**Author details**

Pervin Topcuoglu1 , Sinem Civriz Bozdag2 and Taner Demirer3

\*Address all correspondence to: topcuogl@medicine.ankara.edu.tr

\*Address all correspondence to: scivriz@hotmail.com

\*Address all correspondence to: demirer@medicine.ankara.edu.tr

1 Ankara University, School of Medicine, Dept of Hematology, Stem Cell Transplantation Unit, Ankara, Turkey

Grosbois B, Guillerm G, Benboubker L, Monconduit M, Thieblemont C, Casassus P, Caillot D, Stoppa AM, Sotto JJ, Wetterwald M, Dumontet C, Fuzibet JG, Azais I, Dor‐ vaux V, Zandecki M, Bataille R, Minvielle S, Harousseau JL, Facon T, Mathiot C. Avet-Loiseau H, Attal M, Campion L, Caillot D, Hulin C, Marit G, Stoppa AM, Voil‐ lat L, Wetterwald M, Pegourie B, Voog E, Tiab M, Banos A, Jaubert J, Bouscary D, Macro M, Kolb B, Traulle C, Mathiot C, Magrangeas F, Minvielle S, Facon T, Moreau P. Long-term analysis of the IFM 99 trials for myeloma: cytogenetic abnormalities [t(4;14), del(17p), 1q gains] play a major role in defining long-term survival. J Clin

Allogeneic Hematopoetic Cell Transplantation in Multiple Myeloma

http://dx.doi.org/10.5772/54762

173

[6] Zhou Y, Zhang Q, Stephens O, Heuck CJ, Tian E, Sawyer JR, Cartron-Mizeracki MA, Qu P, Keller J, Epstein J, Barlogie B, Shaughnessy JD Jr. Prediction of cytogenetic ab‐

[7] Roos-Weil D, Moreau P, Avet-Loiseau H, Golmard JL, Kuentz M, Vigouroux S, Socié G, Furst S, Soulier J, Le Gouill S, François S, Thiebaut A, Buzyn A, Maillard N, Ya‐ koub-Agha I, Raus N, Fermand JP, Michallet M, Blaise D, Dhédin N; Société Fran‐ çaise de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC). Impact of genetic abnormalities after allogeneic stem cell transplantation in multiple myeloma: a report of the Société Française de Greffe de Moelle et de Thérapie Cellulaire. Haematologi‐

[8] Gahrton G, Tura S, Ljungman P, Belanger C, Brandt L, Cavo M, Facon T, Granena A, Gore M, Gratwohl A, Löwenberg B, Nikoskelainen J, Reiffers JJ, Samson D, Verdonck L,Volin L, and for the European Group for Bone Marrow Transplantation. Allogeneic bone marrow transplantation in multiple myeloma. European Group for Bone Mar‐

row Transplantation. New England Journal of Medicine 1991;325(18):1267-73.

an analysis of risk factors on outcome. Blood 1996; 88(7):2787-93.

[9] Gahrton G, Tura S, Ljungman P, Bladé J, Brandt L, Cavo M, Façon T, Gratwohl A, Hagenbeek A, Jacobs P, et al. Prognostic factors in allogeneic bone marrow trans‐ plantation for multiple myeloma. Journal of Clinical Oncology 1995;13(6):1312-22. [10] Bensinger WI, Buckner CD, Anasetti C, Clift R, Storb R, Barnett T, Chauncey T, Shul‐ man H, Appelbaum FR. Allogeneic marrow transplantation for multiple myeloma:

[11] Durie BGM, Gale RP, Klein JP, Pelz C, Nugent ML, Horowitz MM. Allogenic Bone Marrow Transplantation In Multiple Myeloma: An IBMTR Analysis. American Soci‐ ety of Clinical Oncology (ASCO). Proceedings- American Society of Clinical Oncolol‐

[12] Barlogie B, Kyle RA, Anderson KC, Greipp PR, Lazarus HM, Hurd DD, McCoy J, Moore DF Jr, Dakhil SR, Lanier KS, Chapman RA, Cromer JN, Salmon SE, Durie B, Crowley JC. Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: final results of phase III US Intergroup Trial S9321. Journal of

normalities with gene expression profiles. Blood 2012; 119(21):e148-50

Oncol. 2012 30(16):1949-52.

ca. 2011; 96(10):1504-11.

ogy 1995; 15:405 (abstr 1358)

Clinical Oncology 2006;24(6):929-936.

2 Ankara Oncology Research and Education Hospital, Hematology and Stem Cell Trans‐ plantation Unit, Ankara, Turkey

3 Ankara University, School of Medicine, Dept of Hematology, Stem Cell Transplantation Unit, Ankara, Turkey

## **References**


Grosbois B, Guillerm G, Benboubker L, Monconduit M, Thieblemont C, Casassus P, Caillot D, Stoppa AM, Sotto JJ, Wetterwald M, Dumontet C, Fuzibet JG, Azais I, Dor‐ vaux V, Zandecki M, Bataille R, Minvielle S, Harousseau JL, Facon T, Mathiot C. Avet-Loiseau H, Attal M, Campion L, Caillot D, Hulin C, Marit G, Stoppa AM, Voil‐ lat L, Wetterwald M, Pegourie B, Voog E, Tiab M, Banos A, Jaubert J, Bouscary D, Macro M, Kolb B, Traulle C, Mathiot C, Magrangeas F, Minvielle S, Facon T, Moreau P. Long-term analysis of the IFM 99 trials for myeloma: cytogenetic abnormalities [t(4;14), del(17p), 1q gains] play a major role in defining long-term survival. J Clin Oncol. 2012 30(16):1949-52.

**Author details**

Pervin Topcuoglu1

Unit, Ankara, Turkey

Unit, Ankara, Turkey

2516-2520.

366(19):1782-91.

**References**

plantation Unit, Ankara, Turkey

, Sinem Civriz Bozdag2

\*Address all correspondence to: scivriz@hotmail.com

172 Multiple Myeloma - A Quick Reflection on the Fast Progress

\*Address all correspondence to: topcuogl@medicine.ankara.edu.tr

\*Address all correspondence to: demirer@medicine.ankara.edu.tr

and Taner Demirer3

1 Ankara University, School of Medicine, Dept of Hematology, Stem Cell Transplantation

2 Ankara Oncology Research and Education Hospital, Hematology and Stem Cell Trans‐

3 Ankara University, School of Medicine, Dept of Hematology, Stem Cell Transplantation

[1] Brenner H, Gondos A, Pulte D. Recent major improvement in long-term survival of

[2] Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Zelden‐ rust SR, Dingli D, Russell SJ, Lust JA, Greipp PR, Kyle RA, Gertz MA. Improved sur‐ vival in multiple myeloma and impact of novel therapies. Blood 2008;111(5):

[3] Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T, Stoppa AM, Hu‐ lin C, Benboubker L, Garderet L, Decaux O, Leyvraz S, Vekemans MC, Voillat L, Mi‐ challet M, Pegourie B, Dumontet C, Roussel M, Leleu X, Mathiot C, Payen C, Avet-Loiseau H, Harousseau JL; IFM Investigators. Lenalidomide maintenance after stemcell transplantation for multiple myeloma. New England Journal of Medicine 2012;

[4] Bjorkstrand BB,Lungjman P, Svensson H,Hermans J, Alegre A,Apperley J,Blade J, Carlson K,Cavo M, Ferrant A, Goldstone AH, Laurenzi A,Majolino I, Marcus R, Prentice HG, Remes K,Samson D,Sureda A,Verdonck LF,Volin L,Gahrton G.Alloge‐ neic bone marrow transplantation versus autologus stem cell transplantation in mul‐ tiple myeloma:a retrospective case matched study from the European group for

[5] Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, Hulin C, Leyvraz S, Michallet M, Yakoub-Agha I, Garderet L, Marit G, Michaux L, Voillat L, Renaud M,

Blood and Marrow Transplantation. Blood 1996:88(12);4711-18.

younger patients with multiple myeloma. Blood 2008;111(5): 2521-2526.


[13] Storb R, Raff RF, Appelbaum FR, Graham TC, Schuening FG, Sale G, Pepe M. Com‐ parison of fractionated to single-dose total body irradiation in conditioning canine littermates for DLA-identical marrow grafts. Blood 1989; 74(3):1139-43.

non C, Blaise D. Comparable outcomes between unrelated and related donors after reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation in patients with high-risk multiple myeloma. European Journal of Haematology

Allogeneic Hematopoetic Cell Transplantation in Multiple Myeloma

http://dx.doi.org/10.5772/54762

175

[23] Bensinger W, Rotta M, Storer B, Chauncey T, Holmberg L, Becker P, Sandmaier BM, Storb R, Maloney D. Allo-SCT for multiple myeloma: a review of outcomes at a sin‐ gle transplant center. Bone Marrow Transplantation 2012 Feb 13. doi: 10.1038/bmt.

[24] Bruno B, Rotta M, Patriarca F, Mattei D, Allione B, Carnevale-Schianca F, Sorasio R, Rambaldi A, Casini M, Parma M, Bavaro P, Onida F, Busca A, Castagna L, Benedetti E, Iori AP, Giaccone L, Palumbo A, Corradini P, Fanin R, Maloney D, Storb R, Baldi I, Ricardi U, Boccadoro M. Nonmyeloablative allografting for newly diagnosed multi‐ ple myeloma: the experience of the Gruppo Italiano Trapianti di Midollo. Blood

[25] Vesole DH, Zhang L, Flomenberg N, Greipp PR, Lazarus HM, Huff CA; ECOG Mye‐ loma and BMT Committees. A Phase II Trial of Autologous Stem Cell Transplanta‐ tion Followed by Mini-Allogeneic Stem Cell Transplantation for the Treatment of Multiple Myeloma: An Analysis of Eastern Cooperative Oncology Group ECOG E4A98 and E1A97. Biology of Blood and Marrow Transplantation 2009;15(1):83-91.

[26] Lokhorst HM, van der Holt B, Cornelissen JJ, Kersten MJ, van Oers M, Raymakers R, Minnema MC, Zweegman S, Janssen JJ, Zijlmans M, Bos G, Schaap N, Wittebol S, de Weerdt O, Ammerlaan R, Sonneveld P. Donor versus no-donor comparison of newly diagnosed myeloma patients included in the HOVON-50 multiple myeloma study.

[27] Garban F, Attal M, Michallet M, Hulin C, Bourhis JH, Yakoub-Agha I, Lamy T, Marit G, Maloisel F, Berthou C, Dib M, Caillot D, Deprijck B, Ketterer N, Harousseau JL, Sotto JJ, Moreau P. Prospective comparison of autologous stem cell transplantation followed by dose-reduced allograft (IFM99-03 trial) with tandem autologous stem cell transplantation (IFM99-04 trial) in high-risk de novo multiple myeloma. Blood

[28] Moreau P, Garban F, Attal M, Michallet M, Marit G, Hulin C, Benboubker L, Doyen C, Mohty M, Yakoub-Agha I, Leyvraz S, Casassus P, Avet-Loiseau H, Garderet L, Mathiot C, Harousseau JL; IFM Group. Long-term follow-up results of IFM99-03 and IFM99-04 trials comparing nonmyeloablative allotransplantation with autologous transplantation in high-risk de novo multiple myeloma. Blood 2008;112(9):3914-5.

[29] Bruno B, Rotta M, Patriarca F, Mordini N, Allione B, Carnevale-Schianca F, Giaccone L, Sorasio R, Omedè P, Baldi I, Bringhen S, Massaia M, Aglietta M, Levis A, Gallami‐ ni A, Fanin R, Palumbo A, Storb R, Ciccone G, Boccadoro M. A comparison of allog‐ rafting with autografting for newly diagnosed myeloma. New England Journal of

2012;88(6):497-503.

2009;113(14):3375-82.

Blood 2012;119(26):6219-25.

2006;107(9):3474-80.

Medicine 2007;356(11):1110-20.

2012.1.


non C, Blaise D. Comparable outcomes between unrelated and related donors after reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation in patients with high-risk multiple myeloma. European Journal of Haematology 2012;88(6):497-503.

[13] Storb R, Raff RF, Appelbaum FR, Graham TC, Schuening FG, Sale G, Pepe M. Com‐ parison of fractionated to single-dose total body irradiation in conditioning canine

[14] Storb R, Yu C, Wagner JL, Deeg HJ, Nash RA, Kiem HP, Leisenring W, Shulman H. Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given suble‐ thal total body irradiation before and pharmacological immunosuppression after

[15] Maloney DG, Molina AJ, Sahebi F, Stockerl-Goldstein KE, Sandmaier BM, Bensinger W, Storer B, Hegenbart U, Somlo G, Chauncey T, Bruno B, Appelbaum FR, Blume KG, Forman SJ, McSweeney P, Storb R. Allografting with nonmyeloablative condi‐ tioning following cytoreductive autografts for the treatment of patients with multiple

[16] Kröger N, Schwerdtfeger R, Kiehl M, Sayer HG, Renges H, Zabelina T, Fehse B, Tö‐ gel F, Wittkowsky G, Kuse R, Zander AR. Autologous stem cell transplantation fol‐ lowed by a dose-reduced allograft induces high complete remission rate in multiple

[17] Giralt S, Aleman A, Anagnostopoulos A, Weber D, Khouri I, Anderlini P, Molldrem J, Ueno NT, Donato M, Korbling M, Gajewski J, Alexanian R, Champlin R. Fludara‐ bine/melphalan conditioning for allogeneic transplantation in patients with multiple

[18] Crawley C, Szydlo R, Lalancette M, Bacigalupo A, Lange A, Brune M, Juliusson G, Nagler A, Gratwohl A, Passweg J, Komarnicki M, Vitek A, Mayer J, Zander A, Sierra J, Rambaldi A, Ringden O, Niederwieser D, Apperley JF; Chronic Leukemia Working Party of the EBMT. Outcomes of reduced-intensity transplantation for chronic mye‐ loid leukemia: an analysis of prognostic factors from the Chronic Leukemia Working

[19] Crawley C, Iacobelli S, Björkstrand B, Apperley JF, Niederwieser D, Gahrton G. Re‐ duced intensity conditioning for myeloma:lower nonrelapse mortality but higher re‐ lapse rates compared with myeloablative conditioning. Blood 2007;109(8):3588-94. [20] Rotta M, Storer BE, Sahebi F, Shizuru JA, Bruno B, Lange T, Agura ED, McSweeney PA, Pulsipher MA, Hari P, Maziarz RT, Chauncey TR, Appelbaum FR, Sorror ML, Bensinger W, Sandmaier BM, Storb RF, Maloney DG. Long-term outcome of patients with multiple myeloma after autologous hematopoietic cell transplantation and non‐

[21] Schimoni A,Hardan I,Ayuk E, Schilling G, Atanakovic D, ZellerW, Yerushalmi R, Zander A,Kroger N, Nagler A. Allogenic Hematopoietic Stem-Cell Transplantation With Reduced-Intensity Conditioning in Patients With Refractory and Recurrent

[22] El-Cheikh J, Crocchiolo R, Boher JM, Furst S, Stoppa AM, Ladaique P, Faucher C, Calmels B, Castagna L, Lemarie C, De Colella JM, Coso D, Bouabdallah R, Chaban‐

littermates for DLA-identical marrow grafts. Blood 1989; 74(3):1139-43.

marrow transplantation. Blood. 1997 Apr 15;89(8):3048-54.

myeloma. Bone Marrow Transplantation 2002;30(6):367-73.

myeloablative allografting. Blood. 2009;113(14):3383-91.

Multiple Myeloma. Cancer 2010;116(15):3621-30.

myeloma. Blood 2003; 102(9):3447-54.

174 Multiple Myeloma - A Quick Reflection on the Fast Progress

myeloma. Blood 2002; 100(3): 755-760.

Party of the EBMT. Blood;106(9):2969-76.


[30] Rosiñol L, Pérez-Simón JA, Sureda A, de la Rubia J, de Arriba F, Lahuerta JJ, Gonzá‐ lez JD, Díaz-Mediavilla J, Hernández B, García-Frade J, Carrera D, León A, Hernán‐ dez M, Abellán PF, Bergua JM, San Miguel J, Bladé J; Programa para el Estudio y la Terapéutica de las Hemopatías Malignas y Grupo Español de Mieloma (PETHEMA/ GEM). A prospective PETHEMA study of tandem autologous transplantation versus autograft followed by reduced-intensity conditioning allogeneic transplantation in newly diagnosed multiple myeloma. Blood 2008;112(9):3591-3.

[38] Peggs KS, Mackinnon S, Williams CD, D'Sa S, Thuraisundaram D, Kyriakou C, Morris EC, Hale G, Waldmann H, Linch DC, Goldstone AH, Yong K. Reduced-intensity trans‐ plantation with in vivo T-cell depletion and adjuvant dose escalating donor lymphocyte infusions for chemotherapy-sensitive myeloma: limited efficacy of graft-versus-tumor

Allogeneic Hematopoetic Cell Transplantation in Multiple Myeloma

http://dx.doi.org/10.5772/54762

177

[39] Teo SK. Properties of thalidomide and its analogues: implications for anticancer ther‐

[40] Mohty M,Attal M,Marit G,Bulobois CE,Garban F,Gratecos N,Rio B,Vernant JP,Sotto JJ, Cahn JY,Blaise D, Jouet JP,Facon T,Yakoub-Agha I. Thalidomide salvage therapy following allogeneic stem cell transplantation for multiple myeloma: a retrospective study from the Intergroupe Francophone du Myélome (IFM) and the Société Fran‐ çaise de Greffe de Moelle et Thérapie Cellulaire (SFGM-TC). Bone Marrow Trans‐

[41] Kröger N, Shimoni A, Zagrivnaja M, Ayuk F, Lioznov M, Schieder H, Renges H, Fehse B, Zabelina T, Nagler A, Zander AR.Low-dose thalidomide and donor lym‐ phocyte infusion as adoptive immunotherapy after allogeneic stem cell transplanta‐

[42] Cheikh J,Crocchiolo R,Furst S,Ladaique P,Castagna L,Faucher C,Granata A,Lemarie C,Calmel B,Stoppa AM,Coella JM Duran S,Chabannon C,Blaise D. Lenalidomide plus donor-lymphocytes infusion after allogeneic stem-cell transplantation with re‐ duced-intensity conditioning in patients with high-risk multiple myeloma. Experi‐

[43] Minnema MC, van der Veer MS, Aarts T, Emmelot M, Mutis T, Lokhorst HM. Lenali‐ domide alone or in combination with dexamethasone is highly effective in patients‐ with relapsed multiple myeloma following allogeneic stem cell transplantation and

increases the frequency of CD4(+)Foxp3(+) T cells. Leukemia 2009;23(3):605-7.

feasible: results of the HOVON 76 Trial. Blood 2011;118(9):2413-9.

[44] Sonneveld P, Lokhorst HM, Mutis T, Minnema MC. Lenalidomide maintenance after nonmyeloablative allogeneic stem cell transplantation in multiple myeloma is not

[45] Koreth J, Stevenson KE, Kim HT, Garcia M, Ho VT, Armand P, Cutler C, Ritz J, Antin JH, Soiffer RJ, Alyea EP 3rd. Bortezomib, tacrolimus, and methotrexate for prophy‐ laxis of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation from HLA-mismatched unrelated donors. Blood 2009;114(18):

[46] El-Cheikh J, Michallet M, Nagler A, de Lavallade H, Nicolini FE, Shimoni A, Faucher C, Sobh M, Revesz D, Hardan I, Fürst S, Blaise D, Mohty M. High response rate and improved graft-versus-host disease following bortezomib as salvage therapy after re‐ duced intensity conditioning allogeneic stem cell transplantation for multiple myelo‐

tion in patients with multiple myeloma. Blood 2004;104(10):3361-3.

activity. Biology of Blood and Marrow Transplantation 2003;9(4):257-65.

apy. The AAPS Journal 2005 22;7(1):E14-9.

plantation 2005;35(2):165-9.

mental Hematology 2012;40(7):521-7.

ma. Haematologica 2008; 93(3):455-8.

3956-9.


[38] Peggs KS, Mackinnon S, Williams CD, D'Sa S, Thuraisundaram D, Kyriakou C, Morris EC, Hale G, Waldmann H, Linch DC, Goldstone AH, Yong K. Reduced-intensity trans‐ plantation with in vivo T-cell depletion and adjuvant dose escalating donor lymphocyte infusions for chemotherapy-sensitive myeloma: limited efficacy of graft-versus-tumor activity. Biology of Blood and Marrow Transplantation 2003;9(4):257-65.

[30] Rosiñol L, Pérez-Simón JA, Sureda A, de la Rubia J, de Arriba F, Lahuerta JJ, Gonzá‐ lez JD, Díaz-Mediavilla J, Hernández B, García-Frade J, Carrera D, León A, Hernán‐ dez M, Abellán PF, Bergua JM, San Miguel J, Bladé J; Programa para el Estudio y la Terapéutica de las Hemopatías Malignas y Grupo Español de Mieloma (PETHEMA/ GEM). A prospective PETHEMA study of tandem autologous transplantation versus autograft followed by reduced-intensity conditioning allogeneic transplantation in

[31] Krishnan A, Pasquini MC, Logan B, Stadtmauer EA, Vesole DH, Alyea E 3rd, Antin JH, Comenzo R, Goodman S, Hari P, Laport G, Qazilbash MH, Rowley S, Sahebi F, Somlo G, Vogl DT, Weisdorf D, Ewell M, Wu J, Geller NL, Horowitz MM, Giralt S, Maloney DG; Blood Marrow Transplant Clinical Trials Network (BMT CTN). Autol‐ ogous haemopoietic stem-cell transplantation followed by allogeneic or autologous haemopoietic stem-cell transplantation in patients with multiple myeloma (BMT CTN 0102): a phase 3 biological assignment trial. Lancet Oncology 2011; 12(13):

[32] Giaccone L, Storer B, Patriarca F, Rotta M, Sorasio R, Allione B, Carnevale-Schianca F, Festuccia M, Brunello L, Omedè P, Bringhen S, Aglietta M, Levis A, Mordini N, Gallamini A, Fanin R, Massaia M, Palumbo A, Ciccone G, Storb R, Gooley TA, Bocca‐ doro M, Bruno B. Long-term follow-up of a comparison of nonmyeloablative allog‐ rafting with autografting for newly diagnosed myeloma. Blood 2011;117(24):6721-7.

[33] Roddie C&Peggs KS. Donor lymphocyte infusion following allogeneic hematopoietic stem cell transplantation. Expert Opinion on Biological Therapy 2011; 11(4): 473-487.

[34] Beitinjaneh A, Saliba R , Bashir Q , Shah N , Parmar S , Hosing C , Popat U, Anderlini P, Dinh Y , Qureshi S , Rondon G , Champlin R , Giralt S, Qazilbash M. Durable re‐ sponses after donor lymphocyte infusion for patients with residual multiple myelo‐ ma following non-myeloablative allogeneic stem cell transplant. Leukemia &

[35] van de Donk NW, Kröger N, Hegenbart U, Corradini P, San Miguel JF, Goldschmidt H, Perez-Simon JA, Zijlmans M, Raymakers RA, Montefusco V, Ayuk FA, van Oers MH, Nagler A, Verdonck LF, Lokhorst HM. Prognostic factors for donor lymphocyte infusions following non-myeloablative allogeneic stem cell transplantation in multi‐

[36] Dazzi F, Szydlo RM, Craddock C, Cross NC, Kaeda J, Chase A, Olavarria E, van Rhee F, Kanfer E, Apperley JF, Goldman JM. Comparison of single-dose and escalatingdose regimens of donor lymphocyte infusion for relapse after allografting for chronic

[37] Peggs KS, Thomson K, Hart DP, Geary J, Morris EC, Yong K, Goldstone AH, Linch DC, Mackinnon S. Dose-escalated donor lymphocyte infusions following reduced in‐ tensity transplantation:toxicity, chimerism, and disease responses. Blood 2004;103(4):

ple myeloma. Bone Marrow Transplantation 2006;37(12):1135-41.

newly diagnosed multiple myeloma. Blood 2008;112(9):3591-3.

1195-203.

176 Multiple Myeloma - A Quick Reflection on the Fast Progress

1548-56.

Lymphoma 2012; 53(8): 1525-1529

myeloid leukemia. Blood 2000;95(1):67-71


**Chapter 9**

**Cellular Immunotherapy Using Dendritic Cells in**

Je-Jung Lee, Youn-Kyung Lee, Hyun Ju Lee,

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/54100

**1. Introduction**

Sung-Hoon Jung and Thanh-Nhan Nguyen-Pham

with increased potency, such as dendritic cells (DCs), in MM [6].

**Multiple Myeloma: New Concept to Enhance Efficacy**

Multiple myeloma (MM) is a clonal B-cell malignancy that is currently incurable with con‐ ventional chemotherapy, even if high-dose chemotherapy with autologous or allogeneic hematopoietic stem cell transplantation (HSCT) and the development of novel molecular target agents have resulted in a marked improvement in overall survival [1, 2]. Allogeneic HSCT, which induces a clinically significant immune-mediated allogeneic graft-versusmyeloma (GVM) effect, has provided the framework for the development of immunothera‐ peutic strategies [3, 4]. To prolong the survival of patients with MM, who are undergoing allogeneic HSCT, a donor lymphocyte infusion can be used successfully as a salvage therapy, which is based on the GVM effect in some cases of MM that relapse after allogeneic HSCT [5, 6]. A clinically significant immune-mediated GVM effect provides the framework for the development of immune-based therapeutic options that use antigen-presenting cells (APCs)

DCs are the most potent APCs for initiating cellular immune responses through the stimulation of naive T cells. Because of their ability to stimulate T cells, DCs act as links between innate immunity and adaptive immunity in antitumor immune responses [7]. DCs orchestrate a variety of immune responses by stimulating the differentiation of naïve CD4+ T cells into helper T effectors such as Th1, Th2 or Th17 type [8, 9]. Cytokines secreted by DCs at the time of initial T cell stimulation play an important role in the subsequent differentiation of effector T cells. Th1 cells, through interferon-gamma (IFN-γ) production, regulate antigen presentation and immunity against intracellular pathogens [8]. DC-based vaccines have become the most attractive tools for cancer immunotherapy and have been used in more than 20 malignancies; most commonly melanoma, renal cell carcinoma, prostate cancer and colorectal carcinoma

> © 2013 Lee et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

© 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

distribution, and reproduction in any medium, provided the original work is properly cited.

and reproduction in any medium, provided the original work is properly cited.
