Blood Journal
Leading the way in experimental and clinical research in hematology

Brief Report
Autologous stem cell transplantation for enteropathy-associated T-cell lymphoma: a retrospective study by the EBMT

  1. Esa Jantunen1,
  2. Ariane Boumendil2,
  3. Herve Finel2,
  4. Jian-Jian Luan2,
  5. Peter Johnson3,
  6. Alessandro Rambaldi4,
  7. Andrew Haynes5,
  8. Michel A. Duchosal6,
  9. Wolfgang Bethge7,
  10. Pierre Biron8,
  11. Kristina Carlson9,
  12. Charles Craddock10,
  13. Claudius Rudin11,
  14. Jurgen Finke12,
  15. Gilles Salles13,
  16. Frank Kroschinsky14,
  17. Anna Sureda15, and
  18. Peter Dreger16,
  19. on behalf of the Lymphoma Working Party of the EBMT
  1. 1University of Eastern Finland/Clinical Medicine and Department of Medicine, Kuopio University Hospital, Kuopio, Finland;
  2. 2EBMT Lymphoma Working Party, Paris, France;
  3. 3Department of Haematology, Western General Hospital, Edinburgh, United Kingdom;
  4. 4Hematology and BMT Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy;
  5. 5Nottingham City Hospital, Nottingham, United Kingdom;
  6. 6Service and Central Laboratory of Hematology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland;
  7. 7Medizinische Klinik II, Universitaet Tuebingen, Tuebingen, Germany;
  8. 8Centre Leon Bernard, Lyon, France;
  9. 9Department of Medicine, University Hospital, Uppsala, Sweden;
  10. 10Centre for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, United Kingdom;
  11. 11Department of Clinical Haematology, Royal Devon and Exeter Hospital, Exeter, United Kingdom;
  12. 12Department of Medicine, University of Freiburg, Freiburg, Germany;
  13. 13Hospices Civils de Lyon and Universite Claude Bernard Lyon-1, Hematologie, Pierre Benite, France;
  14. 14Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Dresden, Germany;
  15. 15Haematology Department, Addenbrookes Hospital, Cambridge, United Kingdom; and
  16. 16Medizinische Klinik V, Universität Heidelberg, Heidelberg, Germany

    Key Points

    • ASCT provides long-term remission in the majority of EATL patients transplanted in first complete or partial remission.

    • ASCT should be considered in transplant-eligible EATL patients.


    Enteropathy-associated T-cell lymphoma (EATL) is a rare subtype of peripheral T-cell lymphomas with a poor prognosis. Autologous stem cell transplantation (ASCT) was retrospectively evaluated as a consolidation or salvage strategy for EATL. The analysis included 44 patients who received ASCT for EATL between 2000 and 2010. Thirty-one patients (70%) were in first complete or partial remission at the time of the ASCT. With a median follow-up of 46 months, relapse incidence, progression-free survival, and overall survival were 39%, 54%, and 59% at 4 years, respectively, with only one relapse occurring beyond 18 months posttransplant. There was a trend for better survival in patients transplanted in first complete or partial remission at 4 years (66% vs 36%; P = .062). ASCT is feasible in selected patients with EATL and can yield durable disease control in a significant proportion of the patients.


    Enteropathy-associated T-cell lymphoma (EATL) is a rare type of systemic peripheral T-cell lymphoma (PTCL). According to the International PTCL Project, EATL comprises 5.4% of all T-cell lymphomas.1 The prognosis of EATL has been considered to be poor.2-5 The median survival of 62 patients identified in the International PTCL Project was only 10 months.1

    Apart from a few anecdotal case series,6-8 autologous stem cell transplantation (ASCT) has been evaluated in a prospective series of 26 EATL patients, of whom 14 proceeded to ASCT after first-line chemotherapy.9 The recently published phase II study of the Nordic Lymphoma Group included 21 EATL patients, of whom 14 received ASCT.10

    To explore the feasibility and efficacy of ASCT as a consolidation or salvage strategy in this lymphoma type within a larger sample size, a retrospective registry study (LWP-2010-R-07/2011/-R-05) was undertaken by the EBMT Lymphoma Working Party.

    Study design

    The objective of this registry analysis was to study the outcome and prognostic factors of ASCT as a consolidation or salvage strategy for EATL. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Eligible patients were aged 18 years or more who had undergone ASCT for EATL between 2000 and 2010 and were registered in the EBMT database. Centers reporting patients to the registry meeting these inclusion criteria were contacted to provide additional data, including potential history of celiac disease, first-line therapy, high-dose regimen used, as well as updated follow-up data. Also, submission of a written histopathology report fitting with a diagnosis of EATL was mandatory for inclusion of the patients into the final analysis set.

    Patient, disease, treatment, and transplant characteristics were compared between groups using χ2 test or Fisher’s exact test for categorical variables and t test or Mann-Whitney U-test for continuous variables.

    The main outcomes analyzed in the study were OS, PFS, relapse incidence, and nonrelapse mortality (NRM). OS was defined as the time from transplantation to death from any cause; surviving patients were censored at the time of last follow-up. PFS was defined as the time from transplantation to relapse, disease progression, or death from any cause. NRM was defined as death with no evidence of relapse or progression of lymphoma at any time after ASCT.

    The probabilities for OS and PFS were estimated from the time of ASCT using a Kaplan-Meier product-limit estimate and were compared by the log-rank test in univariate analysis. Estimates of NRM and relapse or progression were calculated using cumulative incidence rates to accommodate competing risks and were compared by Gray’s test. Due to a limited number of patients, no multivariate analyses were attempted.

    Results and discussion

    The initial search identified a total of 137 patients meeting the eligibility criteria. Complete complementary and follow-up data including a written histopathology report were received for 54 patients (39%). Of these, 10 patients were excluded either because of another type of T-cell lymphoma as an underlying disease or due to a lack of confirmation by the histopathology report. The data set for final analysis thus included 44 patients (supplemental Data; supplemental Figure 1). The main patient and transplant-related characteristics of these patients are summarized in Table 1. These characteristics were compared with excluded patients (supplemental Data; supplemental Table 1).

    View this table:
    Table 1

    Patient and transplant characteristics of 44 EATL patients receiving ASCT in 2000-2010

    Three patients died due to transplant-related causes (infection in all 3), translating into a NRM of 7% at 2 years (Figure 1A). The median follow-up for the living patients was 46 months (2-108) from ASCT. The relapse incidence was 39% at 4 years with only a single relapse occurring after 18 months (Figure 1A). PFS and OS were 54% and 59% at 4 years, respectively (Figure 1B). A trend toward better OS was observed in patients transplanted in complete remission (CR)1/partial remission (PR)1 (66%, 95% confidence interval = 51% to 86% vs 36%, 95% confidence interval = 14% to 96% at 4 years; P = .062) (Figure 1C).

    Figure 1

    (A) NRM and relapse incidence among 44 EATL patients after ASCT. (B) PFS and OS in 44 EATL patients after ASCT. (C) OS of patients with EATL according to disease status at the time of ASCT. Dotted line: patients transplanted in CR1 or PR1; solid line: patients transplanted in other disease status. P = .062. CR, complete remission; PR, partial remission.

    Although patients with a history of celiac disease had superior PFS (71% vs 33% at 4 years; P = .02) and a trend for better OS (71% vs 45%; P = .052), no significant survival difference in favor of celiac disease remained if only patients in first complete or partial remission were considered. Similarly, age, gender, disease stage, B-symptoms at diagnosis, or high-dose regimen used were not associated with significant PFS or OS differences.

    The main characteristics and outcome data of the 44 patients included into the final analyses were compared with those of 93 patients without sufficient information for full analysis. The excluded patients had a significantly longer time from diagnosis to ASCT and a much shorter follow-up (supplemental Data; supplemental Table 1) and significantly worse survival (supplemental Data; supplemental Figures 2 and 3). Possible explanations for these outcome disadvantages could be misdiagnosis, center effect, or just a shorter follow-up.

    In this study, the survival curves showed a plateau, suggesting that ASCT could be a curative approach in the majority of EATL patients who receive high-dose therapy in first CR or PR. The OS of 66% observed in patients transplanted in first CR or PR is about the same as OS of 68% at 5 years observed in the UK study in patients who completed the whole treatment schedule including ASCT.9

    Course and treatment after relapse following ASCT were not addressed in this study. However, considering that the PFS and OS curves were almost superimposable, one might conclude that relapse treatment after ASCT was largely ineffective.

    This study has some important limitations. It included only patients who had actually received ASCT. Patients receiving autotransplants are highly selected in regard to performance status, age, and chemotherapy responsiveness of the lymphoma. However, it can be concluded that patients with EATL who do manage to proceed to ASCT have treatment outcomes that are comparable with other types of PTCL.10-14 It is difficult to estimate the proportion of all EATL patients amenable to intensive therapies, but at least one-half of the patients aged <70 years may be considered for standard-dose chemotherapy. If they respond to therapy, their performance status may improve, thus allowing subsequent ASCT.

    Although optimal first-line therapy in PTCL in general and specifically for EATL still needs to be defined, this study in the largest cohort of patients analyzed to date shows that ASCT is feasible in patients with EATL and may be followed in a significant proportion of patients with long-term disease control. This provides a basis for prospective intent-to-treat studies to conclusively demonstrate that ASCT can improve the hitherto dismal outlook of this disease.


    Contribution: E.J. proposed the study, interpreted the data, and wrote the manuscript; A.S. and P.D. helped in interpreting data and writing the manuscript; A.B. was responsible for statistical analysis; H.F. and J.-J.L. were study coordinators; and P.J., A.R., A.H., M.A.D., W.B., P.B., K.C., C.C., C.R., J.F., G.S., F.K., and P.D. reported updated patient data and read and commented on the manuscript. Additional colleagues reporting data to the study are listed in the Appendix below. All authors proofread the manuscript and agreed on the data presented.

    Conflict-of-interest disclosure: The authors declare no competing financial interests.

    Jian-Jian Luan died on December 26, 2010.

    Correspondence: Esa Jantunen, Department of Medicine, Kuopio University Hospital, P.O.B 1777, 70211 Kuopio, Finland; e-mail: esa.jantunen{at}

    Appendix: study group members

    In addition to the authors listed, the following colleagues reported data on individual patients into this study and are thankfully acknowledged.

    Martin Bornhäuser (Dresden, Germany); Elizabeth Naparstek (Tel Aviv, Israel); Per Ljungman (Stockholm, Sweden); Michael Potter (London, United Kingdom); Xavier Poire (Brussels, Belgium); Giuseppe Rissi (Brescia, Italy); Mark Ringhofer (Karlsruhe, Germany); Werner Linkesch (Graz, Austria); Mario Bargetzi (Aarau, Switzerland); Dominic Culligan (Aberdeen, United Kingdom); Richard Chasty (Stoke-on-Trent, United Kingdom); Harry Schouten (Maastricht, The Netherlands); Karel Indrak (Olomouc, Czech Republic); Norbert Blesing (Swindon, United Kingdom); Rik Shots (Brussels, Belgium); Luigi Gugliotta (Reggio Emilia, Italy); Herman Einsele (Wurtzburg, Germany); Juan Basalduch (Palma de Mallorca, Spain); David Polreich (Prague, Czech Republic); John Snowden (Sheffield, United Kingdom).


    • The online version of this article contains a data supplement.

    • The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked “advertisement” in accordance with 18 USC section 1734.

    • Submitted November 14, 2012.
    • Accepted January 14, 2013.


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