**1. Introduction**

nosed Multiple Myeloma: Results of the Randomized Phase III HOVON-65/ GMMG-

[90] Waage, A, Gimsing, P, Fayers, P, Abildgaard, N, Ahlberg, L, Björkstrand, B, Carlson, K, Dahl, I. M, Forsberg, K, Gulbrandsen, N, Haukås, E, Hjertner, O, Hjorth, M, Karls‐ son, T, Knudsen, L. M, Nielsen, J. L, Linder, O, Mellqvist, U. H, Nesthus, I, Rolke, J, Strandberg, M, Sørbø, J. H, & Wisløff, F. Juliusson G & Turesson I; Nordic Myeloma Study Group. ((2010). Melphalan and prednisone plus thalidomide or placebo in eld‐

[91] Wang, M, Giralt, S, & Delasalle, K. Handy B & Alexanian R. ((2007). Bortezomib in combination with thalidomide-dexamethasone for previously untreated multiple

[92] Wijermans, P, Schaafsma, M, Termorshuizen, F, Ammerlaan, R, Wittebol, S, Sinnige, H, & Zweegman, S. van Marwijk Kooy M, van der Griend R, Lokhorst H & Sonne‐ veld P; Dutch-Belgium Cooperative Group HOVON. ((2010). Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: the HOVON 49 Study. J Clin Oncol.,, 28(19),

[93] Zavrski, I, Krebbel, H, Wildemann, B, Heider, U, & Kaiser, M. Possinger K & Sezer O. ((2005). Proteasome inhibitors abrogate osteoclast differentiation and osteoclast func‐

[94] Zonder, J. A, Crowley, J, Hussein, M. A, & Bolejack, V. Moore DF Sr, Whittenberger BF,Abidi MH, Durie BG & Barlogie B. ((2010). Lenalidomide and high-dose dexame‐ thasone compared with dexamethasone as initial therapy for multiple myeloma: a randomized Southwest Oncology Group trial (S0232). Blood,, 116(26), 5838-41.

HD4 Trial. J Clin Oncol. 2012 Aug 20;, 30(24), 2946-55.

erly patients with multiple myeloma. Blood, , 116(9), 1405-12.

tion. Biochem Biophys Res Commun.,, 333(1), 200-5.

myeloma. Hematology, , 12(3), 235-9.

164 Multiple Myeloma - A Quick Reflection on the Fast Progress

3160-6.

The improvement in the survival of multiple myeloma patients has been attributed to autol‐ ogous stem cell transplantation (ASCT) after induction with novel agents [1,2]. Nevertheless, ASCT has not been considered to have a curative potential, maintenance treatment seems to be one of the solutions to decrease the high relapse rates after ASCT [3]. Therefore, allogeneic stem cell transplantation (Allo-SCT) is a potentially curative approach; the role of allo-SCT is still an ongoing debate due to high transplant-related mortality and lack of large prospective randomized studies in the newly diagnosed patients. A retrospective case-matched analysis was performed comparing myeloma patients treated with Allo-SCT with an equal number of patients who received ASCT by European Group for Blood and Bone Marrow Transplant (EBMT) [4]. Overall survival (OS) for the whole patient group was significantly better for the ASCT group compared with those for allo-SCT (Median survival: 34 months vs 18 months, p=. 001). Therefore, we should answer the question of which patients with multiple myeloma have to be directed to allo-SCT modality.

Prognosis of myeloma patients have been found strongly associated with their cytogenetic features and gene expression profiling [5,6]. Increasing data on the poor prognosis of the 'high risk myeloma patients' changed the trends towards to the allo-transplantation in the earlier period. The Société Française de Greffe de Moelle et de Thérapie Cellulaire evaluated the role of allo-SCT for cytogenetically high-risk myeloma patients in a retrospective multicenter analysis [7]. They showed that allo-SCT could potentially be of benefit to the patients carrying cytogenetic abnormalities such as deletion (del) of (13q), t(4;14), t(14;16) and del(17p) compared to those without the same abnormalities.

© 2013 Topcuoglu 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, distribution, and reproduction in any medium, provided the original work is properly cited. © 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, and reproduction in any medium, provided the original work is properly cited.

In this chapter, we discussed the role of allo-HCT in MM patients, and also we tried to clarify the issues as the intensity of conditioning regimen, the timing of the transplantation, and posttransplantation approaches in relapse or refractory patients.

associated with an adverse effect on non-relapse mortality, PFS and OS. T cell depletion with

Long-term follow-up data was reported in a RIC allo-graft for salvage setting of relapse and/or refractory myeloma patients (Table 1). These data showed that long term remission can be feasible for a subset of myeloma patients with allo-RIC performed in the salvage setting [21]. Seattle group reported the long term comparison data of RIC and MAC regimens [23]. Although the intensity of regimens changed time dependently, RIC regimens resulted in

significantly lower overall mortality, improved PFS and much lower TRM.

**Regimens GvHD prophy‐**

52 52 52 0 TBI (2 Gy) CSP-MMF 38% 46% 2%

22 51 9 9 Fludarabine, Melphalan TAC-MTX 73% 33% 19%

Busulfan or cyclophospha‐ mide or TBI ± ATG or Alemtuzumab

**laxis**

TAC-MMF

96 54 54 0 TBI (2 Gy) CSP-MMF 38% 50% 11% 51% 53%

**Abbreviations:** ASCT: Autologous Stem Cell Transplantation; GvHD: Graft versus Host Disease; TRM: Transplant-Related Mortality; NRM: Non-Relapse Mortality; CR: Complete Remission; PFS. Progression-Free Survival; OS: Overall Survival; TBI: Total Body Irradiation; ATG: Anti-Thymocyte Globulin; CSP: Cyclosporine; MMF: Mycofenolate Mofetif; TAC: Tacrolimus;

MTX: Methotrexate; MP: Methyl-Prednisolone; URD: Unrelated Donor; MRD: Matched Related Donor

**Acute GvHDG rade II-IV**

CSP-MTX 38% 40% 11%

CSP ± MTX 31 % 50% 11%

CSP±MMF 47% 24% 0%

CSP-MP 17% 57% 8.7%

**Chronic GvHD**

**TRM/ NRM**

Allogeneic Hematopoetic Cell Transplantation in Multiple Myeloma

(100 d)

(100 d)

(100 d) 40% (1y)

22% (1y)

11 (1y) 18 (5y)

CSP-MTX 51% 63% 26 (5y) 58% 26% (7y) 34% (7y)

(100 d)

(100 d)

42% 74% 1% (100 d)

**CR PFS OS**

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

167

73% 56% (2y) 74% (2y)

25% 21% (3y) 41% (3y)

69% (2 y)

30% (2y)

64% (5y)

59% (URD) 66% (MRD)

65% (5y)

78% (2y)

57 % 48 % (2 y)

32% 19% (2 y)

65% 36% (5y)

44% (URD) 35% (MRD) 42% (URD) 44% (MRD)

(5 y)

30% 62% (2 y)

alemtuzumab or other(s) led to high relapse rates as well.

**Reference Pa‐**

Maloney [15]

Kröger [16]

Giralt [17]

Crawley [18]

Rotta [20]

Shimoni [21]

Cheikh [22]

Bruno [24]

Vesole [25]

**tients (n)**

**Me‐ dian age (y)** **Prior ASCT (n)**

**URD (n)**

17 51 17 8 Fludarabine, Melphalan,

229 52 169 37 Fludarabine, Melphalan or

50 53 47 23 Fludarabine, Melphalan

40 56 11 17 Fludarabine, Busulfan,

23 23 0 Fludarabine-Cyclop-hos‐

ATG

102 50 102 0 TBI (2Gy) ± Fludarabine CSP-MMF;

±ATG

ATG; Fludarabine,TBI

phamide

**Table 1.** Reduced intensity allogeneic transplantation alone or following autogous-SCT
