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Lookup NU author(s): Professor Anthony MoormanORCiD
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© 2022 The American Society of Hematology. 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 (NHL) 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.
Author(s): Elitzur S, Vora A, Burkhardt B, Inaba H, Attarbaschi A, Baruchel A, Escherich G, Gibson B, Liu H-C, Loh M, Moorman AV, Moricke A, Pieters R, Uyttebroeck A, Baird S, Bartram J, Barzilai-Birenboim S, Batra S, Ben-Harosh M, Bertrand Y, Buitenkamp T, Caldwell K, Drut R, Geerlinks AV, Gilad G, Grainger J, Haouy S, Heaney N, Huang M, Ingham D, Krenova Z, Kuhlen M, Lehrnbecher T, Manabe A, Niggli F, Paris C, Revel-Vilk S, Rohrlich P, Sinno MG, Szczepanski T, Tamesberger M, Warrier R, Wolfl M, Nirel R, Izraeli S, Borkhardt A, Schmiegelow K
Publication type: Article
Publication status: Published
Journal: Blood
Year: 2023
Volume: 141
Issue: 7
Pages: 743-755
Online publication date: 06/11/2022
Acceptance date: 08/10/2022
ISSN (print): 0006-4971
ISSN (electronic): 1528-0020
Publisher: American Society of Hematology
URL: https://doi.org/10.1182/blood.2022016975
DOI: 10.1182/blood.2022016975
PubMed id: 36332176
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