resistant relapse

High-Dose Chemotherapy and Autologous Stem Cells Transplantation for Relapsed/Refractory Hodgkin’s Lymphoma. Is There an Equal Right to Life?

BONE MARROW TRANSPLANTATION , , , ,

N.V. Zhukov1,2, A.G. Rumyantsev1, A.L. Uss3, N.F. Milanovich3, V.V. Ptushkin1, B.V. Afanasyev4, N.B. Mikhaylova4, V.B. Larionova5, E.A. Demina5, E.E. Karamanesht6, N.G. Tyurina7, M.A. Vernyuk7, A.D. Kaprin7

1 Dmitrii Rogachev Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology under the RF MH, Moscow, Russian Federation

2 N.I. Pirogov Russian National Research Medical University, Moscow, Russian Federation

3 National Center for Hematology and Bone Marrow Transplantation, Minsk, Belarus

4 R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation under I.P. Pavlov State Medical University, Saint Petersburg, Russian Federation

5 N.N. Blokhin Cancer Research Center of RAMS, Moscow, Russian Federation

6 Kyiv Center for Bone Marrow Transplantation, Kyiv, Ukraine

7 P.A. Hertsen Moscow Oncological Research Institute, Moscow, Russian Federation

For citation: Zhukov N.V., Rumyantsev A.G., Uss A.L., Milanovich N.F., Ptushkin V.V., Afanas’ev B.V., Mikhailova N.B., Larionova V.B., Demina E.A., Karamanesht E.E., Tyurina N.G., Vernyuk M.A., Kaprin A.D. High-Dose Chemotherapy and Autologous Stem Cells Transplantation for Relapsed/Refractory Hodgkin’s Lymphoma. Is There an Equal Right to Life? Klin. onkogematol. 2014; 7(3): 317–26 (In Russ.).

ABSTRACT

Aim. Hodgkin’s lymphoma (HL) patients with primary refractory (PRef) course of disease or relapses refractory to the previous 2nd line therapy (RRel) often are not given high-dose chemotherapy with autologous stem cell support (ASCS), and this refuse is motivated by its poor efficacy and high toxicity in this population. The objective of this study was to evaluate the efficacy and safety of ASCS in this patient population.

Materials and methods. 372 patients with Hodgkin’s lymphoma undergoing ASCS between 01.1990 and 06.2013 were included in the trial. The reason for ASCS was: primary refractory disease in 132 (35.5 %) patients, relapse of the disease resistant to II line chemotherapy (refractory relapse) in 81 (22 %). The remaining 159 patients (42.5 %) either had a relapse for which they received no II line chemotherapy (a relapse with untested sensitivity) or a relapse that proved to be sensitive to previously performed II line therapy (sensitive relapse). These patients were assigned to a chemosensitive HL group.

Results. With a median follow-up of 51 months, the overall survival rate (OS) and the relapse-free survival rate (RFS) did not differ significantly between patients with RRel, PRef and chemosensitive HL group (p > 0.05). Only freedom from treatment failure survival (FFTS) was significantly worse in patients with PRef HL (5-yrs EFS 42 % vs 58 % in patients with RRel vs 60 % in patients with chemosensitive HL group; p = 0.004). 100-day mortality mostly caused by ASCS toxicity also did not differ significantly between groups (p = 0.2). Irrespectively of primary reason for ASCS, long-term ASCS results significantly depended on response to the cytoreductive therapy. The effect of the cytoreductive therapy was assessed in 309 patients. When patients achieved complete, marked partial or partial remission, the 5-year overall survival rate, FFTS, and relapse-free survival rate was 78 %, 64 %, and 68 %, respectively. In patients with stabilization or progression of disease due to the cytoreductive therapy, these parameters were equal to 33 %, 24 % и 52 %, respectively (p < 0.001 for OS and FFTS, p = 0.005 for RFS).

Conclusion. In patients with primary refractory and refractory relapse of HL, ASCS has acceptable efficacy and early mortality which is comparable to that observed in patients with chemosensitive Hodgkin’s lymphoma, thus permitting to consider ASCS a potential therapeutic approach in patients with primary refractory disease and resistant relapses of Hodgkin’s lymphoma. Irrespectively of the initial disease course, the tumor response to the cytoreductive therapy is the most important predictive factor for the long-term ASCS results.

Keywords: Hodgkin’s lymphoma, high-dose chemotherapy, autologous hematopoietic stem cells transplantation, primary resistance, resistant relapse.

Address correspondence to: zhukov.nikolay@rambler.ru

Accepted: April 13, 2014

Read in PDF (RUS) pdficon

REFERENCES

  1.  Linch D., Winfield D., Goldstone A. et al. Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin’s disease: results of a BNLI randomised trial. Lancet 1993; 341: 1051.
  2. Schmitz N., Sextro M., Pfistner B. HDR-1: high-dose therapy (HDT) followed by hematopoietic stem cell transplantation (HSCT) for relapsed chemosensitive Hodgkin’s disease (HD): final results of a randomized GHSG and EBMT trial (HD-R1). Proc. Am. Soc. Clin. Oncol. 1999; 18(Suppl. 5): 18.
  3. Josting A., Franklin J., May M. et al. New prognostic score based on treatment outcome of patients with relapsed Hodgkin’s lymphoma registered in the database of the German Hodgkin’s lymphoma study group. J. Clin. Oncol. 2002; 20: 221–30.
  4. Longo L., Duffey P.L., Young R.C. et al. Conventional-dose salvage combination chemotherapy in patients relapsing with Hodgkin’s disease after combination chemotherapy: the low probability for cure. J. Clin. Oncol. 1992; 10: 210–8.
  5. Brusamolino E., Orlandi E., Canevari A. et al. Results of CAV regimen (CCNU, melphalan, and VP-16) as third-line salvage therapy for Hodgkin’s disease. Ann. Oncol. 1994; 5: 427–32.
  6. Bonfante V., Santoro A., Viviani S. et al. Outcome of patients with Hodgkin’s disease failing after primary MOPP/ABVD. J. Clin. Oncol. 1997; 15: 528–34.
  7. Josting A., Rueffer U., Franklin J. et al. Prognostic factors and treatment outcome in primary progressive Hodgkin lymphoma: a report from the German Hodgkin Lymphoma Study Group. Blood 2000; 96: 1280–6.
  8. Josting A., Rudolph C., Mapara M. et al. 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. 2005; 16(1): 116–23.
  9. Argiris A., Seropian S., Cooper D.L. High-dose BEAM chemotherapy with autologous peripheral blood progenitor-cell transplantation for unselected patients with primary refractory or relapsed Hodgkin’s disease. Ann. Oncol. 2000; 11: 665–72.
  10. Ferme C., Mounier N., Divine M. et al. 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. 2002; 20: 467–75.
  11. Constans M., Sureda A., Terol M.J. et al. Autologous stem cell transplantation for primary refractory Hodgkin’s disease: Results and clinical variables affecting outcome. Ann. Oncol. 2003; 14: 745–51.
  12. Sweetenham J.W., Carella A.M., Taghipour G. et al. High-dose therapy and autologous stem-cell transplantation for adult patients with Hodgkin’s disease who do not enter remission after induction chemotherapy: Results in 175 patients reported to the European Group for Blood and Marrow Transplantation. Lymphoma Working Party. J. Clin. Oncol. 1999; 17: 3101–9.
  13. Gopal A.K., Metcalfe T.L., Gooley T.A. et al. High-Dose Therapy and Autologous Stem Cell Transplantation for Chemoresistant Hodgkin Lymphoma: The Seattle Experience. Cancer 2008; 113(6): 1344–50.
  14. Sureda A., Arranz R., Iriondo A. et al. 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. 2001; 19(5): 1395–404.
  15. Czyz J., Dziadziuszko R., Knopinska-Postuszuy W. et al. Outcome and prognostic factors in advanced Hodgkin’s disease treated with high-dose chemotherapy and autologous stem cell transplantation: a study of 341 patients. Ann. Oncol. 2004; 15(8): 1222–30.
  16. Sureda A., Constans M., Iriondo A. et al. Prognostic factors affecting long-term outcome after stem cell transplantation in Hodgkin’s lymphoma autografted after a first relapse. Ann. Oncol. 2005; 16(4): 625–33.