EBV-driven lymphoid neoplasms associated with pediatric ALL maintenance therapy

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Authors

ELITZUR Sarah VORA Ajay BURKHARDT Birgit INABA Hiroto ATTARBASCHI Andishe BARUCHEL Andre ESCHERICH Gabriele GIBSON Brenda LIU Hsi-Che LOH Mignon ANTHONY V Moorman MOERICKE Anja PIETERS Rob UYTTEBROECK Anne BAIRD Susan BARTRAM Jack BARZILAI-BIRENBOIM Shlomit BATRA Sandeep BEN-HAROSH Miriam BERTRAND Yves BUITENKAMP Trudy CALDWELL Kenneth DRUT Ricardo GEERLINKS Ashley V GILAD Gil GRAINGER John HAOUY Stephanie HEANEY Nicholas HUANG Mary INGHAM Danielle KŘENOVÁ Zdenka KUHLEN Michaela LEHRNBECHER Thomas MANABE Atsushi NIGGLI Felix PARIS Claudia REVEL-VILK Shoshana ROHRLICH Pierre SINNO Mohamad G SZCZEPANSKI Tomasz TAMESBERGER Melanie WARRIER Rajasekharan WOLFL Matthias NIREL Ronit IZRAELI Shai BORKHARDT Arndt SCHMIEGELOW Kjeld

Year of publication 2023
Type Article in Periodical
Magazine / Source Blood
MU Faculty or unit

Faculty of Medicine

Citation
Web https://ashpublications.org/blood/article-abstract/141/7/743/487024/EBV-driven-lymphoid-neoplasms-associated-with?redirectedFrom=fulltext
Doi http://dx.doi.org/10.1182/blood.2022016975
Keywords EBV-driven lymphoid neoplasms; pediatric ALL; maintenance therapy
Description The development of a second malignancy after the diagnosis of childhood acute lymphoblastic leukemia (ALL) is a rare event. Certain second malignancies have been linked with specific elements of leukemia therapy, yet the etiology of most second neoplasms remains obscure and their optimal management strategies are unclear. This is a first comprehensive report of non-Hodgkin lymphomas (NHLs) following pediatric ALL therapy, excluding stem-cell transplantation. We analyzed data of patients who developed NHL following ALL diagnosis and were enrolled in 12 collaborative pediatric ALL trials between 1980-2018. Eighty-five patients developed NHL, with mature B-cell lymphoproliferations as the dominant subtype (56 of 85 cases). Forty-six of these 56 cases (82%) occurred during or within 6 months of maintenance therapy. The majority exhibited histopathological characteristics associated with immunodeficiency (65%), predominantly evidence of Epstein-Barr virus-driven lymphoproliferation. We investigated 66 cases of post-ALL immunodeficiency-associated lymphoid neoplasms, 52 from our study and 14 additional cases from a literature search. With a median follow-up of 4.9 years, the 5-year overall survival for the 66 patients with immunodeficiency-associated lymphoid neoplasms was 67.4% (95% confidence interval [CI], 56-81). Five-year cumulative risks of lymphoid neoplasm- and leukemia-related mortality were 20% (95% CI, 10.2-30) and 12.4% (95% CI, 2.7-22), respectively. Concurrent hemophagocytic lymphohistiocytosis was associated with increased mortality (hazard ratio, 7.32; 95% CI, 1.62-32.98; P =.01). A large proportion of post-ALL lymphoid neoplasms are associated with an immunodeficient state, likely precipitated by ALL maintenance therapy. Awareness of this underrecognized entity and pertinent diagnostic tests are crucial for early diagnosis and optimal therapy.
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