primary resistance

Autologous Stem Cell Transplantation in Primary Refractory Hodgkin’s Lymphoma: Supposed Zugzwang or Zwischenzug?

BONE MARROW TRANSPLANTATION , , , ,

GD Petrova1, KN Melkova1, TZ Chernyavskaya1, NV Gorbunova1, BV Afanas’ev2, EA Demina1, VN Kostrykina1, VA Doronin1

1 N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

2 R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 12 Rentgena str., Saint Petersburg, Russian Federation, 197022

For correspondence: Galina Dmitrievna Petrova, graduate student, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-13-59; e-mail: galina_petrova@bk.ru

For citation: Petrova GD, Melkova KN, Chernyavskaya TZ, et al. Autologous Stem Cell Transplantation in Primary Refractory Hodgkin’s Lymphoma: Supposed Zugzwang or Zwischenzug? Clinical oncohematology. 2015;8(3):321–30 (In Russ).

ABSTRACT

Background & Aims. The role of single and double autologous hematopoietic stem cell transplantations (autoSCT) in patients with primary refractory Hodgkin’s lymphoma (HL) has not been determined yet. The aim of the study is to present the results of a one-center prospective study evaluating the role of single and double autoSCT in patients with HL who have not achieved the complete remission (CR) after first line induction polychemotherapy (PCT).

Methods. 62 HL patients were enrolled in the study over the period from 2007 till 2014. High-dose chemotherapy (HDCT) with autoSCT was performed once in 53 patients, and twice in 10 patients.

Results. The study demonstrated an unfavorable prognostic impact of the large volume of previous chemotherapy on the overall survival (OS) rate after the autoSCT (p = 0.03). Results of the 1st autoSCT had an independent prognostic value for the OS rate (p = 0.004). The study identified the main indication for the 2nd autoSCT, namely, partial remission (PR) or stable disease (SD) achieved after the 1st autoSCT (when the 2nd HDCT with autoSCT should be preferred to the alternative treatment; p = 0.004). Progressive disease (PD) after the first autoSCT is a contraindication for the second one. Due to low efficacy and high toxicity, the 2nd autoSCT does not improve outcomes when compared to alternative approaches (p = 0.6). The importance of achieving CR at any stage of treatment which is associated with a long life span with no signs of disease and good quality of life has been demonstrated.

Conclusion. AutoSCT is an effective treatment option for patients without complete remission after the first line antitumor treatment. Carrying out 2nd autoSCT is advisable for patients who have reached the PR/SD after the first one. Patients with PD after the 1st autoSCT require an alternative treatment option.

Keywords: Hodgkin’s lymphoma, high-dose chemotherapy, autologous hematopoietic stem cell transplantation, primary resistance, double autoSCT.

Received: May 5, 2015

Accepted: June 2, 2015

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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

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