Incidence and Mortality

T-cell lymphomas make up less than 15% of NHL cases. Most T-cell lymphoma subtypes are associated with worse outcomes than those of B-cell lymphomas.[1]

Anatomy

NHL usually originates in lymphoid tissues.

Anatomy of the lymph system.

Prognosis and Survival

Prognosis in PTCL varies depending on subtype, stage, and other factors. In general, PTCL is associated with a poor prognosis, with a 5-year survival rate of approximately 30% to 40%.[2,3] While outcomes are better for patients with ALK-positive ALCL, with a median 5-year overall survival (OS) closer to 70% to 80%,[2-4] other subsets are associated with worse survival, such as ALK-negative ALCL, AITL, PTCL-NOS, HSTCL, EATL, and ENK/TCL.[5,6]

Unlike B-cell NHLs, which include both indolent and aggressive forms, most PTCLs are considered aggressive.[7] As with most other aggressive lymphomas, PTCLs are often curable with systemic therapy, though effective treatment options are more limited, particularly in the relapsed or refractory setting.[8,9]

Even though existing treatments cure a significant fraction of patients with lymphoma, numerous clinical trials that explore treatment improvements are in progress. If possible, patients can be included in these studies.

In addition to screening for HIV among patients with aggressive lymphomas, active hepatitis B or hepatitis C can be assessed before treatment with chemotherapy.[10,11] Patients with detectable hepatitis B virus (HBV) benefit from prophylaxis with entecavir.[12,13] Patients with a resolved HBV infection (defined as hepatitis B surface antigen-negative but hepatitis B core antibody-positive) are at risk of reactivation of HBV and require monitoring of HBV DNA. Prophylactic nucleoside therapy lowered HBV reactivation from 10.8% to 2.1% in a retrospective study of 326 patients.[14] Prophylaxis for herpes zoster with acyclovir or valacyclovir and prophylaxis for pneumocystis with trimethoprim/sulfamethoxazole or dapsone are usually given to patients receiving combination chemotherapy.

References

1. American Cancer Society: Types of T-cell lymphoma. American Cancer Society, 2018. Available online. Last accessed June 16, 2023.
2. Vose J, Armitage J, Weisenburger D, et al.: International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol 26 (25): 4124-30, 2008. [PubMed: 18626005]
3. Ellin F, Landström J, Jerkeman M, et al.: Real-world data on prognostic factors and treatment in peripheral T-cell lymphomas: a study from the Swedish Lymphoma Registry. Blood 124 (10): 1570-7, 2014. [PubMed: 25006130]
4. Sibon D, Fournier M, Brière J, et al.: Long-term outcome of adults with systemic anaplastic large-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte trials. J Clin Oncol 30 (32): 3939-46, 2012. [PubMed: 23045585]
5. Petrich AM, Helenowski IB, Bryan LJ, et al.: Factors predicting survival in peripheral T-cell lymphoma in the USA: a population-based analysis of 8802 patients in the modern era. Br J Haematol 168 (5): 708-18, 2015. [PubMed: 25382108]
6. Foss FM, Horwitz SM, Civallero M, et al.: Incidence and outcomes of rare T cell lymphomas from the T Cell Project: hepatosplenic, enteropathy associated and peripheral gamma delta T cell lymphomas. Am J Hematol 95 (2): 151-155, 2020. [PMC free article: PMC8025136] [PubMed: 31709579]
7. Armitage JO: The aggressive peripheral T-cell lymphomas: 2017. Am J Hematol 92 (7): 706-715, 2017. [PubMed: 28516671]
8. Bellei M, Foss FM, Shustov AR, et al.: The outcome of peripheral T-cell lymphoma patients failing first-line therapy: a report from the prospective, International T-Cell Project. Haematologica 103 (7): 1191-1197, 2018. [PMC free article: PMC6029527] [PubMed: 29599200]
9. Lansigan F, Horwitz SM, Pinter-Brown LC, et al.: Outcomes for Relapsed and Refractory Peripheral T-Cell Lymphoma Patients after Front-Line Therapy from the COMPLETE Registry. Acta Haematol 143 (1): 40-50, 2020. [PubMed: 31315113]
10. Niitsu N, Hagiwara Y, Tanae K, et al.: Prospective analysis of hepatitis B virus reactivation in patients with diffuse large B-cell lymphoma after rituximab combination chemotherapy. J Clin Oncol 28 (34): 5097-100, 2010. [PubMed: 20837949]
11. Dong HJ, Ni LN, Sheng GF, et al.: Risk of hepatitis B virus (HBV) reactivation in non-Hodgkin lymphoma patients receiving rituximab-chemotherapy: a meta-analysis. J Clin Virol 57 (3): 209-14, 2013. [PubMed: 23562041]
12. Huang YH, Hsiao LT, Hong YC, et al.: Randomized controlled trial of entecavir prophylaxis for rituximab-associated hepatitis B virus reactivation in patients with lymphoma and resolved hepatitis B. J Clin Oncol 31 (22): 2765-72, 2013. [PubMed: 23775967]
13. Li H, Zhang HM, Chen LF, et al.: Prophylactic lamivudine to improve the outcome of HBsAg-positive lymphoma patients during chemotherapy: a systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 39 (1): 80-92, 2015. [PubMed: 25199680]
14. Kusumoto S, Arcaini L, Hong X, et al.: Risk of HBV reactivation in patients with B-cell lymphomas receiving obinutuzumab or rituximab immunochemotherapy. Blood 133 (2): 137-146, 2019. [PMC free article: PMC6337873] [PubMed: 30341058]

References

1. Haddy TB, Adde MA, McCalla J, et al.: Late effects in long-term survivors of high-grade non-Hodgkin's lymphomas. J Clin Oncol 16 (6): 2070-9, 1998. [PubMed: 9626206]
2. Travis LB, Curtis RE, Glimelius B, et al.: Second cancers among long-term survivors of non-Hodgkin's lymphoma. J Natl Cancer Inst 85 (23): 1932-7, 1993. [PubMed: 8230284]
3. Mudie NY, Swerdlow AJ, Higgins CD, et al.: Risk of second malignancy after non-Hodgkin's lymphoma: a British Cohort Study. J Clin Oncol 24 (10): 1568-74, 2006. [PubMed: 16520465]
4. Hemminki K, Lenner P, Sundquist J, et al.: Risk of subsequent solid tumors after non-Hodgkin's lymphoma: effect of diagnostic age and time since diagnosis. J Clin Oncol 26 (11): 1850-7, 2008. [PubMed: 18347006]
5. Major A, Smith DE, Ghosh D, et al.: Risk and subtypes of secondary primary malignancies in diffuse large B-cell lymphoma survivors change over time based on stage at diagnosis. Cancer 126 (1): 189-201, 2020. [PMC free article: PMC9036552] [PubMed: 31509235]
6. Moser EC, Noordijk EM, van Leeuwen FE, et al.: Long-term risk of cardiovascular disease after treatment for aggressive non-Hodgkin lymphoma. Blood 107 (7): 2912-9, 2006. [PubMed: 16339404]
7. Darrington DL, Vose JM, Anderson JR, et al.: Incidence and characterization of secondary myelodysplastic syndrome and acute myelogenous leukemia following high-dose chemoradiotherapy and autologous stem-cell transplantation for lymphoid malignancies. J Clin Oncol 12 (12): 2527-34, 1994. [PubMed: 7989926]
8. Stone RM, Neuberg D, Soiffer R, et al.: Myelodysplastic syndrome as a late complication following autologous bone marrow transplantation for non-Hodgkin's lymphoma. J Clin Oncol 12 (12): 2535-42, 1994. [PubMed: 7989927]
9. Armitage JO, Carbone PP, Connors JM, et al.: Treatment-related myelodysplasia and acute leukemia in non-Hodgkin's lymphoma patients. J Clin Oncol 21 (5): 897-906, 2003. [PubMed: 12610191]
10. André M, Mounier N, Leleu X, et al.: Second cancers and late toxicities after treatment of aggressive non-Hodgkin lymphoma with the ACVBP regimen: a GELA cohort study on 2837 patients. Blood 103 (4): 1222-8, 2004. [PubMed: 14576060]
11. Oddou S, Vey N, Viens P, et al.: Second neoplasms following high-dose chemotherapy and autologous stem cell transplantation for malignant lymphomas: a report of six cases in a cohort of 171 patients from a single institution. Leuk Lymphoma 31 (1-2): 187-94, 1998. [PubMed: 9720728]
12. Lenz G, Dreyling M, Schiegnitz E, et al.: Moderate increase of secondary hematologic malignancies after myeloablative radiochemotherapy and autologous stem-cell transplantation in patients with indolent lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group. J Clin Oncol 22 (24): 4926-33, 2004. [PubMed: 15611507]
13. McLaughlin P, Estey E, Glassman A, et al.: Myelodysplasia and acute myeloid leukemia following therapy for indolent lymphoma with fludarabine, mitoxantrone, and dexamethasone (FND) plus rituximab and interferon alpha. Blood 105 (12): 4573-5, 2005. [PMC free article: PMC1895007] [PubMed: 15741224]
14. Morton LM, Curtis RE, Linet MS, et al.: Second malignancy risks after non-Hodgkin's lymphoma and chronic lymphocytic leukemia: differences by lymphoma subtype. J Clin Oncol 28 (33): 4935-44, 2010. [PMC free article: PMC3020697] [PubMed: 20940199]
15. Mach-Pascual S, Legare RD, Lu D, et al.: Predictive value of clonality assays in patients with non-Hodgkin's lymphoma undergoing autologous bone marrow transplant: a single institution study. Blood 91 (12): 4496-503, 1998. [PubMed: 9616144]
16. Lillington DM, Micallef IN, Carpenter E, et al.: Detection of chromosome abnormalities pre-high-dose treatment in patients developing therapy-related myelodysplasia and secondary acute myelogenous leukemia after treatment for non-Hodgkin's lymphoma. J Clin Oncol 19 (9): 2472-81, 2001. [PubMed: 11331326]
17. Brown JR, Yeckes H, Friedberg JW, et al.: Increasing incidence of late second malignancies after conditioning with cyclophosphamide and total-body irradiation and autologous bone marrow transplantation for non-Hodgkin's lymphoma. J Clin Oncol 23 (10): 2208-14, 2005. [PubMed: 15753460]
18. Jackson GH, Wood A, Taylor PR, et al.: Early high dose chemotherapy intensification with autologous bone marrow transplantation in lymphoma associated with retention of fertility and normal pregnancies in females. Scotland and Newcastle Lymphoma Group, UK. Leuk Lymphoma 28 (1-2): 127-32, 1997. [PubMed: 9498711]
19. Gangaraju R, Chen Y, Hageman L, et al.: Risk of venous thromboembolism in patients with non-Hodgkin lymphoma surviving blood or marrow transplantation. Cancer 125 (24): 4498-4508, 2019. [PMC free article: PMC6891120] [PubMed: 31469420]
20. Westin JR, Thompson MA, Cataldo VD, et al.: Zoledronic acid for prevention of bone loss in patients receiving primary therapy for lymphomas: a prospective, randomized controlled phase III trial. Clin Lymphoma Myeloma Leuk 13 (2): 99-105, 2013. [PMC free article: PMC3881262] [PubMed: 23276888]

Current Classification Systems

The World Health Organization (WHO) modification of the Revised European American Lymphoma (REAL) classification recognizes three major categories of lymphoid malignancies based on morphology and cell lineage: B-cell neoplasms, T-cell/natural killer (NK)-cell neoplasms, and Hodgkin lymphoma (HL). Both lymphomas and lymphoid leukemias are included in this classification because both solid and circulating phases are present in many lymphoid neoplasms and distinction between them is artificial. For example, B-cell chronic lymphocytic leukemia (CLL) and B-cell small lymphocytic lymphoma are simply different manifestations of the same neoplasm, as are lymphoblastic lymphomas and acute lymphocytic leukemias. Within the B-cell and T-cell categories, two subdivisions are recognized: precursor neoplasms, which correspond to the earliest stages of differentiation, and more mature differentiated neoplasms.[3,4]

Subtypes of Peripheral T-Cell Non-Hodgkin Lymphoma

Peripheral T-cell non-Hodgkin lymphoma includes the following subtypes, among others:

• Anaplastic large cell lymphoma.
• Angioimmunoblastic T-cell lymphoma.
• Peripheral T-cell lymphoma, not otherwise specified.
• Extranodal NK/T-cell lymphoma.
• Enteropathy-type intestinal T-cell lymphoma.
• Hepatosplenic T-cell lymphoma.
• Adult T-cell leukemia/lymphoma.
• T-cell prolymphocytic leukemia. For more information, see Chronic Lymphocytic Leukemia Treatment.
• Cutaneous T-cell lymphoma (including mycosis fungoides and Sézary syndrome, subcutaneous panniculitis-like T-cell lymphoma, primary cutaneous anaplastic large cell lymphoma, primary cutaneous gamma-delta T-cell lymphoma, and others). For more information, see Mycosis Fungoides (Including Sézary Syndrome) Treatment.
• T-cell granular lymphocytic leukemia. For more information, see Chronic Lymphocytic Leukemia Treatment.

References

1. Zeppa P, Marino G, Troncone G, et al.: Fine-needle cytology and flow cytometry immunophenotyping and subclassification of non-Hodgkin lymphoma: a critical review of 307 cases with technical suggestions. Cancer 102 (1): 55-65, 2004. [PubMed: 14968418]
2. Young NA, Al-Saleem T: Diagnosis of lymphoma by fine-needle aspiration cytology using the revised European-American classification of lymphoid neoplasms. Cancer 87 (6): 325-45, 1999. [PubMed: 10603186]
3. Pileri SA, Milani M, Fraternali-Orcioni G, et al.: From the R.E.A.L. Classification to the upcoming WHO scheme: a step toward universal categorization of lymphoma entities? Ann Oncol 9 (6): 607-12, 1998. [PubMed: 9681073]
4. Society for Hematopathology Program: Society for Hematopathology Program. Am J Surg Pathol 21 (1): 114-121, 1997.

Staging Subclassification System

Lugano classification

The American Joint Committee on Cancer (AJCC) has adopted the Lugano classification to evaluate and stage lymphoma.[10] The Lugano classification system replaces the Ann Arbor classification system, which was adopted in 1971 at the Ann Arbor Conference,[11] with some modifications 18 years later from the Cotswolds meeting.[12 ,13]

Table 1. Lugano Classification for Hodgkin and Non-Hodgkin Lymphoma^a

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Stage	Stage Description	Illustration
Limited stage
I	Involvement of a single lymphatic site (i.e., nodal region, Waldeyer’s ring, thymus, or spleen).
IE	Single extralymphatic site in the absence of nodal involvement (rare in Hodgkin lymphoma).
II	Involvement of two or more lymph node regions on the same side of the diaphragm.
IIE	Contiguous extralymphatic extension from a nodal site with or without involvement of other lymph node regions on the same side of the diaphragm.
II bulkyb	Stage II with disease bulk.c
Advanced stage
III	Involvement of lymph node regions on both sides of the diaphragm; nodes above the diaphragm with spleen involvement.
IV	Diffuse or disseminated involvement of one or more extralymphatic organs, with or without associated lymph node involvement; or noncontiguous extralymphatic organ involvement in conjunction with nodal stage II disease; or any extralymphatic organ involvement in nodal stage III disease. Stage IV includes any involvement of the CSF, bone marrow, liver, or multiple lung lesions (other than by direct extension in stage IIE disease).
Note: Hodgkin lymphoma uses A or B designation with stage group. A/B is no longer used in NHL.

CSF = cerebrospinal fluid; CT = computed tomography; DLBCL = diffuse large B-cell lymphoma; NHL = non-Hodgkin lymphoma.

^aHodgkin and Non-Hodgkin Lymphomas. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 937–58.

^bStage II bulky may be considered either early or advanced stage based on lymphoma histology and prognostic factors.

^cThe definition of disease bulk varies according to lymphoma histology. In the Lugano classification, bulk ln Hodgkin lymphoma is defined as a mass greater than one-third of the thoracic diameter on CT of the chest or a mass >10 cm. For NHL, the recommended definitions of bulk vary by lymphoma histology. In follicular lymphoma, 6 cm has been suggested based on the Follicular Lymphoma International Prognostic Index-2 and its validation. In DLBCL, cutoffs ranging from 5 cm to 10 cm have been used, although 10 cm is recommended.

Occasionally, specialized staging systems are used. The physician should be aware of the system used in a specific report.

The E designation is used when extranodal lymphoid malignancies arise in tissues separate from, but near, the major lymphatic aggregates. Stage IV refers to disease that is diffusely spread throughout an extranodal site, such as the liver. If pathological proof of involvement of one or more extralymphatic sites has been documented, the symbol for the site of involvement, followed by a plus sign (+), is listed.

Table 2. Notation to Identify Specific Sites

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N = nodes	H = liver	L = lung	M = bone marrow
S = spleen	P = pleura	O = bone	D = skin

Current practice assigns a clinical stage based on the findings of the clinical evaluation and a pathological stage based on the findings made as a result of invasive procedures beyond the initial biopsy.

For example, on percutaneous biopsy, a patient with inguinal adenopathy and a positive lymphangiogram without systemic symptoms might have involvement of the liver and bone marrow. The precise stage of such a patient would be clinical stage IIA, pathological stage IVA(H+)(M+).

Several other factors that are not included in the above staging system are important for the staging and prognosis of patients with PTCL. These factors include the following:

• Age.
• Performance status (PS).
• Tumor size.
• Lactate dehydrogenase (LDH) values.
• The number of extranodal sites.

The National Comprehensive Cancer Network International Prognostic Index for aggressive NHL (diffuse large cell lymphoma) identifies the following five significant risk factors prognostic of overall survival (OS) and their associated risk scores:[14]

• Age.

  -

  <40 years: 0.

  -

  41–60 years: 1.

  -

  61–75 years: 2.

  -

  >75 years: 3.

• Stage III/IV: 1.
• PS 2/3/4: 1.
• Serum LDH.

  -

  Normalized: 0.

  -

  >1x–3x: 1.

  -

  >3x: 2.

• Number of extranodal sites ≥2: 1.

Risk scores:

• Low (0 or 1): 5-year OS rate, 96%; progression-free survival (PFS) rate, 91%.
• Low intermediate (2 or 3): 5-year OS rate, 82%; PFS rate, 74%.
• High intermediate (4 or 5): 5-year OS rate, 64%; PFS rate, 51%.
• High (>6): 5-year OS rate, 33%; PFS rate, 30%.

References

1. Syrykh C, Chaouat C, Poullot E, et al.: Lymph node excisions provide more precise lymphoma diagnoses than core biopsies: a French Lymphopath network survey. Blood 140 (24): 2573-2583, 2022. [PubMed: 35797472]
2. Mann GB, Conlon KC, LaQuaglia M, et al.: Emerging role of laparoscopy in the diagnosis of lymphoma. J Clin Oncol 16 (5): 1909-15, 1998. [PubMed: 9586909]
3. Barrington SF, Mikhaeel NG, Kostakoglu L, et al.: Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol 32 (27): 3048-58, 2014. [PMC free article: PMC5015423] [PubMed: 25113771]
4. Horning SJ, Juweid ME, Schöder H, et al.: Interim positron emission tomography scans in diffuse large B-cell lymphoma: an independent expert nuclear medicine evaluation of the Eastern Cooperative Oncology Group E3404 study. Blood 115 (4): 775-7; quiz 918, 2010. [PMC free article: PMC2815514] [PubMed: 19767508]
5. Moskowitz CH, Schöder H, Teruya-Feldstein J, et al.: Risk-adapted dose-dense immunochemotherapy determined by interim FDG-PET in Advanced-stage diffuse large B-Cell lymphoma. J Clin Oncol 28 (11): 1896-903, 2010. [PMC free article: PMC3651601] [PubMed: 20212248]
6. Pregno P, Chiappella A, Bellò M, et al.: Interim 18-FDG-PET/CT failed to predict the outcome in diffuse large B-cell lymphoma patients treated at the diagnosis with rituximab-CHOP. Blood 119 (9): 2066-73, 2012. [PubMed: 22234681]
7. Sun N, Zhao J, Qiao W, et al.: Predictive value of interim PET/CT in DLBCL treated with R-CHOP: meta-analysis. Biomed Res Int 2015: 648572, 2015. [PMC free article: PMC4331162] [PubMed: 25710013]
8. Khan AB, Barrington SF, Mikhaeel NG, et al.: PET-CT staging of DLBCL accurately identifies and provides new insight into the clinical significance of bone marrow involvement. Blood 122 (1): 61-7, 2013. [PubMed: 23660958]
9. Rutherford SC, Yin J, Pederson L, et al.: Relevance of Bone Marrow Biopsies for Response Assessment in US National Cancer Institute National Clinical Trials Network Follicular Lymphoma Clinical Trials. J Clin Oncol 41 (2): 336-342, 2023. [PMC free article: PMC9839232] [PubMed: 35787017]
10. Hodgkin and non-Hodgkin lymphoma. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp. 937–58.
11. Carbone PP, Kaplan HS, Musshoff K, et al.: Report of the Committee on Hodgkin's Disease Staging Classification. Cancer Res 31 (11): 1860-1, 1971. [PubMed: 5121694]
12. Lister TA, Crowther D, Sutcliffe SB, et al.: Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting. J Clin Oncol 7 (11): 1630-6, 1989. [PubMed: 2809679]
13. National Cancer Institute sponsored study of classifications of non-Hodgkin's lymphomas: summary and description of a working formulation for clinical usage. The Non-Hodgkin's Lymphoma Pathologic Classification Project. Cancer 49 (10): 2112-35, 1982. [PubMed: 6896167]
14. Zhou Z, Sehn LH, Rademaker AW, et al.: An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era. Blood 123 (6): 837-42, 2014. [PMC free article: PMC5527396] [PubMed: 24264230]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References

1. Bai RY, Ouyang T, Miething C, et al.: Nucleophosmin-anaplastic lymphoma kinase associated with anaplastic large-cell lymphoma activates the phosphatidylinositol 3-kinase/Akt antiapoptotic signaling pathway. Blood 96 (13): 4319-27, 2000. [PubMed: 11110708]
2. Hapgood G, Savage KJ: The biology and management of systemic anaplastic large cell lymphoma. Blood 126 (1): 17-25, 2015. [PubMed: 25869285]
3. Gascoyne RD, Aoun P, Wu D, et al.: Prognostic significance of anaplastic lymphoma kinase (ALK) protein expression in adults with anaplastic large cell lymphoma. Blood 93 (11): 3913-21, 1999. [PubMed: 10339500]
4. Sibon D, Fournier M, Brière J, et al.: Long-term outcome of adults with systemic anaplastic large-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte trials. J Clin Oncol 30 (32): 3939-46, 2012. [PubMed: 23045585]
5. Horwitz S, O'Connor OA, Pro B, et al.: Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet 393 (10168): 229-240, 2019. [PMC free article: PMC6436818] [PubMed: 30522922]
6. Younes A, Bartlett NL, Leonard JP, et al.: Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med 363 (19): 1812-21, 2010. [PubMed: 21047225]
7. Pro B, Advani R, Brice P, et al.: Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J Clin Oncol 30 (18): 2190-6, 2012. [PubMed: 22614995]
8. Prince HM, Kim YH, Horwitz SM, et al.: Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial. Lancet 390 (10094): 555-566, 2017. [PubMed: 28600132]
9. Pro B, Advani R, Brice P, et al.: Five-year results of brentuximab vedotin in patients with relapsed or refractory systemic anaplastic large cell lymphoma. Blood 130 (25): 2709-2717, 2017. [PMC free article: PMC5746164] [PubMed: 28974506]
10. Coiffier B, Pro B, Prince HM, et al.: Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy. J Clin Oncol 30 (6): 631-6, 2012. [PubMed: 22271479]
11. O'Connor OA, Horwitz S, Hamlin P, et al.: Phase II-I-II study of two different doses and schedules of pralatrexate, a high-affinity substrate for the reduced folate carrier, in patients with relapsed or refractory lymphoma reveals marked activity in T-cell malignancies. J Clin Oncol 27 (26): 4357-64, 2009. [PMC free article: PMC3651599] [PubMed: 19652067]
12. Smith SM, Burns LJ, van Besien K, et al.: Hematopoietic cell transplantation for systemic mature T-cell non-Hodgkin lymphoma. J Clin Oncol 31 (25): 3100-9, 2013. [PMC free article: PMC3753702] [PubMed: 23897963]
13. Brink M, Meeuwes FO, van der Poel MWM, et al.: Impact of etoposide and ASCT on survival among patients aged <65 years with stage II to IV PTCL: a population-based cohort study. Blood 140 (9): 1009-1019, 2022. [PMC free article: PMC9437712] [PubMed: 35544601]
14. Furqan F, Ahn KW, Chen Y, et al.: Allogeneic haematopoietic cell transplant in patients with relapsed/refractory anaplastic large cell lymphoma. Br J Haematol 200 (1): 54-63, 2023. [PMC free article: PMC9772096] [PubMed: 36120837]
15. Seidemann K, Tiemann M, Schrappe M, et al.: Short-pulse B-non-Hodgkin lymphoma-type chemotherapy is efficacious treatment for pediatric anaplastic large cell lymphoma: a report of the Berlin-Frankfurt-Münster Group Trial NHL-BFM 90. Blood 97 (12): 3699-706, 2001. [PubMed: 11389005]
16. Lowe EJ, Reilly AF, Lim MS, et al.: Crizotinib in Combination With Chemotherapy for Pediatric Patients With ALK+ Anaplastic Large-Cell Lymphoma: The Results of Children's Oncology Group Trial ANHL12P1. J Clin Oncol 41 (11): 2043-2053, 2023. [PMC free article: PMC10082271] [PubMed: 36534942]
17. Mossé YP, Voss SD, Lim MS, et al.: Targeting ALK With Crizotinib in Pediatric Anaplastic Large Cell Lymphoma and Inflammatory Myofibroblastic Tumor: A Children's Oncology Group Study. J Clin Oncol 35 (28): 3215-3221, 2017. [PMC free article: PMC5617123] [PubMed: 28787259]
18. Miranda RN, Aladily TN, Prince HM, et al.: Breast implant-associated anaplastic large-cell lymphoma: long-term follow-up of 60 patients. J Clin Oncol 32 (2): 114-20, 2014. [PMC free article: PMC4062709] [PubMed: 24323027]
19. Clemens MW, Medeiros LJ, Butler CE, et al.: Complete Surgical Excision Is Essential for the Management of Patients With Breast Implant-Associated Anaplastic Large-Cell Lymphoma. J Clin Oncol 34 (2): 160-8, 2016. [PMC free article: PMC4872006] [PubMed: 26628470]
20. Mehta-Shah N, Clemens MW, Horwitz SM: How I treat breast implant-associated anaplastic large cell lymphoma. Blood 132 (18): 1889-1898, 2018. [PMC free article: PMC6536699] [PubMed: 30209119]
21. Jaffe ES, Ashar BS, Clemens MW, et al.: Best Practices Guideline for the Pathologic Diagnosis of Breast Implant-Associated Anaplastic Large-Cell Lymphoma. J Clin Oncol 38 (10): 1102-1111, 2020. [PMC free article: PMC7106983] [PubMed: 32045544]
22. Los-de Vries GT, de Boer M, van Dijk E, et al.: Chromosome 20 loss is characteristic of breast implant-associated anaplastic large cell lymphoma. Blood 136 (25): 2927-2932, 2020. [PubMed: 33331925]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References

1. Siegert W, Agthe A, Griesser H, et al.: Treatment of angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma using prednisone with or without the COPBLAM/IMVP-16 regimen. A multicenter study. Kiel Lymphoma Study Group. Ann Intern Med 117 (5): 364-70, 1992. [PubMed: 1380221]
2. Jaffe ES: Angioimmunoblastic T-cell lymphoma: new insights, but the clinical challenge remains. Ann Oncol 6 (7): 631-2, 1995. [PubMed: 8664181]
3. Siegert W, Nerl C, Agthe A, et al.: Angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma: prognostic impact of clinical observations and laboratory findings at presentation. The Kiel Lymphoma Study Group. Ann Oncol 6 (7): 659-64, 1995. [PubMed: 8664186]
4. Lunning MA, Vose JM: Angioimmunoblastic T-cell lymphoma: the many-faced lymphoma. Blood 129 (9): 1095-1102, 2017. [PubMed: 28115369]
5. Rizvi MA, Evens AM, Tallman MS, et al.: T-cell non-Hodgkin lymphoma. Blood 107 (4): 1255-64, 2006. [PubMed: 16210342]
6. Bräuninger A, Spieker T, Willenbrock K, et al.: Survival and clonal expansion of mutating "forbidden" (immunoglobulin receptor-deficient) epstein-barr virus-infected b cells in angioimmunoblastic t cell lymphoma. J Exp Med 194 (7): 927-40, 2001. [PMC free article: PMC2193480] [PubMed: 11581315]
7. Horwitz S, O'Connor OA, Pro B, et al.: Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet 393 (10168): 229-240, 2019. [PMC free article: PMC6436818] [PubMed: 30522922]
8. Federico M, Rudiger T, Bellei M, et al.: Clinicopathologic characteristics of angioimmunoblastic T-cell lymphoma: analysis of the international peripheral T-cell lymphoma project. J Clin Oncol 31 (2): 240-6, 2013. [PMC free article: PMC3532394] [PubMed: 22869878]
9. Reimer P, Rüdiger T, Geissinger E, et al.: Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: results of a prospective multicenter study. J Clin Oncol 27 (1): 106-13, 2009. [PubMed: 19029417]
10. Le Gouill S, Milpied N, Buzyn A, et al.: Graft-versus-lymphoma effect for aggressive T-cell lymphomas in adults: a study by the Société Francaise de Greffe de Moëlle et de Thérapie Cellulaire. J Clin Oncol 26 (14): 2264-71, 2008. [PubMed: 18390969]
11. Kyriakou C, Canals C, Finke J, et al.: Allogeneic stem cell transplantation is able to induce long-term remissions in angioimmunoblastic T-cell lymphoma: a retrospective study from the lymphoma working party of the European group for blood and marrow transplantation. J Clin Oncol 27 (24): 3951-8, 2009. [PubMed: 19620487]
12. Park SI, Horwitz SM, Foss FM, et al.: The role of autologous stem cell transplantation in patients with nodal peripheral T-cell lymphomas in first complete remission: Report from COMPLETE, a prospective, multicenter cohort study. Cancer 125 (9): 1507-1517, 2019. [PMC free article: PMC8269282] [PubMed: 30694529]
13. Brink M, Meeuwes FO, van der Poel MWM, et al.: Impact of etoposide and ASCT on survival among patients aged <65 years with stage II to IV PTCL: a population-based cohort study. Blood 140 (9): 1009-1019, 2022. [PMC free article: PMC9437712] [PubMed: 35544601]
14. Los-de Vries GT, de Boer M, van Dijk E, et al.: Chromosome 20 loss is characteristic of breast implant-associated anaplastic large cell lymphoma. Blood 136 (25): 2927-2932, 2020. [PubMed: 33331925]
15. Advani R, Horwitz S, Zelenetz A, et al.: Angioimmunoblastic T cell lymphoma: treatment experience with cyclosporine. Leuk Lymphoma 48 (3): 521-5, 2007. [PubMed: 17454592]
16. Amengual JE, Lichtenstein R, Lue J, et al.: A phase 1 study of romidepsin and pralatrexate reveals marked activity in relapsed and refractory T-cell lymphoma. Blood 131 (4): 397-407, 2018. [PMC free article: PMC5790128] [PubMed: 29141948]
17. Damaj G, Gressin R, Bouabdallah K, et al.: Results from a prospective, open-label, phase II trial of bendamustine in refractory or relapsed T-cell lymphomas: the BENTLY trial. J Clin Oncol 31 (1): 104-10, 2013. [PubMed: 23109692]
18. Coiffier B, Pro B, Prince HM, et al.: Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy. J Clin Oncol 30 (6): 631-6, 2012. [PubMed: 22271479]
19. Fanale MA, Horwitz SM, Forero-Torres A, et al.: Five-year outcomes for frontline brentuximab vedotin with CHP for CD30-expressing peripheral T-cell lymphomas. Blood 131 (19): 2120-2124, 2018. [PMC free article: PMC5946765] [PubMed: 29507077]

Prognosis

Most investigators report worse response and survival rates for patients with PTCL-NOS than for patients with comparably staged B-cell aggressive lymphomas.[3,4] Most patients present with multiple adverse prognostic factors (i.e., older age, stage IV, multiple extranodal sites, and elevated lactate dehydrogenase), and these patients have low (<20%) failure-free survival and overall survival (OS) rates at 5 years.[3,4] As with other lymphomas (e.g., diffuse large B-cell lymphoma [DLBCL] or follicular lymphoma), event-free survival (EFS) at 24 months predicts a 5-year OS rate of 78%.[5]

Therapeutic Approaches

Therapy involves doxorubicin-based combination chemotherapy such as cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP plus etoposide (CHOPE). Doses are the same as those used for DLBCL.[6] For CD30-positive cases, brentuximab vedotin combined with cyclophosphamide, doxorubicin, and prednisone is the proposed standard of care.[7][Level of evidence C3] Patients with PTCL-NOS were included in the clinical trial involving mostly patients with anaplastic large cell lymphoma; a benefit for this smaller PTCL-NOS subgroup cannot be established.[7][Level of evidence C3] For more information, see the Treatment of Anaplastic Large Cell Lymphoma section.

For patients with early-stage disease, anecdotal retrospective series disagree on the value of consolidative radiation therapy after combination chemotherapy.[8][Level of evidence C3] Consolidation therapy using high-dose chemotherapy with autologous or allogeneic hematopoietic stem cell transplant (SCT) has been given to patients with advanced-stage PTCL after induction therapy in multiple phase II or retrospective trials. Evidence for this approach is anecdotal.[9-16][Level of evidence C3]

• A randomized prospective trial included 104 patients younger than 61 years with stage II, III, or IV PTCL (excluding ALK-positive anaplastic large cell lymphoma). Patients received either autologous SCT or allogeneic SCT as consolidation therapy after induction with CHOPE followed by DHAP (dexamethasone, cytarabine, and cisplatin).[17][Level of evidence C3]

  -

  With a median follow-up of 42 months, the 3-year EFS rate was 43% for patients who received allogeneic SCT and 38% for patients who received autologous SCT.

  -

  The 3-year OS rate was 57% for patients who received allogeneic SCT and 70% for patients who received autologous SCT (P = nonsignificant).

  -

  None of the 21 responding patients who proceeded to allogeneic SCT relapsed, and 36% of patients who proceeded to autologous SCT relapsed.

  -

  Eight of 26 patients (31%) who received allogeneic SCT died of graft-versus-host disease, and none of the 41 patients who received autologous SCT died of toxicity.

  -

  The benefit of graft-versus-lymphoma effect was negated by increased transplant-related mortality.

• In a prospective trial of 109 evaluable patients with relapsing disease, treatment with pralatrexate resulted in a 30% response rate and a median 10-month duration of response.[18,19][Level of evidence C3]
• Similar response rates were seen in 130 evaluable patients with relapsing disease who received romidepsin in a prospective trial.[19][Level of evidence C3]
• Anecdotal responses have been seen with a combination of pralatrexate and romidepsin,[20] single-agent bendamustine,[21] belinostat,[22] and brentuximab vedotin (even if there is little or no CD30 expression on the lymphoma).[23][Level of evidence C3]
  Incorporation of these new agents with CHOP chemotherapy is under clinical evaluation.[3,7]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References

1. Rüdiger T, Weisenburger DD, Anderson JR, et al.: Peripheral T-cell lymphoma (excluding anaplastic large-cell lymphoma): results from the Non-Hodgkin's Lymphoma Classification Project. Ann Oncol 13 (1): 140-9, 2002. [PubMed: 11863096]
2. Rizvi MA, Evens AM, Tallman MS, et al.: T-cell non-Hodgkin lymphoma. Blood 107 (4): 1255-64, 2006. [PubMed: 16210342]
3. Weisenburger DD, Savage KJ, Harris NL, et al.: Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project. Blood 117 (12): 3402-8, 2011. [PubMed: 21270441]
4. Sonnen R, Schmidt WP, Müller-Hermelink HK, et al.: The International Prognostic Index determines the outcome of patients with nodal mature T-cell lymphomas. Br J Haematol 129 (3): 366-72, 2005. [PubMed: 15842660]
5. Maurer MJ, Ellin F, Srour L, et al.: International Assessment of Event-Free Survival at 24 Months and Subsequent Survival in Peripheral T-Cell Lymphoma. J Clin Oncol 35 (36): 4019-4026, 2017. [PMC free article: PMC5736237] [PubMed: 29072976]
6. Carson KR, Horwitz SM, Pinter-Brown LC, et al.: A prospective cohort study of patients with peripheral T-cell lymphoma in the United States. Cancer 123 (7): 1174-1183, 2017. [PMC free article: PMC5650190] [PubMed: 27911989]
7. Horwitz S, O'Connor OA, Pro B, et al.: Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet 393 (10168): 229-240, 2019. [PMC free article: PMC6436818] [PubMed: 30522922]
8. Briski R, Feldman AL, Bailey NG, et al.: Survival in patients with limited-stage peripheral T-cell lymphomas. Leuk Lymphoma 56 (6): 1665-70, 2015. [PMC free article: PMC4456336] [PubMed: 25248884]
9. Rodriguez J, Munsell M, Yazji S, et al.: Impact of high-dose chemotherapy on peripheral T-cell lymphomas. J Clin Oncol 19 (17): 3766-70, 2001. [PubMed: 11533100]
10. Reimer P, Rüdiger T, Geissinger E, et al.: Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: results of a prospective multicenter study. J Clin Oncol 27 (1): 106-13, 2009. [PubMed: 19029417]
11. Le Gouill S, Milpied N, Buzyn A, et al.: Graft-versus-lymphoma effect for aggressive T-cell lymphomas in adults: a study by the Société Francaise de Greffe de Moëlle et de Thérapie Cellulaire. J Clin Oncol 26 (14): 2264-71, 2008. [PubMed: 18390969]
12. d'Amore F, Relander T, Lauritzsen GF, et al.: Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol 30 (25): 3093-9, 2012. [PubMed: 22851556]
13. Schmitz N, Lenz G, Stelljes M: Allogeneic hematopoietic stem cell transplantation for T-cell lymphomas. Blood 132 (3): 245-253, 2018. [PubMed: 29699989]
14. Park SI, Horwitz SM, Foss FM, et al.: The role of autologous stem cell transplantation in patients with nodal peripheral T-cell lymphomas in first complete remission: Report from COMPLETE, a prospective, multicenter cohort study. Cancer 125 (9): 1507-1517, 2019. [PMC free article: PMC8269282] [PubMed: 30694529]
15. Brink M, Meeuwes FO, van der Poel MWM, et al.: Impact of etoposide and ASCT on survival among patients aged <65 years with stage II to IV PTCL: a population-based cohort study. Blood 140 (9): 1009-1019, 2022. [PMC free article: PMC9437712] [PubMed: 35544601]
16. Los-de Vries GT, de Boer M, van Dijk E, et al.: Chromosome 20 loss is characteristic of breast implant-associated anaplastic large cell lymphoma. Blood 136 (25): 2927-2932, 2020. [PubMed: 33331925]
17. Schmitz N, Truemper L, Bouabdallah K, et al.: A randomized phase 3 trial of autologous vs allogeneic transplantation as part of first-line therapy in poor-risk peripheral T-NHL. Blood 137 (19): 2646-2656, 2021. [PMC free article: PMC9635528] [PubMed: 33512419]
18. O'Connor OA, Pro B, Pinter-Brown L, et al.: Pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma: results from the pivotal PROPEL study. J Clin Oncol 29 (9): 1182-9, 2011. [PMC free article: PMC3083873] [PubMed: 21245435]
19. Coiffier B, Pro B, Prince HM, et al.: Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy. J Clin Oncol 30 (6): 631-6, 2012. [PubMed: 22271479]
20. Amengual JE, Lichtenstein R, Lue J, et al.: A phase 1 study of romidepsin and pralatrexate reveals marked activity in relapsed and refractory T-cell lymphoma. Blood 131 (4): 397-407, 2018. [PMC free article: PMC5790128] [PubMed: 29141948]
21. Damaj G, Gressin R, Bouabdallah K, et al.: Results from a prospective, open-label, phase II trial of bendamustine in refractory or relapsed T-cell lymphomas: the BENTLY trial. J Clin Oncol 31 (1): 104-10, 2013. [PubMed: 23109692]
22. O'Connor OA, Horwitz S, Masszi T, et al.: Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study. J Clin Oncol 33 (23): 2492-9, 2015. [PMC free article: PMC5087312] [PubMed: 26101246]
23. Fanale MA, Horwitz SM, Forero-Torres A, et al.: Five-year outcomes for frontline brentuximab vedotin with CHP for CD30-expressing peripheral T-cell lymphomas. Blood 131 (19): 2120-2124, 2018. [PMC free article: PMC5946765] [PubMed: 29507077]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References

1. Tse E, Kwong YL: How I treat NK/T-cell lymphomas. Blood 121 (25): 4997-5005, 2013. [PubMed: 23652805]
2. Rizvi MA, Evens AM, Tallman MS, et al.: T-cell non-Hodgkin lymphoma. Blood 107 (4): 1255-64, 2006. [PubMed: 16210342]
3. Mansoor A, Pittaluga S, Beck PL, et al.: NK-cell enteropathy: a benign NK-cell lymphoproliferative disease mimicking intestinal lymphoma: clinicopathologic features and follow-up in a unique case series. Blood 117 (5): 1447-52, 2011. [PMC free article: PMC3056587] [PubMed: 20966166]
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18. Hausdorff J, Davis E, Long G, et al.: Non-Hodgkin's lymphoma of the paranasal sinuses: clinical and pathological features, and response to combined-modality therapy. Cancer J Sci Am 3 (5): 303-11, 1997 Sep-Oct. [PubMed: 9327155]
19. Le Gouill S, Milpied N, Buzyn A, et al.: Graft-versus-lymphoma effect for aggressive T-cell lymphomas in adults: a study by the Société Francaise de Greffe de Moëlle et de Thérapie Cellulaire. J Clin Oncol 26 (14): 2264-71, 2008. [PubMed: 18390969]
20. Au WY, Weisenburger DD, Intragumtornchai T, et al.: Clinical differences between nasal and extranasal natural killer/T-cell lymphoma: a study of 136 cases from the International Peripheral T-Cell Lymphoma Project. Blood 113 (17): 3931-7, 2009. [PubMed: 19029440]
21. Jaccard A, Gachard N, Marin B, et al.: Efficacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen) in patients with refractory or relapsing extranodal NK/T-cell lymphoma, a phase 2 study. Blood 117 (6): 1834-9, 2011. [PubMed: 21123825]
22. Yamaguchi M, Kwong YL, Kim WS, et al.: Phase II study of SMILE chemotherapy for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer (NK)/T-cell lymphoma, nasal type: the NK-Cell Tumor Study Group study. J Clin Oncol 29 (33): 4410-6, 2011. [PubMed: 21990393]
23. Li JW, Li YJ, Zhong MZ, et al.: Efficacy and tolerance of GELOXD/P-GEMOXD in newly diagnosed nasal-type extranodal NK/T-cell lymphoma: A multicenter retrospective study. Eur J Haematol 100 (3): 247-256, 2018. [PubMed: 29194798]
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25. Liang R, Gao GX, Chen JP, et al.: A phase 2 study of methotrexate, etoposide, dexamethasone, and pegaspargase chemotherapy for newly diagnosed, relapsed, or refractory extranodal natural killer/T-cell lymphoma, nasal type: a multicenter trial in Northwest China. Hematol Oncol 35 (4): 619-629, 2017. [PMC free article: PMC5763273] [PubMed: 27723108]
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Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References

1. Egan LJ, Walsh SV, Stevens FM, et al.: Celiac-associated lymphoma. A single institution experience of 30 cases in the combination chemotherapy era. J Clin Gastroenterol 21 (2): 123-9, 1995. [PubMed: 8583077]
2. Gale J, Simmonds PD, Mead GM, et al.: Enteropathy-type intestinal T-cell lymphoma: clinical features and treatment of 31 patients in a single center. J Clin Oncol 18 (4): 795-803, 2000. [PubMed: 10673521]
3. Rizvi MA, Evens AM, Tallman MS, et al.: T-cell non-Hodgkin lymphoma. Blood 107 (4): 1255-64, 2006. [PubMed: 16210342]
4. Di Sabatino A, Biagi F, Gobbi PG, et al.: How I treat enteropathy-associated T-cell lymphoma. Blood 119 (11): 2458-68, 2012. [PubMed: 22271451]
5. Daum S, Ullrich R, Heise W, et al.: Intestinal non-Hodgkin's lymphoma: a multicenter prospective clinical study from the German Study Group on Intestinal non-Hodgkin's Lymphoma. J Clin Oncol 21 (14): 2740-6, 2003. [PubMed: 12860953]
6. Le Gouill S, Milpied N, Buzyn A, et al.: Graft-versus-lymphoma effect for aggressive T-cell lymphomas in adults: a study by the Société Francaise de Greffe de Moëlle et de Thérapie Cellulaire. J Clin Oncol 26 (14): 2264-71, 2008. [PubMed: 18390969]
7. Sieniawski M, Angamuthu N, Boyd K, et al.: Evaluation of enteropathy-associated T-cell lymphoma comparing standard therapies with a novel regimen including autologous stem cell transplantation. Blood 115 (18): 3664-70, 2010. [PubMed: 20197551]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References

1. Belhadj K, Reyes F, Farcet JP, et al.: Hepatosplenic gammadelta T-cell lymphoma is a rare clinicopathologic entity with poor outcome: report on a series of 21 patients. Blood 102 (13): 4261-9, 2003. [PubMed: 12907441]
2. Chanan-Khan A, Islam T, Alam A, et al.: Long-term survival with allogeneic stem cell transplant and donor lymphocyte infusion following salvage therapy with anti-CD52 monoclonal antibody (Campath) in a patient with alpha/beta hepatosplenic T-cell non-Hodgkin's lymphoma. Leuk Lymphoma 45 (8): 1673-5, 2004. [PubMed: 15370223]
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Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References

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14. Bazarbachi A, Plumelle Y, Carlos Ramos J, et al.: Meta-analysis on the use of zidovudine and interferon-alfa in adult T-cell leukemia/lymphoma showing improved survival in the leukemic subtypes. J Clin Oncol 28 (27): 4177-83, 2010. [PubMed: 20585095]
15. Bazarbachi A, Suarez F, Fields P, et al.: How I treat adult T-cell leukemia/lymphoma. Blood 118 (7): 1736-45, 2011. [PubMed: 21673346]
16. Ishida T, Fujiwara H, Nosaka K, et al.: Multicenter Phase II Study of Lenalidomide in Relapsed or Recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002. J Clin Oncol 34 (34): 4086-4093, 2016. [PubMed: 27621400]
17. Simone CB, Morris JC, Stewart DM, et al.: Radiation therapy for the management of patients with HTLV-1-associated adult T-cell leukemia/lymphoma. Blood 120 (9): 1816-9, 2012. [PMC free article: PMC3433088] [PubMed: 22730536]
18. Ureshino H, Kamachi K, Kimura S: Mogamulizumab for the Treatment of Adult T-cell Leukemia/Lymphoma. Clin Lymphoma Myeloma Leuk 19 (6): 326-331, 2019. [PubMed: 30981611]
19. Horwitz S, O'Connor OA, Pro B, et al.: Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet 393 (10168): 229-240, 2019. [PMC free article: PMC6436818] [PubMed: 30522922]

Treatment Options for Relapsed or Refractory Peripheral T-Cell Lymphoma

Treatment options for relapsed or refractory peripheral T-cell lymphoma include the following:

1. Combination chemotherapy.

   • ICE (ifosfamide, carboplatin, and etoposide).[1,2]
   • GEMOX (gemcitabine, oxaliplatin, and dexamethasone).[3]
   • DHAP (dexamethasone, high-dose cytarabine, and cisplatin).[4]
   • ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin).[5,6]
   • Hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone).[7]
2. Antibody conjugates.

   • Brentuximab vedotin (for CD30-positive patients).
3. Histone deacetylase inhibitors.

   • Romidepsin.[8]
   • Belinostat.[9,10]
4. Dihydrofolate reductase inhibitors.

   • Pralatrexate.[11]
5. Anti-CD52 monoclonal antibodies.

   • Alemtuzumab (only available through a restricted distribution program).
6. Stem cell transplant.[12-16]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References

1. Jerkeman M, Leppä S, Kvaløy S, et al.: ICE (ifosfamide, carboplatin, etoposide) as second-line chemotherapy in relapsed or primary progressive aggressive lymphoma--the Nordic Lymphoma Group experience. Eur J Haematol 73 (3): 179-82, 2004. [PubMed: 15287915]
2. Zelenetz AD, Hamlin P, Kewalramani T, et al.: Ifosfamide, carboplatin, etoposide (ICE)-based second-line chemotherapy for the management of relapsed and refractory aggressive non-Hodgkin's lymphoma. Ann Oncol 14 (Suppl 1): i5-10, 2003. [PubMed: 12736224]
3. Shen QD, Wang L, Zhu HY, et al.: Gemcitabine, oxaliplatin and dexamethasone (GemDOx) as salvage therapy for relapsed or refractory diffuse large B-cell lymphoma and peripheral T-cell lymphoma. J Cancer 12 (1): 163-169, 2021. [PMC free article: PMC7738829] [PubMed: 33391412]
4. Schmitz N, Truemper L, Bouabdallah K, et al.: A randomized phase 3 trial of autologous vs allogeneic transplantation as part of first-line therapy in poor-risk peripheral T-NHL. Blood 137 (19): 2646-2656, 2021. [PMC free article: PMC9635528] [PubMed: 33512419]
5. Velasquez WS, McLaughlin P, Tucker S, et al.: ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol 12 (6): 1169-76, 1994. [PubMed: 8201379]
6. Mercadal S, Briones J, Xicoy B, et al.: Intensive chemotherapy (high-dose CHOP/ESHAP regimen) followed by autologous stem-cell transplantation in previously untreated patients with peripheral T-cell lymphoma. Ann Oncol 19 (5): 958-63, 2008. [PubMed: 18303032]
7. Hapgood G, Stone JM, Zannino D, et al.: A phase II study of a modified hyper-CVAD frontline therapy for patients with adverse risk diffuse large B-cell and peripheral T-cell non-Hodgkin lymphoma. Leuk Lymphoma 60 (4): 904-911, 2019. [PubMed: 30547695]
8. Iyer SP, Foss FF: Romidepsin for the Treatment of Peripheral T-Cell Lymphoma. Oncologist 20 (9): 1084-91, 2015. [PMC free article: PMC4571813] [PubMed: 26099743]
9. Campbell P, Thomas CM: Belinostat for the treatment of relapsed or refractory peripheral T-cell lymphoma. J Oncol Pharm Pract 23 (2): 143-147, 2017. [PubMed: 26921086]
10. O'Connor OA, Horwitz S, Masszi T, et al.: Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study. J Clin Oncol 33 (23): 2492-9, 2015. [PMC free article: PMC5087312] [PubMed: 26101246]
11. O'Connor OA, Pro B, Pinter-Brown L, et al.: Pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma: results from the pivotal PROPEL study. J Clin Oncol 29 (9): 1182-9, 2011. [PMC free article: PMC3083873] [PubMed: 21245435]
12. Schmitz N, Lenz G, Stelljes M: Allogeneic hematopoietic stem cell transplantation for T-cell lymphomas. Blood 132 (3): 245-253, 2018. [PubMed: 29699989]
13. Chen AI, McMillan A, Negrin RS, et al.: Long-term results of autologous hematopoietic cell transplantation for peripheral T cell lymphoma: the Stanford experience. Biol Blood Marrow Transplant 14 (7): 741-7, 2008. [PMC free article: PMC2980839] [PubMed: 18541192]
14. Hamadani M, Ngoya M, Sureda A, et al.: Outcome of allogeneic transplantation for mature T-cell lymphomas: impact of donor source and disease characteristics. Blood Adv 6 (3): 920-930, 2022. [PMC free article: PMC8945300] [PubMed: 34861680]
15. Mehta-Shah N, Kommalapati A, Teja S: Successful treatment of mature T-cell lymphoma with allogeneic stem cell transplantation: the largest multicenter retrospective analysis. [Abstract] Blood 136 (Suppl 1): A-624, 35-36, 2020.
16. Sterling CH, Hughes MS, Tsai HL, et al.: Allogeneic Blood or Marrow Transplantation with Post-Transplantation Cyclophosphamide for Peripheral T Cell Lymphoma: The Importance of Graft Source. Transplant Cell Ther 29 (4): 267.e1-267.e5, 2023. [PMC free article: PMC10040425] [PubMed: 36549386]

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of adult peripheral T-cell non-Hodgkin lymphoma. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

• be discussed at a meeting,
• be cited with text, or
• replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Peripheral T-Cell Non-Hodgkin Lymphoma Treatment are:

• Eric J. Seifter, MD (Johns Hopkins University)
• Cole H. Sterling, MD (Johns Hopkins University)

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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The preferred citation for this PDQ summary is:

PDQ® Adult Treatment Editorial Board. PDQ Peripheral T-Cell Non-Hodgkin Lymphoma Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/lymphoma/hp/peripheral-t-cell-lymphoma-pdq. Accessed <MM/DD/YYYY>.

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Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

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