Skip to main content
Top
Published in: Journal of Hematology & Oncology 1/2019

Open Access 01-12-2019 | Lymphoma | Research

Allogeneic hematopoietic cell transplantation provides effective salvage despite refractory disease or failed prior autologous transplant in angioimmunoblastic T-cell lymphoma: a CIBMTR analysis

Authors: Narendranath Epperla, Kwang W. Ahn, Carlos Litovich, Sairah Ahmed, Minoo Battiwalla, Jonathon B. Cohen, Parastoo Dahi, Nosha Farhadfar, Umar Farooq, Cesar O. Freytes, Nilanjan Ghosh, Bradley Haverkos, Alex Herrera, Mark Hertzberg, Gerhard Hildebrandt, David Inwards, Mohamed A. Kharfan-Dabaja, Farhad Khimani, Hillard Lazarus, Aleksandr Lazaryan, Lazaros Lekakis, Hemant Murthy, Sunita Nathan, Taiga Nishihori, Attaphol Pawarode, Tim Prestidge, Praveen Ramakrishnan, Andrew R. Rezvani, Rizwan Romee, Nirav N. Shah, Ana Sureda, Timothy S. Fenske, Mehdi Hamadani

Published in: Journal of Hematology & Oncology | Issue 1/2019

Login to get access

Abstract

Background

There is a paucity of data on the role of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with angioimmunoblastic T-cell lymphoma (AITL). Using the CIBMTR registry, we report here the outcomes of AITL patients undergoing an allo-HCT.

Methods

We evaluated 249 adult AITL patients who received their first allo-HCT during 2000–2016.

Results

The median patient age was 56 years (range = 21–77). Majority of the patients were Caucasians (86%), with a male predominance (60%). Graft-versus-host disease (GVHD) prophylaxis was predominantly calcineurin inhibitor-based approaches while the most common graft source was peripheral blood (97%). Median follow-up of survivors was 49 months (range = 4–170 months). The cumulative incidence of grade 2–4 and grade 3–4 acute GVHD at day 180 were 36% (95% CI = 30–42) and 12 (95% CI = 8–17), respectively. The cumulative incidence of chronic GVHD at 1 year was 49% (95%CI 43–56). The 1-year non-relapse mortality (NRM) was 19% (95% CI = 14–24), while the 4-year relapse/progression, progression-free survival (PFS), and overall survival (OS) were 21% (95% CI = 16–27), 49% (95% CI = 42–56), and 56% (95% CI = 49–63), respectively. On multivariate analysis, chemoresistant status at the time of allo-HCT was associated with a significantly higher risk for therapy failure (inverse of PFS) (RR = 1.73 95% CI = 1.08–2.77), while KPS < 90% was associated with a significantly higher risk of mortality (inverse of OS) (RR = 3.46 95% CI = 1.75–6.87).

Conclusion

Our analysis shows that allo-HCT provides durable disease control even in AITL patients who failed a prior auto-HCT and in those subjects with refractory disease at the time of allografting.
Appendix
Available only for authorised users
Literature
1.
go back to reference Gisselbrecht C, Gaulard P, Lepage E, Coiffier B, Briere J, Haioun C, et al. Prognostic significance of T-cell phenotype in aggressive non-Hodgkin’s lymphomas. Groupe d’Etudes des Lymphomes de l’Adulte (GELA). Blood. 1998;92(1):76–82.PubMed Gisselbrecht C, Gaulard P, Lepage E, Coiffier B, Briere J, Haioun C, et al. Prognostic significance of T-cell phenotype in aggressive non-Hodgkin’s lymphomas. Groupe d’Etudes des Lymphomes de l’Adulte (GELA). Blood. 1998;92(1):76–82.PubMed
2.
go back to reference Mourad N, Mounier N, Briere J, Raffoux E, Delmer A, Feller A, et al. Clinical, biologic, and pathologic features in 157 patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d’Etude des Lymphomes de l’Adulte (GELA) trials. Blood. 2008;111(9):4463–70.CrossRef Mourad N, Mounier N, Briere J, Raffoux E, Delmer A, Feller A, et al. Clinical, biologic, and pathologic features in 157 patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d’Etude des Lymphomes de l’Adulte (GELA) trials. Blood. 2008;111(9):4463–70.CrossRef
3.
go back to reference Federico M, Rudiger T, Bellei M, Nathwani BN, Luminari S, Coiffier B, et al. Clinicopathologic characteristics of angioimmunoblastic T-cell lymphoma: analysis of the international peripheral T-cell lymphoma project. J Clin Oncol. 2013;31(2):240–6.CrossRef Federico M, Rudiger T, Bellei M, Nathwani BN, Luminari S, Coiffier B, et al. Clinicopathologic characteristics of angioimmunoblastic T-cell lymphoma: analysis of the international peripheral T-cell lymphoma project. J Clin Oncol. 2013;31(2):240–6.CrossRef
4.
go back to reference Siegert W, Agthe A, Griesser H, Schwerdtfeger R, Brittinger G, Engelhard M, 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. 1992;117(5):364–70.CrossRef Siegert W, Agthe A, Griesser H, Schwerdtfeger R, Brittinger G, Engelhard M, 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. 1992;117(5):364–70.CrossRef
5.
go back to reference Pautier P, Devidas A, Delmer A, Dombret H, Sutton L, Zini JM, et al. Angioimmunoblastic-like T-cell non Hodgkin’s lymphoma: outcome after chemotherapy in 33 patients and review of the literature. Leuk Lymphoma. 1999;32(5–6):545–52.CrossRef Pautier P, Devidas A, Delmer A, Dombret H, Sutton L, Zini JM, et al. Angioimmunoblastic-like T-cell non Hodgkin’s lymphoma: outcome after chemotherapy in 33 patients and review of the literature. Leuk Lymphoma. 1999;32(5–6):545–52.CrossRef
6.
go back to reference Schmitz N, Trumper L, Ziepert M, Nickelsen M, Ho AD, Metzner B, et al. Treatment and prognosis of mature T-cell and NK-cell lymphoma: an analysis of patients with T-cell lymphoma treated in studies of the German high-grade non-Hodgkin lymphoma study group. Blood. 2010;116(18):3418–25.CrossRef Schmitz N, Trumper L, Ziepert M, Nickelsen M, Ho AD, Metzner B, et al. Treatment and prognosis of mature T-cell and NK-cell lymphoma: an analysis of patients with T-cell lymphoma treated in studies of the German high-grade non-Hodgkin lymphoma study group. Blood. 2010;116(18):3418–25.CrossRef
7.
go back to reference Vose J, Armitage J, Weisenburger D, International TCLP. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008;26(25):4124–30.CrossRef Vose J, Armitage J, Weisenburger D, International TCLP. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008;26(25):4124–30.CrossRef
8.
go back to reference Schetelig J, Fetscher S, Reichle A, Berdel WE, Beguin Y, Brunet S, et al. Long-term disease-free survival in patients with angioimmunoblastic T-cell lymphoma after high-dose chemotherapy and autologous stem cell transplantation. Haematologica. 2003;88(11):1272–8.PubMed Schetelig J, Fetscher S, Reichle A, Berdel WE, Beguin Y, Brunet S, et al. Long-term disease-free survival in patients with angioimmunoblastic T-cell lymphoma after high-dose chemotherapy and autologous stem cell transplantation. Haematologica. 2003;88(11):1272–8.PubMed
9.
go back to reference Rodriguez J, Conde E, Gutierrez A, Arranz R, Gandarillas M, Leon A, et al. Prolonged survival of patients with angioimmunoblastic T-cell lymphoma after high-dose chemotherapy and autologous stem cell transplantation: the GELTAMO experience. Eur J Haematol. 2007;78(4):290–6.CrossRef Rodriguez J, Conde E, Gutierrez A, Arranz R, Gandarillas M, Leon A, et al. Prolonged survival of patients with angioimmunoblastic T-cell lymphoma after high-dose chemotherapy and autologous stem cell transplantation: the GELTAMO experience. Eur J Haematol. 2007;78(4):290–6.CrossRef
10.
go back to reference Kyriakou C, Canals C, Goldstone A, Caballero D, Metzner B, Kobbe G, et al. High-dose therapy and autologous stem-cell transplantation in angioimmunoblastic lymphoma: complete remission at transplantation is the major determinant of outcome-lymphoma working Party of the European Group for blood and marrow transplantation. J Clin Oncol. 2008;26(2):218–24.PubMed Kyriakou C, Canals C, Goldstone A, Caballero D, Metzner B, Kobbe G, et al. High-dose therapy and autologous stem-cell transplantation in angioimmunoblastic lymphoma: complete remission at transplantation is the major determinant of outcome-lymphoma working Party of the European Group for blood and marrow transplantation. J Clin Oncol. 2008;26(2):218–24.PubMed
11.
go back to reference Le Gouill S, Milpied N, Buzyn A, De Latour RP, Vernant JP, Mohty M, et al. Graft-versus-lymphoma effect for aggressive T-cell lymphomas in adults: a study by the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire. J Clin Oncol. 2008;26(14):2264–71.CrossRef Le Gouill S, Milpied N, Buzyn A, De Latour RP, Vernant JP, Mohty M, et al. Graft-versus-lymphoma effect for aggressive T-cell lymphomas in adults: a study by the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire. J Clin Oncol. 2008;26(14):2264–71.CrossRef
12.
go back to reference Hamadani M, Awan FT, Elder P, Lin TS, Porcu P, Blum KA, et al. Allogeneic hematopoietic stem cell transplantation for peripheral T cell lymphomas; evidence of graft-versus-T cell lymphoma effect. Biol Blood Marrow Transplant. 2008;14(4):480–3.CrossRef Hamadani M, Awan FT, Elder P, Lin TS, Porcu P, Blum KA, et al. Allogeneic hematopoietic stem cell transplantation for peripheral T cell lymphomas; evidence of graft-versus-T cell lymphoma effect. Biol Blood Marrow Transplant. 2008;14(4):480–3.CrossRef
13.
go back to reference Urbano-Ispizua A, Pavletic SZ, Flowers ME, Klein JP, Zhang MJ, Carreras J, et al. The impact of graft-versus-host disease on the relapse rate in patients with lymphoma depends on the histological subtype and the intensity of the conditioning regimen. Biol Blood Marrow Transplant. 2015;21(10):1746–53.CrossRef Urbano-Ispizua A, Pavletic SZ, Flowers ME, Klein JP, Zhang MJ, Carreras J, et al. The impact of graft-versus-host disease on the relapse rate in patients with lymphoma depends on the histological subtype and the intensity of the conditioning regimen. Biol Blood Marrow Transplant. 2015;21(10):1746–53.CrossRef
14.
go back to reference Kyriakou C, Canals C, Finke J, Kobbe G, Harousseau JL, Kolb HJ, 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. 2009;27(24):3951–8.CrossRef Kyriakou C, Canals C, Finke J, Kobbe G, Harousseau JL, Kolb HJ, 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. 2009;27(24):3951–8.CrossRef
15.
go back to reference Dodero A, Spina F, Narni F, Patriarca F, Cavattoni I, Benedetti F, et al. Allogeneic transplantation following a reduced-intensity conditioning regimen in relapsed/refractory peripheral T-cell lymphomas: long-term remissions and response to donor lymphocyte infusions support the role of a graft-versus-lymphoma effect. Leukemia. 2012;26(3):520–6.CrossRef Dodero A, Spina F, Narni F, Patriarca F, Cavattoni I, Benedetti F, et al. Allogeneic transplantation following a reduced-intensity conditioning regimen in relapsed/refractory peripheral T-cell lymphomas: long-term remissions and response to donor lymphocyte infusions support the role of a graft-versus-lymphoma effect. Leukemia. 2012;26(3):520–6.CrossRef
16.
go back to reference Smith SM, Burns LJ, van Besien K, Lerademacher J, He W, Fenske TS, et al. Hematopoietic cell transplantation for systemic mature T-cell non-Hodgkin lymphoma. J Clin Oncol. 2013;31(25):3100–9.CrossRef Smith SM, Burns LJ, van Besien K, Lerademacher J, He W, Fenske TS, et al. Hematopoietic cell transplantation for systemic mature T-cell non-Hodgkin lymphoma. J Clin Oncol. 2013;31(25):3100–9.CrossRef
17.
go back to reference Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15(12):1628–33.CrossRef Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15(12):1628–33.CrossRef
18.
go back to reference Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25(5):579–86.CrossRef Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25(5):579–86.CrossRef
19.
go back to reference Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995;15(6):825–8. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995;15(6):825–8.
20.
go back to reference Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980;69(2):204–17.CrossRef Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980;69(2):204–17.CrossRef
21.
go back to reference Copelan E, Casper JT, Carter SL, van Burik JA, Hurd D, Mendizabal AM, et al. A scheme for defining cause of death and its application in the T cell depletion trial. Biol Blood Marrow Transplant. 2007;13(12):1469–76.CrossRef Copelan E, Casper JT, Carter SL, van Burik JA, Hurd D, Mendizabal AM, et al. A scheme for defining cause of death and its application in the T cell depletion trial. Biol Blood Marrow Transplant. 2007;13(12):1469–76.CrossRef
22.
go back to reference Commenges D, Andersen PK. Score test of homogeneity for survival data. Lifetime Data Anal. 1995;1(2):145–56. discussion 57-9CrossRef Commenges D, Andersen PK. Score test of homogeneity for survival data. Lifetime Data Anal. 1995;1(2):145–56. discussion 57-9CrossRef
23.
go back to reference Kharfan-Dabaja MA, Kumar A, Ayala E, Hamadani M, Reimer P, Gisselbrecht C, et al. Clinical practice recommendations on indication and timing of hematopoietic cell transplantation in mature T cell and NK/T cell lymphomas: an international collaborative effort on behalf of the guidelines Committee of the American Society for blood and marrow transplantation. Biol Blood Marrow Transplant. 2017;23(11):1826–38.CrossRef Kharfan-Dabaja MA, Kumar A, Ayala E, Hamadani M, Reimer P, Gisselbrecht C, et al. Clinical practice recommendations on indication and timing of hematopoietic cell transplantation in mature T cell and NK/T cell lymphomas: an international collaborative effort on behalf of the guidelines Committee of the American Society for blood and marrow transplantation. Biol Blood Marrow Transplant. 2017;23(11):1826–38.CrossRef
24.
go back to reference d’Amore F, Relander T, Lauritzsen GF, Jantunen E, Hagberg H, Anderson H, et al. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol. 2012;30(25):3093–9.CrossRef d’Amore F, Relander T, Lauritzsen GF, Jantunen E, Hagberg H, Anderson H, et al. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol. 2012;30(25):3093–9.CrossRef
25.
go back to reference Hamadani M, Kanate AS, DiGilio A, Ahn KW, Smith SM, Lee JW, et al. Allogeneic hematopoietic cell transplantation for aggressive NK cell leukemia. A Center for International Blood and Marrow Transplant Research Analysis. Biol Blood Marrow Transplant. 2017;23(5):853–6.CrossRef Hamadani M, Kanate AS, DiGilio A, Ahn KW, Smith SM, Lee JW, et al. Allogeneic hematopoietic cell transplantation for aggressive NK cell leukemia. A Center for International Blood and Marrow Transplant Research Analysis. Biol Blood Marrow Transplant. 2017;23(5):853–6.CrossRef
26.
go back to reference Kanate AS, DiGilio A, Ahn KW, Al Malki M, Jacobsen E, Steinberg A, et al. Allogeneic haematopoietic cell transplantation for extranodal natural killer/T-cell lymphoma, nasal type: a CIBMTR analysis. Br J Haematol. 2018;182(6):916–20.CrossRef Kanate AS, DiGilio A, Ahn KW, Al Malki M, Jacobsen E, Steinberg A, et al. Allogeneic haematopoietic cell transplantation for extranodal natural killer/T-cell lymphoma, nasal type: a CIBMTR analysis. Br J Haematol. 2018;182(6):916–20.CrossRef
27.
go back to reference Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene Ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531–44.CrossRef Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene Ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531–44.CrossRef
Metadata
Title
Allogeneic hematopoietic cell transplantation provides effective salvage despite refractory disease or failed prior autologous transplant in angioimmunoblastic T-cell lymphoma: a CIBMTR analysis
Authors
Narendranath Epperla
Kwang W. Ahn
Carlos Litovich
Sairah Ahmed
Minoo Battiwalla
Jonathon B. Cohen
Parastoo Dahi
Nosha Farhadfar
Umar Farooq
Cesar O. Freytes
Nilanjan Ghosh
Bradley Haverkos
Alex Herrera
Mark Hertzberg
Gerhard Hildebrandt
David Inwards
Mohamed A. Kharfan-Dabaja
Farhad Khimani
Hillard Lazarus
Aleksandr Lazaryan
Lazaros Lekakis
Hemant Murthy
Sunita Nathan
Taiga Nishihori
Attaphol Pawarode
Tim Prestidge
Praveen Ramakrishnan
Andrew R. Rezvani
Rizwan Romee
Nirav N. Shah
Ana Sureda
Timothy S. Fenske
Mehdi Hamadani
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2019
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-018-0696-z

Other articles of this Issue 1/2019

Journal of Hematology & Oncology 1/2019 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine