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GEM-P chemotherapy is active in the treatment of relapsed Hodgkin lymphoma

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Abstract

Hodgkin lymphoma (HL) is a relatively chemosensitive malignancy. However, for those who relapse, high-dose chemotherapy with autologous stem cell transplant is the treatment of choice which relies on adequate disease control with salvage chemotherapy. Regimens commonly used often require inpatient administration and can be difficult to deliver due to toxicity. Gemcitabine and cisplatin have activity in HL, non-overlapping toxicity with first-line chemotherapeutics, and may be delivered in an outpatient setting. In this retrospective single-centre analysis, patients with relapsed or refractory HL treated with gemcitabine 1,000 mg/m2 day (D)1, D8 and D15; methylprednisolone 1,000 mg D1–5; and cisplatin 100 mg/m2 D15, every 28 days (GEM-P) were included. Demographic, survival, response and toxicity data were recorded. Forty-one eligible patients were identified: median age 27. One hundred and twenty-two cycles of GEM-P were administered in total (median 3 cycles; range 1–6). Twenty of 41 (48 %) patients received GEM-P as second-line treatment and 11/41 (27 %) as third-line therapy. Overall response rate (ORR) to GEM-P in the entire cohort was 80 % (complete response (CR) 37 %, partial response 44 %) with 14/15 CR confirmed as a metabolic CR on PET and ORR of 85 % in the 20 second-line patients. The most common grade 3/4 toxicities were haematological: neutropenia 54 % and thrombocytopenia 51 %. Median follow-up from the start of GEM-P was 4.5 years. Following GEM-P, 5-year progression-free survival was 46 % (95 % confidence interval (CI), 30–62 %) and 5-year overall survival was 59 % (95 % CI, 43–74 %). Fourteen of 41 patients proceeded directly to autologous transplant. GEM-P is a salvage chemotherapy with relatively high response rates, leading to successful transplantation in appropriate patients, in the treatment of relapsed or refractory HL.

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References

  1. Viviani S, Zinzani PL, Rambaldi A et al (2011) ABVD versus BEACOPP for Hodgkin’s lymphoma when high-dose salvage is planned. N Engl J Med 365:203–212

    Article  PubMed  CAS  Google Scholar 

  2. Diehl V, Franklin J, Pfreundschuh M et al (2003) Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin’s disease. N Engl J Med 348:2386–2395

    Article  PubMed  CAS  Google Scholar 

  3. Linch DC, Winfield D, Goldstone AH et al (1993) Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin’s disease: results of a BNLI randomised trial. Lancet 341:1051–1054

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  5. Goda JS, Massey C, Kuruvilla J et al (2012) Role of salvage radiation therapy for patients with relapsed or refractory Hodgkin lymphoma who failed autologous stem cell transplant. Int J Radiat Oncol Biol Phys 84:e329–e335

    Article  PubMed  Google Scholar 

  6. Sureda A, Canals C, Arranz R et al (2012) 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 97:310–317

    Article  PubMed Central  PubMed  Google Scholar 

  7. Abali H, Urun Y, Oksuzoglu B et al (2008) Comparison of ICE (ifosfamide-carboplatin-etoposide) versus DHAP (cytosine arabinoside-cisplatin-dexamethasone) as salvage chemotherapy in patients with relapsed or refractory lymphoma. Cancer Investig 26:401–406

    Article  CAS  Google Scholar 

  8. Chen R, Palmer JM, Thomas SH et al (2012) Brentuximab vedotin enables successful reduced-intensity allogeneic hematopoietic cell transplantation in patients with relapsed or refractory Hodgkin lymphoma. Blood 119:6379–6381

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  9. Gopal AK, Ramchandren R, O’Connor OA et al (2012) Safety and efficacy of brentuximab vedotin for Hodgkin lymphoma recurring after allogeneic stem cell transplantation. Blood 120:560–568

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  10. Younes A, Gopal AK, Smith SE et al (2012) Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol Off J Am Soc Clin Oncol 30:2183–2189

    Article  CAS  Google Scholar 

  11. Younes A, Sureda A, Ben-Yehuda D et al (2012) Panobinostat in patients with relapsed/refractory Hodgkin’s lymphoma after autologous stem-cell transplantation: results of a phase II study. J Clin Oncol Off J Am Soc Clin Oncol 30:2197–2203

    Article  CAS  Google Scholar 

  12. Peters GJ, Bergman AM, van Haperen VW R et al (1995) Interaction between cisplatin and gemcitabine in vitro and in vivo. Semin Oncol 22:72–79

    PubMed  CAS  Google Scholar 

  13. Aviles A, Neri N, Huerta-Guzman J, Fernandez R (2004) Gemcitabine and cisplatin in refractory malignant lymphoma. Oncology 66:197–200

    Article  PubMed  CAS  Google Scholar 

  14. Emmanouilides C, Colovos C, Pinter-Brown L et al (2004) Pilot study of fixed-infusion rate gemcitabine with cisplatin and dexamethasone in patients with relapsed or refractory lymphoma. Clin Lymphoma 5:45–49

    Article  PubMed  CAS  Google Scholar 

  15. Chau I, Harries M, Cunningham D et al (2003) Gemcitabine, cisplatin and methylprednisolone chemotherapy (GEM-P) is an effective regimen in patients with poor prognostic primary progressive or multiply relapsed Hodgkin’s and non-Hodgkin’s lymphoma. Br J Haematol 120:970–977

    Article  PubMed  CAS  Google Scholar 

  16. Ng M, Waters J, Cunningham D et al (2005) Gemcitabine, cisplatin and methylprednisolone (GEM-P) is an effective salvage regimen in patients with relapsed and refractory lymphoma. Br J Cancer 92:1352–1357

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  17. Sirohi B, Cunningham D, Norman A et al (2007) Gemcitabine, cisplatin and methylprednisolone (GEM-P) with or without rituximab in relapsed and refractory patients with diffuse large B cell lymphoma (DLBCL). Hematology 12:149–153

    Article  PubMed  CAS  Google Scholar 

  18. Cheson BD, Horning SJ, Coiffier B et al (1999) Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. NCI Sponsored International Working Group. J Clin Oncol Off J Am Soc Clin Oncol 17:1244

    CAS  Google Scholar 

  19. Meignan M, Gallamini A, Haioun C (2009) Report on the First International Workshop on interim-PET-scan in lymphoma. Leuk Lymphoma 50:1257–1260

    Article  PubMed  Google Scholar 

  20. Baetz T, Belch A, Couban S et al (2003) Gemcitabine, dexamethasone and cisplatin is an active and non-toxic chemotherapy regimen in relapsed or refractory Hodgkin’s disease: a phase II study by the National Cancer Institute of Canada Clinical Trials Group. Ann Oncol Off J Eur Soc Med Oncol ESMO 14:1762–1767

    Article  CAS  Google Scholar 

  21. Bartlett NL, Niedzwiecki D, Johnson JL et al (2007) Gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD), a salvage regimen in relapsed Hodgkin’s lymphoma: CALGB 59804. Ann Oncol Off J Eur Soc Med Oncol ESMO 18:1071–1079

    Article  CAS  Google Scholar 

  22. Suyani E, Sucak GT, Aki SZ et al (2011) Gemcitabine and vinorelbine combination is effective in both as a salvage and mobilization regimen in relapsed or refractory Hodgkin lymphoma prior to ASCT. Ann Hematol 90:685–691

    Article  PubMed  CAS  Google Scholar 

  23. Josting A, Rudolph C, Mapara M et al (2005) Cologne high-dose sequential chemotherapy in relapsed and refractory Hodgkin lymphoma: results of a large multicenter study of the German Hodgkin Lymphoma Study Group (GHSG). Ann Oncol Off J Eur Soc Med Oncol ESMO 16:116–123

    Article  CAS  Google Scholar 

  24. Colpo A, Hochberg E, Chen YB (2012) Current status of autologous stem cell transplantation in relapsed and refractory Hodgkin’s lymphoma. Oncologist 17:80–90

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  25. Josting A, Rudolph C, Reiser M et al (2002) Time-intensified dexamethasone/cisplatin/cytarabine: an effective salvage therapy with low toxicity in patients with relapsed and refractory Hodgkin’s disease. Ann Oncol Off J Eur Soc Med Oncol ESMO 13:1628–1635

    Article  CAS  Google Scholar 

  26. Sibon D, Ertault M, Al Nawakil C et al (2011) Combined ifosfamide, etoposide and oxalipatin chemotherapy, a low-toxicity regimen for first-relapsed or refractory Hodgkin lymphoma after ABVD/EBVP: a prospective monocentre study on 34 patients. Br J Haematol 153:191–198

    Article  PubMed  CAS  Google Scholar 

  27. Ferme C, Mounier N, Divine M et al (2002) Intensive salvage therapy with high-dose chemotherapy for patients with advanced Hodgkin’s disease in relapse or failure after initial chemotherapy: results of the Groupe d’Etudes des Lymphomes de l’Adulte H89 Trial. J Clin Oncol Off J Am Soc Clin Oncol 20:467–475

    Article  CAS  Google Scholar 

  28. Aparicio J, Segura A, Garcera S et al (1999) ESHAP is an active regimen for relapsing Hodgkin’s disease. Ann Oncol Off J Eur Soc Med Oncol ESMO 10:593–595

    Article  CAS  Google Scholar 

  29. Kuruvilla J, Nagy T, Pintilie M et al (2006) Similar response rates and superior early progression-free survival with gemcitabine, dexamethasone, and cisplatin salvage therapy compared with carmustine, etoposide, cytarabine, and melphalan salvage therapy prior to autologous stem cell transplantation for recurrent or refractory Hodgkin lymphoma. Cancer 106:353–360

    Article  PubMed  CAS  Google Scholar 

  30. Villa D, Seshadri T, Puig N et al (2012) Second-line salvage chemotherapy for transplant-eligible patients with Hodgkin’s lymphoma resistant to platinum-containing first-line salvage chemotherapy. Haematologica 97:751–757

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  31. Todd T, Raj S, Camilleri D et al (2009) Intermediate dose gemcitabine-cisplatin combination chemotherapy without treatment delay for cytopenia followed by autografting–a new standard of care in relapsed or refractory Hodgkin lymphoma? Ann Hematol 88:1107–1112

    Article  PubMed  CAS  Google Scholar 

  32. Czyz A, Romejko-Jarosinska J, Knopinska-Posluszny W et al. (2012) Treatment strategy based on gemcitabine-containing salvage chemotherapy used with intent to proceed to second stem cell transplant for patients with Hodgkin lymphoma relapsing after a prior autologous transplant. Leuk Lymphoma, 54(5):973-978

    Google Scholar 

  33. Smeltzer JP, Cashen AF, Zhang Q et al (2011) Prognostic significance of FDG-PET in relapsed or refractory classical Hodgkin lymphoma treated with standard salvage chemotherapy and autologous stem cell transplantation. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 17:1646–1652

    Article  Google Scholar 

  34. Moskowitz CH, Matasar MJ, Zelenetz AD et al (2012) Normalization of pre-ASCT, FDG-PET imaging with second-line, non-cross-resistant, chemotherapy programs improves event-free survival in patients with Hodgkin lymphoma. Blood 119:1665–1670

    Article  PubMed Central  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors acknowledge National Health Service funding to the National Institute for Health Research Biomedical Research Centre at the Royal Marsden NHS Foundation Trust and Institute of Cancer Research.

Conflict of interest

Eliza A. Hawkes travel expenses from Roche. David Cunningham is a recipient of research grants from Roche, Amgen, Sanofi-Aventis, Merck KGA and Celgene and uncompensated advisory boards from Amgen and Roche. Ian Chau received a research grant from Roche, compensated advisory board from Roche and Sanofi and honoraria from Roche and Sanofi. Sarah Barton, Claire Peckitt, Sue Chua, Andrew Wotherspoon, Alan Horwich, Mike Potter, Mark Ethel and Claire Dearden have no disclosures.

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  1. Royal Marsden NHS Foundation Trust, Downs Rd Sutton, Surrey, SM2 5PT, UK

    Eliza A. Hawkes, Sarah Barton, David Cunningham, Clare Peckitt, Sue Chua, Andrew Wotherspoon, Alan Horwich, Mike Potter, Mark Ethel, Claire Dearden & Ian Chau

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  1. Eliza A. Hawkes
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Correspondence to David Cunningham.

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Hawkes, E.A., Barton, S., Cunningham, D. et al. GEM-P chemotherapy is active in the treatment of relapsed Hodgkin lymphoma. Ann Hematol 93, 827–834 (2014). https://doi.org/10.1007/s00277-013-1930-y

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  • DOI: https://doi.org/10.1007/s00277-013-1930-y

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