Young adults diagnosed with Hodgkin lymphoma are at risk of relapsing late: a comprehensive analysis of late relapse in Hodgkin lymphoma

  • László Pinczés
  • Zsófia Miltényi
  • Árpád Illés
Original Article – Clinical Oncology



Majority of relapses in Hodgkin lymphoma (HL) occur within 3 years after initial treatment, late relapses (LR), happening 5 or more years after first diagnosis is rare events. Neither clinical characteristics, risk factors, nor optimal treatment is well described for LR patients. Our aim was to provide a comprehensive analysis on the LR of HL to outline a patient population at risk of relapsing late.

Patients and methods

637 HL patients were treated at the University of Debrecen between 1981 and 2010. Patient data was evaluated retrospectively. Survival analysis was performed using the Kaplan–Meier method and odds ratios (OR) were identified by binary logistic regression models.


With a median observational time of 9.08 years 584 (91%) HL patients achieved complete remission (CR) after first line treatment. Relapse occurred in 176 (28%) patients, 26 (4%) of them 5 or more years after first diagnosis. With multivariable analysis, initial diagnosis before the age of 24 (p < 0.001), initial presentation between 1981 and 1990 or 1991–2000 (p = 0.025 and p = 0.023, respectively) and first line treatment with radiotherapy only (p = 0.034) were identified as independent risk factors for LR. We observed a significantly impaired OS for patients with early relapse HL compared to those in long-term remission or experiencing LR (p < 0.001).


Late relapse of HL presents with clinical characteristics very similar to primary disease and appears to have a good prognosis. First diagnosis in childhood or young adulthood and first line treatment before the ABVD era increases the risk of relapsing late.


Hodgkin lymphoma Late relapse Early relapse Risk factors Overall survival ABVD 



The authors would like to acknowledge the enormous support of Katalin Hodosi regarding data cleaning and statistical analysis.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the Regional and Institutional Ethics Committee, Clinical Center, University of Debrecen. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants or legally authorized representatives of participants included in the study.


  1. Bodis S, Henry-Amar M, Bosq J et al (1993) Late relapse in early-stage Hodgkin’s disease patients enrolled on European Organization for Research and Treatment of Cancer protocols. J Clin Oncol 11:225–232CrossRefPubMedGoogle Scholar
  2. Brierley JD, Rathmell AJ, Gospodarowicz MK et al (1997) Late relapse after treatment for clinical Stage I and II Hodgkin’s disease. Cancer 79:1422–1427.<1422::AI D-CNCR20>3.0.CO;2-0Google Scholar
  3. Bröckelmann PJ, Grögen H, Kohnhorst C et al (2016) Very late relapse 5 years after first diagnosis of Hodgkin lymphoma: an analysis of the German Hodgkin Study Group HD7-HD12 trials. Haematologica 101:46CrossRefGoogle Scholar
  4. Bröckelmann PJ, Goergen H, Kohnhorst C et al (2017) Late relapse of classical Hodgkin lymphoma: an analysis of the German Hodgkin Study Group HD7 to HD12 Trials. J Clin Oncol 35:1444–1450. CrossRefPubMedGoogle Scholar
  5. Brousset P, Schlaifer D, Meggetto F et al (1994) Persistence of the same viral strain in Early and Late Relapses of Epstein–Barr virus-associated Hodgkin’s disease. Blood 84:2447–2451PubMedGoogle Scholar
  6. Carbone PP, Kaplan HS, Musshoff K et al (1971) Report of the Committee on Hodgkin’s disease staging classification. Cancer Res 31:1860–1861PubMedGoogle Scholar
  7. Dann EJ, Berkahn L, Mashiach T et al (2014) Hodgkin lymphoma patients in first remission: routine positron emission tomography/computerized tomography imaging is not superior to clinical follow-up for patients with no residual mass. Br J Haematol 164:694–700. CrossRefPubMedGoogle Scholar
  8. Dilek İ, Gürman G, Kuzu I, Erekul S (1999) Very late relapse in Hodgkin’s disease. Tr J Med Sci 29:493–496Google Scholar
  9. El-Galaly TC, Mylam KJ, Brown P et al (2012) Positron emission tomography/computed tomography surveillance in patients with Hodgkin lymphoma in first remission has a low positive predictive value and high costs. Haematologica 97:931–936. CrossRefPubMedPubMedCentralGoogle Scholar
  10. Garcia-Carbonero R, Paz-Ares L, Arcediano A et al (1998) Favorable prognosis after late relapse of hodgkin’s disease. Cancer 83:560–565.<560::AID-CNCR26>3.0.CO;2-TGoogle Scholar
  11. Gaudio F, Giordano A, Pavone V et al (2011) Outcome of Very Late Relapse in Patients with Hodgkin’s Lymphomas. Adv Hematol 2011:707542. CrossRefPubMedGoogle Scholar
  12. Green JA, Arnold AM, Macbeth FR et al (1984) Late recurrence in Hodgkin’s disease: a report of two cases. Med Pediatr Oncol 12:148–149CrossRefPubMedGoogle Scholar
  13. Harris NL, Jaffe ES, Diebold J et al (1999) World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol 17:3835–3849CrossRefPubMedGoogle Scholar
  14. Illés A, Bányai A, Vadász G, Szegedi G (1995) Relapse of Hodgkin’s disease after ten years. Oncology 52:284–286CrossRefPubMedGoogle Scholar
  15. Jakobsen LH, Hutchings M, de Nully Brown P et al (2016) No survival benefit associated with routine surveillance imaging for Hodgkin lymphoma in first remission: a Danish-Swedish population-based observational study. Br J Haematol 173:236–244. CrossRefPubMedGoogle Scholar
  16. Keller SF, Kelly JL, Sensenig E et al (2012) Late relapses following high-dose autologous stem cell transplantation (HD-ASCT) for Hodgkin’s lymphoma (HL) in the ABVD therapeutic era. Biol Blood Marrow Transpl 18:640–647. CrossRefGoogle Scholar
  17. Kutchuk M, Edelstein Y, Ellis MH (2009) Late relapse of Hodgkin’s lymphoma presenting as fatal hematemesis caused by an esophago–tracheo–arterial fistula. Isr Med Assoc J 11:637–638PubMedGoogle Scholar
  18. Lazarovici J, Dartigues P, Brice P et al (2015) Nodular lymphocyte predominant Hodgkin lymphoma: a lymphoma study association retrospective study. Haematologica 100Google Scholar
  19. Lee KM, Spittle MF (1993) Hodgkin’s disease: a case of late relapse. Clin Oncol 5Google Scholar
  20. Lister TA, Crowther D, Sutcliffe SB et al (1989) Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin’s disease: Cotswolds meeting. J Clin Oncol 7:1630–1636CrossRefPubMedGoogle Scholar
  21. Lukes RJ, Craver LF, Hall TC et al (1966) Report of the nomenclature committee. Cancer Res 26:1311–1311Google Scholar
  22. Magyari F, Kósa K, Berecz R et al (2017) Employment status and health related quality of life among Hodgkin-lymphoma survivors’—results based on data from a major treatment center in Hungary. Health Qual Life Outcomes 15:180. CrossRefPubMedPubMedCentralGoogle Scholar
  23. Markovic O, Andjelic B (2016) Late relapse of Hodgkin lymphoma—is it different in clinical characteristics and outcome? Haematologica 101:750Google Scholar
  24. Mihaljevic BS, Jovanovic MDP, Jakovic LR et al (2008) Hodgkin’s lymphoma relapse in the uterine cervix 15 years after the initial cure. Med Oncol 25:245–247. CrossRefPubMedGoogle Scholar
  25. Pinczés L, Miltényi Z, Jóna Á et al (2016) How the epidemiology of Hodgkin lymphoma changed in Debrecen, Hungary. Med Res Arch 4:1–13. CrossRefGoogle Scholar
  26. Provencio M, Salas C, Millán I et al (2010) Late relapses in Hodgkin lymphoma: a clinical and immunohistochemistry study. Leuk Lymphoma 51:1686–1691. PubMedGoogle Scholar
  27. Shihabi S, Deutsch M, Jacobs SA (2001) Very late relapse of Hodgkin’s disease. Am J Clin Oncol 24:576–578. CrossRefPubMedGoogle Scholar
  28. Siebert R, Fossa A, Kaiser W et al (1997) Recurrence of Hodgkin’s disease after 10 or more years: late relapse or de-novo malignancy due to HLA-DPB 1 *0301 = Linked Susceptibility? Leuk Lymphoma 26:121–125CrossRefPubMedGoogle Scholar
  29. Vardiman JW, Thiele J, Arber DA et al (2009) The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114:937–951. CrossRefPubMedGoogle Scholar
  30. Vassilakopoulos TP, Pangalis GA, Dimopoulou MN et al (2016) Very late relapses occuring at least 5 years after the initiation of treatment with chemotherapy or combined modality therapy in patients with Hodgkin: incidence, risk factors and outcome. Haematologica 101:52CrossRefGoogle Scholar
  31. Viviani S, Mussetti A, Bartolo O, Di et al (2015) Late relapse in Hodgkin lymphoma (HL): a retrospective analysis of patients enrolled on clinical trials at the Istituto Nazionale Tumori of Milan (INT-MI). Blood 126:2697Google Scholar
  32. Volkova M, Russell R (2011) Anthracycline cardiotoxicity: prevalence, pathogenesis and treatment. Curr Cardiol Rev 7:214–220CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • László Pinczés
    • 1
  • Zsófia Miltényi
    • 1
  • Árpád Illés
    • 1
  1. 1.Department of Hematology, Faculty of MedicineUniversity of DebrecenDebrecenHungary

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