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					   Stem Cell Transplantation in Multiple
                        Myeloma
                          Patients Day
                      11.9.2010, Bukarest
                       Nicolaus Kröger
Dept. of Stem Cell Transplantation, University Hospital Hamburg
                     Hamburg, Germany
Main goals in cancer treatment



   • Complete remission

   • Cure

   • Prolonged survival

   • Quality of life
            Standard-Chemotherapy

             Melphalan / Prednison


   Response:       ca. 50 - 60% (CR < 5%)

   Survival:       30 - 36 Months (Median)

   Cure:           no
New development in Multiple Myeloma




1. Transplant candidate
  (mainly younger patients < 65 years)

2. Non-transplant candidate
  (mainly elder patients > 65 years)
High-dose Chemotherapy with Stem cell
           Transplantation



                 Stemcell


    autologous                 allogeneic
                      HLA-identical sibling
                      matched unrelated donor

   EBMT 2007:n=5494             EBMT 2007: n=469
                      Hämatopoieses
        Bone Marrow                 Megakaryocyt      Peripheral blood

                Multipotente
                                                      Platelets
Hematopoietic    Stemcell
  stemcell                           Erythroblast
                                                      Erythrocyts
                               Myeloblast

                                                      Granulocyts
                Hämatopoietic
                  Stemcell             Myeloid
                                                      Monocyts
                                    Progenitorcells



  Stemcell
                                                      T-Lymphocyts
 (neuronal,      Lymphoide             prä T-Cell
mesenchymal)      Stemcell
                                                      B-Lymphocyts
                                       prä B-Cell
          Development of plasma-cell


                           µ




Stem-        Pro B-   Pre B-          B-        Plasma-
 c
 cell         cell     cell          cell         cell


   Bone marrow           Lymphnode          Bone Marrow
                      Hämatopoieses
        Bone Marrow                 Megakaryocyt      Peripheral blood

                Multipotente
                                                      Platelets
Hematopoietic    Stemcell
  stemcell                           Erythroblast
                                                      Erythrocyts
                               Myeloblast

                                                      Granulocyts
                Hämatopoietic
                  Stemcell             Myeloid
                                                      Monocyts
                                    Progenitorcells



  Stemcell
                                                      T-Lymphocyts
 (neuronal,      Lymphoide             prä T-Cell
mesenchymal)      Stemcell
                                                      B-Lymphocyts
                                       prä B-Cell
                                  Plasmacell
   Principal of high-dose chemotherapy



         HD-Chemo-
          therapy                ca. 30
                                 Days

                                ca. 10-14
                                  Days
CD34+         Cryo-       Thawed and
 cells     conservation     infused
                        High-dose therapy in Multiple Myeloma

                                        IFM901                                                                              MRC72
                       100                                                                     100




                                                                        Overall survival (%)
Overall survival (%)




                       75                       Transplant                                     75
                                                                                                                                     Transplant


                       50                                                                      50
                                 Conventional
                                                             p = 0.03                                                 Conventional         p = 0.04

                                                                                               25
                       25


                                                                                                    0
                             0    15      30         45          60                                     0            20     40        60          80

                                 Treatment (months)                                                                  Treatment (months)

                                                                                                            1Attal
                                                                                                            M, et al. N Engl J Med. 1996;335:91.
                                                                                                2   Child JA, et al. N Engl J Med. 2003;348:1875.
Impact of CR + VGPR on outcome after
           autologous SCT




   Attal NEJM 96         Haroussesau ASH 2006
Improvement of stem cell transplantation


    Including novel agents
    (thalidomide, bortezomib, lenalidomide)
    before (as induction) or after
    (as maintenance or consolidation)
    stem cell transplantation
         Maintenance therapy with thalidomide
                     after ASCT
                                           Maintenance vs no maintenance
                   n     Initial dose     CR         EFS or PFS       OS
                              mg          %              %

Barlogie                                             5 year EFS
                   668       400        62 vs 43                       +
et al.                                                56 vs 44


Attal                                                3-year EFS    4 year OS
                   597       400        67 vs 55*
et al.                                                52 vs 36      87 vs 77


Spencer                                              3 year PFS    3-year OS
                   243       200        63 vs 40
et al.                                                42 vs 23      86 vs 75


Lokhorst                                              med PFS       med. OS
                   556       50         31 vs 23
et al.                                                34 vs 25    73 vs 60 (ns)

*CR + VGPR rates
     Remission rate of novel agents in
       relapsed / refractory patients


              single agent    + Dex     + chemotherapy


Thalidomide      29%         35 – 55%      55 – 76%


Lenalidomide     25%           60%           60%


Bortezomib       43%            ---        50 – 76%
     Myeloma treatment < 65 y

< 2007
VAD
(4 – 6 Cycles)

1. HDT

2. HDT
(?)
     Myeloma treatment <65 y

< 2007              2008
VAD                 novel agents
(4 – 6 Cycles)      bortezomib
                    lenalidomide       CR 
1. HDT              thalidomide

                    1. HDT
2. HDT
(?)                 2. HDT
                    auto or allo RIC

                    Maintenance
                    (novel agents)

				
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