Browse > Article
http://dx.doi.org/10.3904/kjim.2015.30.3.362

Role of frontline autologous stem cell transplantation in young, high-risk diffuse large B-cell lymphoma patients  

Yoon, Jae-Ho (Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
Kim, Jong-Wook (Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
Jeon, Young-Woo (Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
Lee, Sung-Eun (Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
Eom, Ki-Seong (Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
Kim, Yoo-Jin (Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
Lee, Seok (Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
Kim, Hee-Je (Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
Min, Chang-Ki (Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
Lee, Jong-Wook (Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
Min, Woo-Sung (Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
Park, Chong-Won (Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
Cho, Seok-Goo (Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
Publication Information
The Korean journal of internal medicine / v.30, no.3, 2015 , pp. 362-371 More about this Journal
Abstract
Background/Aims: Several studies have demonstrated the effect of autologous hematopoietic stem cell transplantation (auto-HSCT) as a salvage treatment for patients with relapsed diffuse large B-cell lymphoma (DLBCL). However, the role of auto-HSCT as a frontline treatment has not been fully investigated in the rituximab era. We validated the age-adjusted International Prognostic Index (aaIPI) score for high-risk DLBCL patients and identified a possible role for frontline auto-HSCT. Methods: We recommended frontline auto-HSCT for high-risk DLBCL patients who satisfied the criteria of both a higher Ann-Arbor stage (III to IV) and an elevated lactate dehydrogenase (LDH) level at diagnosis with an aaIPI $score{\geq}2$. From 2006 to 2011, among the 150 DLBCL patients aged ${\leq}60$ years who were treated with six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), 23 high-risk patients with a complete response (CR) were treated with auto-HSCT. For comparison, we selected 35 well-matched high-risk patients with CR who completed R-CHOP treatment alone. In addition, there were 81 low-risk patients and 11 refractory patients. Results: DLBCL patients with an aaIPI $score{\geq}2$ showed inferior overall survival (OS; p = 0.040) and progression-free survival (PFS; p = 0.007) compared to the aaIPI score 0 to 1. Between the two treatment arms among the high-risk DLBCL patients, the clinical parameters were not different. The high-risk group treated with frontline auto-HSCT showed similar OS (p = 0.392) and PFS (p = 0.670) to those in the low-risk group. Thus, frontline auto-HSCT showed superior PFS (p = 0.004), but only a trend towards favorable OS (p = 0.091) compared to R-CHOP alone. Conclusions: We identified the possible role of frontline auto-HSCT for high-risk DLBCL with a higher stage (III to IV) and elevated LDH level.
Keywords
Lymphoma; Lymphoma, large B-cell, diffuse; Autologous hematopoietic cell transplantation;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Philip T, Armitage JO, Spitzer G, et al. High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin's lymphoma. N Engl J Med 1987;316:1493-1498.   DOI
2 Blay J, Gomez F, Sebban C, et al. The International Prognostic Index correlates to survival in patients with aggressive lymphoma in relapse: analysis of the PARMA trial. Parma Group. Blood 1998;92:3562-3568.
3 Haioun C, Lepage E, Gisselbrecht C, et al. Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's lymphoma: final analysis of the prospective LNH87-2 protocol--a groupe d'Etude des lymphomes de l'Adulte study. J Clin Oncol 2000;18:3025-3030.   DOI
4 Santini G, Salvagno L, Leoni P, et al. VACOP-B versus VACOP-B plus autologous bone marrow transplantation for advanced diffuse non-Hodgkin's lymphoma: results of a prospective randomized trial by the non-Hodgkin's Lymphoma Cooperative Study Group. J Clin Oncol 1998;16:2796-2802.   DOI
5 Greb A, Bohlius J, Trelle S, et al. High-dose chemotherapy with autologous stem cell support in first-line treatment of aggressive non-Hodgkin lymphoma: results of a comprehensive meta-analysis. Cancer Treat Rev 2007;33:338-346.   DOI
6 Gisselbrecht C, Lepage E, Molina T, et al. Shortened first-line high-dose chemotherapy for patients with poor-prognosis aggressive lymphoma. J Clin Oncol 2002;20:2472-2479.   DOI
7 Martelli M, Gherlinzoni F, De Renzo A, et al. Early autologous stem-cell transplantation versus conventional chemotherapy as front-line therapy in high-risk, aggressive non-Hodgkin's lymphoma: an Italian multicenter randomized trial. J Clin Oncol 2003;21:1255-1262.   DOI
8 Vitolo U, Chiappella A, Brusamolino E, et al. Rituximab dose-dense chemotherapy followed by intensified highdose chemotherapy and autologous stem cell transplantation (HDC+ASCT) significantly reduces the risk of progression compared to standard rituximab dose-dense chemotherapy as first line treatment in young patients with high-risk (aa-IPI 2-3) diffuse large B-cell lymphoma (DLBCL): final results of phase III randomized trial DLCL04 of the Fondazione Italiana Linfomi (FIL). Paper presented at: 54th ASH Annual Meeting Abstracts 2012; 2012 Dec 8-11; Atlanta, GA. Washington, DC: American Society of Hematology, 2012: 688.
9 Stiff PJ, Unger JM, Cook J, et al. Randomized phase III U.S./Canadian intergroup trial (SWOG S9704) comparing CHOP $\pm$ R for eight cycles to CHOP $\pm$ R for six cycles followed by autotransplant for patients with high-intermediate (H-Int) or high IPI grade diffuse aggressive non-Hodgkin lymphoma (NHL). J Clin Oncol 2011;29(Suppl):abstr8001.
10 Stiff PJ, Unger JM, Cook JR, et al. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med 2013;369:1681-1690.   DOI
11 Pfreundschuh M, Trumper L, Osterborg A, et al. CHOPlike chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol 2006;7:379-391.   DOI
12 Coiffier B. Rituximab in combination with CHOP improves survival in elderly patients with aggressive non-Hodgkin's lymphoma. Semin Oncol 2002;29:18-22.   DOI
13 Gang AO, Strom C, Pedersen M, et al. R-CHOEP-14 improves overall survival in young high-risk patients with diffuse large B-cell lymphoma compared with R-CHOP-14: a population-based investigation from the Danish Lymphoma Group. Ann Oncol 2012;23:147-153.   DOI
14 Jardin F, Jais JP, Molina TJ, et al. Diffuse large B-cell lymphomas with CDKN2A deletion have a distinct gene expression signature and a poor prognosis under R-CHOP treatment: a GELA study. Blood 2010;116:1092-1104.   DOI
15 Juweid ME, Stroobants S, Hoekstra OS, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol 2007;25:571-578.   DOI
16 The International Non-Hodgkin's Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med 1993;329:987-994.   DOI
17 Hamlin PA, Zelenetz AD, Kewalramani T, et al. Age-adjusted International Prognostic Index predicts autologous stem cell transplantation outcome for patients with relapsed or primary refractory diffuse large B-cell lymphoma. Blood 2003;102:1989-1996.   DOI
18 Papageorgiou SG, Diamantopoulos P, Levidou G, et al. Isolated central nervous system relapses in primary mediastinal large B-cell lymphoma after CHOP-like chemotherapy with or without Rituximab. Hematol Oncol 2013;31:10-17.   DOI
19 Wolff JE, Finlay JL. High-dose chemotherapy in childhood brain tumors. Onkologie 2004;27:239-245.   DOI
20 DE Ioris MA, Contoli B, Jenkner A, et al. Comparison of two different conditioning regimens before autologous transplantation for children with high-risk neuroblastoma. Anticancer Res 2012;32:5527-5533.
21 Lee SC, Kim SJ, Lee DH, Kim WS, Suh C, Won JH. Excessive toxicity of once daily i.v. BU, melphalan and thiotepa followed by auto SCT on patients with non-Hodgkin's lymphoma. Bone Marrow Transplant 2010;45:801-802.   DOI
22 Spaepen K, Stroobants S, Dupont P, et al. Prognostic value of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose ([18F]FDG) after first-line chemotherapy in non-Hodgkin's lymphoma: is [18F]FDG-PET a valid alternative to conventional diagnostic methods? J Clin Oncol 2001;19:414-419.   DOI
23 Kaiser U, Uebelacker I, Abel U, et al. Randomized study to evaluate the use of high-dose therapy as part of primary treatment for “aggressive” lymphoma. J Clin Oncol 2002;20:4413-4419.   DOI
24 Schmitz N, Nickelsen M, Ziepert M, et al. Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1). Lancet Oncol 2012;13:1250-1259.   DOI
25 Alousi AM, Saliba RM, Okoroji GJ, et al. Disease staging with positron emission tomography or gallium scanning and use of rituximab predict outcome for patients with diffuse large B-cell lymphoma treated with autologous stem cell transplantation. Br J Haematol 2008;142:786-792.   DOI
26 Derenzini E, Musuraca G, Fanti S, et al. Pretransplantation positron emission tomography scan is the main predictor of autologous stem cell transplantation outcome in aggressive B-cell non-Hodgkin lymphoma. Cancer 2008;113:2496-2503.   DOI
27 Schot BW, Zijlstra JM, Sluiter WJ, et al. Early FDG-PET assessment in combination with clinical risk scores determines prognosis in recurring lymphoma. Blood 2007;109:486-491.   DOI
28 Lee JL, Gooley T, Bensinger W, Schiffman K, McDonald GB. Veno-occlusive disease of the liver after busulfan, melphalan, and thiotepa conditioning therapy: incidence, risk factors, and outcome. Biol Blood Marrow Transplant 1999;5:306-315.   DOI
29 Milpied N, Deconinck E, Gaillard F, et al. Initial treatment of aggressive lymphoma with high-dose chemotherapy and autologous stem-cell support. N Engl J Med 2004;350:1287-1295.   DOI
30 Cortelazzo S, Tarella C, Gianni AM, et al. Chemoimmunotherapy with R-CHOP or high dose sequential therapy with autologous stem cell transplantation (R-HDS) for high risk diffuse large B-cell lymphomas patients: results of the randomized R-HDS0305 trial by Gruppo Italiano Terapie Innovative Nei Linfomi (GITIL). Paper presented at: 54th ASH Annual Meeting Abstracts 2012; 2012 Dec 8-11; Atlanta, GA. Washington, DC: American Society of Hematology, 2012: 746.
31 Filmont JE, Gisselbrecht C, Cuenca X, et al. The impact of pre- and post-transplantation positron emission tomography using 18-fluorodeoxyglucose on poor-prognosis lymphoma patients undergoing autologous stem cell transplantation. Cancer 2007;110:1361-1369.   DOI