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EBV-driven lymphoid neoplasms associated with pediatric ALL maintenance therapy

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EBV-driven lymphoid neoplasms associated with pediatric ALL maintenance therapy. / Elitzur, Sarah; Vora, Ajay; Burkhardt, Birgit; Inaba, Hiroto; Attarbaschi, Andishe; Baruchel, Andre; Escherich, Gabriele; Gibson, Brenda Es; Liu, Hsi-Che; Loh, Mignon L; Moorman, Anthony V; Möricke, 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 Benjamin; Huang, Mary; Ingham, Danielle; Krenova, Zdenka; Kuhlen, Michaela; Lehrnbecher, Thomas; Manabe, Atsushi; Niggli, Felix; Paris, Claudia; Revel-Vilk, Shoshana; Rohrlich, Pierre; Sinno, Mohamad Ghazi; Szczepanski, Tomasz; Tamesberger, Melanie; Warrier, Rajasekharan; Wolfl, Matthias; Nirel, Ronit; Izraeli, Shai; Borkhardt, Arndt; Schmiegelow, Kjeld.

In: BLOOD, Vol. 141, No. 7, 16.02.2023, p. 743-755.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Elitzur, S, Vora, A, Burkhardt, B, Inaba, H, Attarbaschi, A, Baruchel, A, Escherich, G, Gibson, BE, Liu, H-C, Loh, ML, Moorman, AV, Möricke, 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, NB, 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 2023, 'EBV-driven lymphoid neoplasms associated with pediatric ALL maintenance therapy', BLOOD, vol. 141, no. 7, pp. 743-755. https://doi.org/10.1182/blood.2022016975

APA

Elitzur, S., Vora, A., Burkhardt, B., Inaba, H., Attarbaschi, A., Baruchel, A., Escherich, G., Gibson, B. E., Liu, H-C., Loh, M. L., Moorman, A. V., Möricke, A., Pieters, R., Uyttebroeck, A., Baird, S., Bartram, J., Barzilai-Birenboim, S., Batra, S., Ben-Harosh, M., ... Schmiegelow, K. (2023). EBV-driven lymphoid neoplasms associated with pediatric ALL maintenance therapy. BLOOD, 141(7), 743-755. https://doi.org/10.1182/blood.2022016975

Vancouver

Elitzur S, Vora A, Burkhardt B, Inaba H, Attarbaschi A, Baruchel A et al. EBV-driven lymphoid neoplasms associated with pediatric ALL maintenance therapy. BLOOD. 2023 Feb 16;141(7):743-755. https://doi.org/10.1182/blood.2022016975

Bibtex

@article{0744ddb023024f4e953b24a99a03c9f5,
title = "EBV-driven lymphoid neoplasms associated with pediatric ALL maintenance therapy",
abstract = "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.",
author = "Sarah Elitzur and Ajay Vora and Birgit Burkhardt and Hiroto Inaba and Andishe Attarbaschi and Andre Baruchel and Gabriele Escherich and Gibson, {Brenda Es} and Hsi-Che Liu and Loh, {Mignon L} and Moorman, {Anthony V} and Anja M{\"o}ricke and Rob Pieters and Anne Uyttebroeck and Susan Baird and Jack Bartram and Shlomit Barzilai-Birenboim and Sandeep Batra and Miriam Ben-Harosh and Yves Bertrand and Trudy Buitenkamp and Kenneth Caldwell and Ricardo Drut and Geerlinks, {Ashley V} and Gil Gilad and John Grainger and Stephanie Haouy and Heaney, {Nicholas Benjamin} and Mary Huang and Danielle Ingham and Zdenka Krenova and Michaela Kuhlen and Thomas Lehrnbecher and Atsushi Manabe and Felix Niggli and Claudia Paris and Shoshana Revel-Vilk and Pierre Rohrlich and Sinno, {Mohamad Ghazi} and Tomasz Szczepanski and Melanie Tamesberger and Rajasekharan Warrier and Matthias Wolfl and Ronit Nirel and Shai Izraeli and Arndt Borkhardt and Kjeld Schmiegelow",
note = "Copyright {\textcopyright} 2022 American Society of Hematology.",
year = "2023",
month = feb,
day = "16",
doi = "10.1182/blood.2022016975",
language = "English",
volume = "141",
pages = "743--755",
journal = "BLOOD",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "7",

}

RIS

TY - JOUR

T1 - EBV-driven lymphoid neoplasms associated with pediatric ALL maintenance therapy

AU - Elitzur, Sarah

AU - Vora, Ajay

AU - Burkhardt, Birgit

AU - Inaba, Hiroto

AU - Attarbaschi, Andishe

AU - Baruchel, Andre

AU - Escherich, Gabriele

AU - Gibson, Brenda Es

AU - Liu, Hsi-Che

AU - Loh, Mignon L

AU - Moorman, Anthony V

AU - Möricke, Anja

AU - Pieters, Rob

AU - Uyttebroeck, Anne

AU - Baird, Susan

AU - Bartram, Jack

AU - Barzilai-Birenboim, Shlomit

AU - Batra, Sandeep

AU - Ben-Harosh, Miriam

AU - Bertrand, Yves

AU - Buitenkamp, Trudy

AU - Caldwell, Kenneth

AU - Drut, Ricardo

AU - Geerlinks, Ashley V

AU - Gilad, Gil

AU - Grainger, John

AU - Haouy, Stephanie

AU - Heaney, Nicholas Benjamin

AU - Huang, Mary

AU - Ingham, Danielle

AU - Krenova, Zdenka

AU - Kuhlen, Michaela

AU - Lehrnbecher, Thomas

AU - Manabe, Atsushi

AU - Niggli, Felix

AU - Paris, Claudia

AU - Revel-Vilk, Shoshana

AU - Rohrlich, Pierre

AU - Sinno, Mohamad Ghazi

AU - Szczepanski, Tomasz

AU - Tamesberger, Melanie

AU - Warrier, Rajasekharan

AU - Wolfl, Matthias

AU - Nirel, Ronit

AU - Izraeli, Shai

AU - Borkhardt, Arndt

AU - Schmiegelow, Kjeld

N1 - Copyright © 2022 American Society of Hematology.

PY - 2023/2/16

Y1 - 2023/2/16

N2 - 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.

AB - 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.

U2 - 10.1182/blood.2022016975

DO - 10.1182/blood.2022016975

M3 - SCORING: Journal article

C2 - 36332176

VL - 141

SP - 743

EP - 755

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 7

ER -