Adult T-cell leukemia/lymphoma
Human T-cell(normal)
SpecialtyOncology, hematology Edit this on Wikidata

Adult T-cell leukemia/lymphoma (ATL or ATLL) is a rare cancer of the immune system's T-cells[1][2][3] caused by human T cell leukemia/lymphotropic virus type 1 (HTLV-1).[4] All ATL cells contain integrated HTLV-1 provirus further supporting that causal role of the virus in the cause of the neoplasm.[4] A small amount of HTLV-1 individuals progress to develop ATL with a long latency period between infection and ATL development.  ATL is categorized into 4 subtypes: acute, smoldering, lymphoma-type, chronic. Acute and Lymphoma-type are known to particularity be aggressive with poorer prognosis.[5]

Globally, the retrovirus HTLV-1 is estimated to infect 20 million people per year with the incidence of ATL approximately 0.05 per 100,000 per year with endemic regions such as regions of Japan, as high as 27 per 100,000 per year.[6] However, cases have increased in non-endemic regions with highest incidence of HTLV-1 in southern/northern islands of Japan, Caribbean, Central and South America, intertropical Africa, Romania, northern Iran. ATL normally occurs around the age of 62 years but median age at diagnosis does depend on prevalence of the HTLV-1 infection in the geographic location.[7]

Current treatment regiments for ATL are based on clinical subtype and response to initial therapy. Some therapy modalities for treatment may not available in all countries therefore strategies differ across the world. All patients are referred to clinical trials if available. Beyond clinical trials, treatments are centered on multiagent chemotherapy, zidovudine plus interferon a (AZT/IFN), and allogenic hematopoietic stem cell transplantation (alloHSCT).[6]

Signs and symptoms

ATL is usually a highly aggressive non-Hodgkin's lymphoma with no characteristic histologic appearance except for a diffuse pattern and a mature T-cell phenotype.[8] Circulating lymphocytes with an irregular nuclear contour (leukemic cells) are frequently seen. Several lines of evidence suggest that HTLV-1 causes ATL. This evidence includes the frequent isolation of HTLV-1 from patients with this disease and the detection of HTLV-1 proviral genome in ATL leukemic cells. ATL is frequently accompanied by visceral involvement, hypercalcemia, skin lesions, and lytic bone lesions. Bone invasion and osteolysis, features of bone metastases, commonly occur in the setting of advanced solid tumors, such as breast, prostate, and lung cancers, but are less common in hematologic malignancies. However, patients with HTLV-1–induced ATL and multiple myeloma are predisposed to the development of tumor-induced osteolysis and hypercalcemia. One of the striking features of ATL and multiple myeloma induced bone disease is that the bone lesions are predominantly osteolytic with little associated osteoblastic activity. In patients with ATL, elevated serum levels of IL-1, TGFβ, PTHrP, macrophage inflammatory protein (MIP-1α), and receptor activator of nuclear factor-κB ligand (RANKL) have been associated with hypercalcemia. Immunodeficient mice that received implants with leukemic cells from patients with ATL or with HTLV-1–infected lymphocytes developed hypercalcemia and elevated serum levels of PTHrP.[9] Most patients die within one year of diagnosis.[10]

Infection with HTLV-1, like infection with other retroviruses, probably occurs for life and can be inferred when antibody against HTLV-1 is detected in the serum.[11]

Transmission

Transmission of HTLV-1 is believed to occur from mother to child; by sexual contact; and through exposure to contaminated blood, either through blood transfusion or sharing of contaminated needles.[12]

Diagnosis

Diagnosis is made based on the combination of clinical features, characteristic morphologic and immunophenotypic changes of malignant cells. As clinical features and prognosis can be diverse, the disease is subtype-classified into four categories according to the Shimoyama classification: acute, lymphoma, chronic, smoldering.[13] Normally, identification of at least 5 percent of tumor cells in peripheral blood and confirmation of human T-lymphotropic virus type-1 are sufficient for diagnosis of acute, chronic, and smoldering types. For the lymphoma type, histopathologic examination by biopsy of lymph nodes may be needed.[14]

Treatment

Treatment options that have been tried include zidovudine and the CHOP regimen.[11] Pralatrexate has also been investigated.[15] Recently, it has been reported that the traditional glucocorticoid-based chemotherapy toward ATL are largely mediated by thioredoxin binding protein-2 (TBP-2/TXNIP/VDUP1), suggesting the potential use of a TBP-2 inducer as a novel therapeutic target.[16][17]

In 2021, mogamulizumab was approved for relapsed/refractor treatment of ATL in Japan.[18]

At a medical conference in December 2013, researchers reported anywhere from 21 to 50% of ATL patients have disease expressing CD30.[19] Although not FDA approved, treatment with CD30-targeting brentuximab vedotin in CD 30+ cases may be beneficial and supported by current NCCN guidelines.[20]

Epidemiology

HTLV-1 infection in the United States appears to be rare. Although little serologic data exist, the prevalence of infection is thought to be highest among blacks living in the Southeast. A prevalence rate of 30% has been found among black intravenous drug abusers in New Jersey, and a rate of 49% has been found in a similar group in New Orleans. It is possible that the prevalence of infection is increasing in this risk group. Studies of HTLV-1 antibody indicate that the virus is endemic in southern Japan, in the Caribbean, South America, and in Africa.[7]

ATL is relatively uncommon among those infected with HTLV-1. The overall incidence of ATL is estimated at 1 per 1,500 adult HTLV-1 carriers per year. Those cases that have been reported have occurred mostly among persons from the Caribbean or blacks from the Southeast (National Institutes of Health, unpublished data). There appears to be a long latent period between HTLV-1 infection and the start of ATL.[5]

Research

Novel approaches to the treatment of PTCL in the relapsed or refractory setting are under investigation. Pralatrexate is one compound currently under investigations for the treatment of PTCL.[15]

References

  1. ^ Yodoi, J; Takatsuki, K; Masuda, T (1974). "Letter: Two cases of T-cell chronic lymphocytic leukemia in Japan". New England Journal of Medicine. 290 (10): 572–3. doi:10.1056/NEJM197403072901018. PMID 4544052.
  2. ^ Uchiyama, T; Yodoi, J; Sagawa, K; Takatsuki, K; Uchino, H (1977). "Adult T-cell leukemia: Clinical and hematologic features of 16 cases". Blood. 50 (3): 481–92. doi:10.1182/blood.V50.3.481.481. PMID 301762.
  3. ^ Yodoi, J; Maeda, M (2011). "The discovery of ATL: an odyssey in restrospect". International Journal of Hematology. 94 (5): 423–8. doi:10.1007/s12185-011-0957-x. PMID 22068231. S2CID 9299403.
  4. ^ a b Nicot, Christophe (2005). "Current views in HTLV-I-associated adult T-cell leukemia/lymphoma". American Journal of Hematology. 78 (3): 232–9. doi:10.1002/ajh.20307. PMID 15726602. S2CID 30160899.
  5. ^ a b Matsuoka, M; Jeang, K (2007). "Human T-cell leukaemia virus type 1 (HTLV-1) infectivity and cellular transformation". Nature Reviews Cancer. 7 (4): 270–280. doi:10.1038/nrc2111. ISSN 1474-175X. PMID 17384582. S2CID 7824653.
  6. ^ a b Phillips, A; Harewood, J (2018). "Adult T Cell Leukemia-Lymphoma (ATL): State of the Art". Current Hematologic Malignancy Reports. 13 (4): 300–307. doi:10.1007/s11899-018-0458-6. ISSN 1558-822X. PMID 30047026. S2CID 51719877.
  7. ^ a b Chihara, D; Ito, H; Katanoda, K; Shibata, A; Matsuda, T; Tajima, K; Sobue, T; Matsuo, K (2012). "Increase in incidence of adult T-cell leukemia/lymphoma in non-endemic areas of Japan and the United States". Cancer Science. 103 (10): 1857–1860. doi:10.1111/j.1349-7006.2012.02373.x. ISSN 1349-7006. PMC 7659271. PMID 22738276.
  8. ^ Ishida, T; Joh, T; Uike, N; Yamamoto, K; Utsunomiya, A; Yoshida, S; Saburi, Y; Miyamoto, T; Takemoto, S; Suzushima, H; Tsukasaki, K (2012). "Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma: a multicenter phase II study". Journal of Clinical Oncology. 30 (8): 837–842. doi:10.1200/JCO.2011.37.3472. ISSN 1527-7755. PMID 22312108.
  9. ^ Gao, L; Deng, H; Zhao, H; Hirbe, A; Harding, J; Ratner, L; Weilbaecher, K (2005). "HTLV-1 Tax transgenic mice develop spontaneous osteolytic bone metastases prevented by osteoclast inhibition". Blood. 106 (13): 4294–302. doi:10.1182/blood-2005-04-1730. PMC 1895233. PMID 16118323.
  10. ^ Matsuoka, M; Suzuki, R (2020). "Treatment and prognosis of adult T cell leukemia-lymphoma". UpToDate. Archived from the original on 2012-07-23. Retrieved 27 July 2012.
  11. ^ a b Taylor, G; Matsuoka, M (2005). "Natural history of adult T-cell leukemia/lymphoma and approaches to therapy". Oncogene. 24 (39): 6047–57. doi:10.1038/sj.onc.1208979. PMID 16155611.
  12. ^ Gotuzzo, E; Verdonck, K (2004). "HTLV-1: CLINICAL IMPACT OF A CHRONIC INFECTION". NCBI. Archived from the original on 2020-02-22. Retrieved 22 July 2013.
  13. ^ Tsukasaki, K (2012). "Adult T-cell leukemia–lymphoma". Hematology. 17 (sup1): s32–s35. doi:10.1179/102453312X13336169155330. hdl:10069/28943. ISSN 1607-8454. PMID 22507774. S2CID 40003053.
  14. ^ Yamada, Y; Tomonaga, M; Fukuda, H; Hanada, S; Utsunomiya, A; Tara, M; Sano, M; Ikeda, S; Takatsuki, K; Kozuru, M; Araki, K (2001). "A new G-CSF-supported combination chemotherapy, LSG15, for adult T-cell leukaemia-lymphoma: Japan Clinical Oncology Group Study 9303: A New G-CSF-Supported Chemotherapy for ATL". British Journal of Haematology. 113 (2): 375–382. doi:10.1046/j.1365-2141.2001.02737.x. PMID 11380402.
  15. ^ a b Marneros, A; Grossman, M; Silvers, D; Husain, S; Nuovo, G; Macgregor-Cortelli, B; Neylon, E; Patterson, M; O'Connor, O (2009). "Pralatrexate-induced tumor cell apoptosis in the epidermis of a patient with HTLV-1 adult T-cell lymphoma/leukemia causing skin erosions". Blood. 113 (25): 6338–41. doi:10.1182/blood-2009-03-210989. PMID 19389878.
  16. ^ Chen, Z; Lopez-Ramos, D (2011). "Thioredoxin-binding protein-2 (TBP-2/VDUP1/TXNIP) regulates T-cell sensitivity to glucocorticoid during HTLV-I-induced transformation". Leukemia. 25 (3): 440–8. doi:10.1038/leu.2010.286. PMC 3072512. PMID 21151022.
  17. ^ Chen, Z; Yoshihara E (2010). "Differential roles of Annexin A1 (ANXA1/lipocortin-1/lipomodulin) and thioredoxin binding protein-2 (TBP-2/VDUP1/TXNIP) in glucocorticoid signaling of HTLV-I-transformed T cells". Immunology Letters. 131 (1): 11–18. doi:10.1016/j.imlet.2010.04.003. hdl:2433/126715. PMID 20398702.
  18. ^ Subramaniam, J; Whiteside, G; McKeage, K; Croxtall, J (2012). "Mogamulizumab: first global approval". Drugs. 72 (9): 1293–8. doi:10.2165/11631090-000000000-00000. PMID 22686619.
  19. ^ Campuzano-Zuluaga, G; Pimentel, A; Diaz, L; Chapman-Fredricks, J; and Ramos, J (2013). "CD30 Expression Is Associated With Decreased Survival In Patients With Acute and Unfavorable Chronic Types Of Adult T-Cell Leukemia-Lymphoma" https://ash.confex.com/ash/2013/webprogram/Paper64702.html
  20. ^ Cook, L; Fuji, S; Hermine, O; Bazarbachi, A; Ramos, J; Ratner, L; Horwitz, S; Fields, P; Tanase, A; Bumbea, H; Cwynarski, K (2019). "Revised Adult T-Cell Leukemia-Lymphoma International Consensus Meeting Report". Journal of Clinical Oncology. 37 (8): 677–687. doi:10.1200/JCO.18.00501. ISSN 1527-7755. PMC 6494249. PMID 30657736.

Further reading

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