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Chapter 86 Plasma Cell Neoplasms 1411

100 100
90 Autologous transplant 90
Probability of survival (%) 60 HLA-matched sibling, 60
80
80
70
70
(n = 22,254)
50
50
40
40
allogeneic (n = 878)
30
30
20
10
10 Unrelated, allogeneic (n = 143) 20
P <.0001
0 0
0 1 2 3 4 5 6
Years
Fig. 86.16 CENTER FOR INTERNATIONAL BLOOD AND MARROW TRANSPLANT RESEARCH
ANALYSIS OF MYELOMA TRANSPLANTS. Among 23,197 patients who received an autotransplant for
multiple myeloma (MM) between 2000 and 2009, the 3-year probability of survival was 70% ± 1%. Allogeneic
stem cell transplant for MM is reserved for patients with high-risk disease, and the majority of transplants
were performed after an autologous hematopoietic cell transplant (HCT) with reduced-intensity or nonmy-
eloablative conditioning regimens. Among the 979 patients who received an allogeneic HCT between 2000
and 2009, the 3-year probabilities of survival were 51% ± 2% for the 827 recipients of human leukocyte
antigen (HLA)–matched sibling donor grafts and 26% ± 2% for the 470 recipients of unrelated donor grafts.
(From Pasquini MD, Wang Z: CIBMTR summary slides, 2010. Adapted from http://www.cibmtr.org/.)

TABLE Studies of Myeloablative and Reduced-Intensity Allogeneic Stem Cell Transplant for Newly Diagnosed Myeloma
86.21
Authors Number of Patients TRM (%) CR (%) OS (Actuarial, Mo) EFS (Actuarial, Mo)
Gahrton et al 162 41 44 28% at 84 45% at 60
Bensinger et al 80 44 36 20% at 54 24% at 54
Alyea et al 61 a 5 28 40% at 36 20% at 38
Lee et al 45 36 64 3-Yr EFS 13% Median 14 mo
Kroger et al 17 18 73 2-Yr PFS 55% 2-Yr OS 74%
Maloney et al 54 7 57 2-Yr DFS 56% 18-Mo OS 78%
Giralt et al 13 38 54 NA NA
Bruno et al 58 7 55 Median 43 mo Median >46 mo
a T cell depleted.
CR, Complete remission; DFS, disease-free survival; EFS, event-free survival; NA, not available; OS, overall survival; PFS, progression-free survival; TRM, treatment-related
mortality.

trial in the United States, there was no difference in outcome between Maintenance therapy is administered when the disease is in remission,
auto-/mini-allotransplant and tandem autologous transplant. In at either undetectable or low levels. The purpose of maintenance
order to increase the effect of donor lymphocyte infusions against the therapy is to prolong remission duration and thereby life expectancy.
tumor cells, vaccination strategies are currently being pursued. Maintenance therapy improves the quality of response, supporting
the notion that an additional antitumor response during the mainte-
nance phase will be beneficial. Immunomodulatory molecules are
Syngeneic Transplantation well suited for maintenance therapy because they can be administered
orally at low doses for a prolonged period. 36
Results of syngeneic transplant are superior to autologous transplant The first two randomized trials published on thalidomide main-
and allogeneic stem cell transplant. The results are better than autolo- tenance after autotransplant showed an improvement in PFS and OS.
gous transplant because of lower relapse rates with twin transplant. In the Total Therapy II trial, researchers randomized patients to
This may be related to the lack of tumor cells in the graft and/or a thalidomide induction and a maintenance arm versus a no thalido-
graft-versus-myeloma effect without GVHD. The results of syngeneic mide arm; this study showed improvement in PFS and a delayed
transplant are also superior to allogeneic stem cell transplant on the improvement in OS after 8 years of follow-up. In the HOVON 50
basis of low transplant-related mortality and the absence of clinical trial, patients were similarly randomized to thalidomide induction
GVHD. These conclusions were based on reports published by two followed by thalidomide maintenance after transplant or VAD induc-
large transplant registries (CIBMTR and EBMTR). tion followed by interferon maintenance. This trial also showed
improvement in PFS and OS for patients in the thalidomide arm. A
meta-analysis of published results to date indicated a significant
Maintenance reduction of the risk for progression with thalidomide maintenance
therapy. Outcome did not differ between trials that used thalidomide
Maintenance therapy is the use of ongoing low-intensity chemo- during the maintenance phase only and those that used thalidomide
therapy to eliminate or suppress MRD over a prolonged period. for both induction and maintenance treatment. The MRC IX trial