Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Lymphoma

Allogeneic hematopoietic stem cell transplantation in Hodgkin lymphoma: a systematic review and meta-analysis

Bone Marrow Transplantation volume 51, pages 521–528 (2016)Cite this article

Subjects

Abstract

Allogeneic stem cell transplantation (allo-SCT) outcomes in patients with Hodgkin lymphoma (HL) remain poorly defined. We performed a meta-analysis of allo-SCT studies in HL patients. The primary endpoints were 6-month, 1-year, 2-year and 3-year relapse-free survival (RFS) and overall survival (OS). A total of 42 reports (1850 patients) was included. The pooled estimates (95% confidence interval) for 6-month, 1-year, 2-year and 3-year RFS were 77 (59–91)%, 50 (42–57)%, 37 (31–43)% and 31 (25–37)%, respectively. The corresponding numbers for OS were 83 (75–91)%, 68 (62–74)%, 58 (52–64)% and 50 (41–58)%, respectively. There was statistical heterogeneity among studies in all outcomes. In meta-regression, accrual initiation year in 2000 or later was associated with higher 6-month (P=0.012) and 1-year OS (P=0.046), and pre-SCT remission with higher 2-year OS (P=0.047) and 1-year RFS (P=0.016). In conclusion, outcomes of allo-SCT in HL have improved over time, with 5–10% lower non-relapse mortality and relapse rates, and 15–20% higher RFS and OS in studies that initiated accrual in 2000 or later compared with earlier studies. However, there is no apparent survival plateau, demonstrating the need to improve on current allo-SCT strategies in relapsed/refractory HL.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Schmitz N, Pfistner B, Sextro M, Sieber M, Carella AM, Haenel M et al. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin’s disease: a randomised trial. Lancet 2002; 359: 2065–2071.

    Article  CAS  Google Scholar 

  2. Rancea M, Monsef I, von Tresckow B, Engert A, Skoetz N . High-dose chemotherapy followed by autologous stem cell transplantation for patients with relapsed/refractory Hodgkin lymphoma. Cochrane Database Syst Rev 2013; 6: CD009411.

    Google Scholar 

  3. Appelbaum FR, Sullivan KM, Thomas ED . Allogeneic marrow transplantation in the treatment of MOPP-resistant Hodgkin’s disease. J Clin Oncol 1985; 3: 1490–1494.

    Article  CAS  Google Scholar 

  4. Carella AM, Champlin R, Slavin S, McSweeney P, Storb R . Mini-allografts: ongoing trials in humans. Bone Marrow Transplant 2000; 25: 345–350.

    Article  CAS  Google Scholar 

  5. Perales MA, Ceberio I, Armand P, Burns LJ, Chen R, Cole PD et al. Role of cytotoxic therapy with hematopoietic cell transplantation in the treatment of Hodgkin lymphoma: guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 2015; 21: 971–983.

    Article  Google Scholar 

  6. Sureda A, Bader P, Cesaro S, Dreger P, Duarte RF, Dufour C et al. Indications for allo- and auto-SCT for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2015. Bone Marrow Transplant 2015; 50: 1037–1056.

    Article  CAS  Google Scholar 

  7. Moher D, Liberati A, Tetzlaff J, Altman DG,, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009; 339: b2535.

    Article  Google Scholar 

  8. DerSimonian R, Laird N . Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177–188.

    Article  CAS  Google Scholar 

  9. Anderlini P, Saliba R, Acholonu S, Giralt SA, Andersson B, Ueno NT et al. Fludarabine-melphalan as a preparative regimen for reduced-intensity conditioning allogeneic stem cell transplantation in relapsed and refractory Hodgkin’s lymphoma: the updated M.D. Anderson Cancer Center experience. Haematologica 2008; 93: 257–264.

    Article  CAS  Google Scholar 

  10. Anderlini P, Saliba R, Acholonu S, Okoroji GJ, Donato M, Giralt S et al. Reduced-intensity allogeneic stem cell transplantation in relapsed and refractory Hodgkin’s disease: low transplant-related mortality and impact of intensity of conditioning regimen. Bone Marrow Transplant 2005; 35: 943–951.

    Article  CAS  Google Scholar 

  11. Anderlini P, Saliba RM, Ledesma C, Chancoco C, Alousi AM, Shpall EJ et al. Gemcitabine, fludarabine and melphalan as a reduced-intensity conditioning regimen for allogeneic stem cell transplant in relapsed and refractory Hodgkin lymphoma: preliminary results. Leuk Lymphoma 2012; 53: 499–502.

    Article  CAS  Google Scholar 

  12. Anderson JE, Litzow MR, Appelbaum FR, Schoch G, Fisher LD, Buckner CD et al. Allogeneic, syngeneic, and autologous marrow transplantation for Hodgkin’s disease: the 21-year Seattle experience. J Clin Oncol 1993; 11: 2342–2350.

    Article  CAS  Google Scholar 

  13. Armand P, Kim HT, Ho VT, Cutler CS, Koreth J, Antin JH et al. Allogeneic transplantation with reduced-intensity conditioning for Hodgkin and non-Hodgkin lymphoma: importance of histology for outcome. Biol Blood Marrow Transplant 2008; 14: 418–425.

    Article  CAS  Google Scholar 

  14. Brunstein CG, Cantero S, Cao Q, Majhail N, McClune B, Burns LJ et al. Promising progression-free survival for patients low and intermediate grade lymphoid malignancies after nonmyeloablative umbilical cord blood transplantation. Biol Blood Marrow Transplant 2009; 15: 214–222.

    Article  Google Scholar 

  15. Burroughs LM, O’Donnell PV, Sandmaier BM, Storer BE, Luznik L, Symons HJ et al. Comparison of outcomes of HLA-matched related, unrelated, or HLA-haploidentical related hematopoietic cell transplantation following nonmyeloablative conditioning for relapsed or refractory Hodgkin lymphoma. Biol Blood Marrow Transplant 2008; 14: 1279–1287.

    Article  Google Scholar 

  16. Carella AM, Cavaliere M, Lerma E, Ferrara R, Tedeschi L, Romanelli A et al. Autografting followed by nonmyeloablative immunosuppressive chemotherapy and allogeneic peripheral-blood hermatopoietic stem-cell transplantation as treatment of resistant Hodgkin’s disease and non-Hodgkin’s lymphoma. J Clin Oncol 2000; 18: 3918–3924.

    Article  CAS  Google Scholar 

  17. Chen R, Palmer JM, Popplewell L, Shen J, Smith E, Delioukina M et al. Reduced intensity allogeneic hematopoietic cell transplantation can induce durable remission in heavily pretreated relapsed Hodgkin lymphoma. Ann Hematol 2011; 90: 803–808.

    Article  Google Scholar 

  18. Chen R, Palmer JM, Tsai NC, Thomas SH, Siddiqi T, Popplewell L et al. Brentuximab vedotin is associated with improved progression-free survival after allogeneic transplantation for Hodgkin lymphoma. Biol Blood Marrow Transplant 2014; 20: 1864–1868.

    Article  CAS  Google Scholar 

  19. Claviez A, Canals C, Dierickx D, Stein J, Badell I, Pession A et al. Allogeneic hematopoietic stem cell transplantation in children and adolescents with recurrent and refractory Hodgkin lymphoma: an analysis of the European Group for Blood and Marrow Transplantation. Blood 2009; 114: 2060–2067.

    Article  CAS  Google Scholar 

  20. Cooney JP, Stiff PJ, Toor AA, Parthasarathy M . BEAM allogeneic transplantation for patients with Hodgkin’s disease who relapse after autologous transplantation is safe and effective. Biol Blood Marrow Transplant 2003; 9: 177–182.

    Article  Google Scholar 

  21. Devetten MP, Hari PN, Carreras J, Logan BR, van Besien K, Bredeson CN et al. Unrelated donor reduced-intensity allogeneic hematopoietic stem cell transplantation for relapsed and refractory Hodgkin lymphoma. Biol Blood Marrow Transplant 2009; 15: 109–117.

    Article  Google Scholar 

  22. Garciaz S, Coso D, Peyrade F, Furst S, Duran S, Chetaille B et al. Brentuximab vedotin followed by allogeneic transplantation as salvage regimen in patients with relapsed and/or refractory Hodgkin’s lymphoma. Hematol Oncol 2014; 32: 187–191.

    Article  CAS  Google Scholar 

  23. Hahn T, Benekli M, Wong C, Moysich KB, Hyland A, Michalek AM et al. A prognostic model for prolonged event-free survival after autologous or allogeneic blood or marrow transplantation for relapsed and refractory Hodgkin’s disease. Bone Marrow Transplant 2005; 35: 557–566.

    Article  CAS  Google Scholar 

  24. Illidge T, Bouabdallah R, Chen R, Gopal AK, Moskowitz CH, Ramchandren R et al. Allogeneic transplant following brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Leuk Lymphoma 2015; 56: 703–710.

    Article  CAS  Google Scholar 

  25. Johansson JE, Remberger M, Lazarevic V, Hallbook H, Wahlin A, Kimby E et al. Allogeneic haematopoietic stem-cell transplantation with reduced intensity conditioning for advanced stage Hodgkin’s lymphoma in Sweden: high incidence of post transplant lymphoproliferative disorder. Bone Marrow Transplant 2011; 46: 870–875.

    Article  CAS  Google Scholar 

  26. Jones RJ, Piantadosi S, Mann RB, Ambinder RF, Seifter EJ, Vriesendorp HM et al. High-dose cytotoxic therapy and bone marrow transplantation for relapsed Hodgkin’s disease. J Clin Oncol 1990; 8: 527–537.

    Article  CAS  Google Scholar 

  27. Kako S, Izutsu K, Kato K, Kim SW, Mori T, Fukuda T et al. The role of hematopoietic stem cell transplantation for relapsed and refractory Hodgkin lymphoma. Am J Hematol 2015; 90: 132–138.

    Article  Google Scholar 

  28. Majhail NS, Weisdorf DJ, Wagner JE, Defor TE, Brunstein CG, Burns LJ . Comparable results of umbilical cord blood and HLA-matched sibling donor hematopoietic stem cell transplantation after reduced-intensity preparative regimen for advanced Hodgkin lymphoma. Blood 2006; 107: 3804–3807.

    Article  CAS  Google Scholar 

  29. Marcais A, Porcher R, Robin M, Mohty M, Michalet M, Blaise D et al. Impact of disease status and stem cell source on the results of reduced intensity conditioning transplant for Hodgkin’s lymphoma: a retrospective study from the French Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC). Haematologica 2013; 98: 1467–1475.

    Article  Google Scholar 

  30. Nachbaur D, Oberaigner W, Fritsch E, Nussbaumer W, Gast G . Allogeneic or autologous stem cell transplantation (SCT) for relapsed and refractory Hodgkin’s disease and non-Hodgkin’s lymphoma: A single-centre experience. Eur J Haematol 2001; 66: 43–49.

    Article  CAS  Google Scholar 

  31. Paillard C, Rochette E, Lutz P, Bertrand Y, Michel G, Bordigoni P et al. Reduced-intensity conditioning followed by allogeneic transplantation in pediatric malignancies: a report from the Societe Francaise des Cancers de l’Enfant and the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire. Bone Marrow Transplant 2013; 48: 1401–1408.

    Article  CAS  Google Scholar 

  32. Phillips GL, Reece DE, Barnett MJ, Connors JM, Fay JW, Herzig GP et al. Allogeneic marrow transplantation for refractory Hodgkin’s disease. J Clin Oncol 1989; 7: 1039–1045.

    Article  CAS  Google Scholar 

  33. Raiola A, Dominietto A, Varaldo R, Ghiso A, Galaverna F, Bramanti S et al. Unmanipulated haploidentical BMT following non-myeloablative conditioning and post-transplantation CY for advanced Hodgkin’s lymphoma. Bone Marrow Transplant 2014; 49: 190–194.

    Article  CAS  Google Scholar 

  34. Ramirez P, Ocqueteau M, Rodriguez A, Garcia MJ, Sarmiento M, Ernst D et al. Outcomes in relapsed Hodgkin’s lymphoma treated with autologous and allogeneic hematopoietic cell transplantation at the Pontificia Universidad Catolica de Chile. Rev Bras Hematol Hemoter 2015; 37: 184–189.

    Article  Google Scholar 

  35. Robinson SP, Sureda A, Canals C, Russell N, Caballero D, Bacigalupo A et al. Reduced intensity conditioning allogeneic stem cell transplantation for Hodgkin’s lymphoma: identification of prognostic factors predicting outcome. Haematologica 2009; 94: 230–238.

    Article  Google Scholar 

  36. Rodrigues CA, Sanz G, Brunstein CG, Sanz J, Wagner JE, Renaud M et al. Analysis of risk factors for outcomes after unrelated cord blood transplantation in adults with lymphoid malignancies: a study by the Eurocord-Netcord and lymphoma working party of the European group for blood and marrow transplantation. J Clin Oncol 2009; 27: 256–263.

    Article  Google Scholar 

  37. Sarina B, Castagna L, Farina L, Patriarca F, Benedetti F, Carella AM et al. Allogeneic transplantation improves the overall and progression-free survival of Hodgkin lymphoma patients relapsing after autologous transplantation: a retrospective study based on the time of HLA typing and donor availability. Blood 2010; 115: 3671–3677.

    Article  CAS  Google Scholar 

  38. Satwani P, Jin Z, Martin PL, Bhatia M, Garvin JH, George D et al. Sequential myeloablative autologous stem cell transplantation and reduced intensity allogeneic hematopoietic cell transplantation is safe and feasible in children, adolescents and young adults with poor-risk refractory or recurrent Hodgkin and non-Hodgkin lymphoma. Leukemia 2015; 29: 448–455.

    Article  CAS  Google Scholar 

  39. Shafer JA, Heslop HE, Brenner MK, Carrum G, Wu MF, Liu H et al. Outcome of hematopoietic stem cell transplant as salvage therapy for Hodgkin’s lymphoma in adolescents and young adults at a single institution. Leuk Lymphoma 2010; 51: 664–670.

    Article  CAS  Google Scholar 

  40. Sobol U, Rodriguez T, Smith S, Go A, Vimr R, Parthasarathy M et al. Seven-year follow-up of allogeneic transplant using BCNU, etoposide, cytarabine and melphalan chemotherapy in patients with Hodgkin lymphoma after autograft failure: importance of minimal residual disease. Leuk Lymphoma 2014; 55: 1281–1287.

    Article  CAS  Google Scholar 

  41. Sureda A, Canals C, Arranz R, Caballero D, Ribera JM, Brune M et al. Allogeneic stem cell transplantation after reduced intensity conditioning in patients with relapsed or refractory Hodgkin’s lymphoma. Results of the HDR-ALLO study - a prospective clinical trial by the Grupo Espanol de Linfomas/ Trasplante de Medula Osea (GEL/TAMO) and the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Haematologica 2012; 97: 310–317.

    Article  Google Scholar 

  42. Sureda A, Robinson S, Canals C, Carella AM, Boogaerts MA, Caballero D et al. Reduced-intensity conditioning compared with conventional allogeneic stem-cell transplantation in relapsed or refractory Hodgkin’s lymphoma: an analysis from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 2008; 26: 455–462.

    Article  CAS  Google Scholar 

  43. Tey S, Butler J, Durrant S, Hill G, Morton J, Kennedy G . A prognostic model for prolonged event-free survival after autologous or allogeneic blood or marrow transplantation for relapsed and refractory Hodgkin’s disease. Bone Marrow Transplant 2005; 36: 553–554.

    Article  CAS  Google Scholar 

  44. Thomson KJ, Peggs KS, Smith P, Cavet J, Hunter A, Parker A et al. Superiority of reduced-intensity allogeneic transplantation over conventional treatment for relapse of Hodgkin’s lymphoma following autologous stem cell transplantation. Bone Marrow Transplant 2008; 41: 765–770.

    Article  CAS  Google Scholar 

  45. Verholen F, Terrettaz M, Roosnek E, Passweg JR, Chalandon Y . Hodgkin’s lymphoma relapsing after autologous transplantation: allogeneic hematopoietic stem cell transplantation using a strategy of reduced intensity conditioning, and T-cell depletion with T-cell add-back. Eur J Haematol 2009; 83: 273–275.

    Article  Google Scholar 

  46. Moskowitz AJ, Perales MA, Kewalramani T, Yahalom J, Castro-Malaspina H, Zhang Z et al. Outcomes for patients who fail high dose chemoradiotherapy and autologous stem cell rescue for relapsed and primary refractory Hodgkin lymphoma. Br J Haematol 2009; 146: 158–163.

    Article  Google Scholar 

Download references

Acknowledgements

AR was supported by the Washington University Institute of Clinical and Translational Sciences grant UL1 TR000448 from the National Center for Advancing Translational Sciences. The funding sources had no role in study design, data collection, analysis or interpretation of results. We thank Drs R Chen, A Claviez, S Kako, and MP Devetten for providing additional data.

Author contributions

AR and ME reviewed the studies and extracted the data. AR analyzed the data. AR, ME and AFC interpreted the results and wrote the manuscript.

Author information

Authors and Affiliations

  1. Division of Oncology, BMT and Leukemia Program, Washington University School of Medicine, St Louis, MO, USA,

    A Rashidi & A F Cashen

  2. Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA,

    M Ebadi

Authors
  1. A Rashidi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Ebadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A F Cashen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A F Cashen.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on Bone Marrow Transplantation website

Supplementary information

Appendix

Appendix

The analysis of study heterogeneity revealed the following results: 6-month CIR (n=8, χ2=28, I2=75%), 1-year CIR (n=21, χ2=43, I2=53%), 2-year CIR (n=19, χ2=57, I2=68%), 3-year CIR (n=21, χ2=65, I2=69%), 6-month NRM (n==15, χ2=68, I2=79%), 1-year NRM (n=28, χ2=111, I2=76%), 2-year NRM (n=24, χ2=83, I2=72%), 3-year NRM (n=22, χ2=73, I2=72%), 6-month RFS (n=9, χ2=62, I2=87%), 1-year RFS (n=22, χ2=22, I2=78%), 2-year RFS (n=26, χ2=99, I2=75%), 3-year RFS (n=22, χ2=99, I2=79%), 6-month OS (n=16, χ2=59, I2=75%), 1-year OS (n=28, χ2=116, I2=77%), 2-year OS (n=24, χ2=83, I2=72%) and 3-year OS (n=20, χ2=138, I2=86%).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rashidi, A., Ebadi, M. & Cashen, A. Allogeneic hematopoietic stem cell transplantation in Hodgkin lymphoma: a systematic review and meta-analysis. Bone Marrow Transplant 51, 521–528 (2016). https://doi.org/10.1038/bmt.2015.332

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2015.332

This article is cited by

Search

Advanced search

Quick links