - Vermaat, Joost S P
AU - Nooijen, Peet
AU - Hebeda, Konnie M
AU - Fend, Falko
AU - Diepstra, Arjan
AU - van Krieken, J Han Jm
AU - Groenen, Patricia J T A
AU - van den Brand, Michiel
AU - Scheijen, Blanca
N1 - Copyright © 2023 American Society of Hematology.
PY - 2023/9/29
Y1 - 2023/9/29
N2 - 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.
AB - 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.
U2 - 10.1182/bloodadvances.2023010412
DO - 10.1182/bloodadvances.2023010412
M3 - Article
C2 - 37552109
SN - 0006-4971
VL - 7
SP - 5911
EP - 5924
JO - -
JF - -
IS - 19
ER -