EBV-driven lymphoid neoplasms associated with pediatric ALL maintenance therapy
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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.
Originalsprog | Engelsk |
---|---|
Tidsskrift | Blood |
Vol/bind | 141 |
Udgave nummer | 7 |
Sider (fra-til) | 743-755 |
ISSN | 0006-4971 |
DOI | |
Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
This work was supported by the Israel Cancer Association, the Chaim Association, and the Israel Childhood Cancer Fund (New York) (S.E. and S.I.); and by the Dora and Giorgio Professorship at Tel Aviv University (S.I.).
Funding Information:
The authors thank the patients, families, and clinical teams who participated in the treatment of these patients; the members of the ALL and NHL Committees of the I-BFM Study Group for their contributions to this study; and Naomi Litichever and Dina Kugel, data managers of the Israeli Study Group of Childhood ALL and Gioia Blayer for assistance with the statistical analysis. Contribution: S.E. S.I. and K.S. were responsible for conception and design of the study; S.E. B.B. R.N. A.B. and K.S. performed data analysis and interpretation; S.E. provided administrative support; S.E. and K.S. wrote the manuscript; all authors collected and assembled data; and all authors approved the final manuscript. This work was supported by the Israel Cancer Association, the Chaim Association, and the Israel Childhood Cancer Fund (New York) (S.E. and S.I.); and by the Dora and Giorgio Professorship at Tel Aviv University (S.I.).
Publisher Copyright:
© 2022 The American Society of Hematology
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