Adult T-cell leukemia/lymphoma

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Adult T-cell leukemia/lymphoma
Classification and external resources
ICD-10 C83-C88
ICD-9 204.0-208.9
ICD-O: M9827/3
DiseasesDB 29486
MeSH D015459

Adult T-cell leukemia/lymphoma (ATL or ATLL) is a rare cancer of the immune system's own T-cells.[1][2][3]

Human T cell leukemia/lymphotropic virus type 1 (HTLV-1) is believed to be the cause of it,[4] in addition to several other diseases.

Signs and symptoms[edit]

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. 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.[5] Most patients die within one year of diagnosis.[6]

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.[citation needed]

Transmission[edit]

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.[7]

Treatment[edit]

Treatment options that have been tried include zidovudine and the CHOP regimen.[8] Pralatrexate has also been investigated.[9] Most therapy is directed towards the cancer rather than the virus itself.[citation needed] 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.[10][11]

Recently, mogamulizumab (Poteligeo), has been approved for the treatment of ATL in Japan.

At a medical conference in December 2013, researchers reported anywhere from 21-50% of ATL patients have disease expressing CD30.[12] This suggests treatment with CD30-targeting brentuximab vedotin may be beneficial.

Epidemiology[edit]

HTLV-1 infection in the United States appears to be rare. Although little serologic data exist, 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 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.[citation needed]

ATL is relatively uncommon among those infected with HTLV-1. The overall incidence of ATL is estimated at about 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.[citation needed]

Research[edit]

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.[citation needed]

In pregnancy[edit]

Leukemia is rarely associated with pregnancy, affecting only about 1 in 10,000 pregnant women.[13] How it is handled depends primarily on the type of leukemia. Acute leukemias normally require prompt, aggressive treatment, despite significant risks of pregnancy loss and birth defects, especially if chemotherapy is given during the developmentally sensitive first trimester.[13]

References[edit]

  1. ^ Yodoi, J; Takatsuki, K; Masuda, T (1974). "Still More on NBT Technic". 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. 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. 
  4. ^ 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. 
  5. ^ bloodjournal.hematologylibrary.org/content/106/13/4294.full HTLV-1 Tax transgenic mice develop spontaneous osteolytic bone metastases prevented by osteoclast inhibition
  6. ^ "Treatment and prognosis of adult T cell leukemia-lymphoma". Retrieved 27 July 2012. 
  7. ^ "HTLV-1: CLINICAL IMPACT OF A CHRONIC INFECTION". Retrieved 22 July 2013. 
  8. ^ Taylor, Graham P; Matsuoka, Masao (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. 
  9. ^ Marneros, A. G.; Grossman, M. E.; Silvers, D. N.; Husain, S.; Nuovo, G. J.; Macgregor-Cortelli, B.; Neylon, E.; Patterson, M.; O'Connor, O. A. (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. 
  10. ^ 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. 
  11. ^ 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. PMID 20398702. 
  12. ^ Campuzano-Zuluaga, G; Pimentel, A; Diaz, L; Chapman-Fredricks, JR; and Ramos, JC " CD30 Expression Is Associated With Decreased Survival In Patients With Acute and Unfavorable Chronic Types Of Adult T-Cell Leukemia-Lymphoma" December 2013 https://ash.confex.com/ash/2013/webprogram/Paper64702.html
  13. ^ a b Shapira T, Pereg D, Lishner M (September 2008). "How I treat acute and chronic leukemia in pregnancy". Blood Rev. 22 (5): 247–59. doi:10.1016/j.blre.2008.03.006. PMID 18472198. 

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