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ESHAP as salvage therapy for relapsed or refractory Hodgkin’s lymphoma

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Abstract

The management of relapsed or refractory Hodgkin’s lymphoma (RR-HL) remains a challenge for hematologists and oncologists. Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for RR-HL. However, one of the most controversial aspects is which the best salvage protocol could be. We retrospectively analyzed 82 consecutive RR-HL who received etoposide, steroids, ara-C, and cisplatin (ESHAP) as salvage therapy followed by ASCT. Fifty percent of patients were refractory and 23 % early relapses. Overall response rate (ORR) was 67 % (50 % complete remission (CR)). Ninety one percent of patients (75/82) were transplanted. With a mean follow-up of 87 ± 53 months, the median progression-free survival (PFS) and time to tumor progression (TTP) for the whole population were 52 and 56 months, respectively, and the 5-year overall survival was 72.6 %. Achieving CR after ESHAP was associated with a longer PFS (78 vs 16 % 5-year PFS, respectively, P < 0.01) and TTP (80 vs 19 % 5-year TTP, respectively, P < 0.01). However, there were no differences for overall survival (OS) when comparing CR and partial response (PR) after ESHAP. Toxicity was low and <10 % of patients developed neutropenic fever, with no toxic deaths. Mobilization was possible in 94 % of patients. ESHAP is a safe and efficient therapeutic option for patients with RR-HL who are candidates for ASCT, since it combines a high response rate and mobilizing potential with a low toxicity profile.

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References

  1. Kuruvilla J, Keating A, Crump M (2011) How I treat relapsed and refractory Hodgkin lymphoma. Blood 117(16):4208–4217. doi:10.1182/blood-2010-09-288373

    Article  CAS  PubMed  Google Scholar 

  2. Sureda A, Arranz R, Iriondo A, Carreras E, Lahuerta JJ, Garcia-Conde J, Jarque I, Caballero MD, Ferra C, Lopez A, Garcia-Larana J, Cabrera R, Carrera D, Ruiz-Romero MD, Leon A, Rifon J, Diaz-Mediavilla J, Mataix R, Morey M, Moraleda JM, Altes A, Lopez-Guillermo A, de la Serna J, Fernandez-Ranada JM, Sierra J, Conde E (2001) Autologous stem-cell transplantation for Hodgkin’s disease: results and prognostic factors in 494 patients from the Grupo Espanol de Linfomas/Transplante Autologo de Medula Osea Spanish Cooperative Group. J Clin Oncol 19(5):1395–1404

    CAS  PubMed  Google Scholar 

  3. Martin A, Fernandez-Jimenez MC, Caballero MD, Canales MA, Perez-Simon JA, Garcia de Bustos J, Vazquez L, Hernandez-Navarro F, San Miguel JF (2001) Long-term follow-up in patients treated with Mini-BEAM as salvage therapy for relapsed or refractory Hodgkin’s disease. Br J Haematol 113(1):161–171

    Article  CAS  PubMed  Google Scholar 

  4. Chopra R, Linch DC, McMillan AK, Blair S, Patterson KG, Moir D, Richards JD, Cervi P, Kinsey S, Goldstone AH (1992) Mini-BEAM followed by BEAM and ABMT for very poor risk Hodgkin’s disease. Br J Haematol 81(2):197–202

    Article  CAS  PubMed  Google Scholar 

  5. Colwill R, Crump M, Couture F, Danish R, Stewart AK, Sutton DM, Scott JG, Sutcliffe SB, Brandwein JM, Keating A (1995) Mini-BEAM as salvage therapy for relapsed or refractory Hodgkin’s disease before intensive therapy and autologous bone marrow transplantation. J Clin Oncol 13(2):396–402

    CAS  PubMed  Google Scholar 

  6. Fernandez-Jimenez MC, Canales MA, Ojeda E, de Bustos JG, Aguado MJ, Hernandez-Navarro F (1999) Salvage chemotherapy with mini-BEAM for relapsed or refractory Hodgkin’s disease prior to autologous peripheral blood stem cell transplantation. Haematologica 84(11):1007–1011

    CAS  PubMed  Google Scholar 

  7. Brandwein JM, Callum J, Sutcliffe SB, Scott JG, Keating A (1990) Evaluation of cytoreductive therapy prior to high dose treatment with autologous bone marrow transplantation in relapsed and refractory Hodgkin’s disease. Bone Marrow Transplant 5(2):99–103

    CAS  PubMed  Google Scholar 

  8. Josting A, Rudolph C, Reiser M, Mapara M, Sieber M, Kirchner HH, Dorken B, Hossfeld DK, Diehl V, Engert A (2002) Time-intensified dexamethasone/cisplatin/cytarabine: an effective salvage therapy with low toxicity in patients with relapsed and refractory Hodgkin’s disease. Ann Oncol 13(10):1628–1635

    Article  CAS  PubMed  Google Scholar 

  9. Sibon D, Ertault M, Al Nawakil C, de Bazelaire C, Franchi P, Briere J, de Kerviler E, Beranger N, Thieblemont C, Brice P (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(2):191–198. doi:10.1111/j.1365-2141.2011.08594.x

    Article  CAS  PubMed  Google Scholar 

  10. Bartlett NL, Niedzwiecki D, Johnson JL, Friedberg JW, Johnson KB, van Besien K, Zelenetz AD, Cheson BD, Canellos GP (2007) Gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD), a salvage regimen in relapsed Hodgkin’s lymphoma: CALGB 59804. Ann Oncol 18(6):1071–1079. doi:10.1093/annonc/mdm090

    Article  CAS  PubMed  Google Scholar 

  11. Santoro A, Magagnoli M, Spina M, Pinotti G, Siracusano L, Michieli M, Nozza A, Sarina B, Morenghi E, Castagna L, Tirelli U, Balzarotti M (2007) Ifosfamide, gemcitabine, and vinorelbine: a new induction regimen for refractory and relapsed Hodgkin’s lymphoma. Haematologica 92(1):35–41

    Article  CAS  PubMed  Google Scholar 

  12. Aparicio J, Segura A, Garcera S, Oltra A, Santaballa A, Yuste A, Pastor M (1999) ESHAP is an active regimen for relapsing Hodgkin’s disease. Ann Oncol 10(5):593–595

    Article  CAS  PubMed  Google Scholar 

  13. Martin A, Conde E, Arnan M, Canales MA, Deben G, Sancho JM, Andreu R, Salar A, Garcia-Sanchez P, Vazquez L, Nistal S, Requena MJ, Donato EM, Gonzalez JA, Leon A, Ruiz C, Grande C, Gonzalez-Barca E, Caballero MD (2008) R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study. Haematologica 93(12):1829–1836. doi:10.3324/haematol.13440

    Article  CAS  PubMed  Google Scholar 

  14. Fernandez de Larrea C, Martinez C, Gaya A, Lopez-Guillermo A, Rovira M, Fernandez-Aviles F, Lozano M, Bosch F, Esteve J, Nomdedeu B, Montserrat E, Carreras E (2010) Salvage chemotherapy with alternating MINE-ESHAP regimen in relapsed or refractory Hodgkin’s lymphoma followed by autologous stem-cell transplantation. Ann Oncol 21(6):1211–1216. doi:10.1093/annonc/mdp487

    Article  CAS  PubMed  Google Scholar 

  15. Caballero MD, Amigo ML, Hernandez JM, Vazquez L, del Canizo C, Gonzalez M, Garcia R, San Miguel JF (1997) Alternating mini-BEAM/ESHAP as salvage therapy for refractory non-Hodgkin’s lymphomas. Ann Hematol 74(2):79–82

    Article  CAS  PubMed  Google Scholar 

  16. Caballero MD, Rubio V, Rifon J, Heras I, Garcia-Sanz R, Vazquez L, Vidriales B, del Canizo MC, Corral M, Gonzalez M, Leon A, Jean-Paul E, Rocha E, Moraleda JM, San Miguel JF (1997) BEAM chemotherapy followed by autologous stem cell support in lymphoma patients: analysis of efficacy, toxicity and prognostic factors. Bone Marrow Transplant 20(6):451–458. doi:10.1038/sj.bmt.1700913

    Article  CAS  PubMed  Google Scholar 

  17. Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V (2007) Revised response criteria for malignant lymphoma. J Clin Oncol 25(5):579–586. doi:10.1200/JCO.2006.09.2403

    Article  PubMed  Google Scholar 

  18. Petit J, Boque C, Cancelas JA, Sarra J, Munoz J, Garcia J, Granena A (1999) Feasibility of ESHAP + G-CSF as peripheral blood hematopoietic progenitor cell mobilisation regimen in resistant and relapsed lymphoma: a single-center study of 22 patients. Leuk Lymphoma 34(1–2):119–127. doi:10.3109/10428199909083387

    CAS  PubMed  Google Scholar 

  19. Minn AY, Riedel E, Halpern J, Johnston LJ, Horning SJ, Hoppe RT, Goodman KA (2012) Long-term outcomes after high dose therapy and autologous haematopoietic cell rescue for refractory/relapsed Hodgkin lymphoma. Br J Haematol 159(3):329–339. doi:10.1111/bjh.12038

    Article  PubMed  Google Scholar 

  20. Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Wells WA, Winter JN, Horning SJ, Dar AR, Shustik C, Stewart DA, Crump M, Djurfeldt MS, Chen BE, Shepherd LE (2012) ABVD alone versus radiation-based therapy in limited-stage Hodgkin’s lymphoma. N Engl J Med 366(5):399–408. doi:10.1056/NEJMoa1111961

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Engert A, Diehl V, Franklin J, Lohri A, Dorken B, Ludwig WD, Koch P, Hanel M, Pfreundschuh M, Wilhelm M, Trumper L, Aulitzky WE, Bentz M, Rummel M, Sezer O, Muller-Hermelink HK, Hasenclever D, Loffler M (2009) Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin’s lymphoma: 10 years of follow-up of the GHSG HD9 study. J Clin Oncol 27(27):4548–4554. doi:10.1200/JCO.2008.19.8820

    Article  PubMed  Google Scholar 

  22. Sasse S, Alram M, Mueller H, Smardova L, Metzner B, Dohner H, Fischer T, Vucinic V, Schmitz N, Schafer-Eckart K, Raemaekers JM, Schmalz O, von Tresckow B, Engert A, Borchmann P (2012) Prognostic relevance of dose-density of DHAP-reinduction therapy in relapsed HL: an analysis of the German Hodgkin-Study Group (GHSG). ASH Ann Meet Abstr 120(21):552

    Google Scholar 

  23. Tempescul A, Ianotto JC, Eveillard JR, Guillerm G, Berthou C (2011) ESHAP chemotherapy regimen associated to lenalidomide induces complete isotopic remission in Hodgkin’s lymphoma relapsing after autologous stem cell transplantation. Ann Hematol 90(8):971–973. doi:10.1007/s00277-010-1107-x

    Article  CAS  PubMed  Google Scholar 

  24. Martinez C, Rodriguez-Calvillo M, Terol MJ, Xicoy B, Garcia-Sanz R, Perez-Ceballos E, Cantalapiedra A, Domingo-Domenech E, Hernandez M, Sampol A, Espeso M, Briones J, Lopez J, Sureda A (2012) Salvage treatment with ofatumumab and ESHAP (O-ESHAP) for patients with relapsed or refractory classical Hodgkin’s lymphoma after first-line chemotherapy: interim analysis of a phase II trial of the Spanish Group of Lymphoma and Bone Marrow Transplantation (GELTAMO). ASH Ann Meet Abstr 120(21):1630

    Google Scholar 

  25. Moskowitz AJ (2012) Novel agents in Hodgkin lymphoma. Curr Oncol Rep 14(5):419–423. doi:10.1007/s11912-012-0251-y

    Article  CAS  PubMed  Google Scholar 

  26. Engert A, Franklin J, Eich HT, Brillant C, Sehlen S, Cartoni C, Herrmann R, Pfreundschuh M, Sieber M, Tesch H, Franke A, Koch P, de Wit M, Paulus U, Hasenclever D, Loeffler M, Muller RP, Muller-Hermelink HK, Duhmke E, Diehl V (2007) Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin’s lymphoma: final results of the GHSG HD7 trial. J Clin Oncol 25(23):3495–3502. doi:10.1200/JCO.2006.07.0482

    Article  CAS  PubMed  Google Scholar 

  27. Engert A, Schiller P, Josting A, Herrmann R, Koch P, Sieber M, Boissevain F, De Wit M, Mezger J, Duhmke E, Willich N, Muller RP, Schmidt BF, Renner H, Muller-Hermelink HK, Pfistner B, Wolf J, Hasenclever D, Loffler M, Diehl V (2003) Involved-field radiotherapy is equally effective and less toxic compared with extended-field radiotherapy after four cycles of chemotherapy in patients with early-stage unfavorable Hodgkin’s lymphoma: results of the HD8 trial of the German Hodgkin’s Lymphoma Study Group. J Clin Oncol 21(19):3601–3608. doi:10.1200/JCO.2003.03.023

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors thank Manuel Delgado, Manuela Salinero, and Marta García-Blázquez for their technical assistance, and Phil Mason for checking the English usage and grammar of the manuscript.

Author contribution

RG-S and MDC conceived the study. RG-S, JL, MC-C, EP-L, MVM, and LV provided the patients. JL collected data and performed the interpretation and statistical analysis. JL, RGS, and MDC wrote the paper. All authors critically reviewed the paper and approved the final version of the paper.

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The authors declare no conflicts of interest.

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Correspondence to Jorge Labrador.

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Labrador, J., Cabrero-Calvo, M., Pérez-López, E. et al. ESHAP as salvage therapy for relapsed or refractory Hodgkin’s lymphoma. Ann Hematol 93, 1745–1753 (2014). https://doi.org/10.1007/s00277-014-2114-0

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  • DOI: https://doi.org/10.1007/s00277-014-2114-0

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