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

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 (> 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; = 0.004). 100-day mortality mostly caused by ASCS toxicity also did not differ significantly between groups (= 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 (< 0.001 for OS and FFTS, = 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

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