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Outcome analysis of high-dose chemotherapy and autologous stem cell transplantation in adolescent and young adults with relapsed or refractory Hodgkin lymphoma

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Abstract

High-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT) can salvage many patients with relapsed or refractory Hodgkin’s lymphoma (HL). We are reporting the outcome of HDC auto-SCT and the impact of 21 prognostic factors in relapsed and refractory adolescent (14–21 years) and young adult (>21–30 years) (AYA) HL patients. We used Fine and Gray’s competing risk analysis method and regression model for outcome analysis. From 1996 to 2013, 290 consecutive patients with biopsy-proven HL underwent HDC auto-SCT for relapsed/refractory HL; 216 patients (74.5 %) were AYA at the time of auto-SCT. Male/female were equal, median age at auto-SCT was 22.4 years, and there were 94 adolescent (43.5 %) and 122 young adults (56.5 %). There was refractory disease in 121 (56 %) patients, relapsed in 95 (44 %). Median follow-up was 72.6 months. The Kaplan-Meier method estimated that 5-year overall survival is 62.7 % (adolescents (63.5 %), young adults (62 %)) and event-free survival was 51.3 %. Five-year cumulative incidence of disease-specific death (DS-death) is 33 % and that of DS-event is 45 %. For DS-death, the multivariate analysis identified complete remission (CR) duration of <12 months (hazard ratio (HR) 3.61, P = 0.0009), no CR after salvage (HR: 3.93, P = 0.0002), and nodular sclerosis pathology (HR 3.3, P = 0.016) and positive B symptoms (HR 2, P = 0.028) as negative factors. For DS-event, CR duration of <12 months (HR 1.88, P = 0.02), no CR after salvage (HR 3.47, P = 0.000005) and nodular sclerosis pathology (HR 1.88, P = 0.02) were found significant. The Kaplan-Meier method estimated overall survival (OS) at 36 months with 0–2:3:4 factors being 93.6:54:21 %, respectively (P value <0.001). Kaplan-Meier estimated event-free survival (EFS) at 36 months with 0–1:2:3 factors being 84.6:65:31 %, respectively (P value <0.001). Clinically, adolescents have similar outcomes as young adults.

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References

  1. 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  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  3. Bonfante V, Santoro A, Viviani S et al (1997) Outcome of patients with Hodgkin’s disease failing after primary MOPP-ABVD. J Clin Oncol 15:528–534

    CAS  PubMed  Google Scholar 

  4. Longo DL, Duffey PL, Young RC et al (1992) Conventional-dose salvage combination chemotherapy in patients relapsing with Hodgkin’s disease after combination chemotherapy: the low probability for cure. J Clin Oncol 10:210–218

    CAS  PubMed  Google Scholar 

  5. Reece DE, Barnett MJ, Shepherd JD et al (1995) High-dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16-213) with or without cisplatin (CBV +/− P) and autologous transplantation for patients with Hodgkin’s disease who fail to enter a complete remission after combination chemotherapy. Blood 86:451–456

    CAS  PubMed  Google Scholar 

  6. Horning SJ, Chao NJ, Negrin RS et al (1997) High-dose therapy and autologous hematopoietic progenitor cell transplantation for recurrent or refractory Hodgkin’s disease: analysis of the Stanford University results and prognostic indices. Blood 89:801–813

    CAS  PubMed  Google Scholar 

  7. Lazarus HM, Rowlings PA, Zhang MJ et al (1999) Autotransplants for Hodgkin’s disease in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry. J Clin Oncol 17:534–545

    CAS  PubMed  Google Scholar 

  8. André M, Henry-Amar M, Pico JL et al (1999) Comparison of high-dose therapy and autologous stem-cell transplantation with conventional therapy for Hodgkin’s disease induction failure: a case-control study. Société Francaise de Greffe de Moelle. J Clin Oncol 17:222–229

    PubMed  Google Scholar 

  9. Akhtar S, El Weshi A, Abdelsalam M, Hussaini HJI, Rahal M, Maghfoor I (2007) Primary refractory Hodgkin’s lymphoma: out come after high dose chemotherapy and autologous stem cell transplantation and impact of various prognostic factors on overall and event free survival. A single institution result of 66 patients. Bone Marrow Transplant 40:651–658

    Article  CAS  PubMed  Google Scholar 

  10. Josting A, Rueffer U, Franklin J et al (2000) Prognostic factors and treatment outcome in primary progressive Hodgkin lymphoma: a report from the German Hodgkin Lymphoma Study Group. Blood 96:1280–1286

    CAS  PubMed  Google Scholar 

  11. Satwani P, Ahn KW, Carreras J et al (2015) A prognostic model predicting autologous transplantation outcomes in children, adolescents and young adults with Hodgkin lymphoma. Bone Marrow Transplant 50:1416–1423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Shankar A, Hayward J, Kirkwood A et al (2014) Treatment outcome in children and adolescents with relapsed Hodgkin lymphoma—results of the UK HD3 relapse treatment strategy. Br J Haematol 165:534–544

    Article  CAS  PubMed  Google Scholar 

  13. Gorde-Grosjean S, Oberlin O, Leblanc T et al (2012) Outcome of children and adolescents with recurrent/refractory classical Hodgkin lymphoma, a study from the Societe Francaise de Lutte contre le Cancer des Enfants et des Adolescents (SFCE). Br J Haematol 158:649–656

    Article  PubMed  Google Scholar 

  14. Harris RE, Termuhlen AM, Smith LM et al (2011) Autologous peripheral blood stem cell transplantation in children with refractory or relapsed lymphoma: results of Children’s Oncology Group study A5962. Biol Blood Marrow Transplant 17:249–258

    Article  PubMed  Google Scholar 

  15. Shafer JA, Heslop HE, Brenner MK et al (2010) Outcome of hematopoietic stem cell transplant as salvage therapy for Hodgkin’s lymphoma in adolescents and young adults at a single institution. Leuk Lymphoma 51:664–670

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Schellong G, Dörffel W, Claviez A et al (2005) Salvage therapy of progressive and recurrent Hodgkin’s disease: results from a multicenter study of the pediatric DAL/GPOH-HD study group J. Clin Oncol 23:6181–6189

    Article  Google Scholar 

  17. Prete A, Bonetti F, Rondelli R et al (2005) High dose therapy (HDCT) and autologous haematopoietic stem cell transplantation (aSCT) in paediatric patients with recurrent or refractory Hodgkin’s disease (HD): results and outcome. ASH Annual Meeting Abstracts 106:2088

    Google Scholar 

  18. Lieskovsky YE, Donaldson SS, Torres MA et al (2004) High-dose therapy and autologous hematopoietic stem-cell transplantation for recurrent or refractory pediatric Hodgkin’s disease: results and prognostic indices. J Clin Oncol 22:4532–4540

    Article  PubMed  Google Scholar 

  19. Claviez A, Canals C, Dierickx D et al (2009) 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 114:2060–2067

    Article  CAS  PubMed  Google Scholar 

  20. Stoneham S, Ashley S, Pinkerton CR et al (2004) Outcome after autologous hemopoietic stem cell transplantation in relapsed or refractory childhood Hodgkin disease. J Pediatr Hematol Oncol 26:740–745

    Article  PubMed  Google Scholar 

  21. Frankovich J, Donaldson SS, Lee Y et al (2001) High-dose therapy and autologous hematopoietic cell transplantation in children with primary refractory and relapsed Hodgkin’s disease: atopy predicts idiopathic diffuse lung injury syndromes. Biol Blood Marrow Transplant 7:49–57

    Article  CAS  PubMed  Google Scholar 

  22. Verdeguer A, Pardo N, Madero L et al (2000) Autologous stem cell transplantation for advanced Hodgkin’s disease in children. Spanish group for BMT in children (GETMON), Spain. Bone Marrow Transplant 25:31–34

    Article  CAS  PubMed  Google Scholar 

  23. Baker KS, Gordon BG, Gross TG et al (1999) Autologous hematopoietic stem-cell transplantation for relapsed or refractory Hodgkin’s disease in children and adolescents. J Clin Oncol 17:825–831

    CAS  PubMed  Google Scholar 

  24. Rauf MS, Maghfoor I, Elhassan TA, Akhtar S (2015) High-dose chemotherapy and auto-SCT for relapsed and refractory Hodgkin’s lymphoma patients refractory to first-line salvage chemotherapy but responsive to second-line salvage chemotherapy. Med Oncol 32:388

    Article  PubMed  Google Scholar 

  25. Akhtar S, Tbakhi A, Humaidan H et al (2006) ESHAP + fixed dose G-CSF as autologous peripheral blood stem cell mobilization regimen in patients with relapsed or refractory diffuse large cell and Hodgkin’s lymphoma: a single institution result of 127 patients. Bone Marrow Transplant 37:277–282

    Article  CAS  PubMed  Google Scholar 

  26. Akhtar S, Al-Sugair A, Abouzied M et al (2013) Pre-transplant FDG-PET-based survival model in relapsed and refractory Hodgkin’s lymphoma: outcome after high-dose chemotherapy and auto-SCT. Bone Marrow Transplant 48:1530–1536

    Article  CAS  PubMed  Google Scholar 

  27. 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 17:1244–1253

    CAS  PubMed  Google Scholar 

  28. Hasenclever D, Diehl V (1998) A prognostic score for advanced Hodgkin’s disease. International prognostic factors project on advanced Hodgkin’s disease. N Engl J Med 339:1506–1514

    Article  CAS  PubMed  Google Scholar 

  29. Fine JP, Gray RJ (1999) A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94:496–509

    Article  Google Scholar 

  30. Scrucca L, Santucci A, Aversa F (2010) Regression modeling of competing risk using R: an in depth guide for clinicians. Bone Marrow Transplant 45:1388–1395

    Article  CAS  PubMed  Google Scholar 

  31. Rauf MS, Akhtar S, Maghfoor I (2015) Changing trends of adult lymphoma in the Kingdom of Saudi Arabia—comparison of data sources. Asian Pac J Cancer Prev 16:2069–2072

    Article  PubMed  Google Scholar 

  32. Akhtar S, Elhassan TA, Edesa W et al (2016) High-dose chemotherapy and autologous stem cell transplantation for relapsed or refractory nodular lymphocyte predominant Hodgkin lymphoma. Ann Hematol 95:49–54

    Article  CAS  PubMed  Google Scholar 

  33. Daw S, Wynn R, Wallace H (2011) Management of relapsed and refractory classical Hodgkin lymphoma in children and adolescents. Br J Haematol 152:249–260

    Article  PubMed  Google Scholar 

  34. Smith SD, Moskowitz CH, Dean R et al (2011) Autologous stem cell transplant for early relapsed/refractory Hodgkin lymphoma: results from two transplant centres. Br J Haematol 153:358–363

    Article  PubMed  Google Scholar 

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Acknowledgments

We appreciate Ms. Ruqaya Belkhedim, Mr. Fayez Abu Zeid, and Ms. Reena Ulahannan from BMT clinic; Mr. Edgardo Colcol, Riad Youniss, and Dr. Abida Rehman from Oncology Research Unit; and Ms. Iman Youssef, clinical nurse coordinator for their valuable contribution.

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Correspondence to Saad Akhtar.

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SA was the principal investigator, conducted analysis of the data, and takes primary responsibility for the paper; SR helped in the analysis of data and manuscript writing; TAME performed statistical analysis and helped in manuscript writing; and IM was the co-principal investigator and helped in data interpretation, analysis, and in manuscript writing.

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The authors declare that they have no conflict of interest.

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Akhtar, S., Rauf, S.M., Elhassan, T.A.M. et al. Outcome analysis of high-dose chemotherapy and autologous stem cell transplantation in adolescent and young adults with relapsed or refractory Hodgkin lymphoma. Ann Hematol 95, 1521–1535 (2016). https://doi.org/10.1007/s00277-016-2736-5

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  • DOI: https://doi.org/10.1007/s00277-016-2736-5

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