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T-cell non-Hodgkin lymphoma arising in patients with immunodeficiencies
about 11.9 % of all T-NHL, particularly in AITL and PTCL, in NOS, and in about 2% of B-NHL. The same TET2 mutations, for example, have been found in patients with AML/MDS secondary to a previous lymphoma, suggest- ing a shared genetic origin.46,47 Moreover, it has been observed that TET2 loss in mice leads to hypermutagenic- ity in hematopoietic stem cells and progenitor cells, result- ing in an increased risk of various hematologic malignan- cies.48
Considering that most patients had been treated with immunosuppressive drugs or chemotherapy for intervals of longer than two years, it seems that prolonged treat- ment with these types of drugs increases the risk of malig- nant lymphoma development. An association between the use of thiopurines alone or combined with TNF-α inhibitors and the development of HSTCL in IBD patients has been reported previously.15 The majority of patients with IBD in our series and in the reported cases had been using azathioprine. It is possible, therefore, that the use of thiopurines also contributes to the development of other T-NHL.
Obviously, inherent to its retrospective design, our study has some limitations. The clinical data were not complete for all patients, thus making it difficult to assess the temporal relationship between the underlying disor- ders or drug use and the development of T-NHL for some. In addition, the group was too small to run subgroup analyses. Moreover, since the overall prevalence of immunodeficiencies in the general population is not known, we could only compare the prevalence of specific underlying disorders in our cohort of patients with T-NHL to those in the general population.
Conclusion
The 25 cases presented herein, together with the 596 cases found in the literature of T-NHL in patients with varying causes of immunodeficiencies suggest that patients with a secondary immunodeficiency are at increased risk for the development of T-NHL. Prolonged treatment with immunosuppressive or chemotherapeutic drugs seems to contribute to the risk. T-NHL in immunod- eficient patients are histologically very heterogeneous. The distribution of subtypes resembles that present in the general population, with the exception of primary cuta- neous T-NHL and HSTCL, both of which have been reported more often in patients with an immunodeficien- cy, and AITL, which has been reported less frequently in this group. Overall, the prognosis seems worse compared to T-NHL of similar subtypes in the general population. T- NHL occur predominantly in men, and in immunodefi- cient patients they tend to be more often located extran- odally, which is in line with B-cell lymphomas in this group of patients. In our series of immunodeficient patients, the lymphomas occurred on average nine to ten years earlier than T-NHL in the general population.
The observations in the study herein should raise awareness of the possible development of T-NHL in immunodeficient patients and challenge the prolonged use of immunosuppressive drugs in patients who are in clinical remission of their autoimmune disease.
Funding
The study was supported by Lymph&Co and by a grant from the Egbers Foundation.
References
1. Gatti RA, Good RA. Occurrence of malig- nancy in immunodeficiency diseases. A lit- erature review. Cancer. 1971;28(1):89-98.
2. Penn I, Hammond W, Brettschneider L, Starzl TE. Malignant lymphomas in trans- plantation patients. Transplant Proc. 1969;1(1):106-112.
3. Parker A, Bowles K, Bradley JA, et al. Diagnosis of post-transplant lymphoprolif- erative disorder in solid organ transplant recipients - BCSH and BTS Guidelines. Br J Haematol. 2010;149(5):675-692.
4. Beral V, Peterman T, Berkelman R, Jaffe H. AIDS-associated non-Hodgkin lymphoma. Lancet. 1991;337(8745):805-809.
5. Levine AM, Seneviratne L, Espina BM, et al. Evolving characteristics of AIDS-related lymphoma. Blood. 2000;96(13):4084-4090.
6. Bewtra M. Lymphoma in inflammatory bowel disease and treatment decisions. Am J Gastroenterol. 2012;107(7):964-970.
7. Beaugerie L, Brousse N, Bouvier AM, et al. Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Lancet. 2009;374(9701):1617- 1625.
8. Gratzinger D, Jaffe ES, Chadburn A, et al. Primary/congenital immunodeficiency: 2015 SH/EAHP workshop report-part 5. Am J Clin Pathol. 2017;147(2):204-216.
9. Simon TA, Thompson A, Gandhi KK, Hochberg MC, Suissa S. Incidence of
malignancy in adult patients with rheuma- toid arthritis: a meta-analysis. Arthritis Res Ther. 2015;17:212.
10. Wolfe F, Michaud K. Lymphoma in rheumatoid arthritis: the effect of methotrexate and anti-tumor necrosis fac- tor therapy in 18,572 patients. Arthritis Rheum. 2004;50(6):1740-1751.
11. Zintzaras E, Voulgarelis M, Moutsopoulos HM. The risk of lymphoma development in autoimmune diseases: a meta-analysis. Arch Intern Med. 2005;165(20):2337-2344.
AIDS. J Acquir Immune Defic Syndr.
2001;26(4):371-376.
17. Herreman A, Dierickx D, Morscio J, et al.
Clinicopathological characteristics of post- transplant lymphoproliferative disorders of T-cell origin: single-center series of nine cases and meta-analysis of 147 reported cases. Leuk Lymphoma. 2013;54(10):2190- 2199.
18. Perez K, Castillo J, Dezube BJ, Pantanowitz L. Human immunodeficiency virus-associ- ated anaplastic large cell lymphoma. Leuk Lymphoma. 2010;51(3):430-438.
19. Swerdlow SH. T-cell and NK-cell post- transplantation lymphoproliferative disor- ders. Am J Clin Pathol. 2007;127(6):887-
12. Askling J, Fored CM, Baecklund E, et al. Haematopoietic malignancies in rheuma-
toid arthritis: lymphoma risk and charac-
teristics after exposure to tumour necrosis
factor antagonists. Ann Rheum Dis. 895.
2005;64(10):1414-1420.
13. Baecklund E, Iliadou A, Askling J, et al.
Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum. 2006;54(3):692-701.
14. Castillo JJ, Beltran BE, Bibas M, et al. Prognostic factors in patients with HIV- associated peripheral T-cell lymphoma: a multicenter study. Am J Hematol. 2011;86(3):256-261.
15. Gilardin L, Copie-Bergman C, Galicier L, et al. Peripheral T-cell lymphoma in HIV- infected patients: a study of 17 cases in the combination antiretroviral therapy era. Br J Haematol. 2013;161(6):843-851.
16. Biggar RJ, Engels EA, Frisch M, Goedert JJ. Risk of T-cell lymphomas in persons with
20. Seckin D, Barete S, Euvrard S, et al. Primary cutaneous posttransplant lymphoprolifera- tive disorders in solid organ transplant recipients: a multicenter European case series. Am J Transplant. 2013;13(8):2146- 2153.
21. Deepak P, Sifuentes H, Sherid M, Stobaugh D, Sadozai Y, Ehrenpreis ED. T-cell non- Hodgkin's lymphomas reported to the FDA AERS with tumor necrosis factor- alpha (TNF-alpha) inhibitors: results of the REFURBISH study. Am J Gastroenterol. 2013;108(1):99-105.
22. Kotlyar DS, Osterman MT, Diamond RH, et al. A systematic review of factors that contribute to hepatosplenic T-cell lym- phoma in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol.
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