**5. Conclusion**

availability of HLA-identical donor. There was a higher increase in CR rate (40% vs 11%, p=. 001) and a trend toward a longer PFS (p=.08) in favor of tandem auto-allo transplantation. In contrast, TRM was higher in the tandem auto-allo transplantation (16% vs 5%, p=.07), EFS and

The Blood and Marrow Transplant Clinical Trials Network reported a multicenter phase III trial (BMT CTN 0102) in which patients were biologically assigned based on the availability of a matched related donor to either tandem ASCT using melphalan 200sqm or tandem autoalloHCT using melphalan 200 sqm followed by alloHCT with 2 Gy TBI [31]. Among the 710 patients enrolled between 2003 and 2007 from 37 US centers, 625 patients had standard risk. Patients assigned to receive an ASCT followed by an allo-SCT or tandem ASCT on the basis of the availability of an HLA-matched sibling donor. The study showed no difference of

Recently, the long-term results of a trial in which treatment of newly diagnosed myeloma patients (n=245) was based on the presence or absence of HLA-identical donor was reported from Italy [32]. Patients with HLA-identical siblings were offered by a standard autograft with high-dose melphalan (200sqm) followed by an allograft with NMA TBI (2 Gy) (n=82), while patients without HLA-identical siblings were assigned to double ASCT after intermediatedose (100 sqm) or high-dose (140-200 sqm) melphalan (n=80). At a median follow-up of 7.1 year, both OS and EFS were significantly longer in patients with HLA-identical siblings than those without, and median OS and EFS remained significantly longer in the patients trans‐ planted with tandem auto-allo than those patients treated double ASCT. This comparative study showed that allograft conferred a long-term survival and disease-free survival advant‐

High rate of CR after allo-SCT was reported in above studies. But relapse still seems to be a remaining problem. The importance of molecular remission on long-term disease control has been mentioned in the studies of allogeneic transplantation with MAC or RIC regimes. Therefore, post-transplant strategies for preventing and treatment of relapse/refractory disease are of clinical importance. The role of adaptive immunotherapy, donor lymphocyte infusion

Donor lymphocyte infusion can enhance GvM and also induce graft versus host disease (GvHD) rates [33,34] Van de Donk, et al evaluated DLIs given in eight European transplan‐ tation centers for relapsed (n=48) or persistent (n=15) myeloma following NMA allo-SCT [35]. Overall response was 38%, acute GvHD was 38% and chronic GvHD was 42%. The development of GvHD and response to DLI seems to be associated with GvM effect, and durable remissions are restricted to a minority of patients who achieve CR in this retrospec‐ tive evaluation. Escalating doses of DLI were found to have lower GvHD risk and better

median estimated PFS and OS in comparison of double auto with tandem auto-allo.

OS was not significantly different between 2nd ASCT and allo-RIC.

170 Multiple Myeloma - A Quick Reflection on the Fast Progress

age over standard autografting.

survival rates [36-38].

**4. Post-transplant approaches**

(DLI), and novel agents has been assessed in several studies.

The role and timing of allo SCT still cannot be defined clearly. Due to high TRM rates, myeloablative conditioning in allo-SCT has shifted to reduced intensity conditioning. The studies can be summarized as: (1) -early-day 100 TRM as low as 0 -20%, (2) Acute grade II-IV GvHD and chronic GvHD rates as 30 to 70%, (3) chemosensitivity prior to the transplantation as main factors of survival after transplantation (4) negative PFS effects of in vitro T cell depletion with Alemtuzumab or other(s).

Most of the studies were performed in the relapsed/refractory setting and currently there is no strong data to support allo-RIC as part of a frontline therapy. Reduction of tumor burden by high dose therapy with autologous stem cell rescue has found to have impacts on the transplant outcome and these results brought the comparative studies of auto/auto vs auto/ allo transplantation. There are contradictory results in this era and lack of strong evidence to support one to the other procedure.

Relapse after allo RIC transplantation is still a remaining problem to be solved. Introduction of novel agents such as bortezomib, thalidomide, and lenalidomide with/without DLI(s) can provide solutions to this problem.

In conclusion, allo-SCT has been recognized as a potential therapeutic modality in MM, especially since the introduction of RIC regimens and the use of a tandem auto-allo transplants has shown promise by reducing the TRM and inducing high CR rates. Nevertheless, long-term control of the disease remains a key issue, even in patients treated first by RIC allo-SCT. The role of allo-SCT should be re-evaluated when taking into consideration of promising effects of novel agents in myeloma treatment in randomized clinical trials.
