To define consensus statement regarding allogeneic stem-cell transplantation (Allo-SCT) as a treatment option for multiple myeloma (MM) on behalf of International Myeloma Working Group.
In this review, results from prospective and retrospective studies of Allo-SCT in MM are summarized.
Although the introduction of reduced-intensity conditioning (RIC) has lowered the high treatment-related mortality associated with myeloablative conditioning, convincing evidence is lacking that Allo-RIC improves the survival compared with autologous stem-cell transplantation.
New strategies are necessary to make Allo-SCT safer and more effective for patients with MM. Until this is achieved, Allo-RIC in myeloma should only be recommended in the context of clinical trials.
"Single or double autologous stem cell transplantation (ASCT) remains the milestone for a frontline approach in MM patients eligible for high-dose therapy, and the second ASCT represents a safe option for MM patients who were firstly treated with single ASCT.13–16 Although data support the use of a late second ASCT in patients with relapsed/progressive MM,17 researchers of the European Group for Blood and Marrow Transplantation found that outcomes were better when the second ASCT was performed before relapse, within 6–12 months from the first ASCT.18 "
[Show abstract][Hide abstract] ABSTRACT: Multiple myeloma (MM) is a neoplastic disorder. It results from proliferation of clonal plasma cells in bone marrow with production of monoclonal proteins, which are detectable in serum or urine. MM is clinically characterized by destructive bone lesions, anemia, hypercalcemia and renal insufficiency. Its prognosis is severe, with a median survival after diagnosis of approximately 3 years due to frequent relapses. Treatments for patients with relapsed/refractory MM include hematopoietic cell transplantation, a rechallenge using a previous chemotherapy regimen or a trial of a new regimen. The introduction of new drugs such as thalidomide, lenalidomide and bortezomib has markedly improved MM outcomes. When relapse occurs, the clinician's challenge is to select the optimal treatment for each patient while balancing efficacy and toxicity. Patients with indolent relapse can be first treated with a 2-drug or a 3-drug combination. Patients with more aggressive relapse often require therapy with a combination of multiple active agents. Autologous stem cell transplantation should be considered as salvage therapy at first relapse for patients who have cryopreserved stem cells early in the disease course. The aim of this review is to provide an overview on the pharmacological and molecular action of treatments used for patients with relapsed/refractory multiple myeloma.
Clinical Medicine Insights: Oncology 08/2013; 7:209-219. DOI:10.4137/CMO.S8014
"With a highly comparable cPFS and relapse rate in the MM group our data further suggest that T-cell depletion (Kroger et al, 2002; Peggs et al, 2003) is not appropriate in this disease (Blade et al, 2010) where often the onset of GVHD itself was associated with achievement of CR. The introduction of novel agents in this setting was also remarkably effective at inducing CR through their ability to potentiate a graft-versus-myeloma effect (Lokhorst et al, 2010). Whether a meaningful survival plateau exists remains controversial (Blade et al, 2010). "
[Show abstract][Hide abstract] ABSTRACT: The relative merits of reduced-intensity allogeneic stem cell transplantation (RISCT) for high-risk indolent lymphoid malignancies are emerging, although the preferred conditioning regimen to manage the risks of graft-versus-host disease (GVHD) is not clearly defined. Here we report the outcome of 73 patients with lymphoid malignancies who received RISCT with a fludarabine/cyclophosphosphamide conditioning regimen and a median follow-up of 3 years. Median age was 54 years. Forty-eight per cent of patients had previously undergone autologous stem cell transplantation with a median of three prior therapies. Non-relapse mortality at 3 years was 19% but only 5% for patients with multiple myeloma (MM). Three-year overall survival and current progression-free survival was 67% and 63% respectively. Grade 2-4 acute GVHD occurred in 14% of patients while 49% had chronic GVHD requiring systemic immunosuppression. The preparatory regimen in this study has the advantage of reduced acute GVHD and low mortality, notably in patients with MM. In addition, this strategy provides long-term disease control in a significant proportion of patients with particular benefit in those with high-risk follicular lymphoma.
British Journal of Haematology 03/2012; 157(5):580-5. DOI:10.1111/j.1365-2141.2012.09106.x · 4.71 Impact Factor
"The transfer of a healthy, donor-derived immune system, which is not tolerant to the malignant plasma cell clone, is currently the only potentially curative approach for MM patients . The immunological graft-versus-myeloma effect (GvM) is powerful , but it comes along with a significant risk of developing a graft-versus-host reaction (GvHD), which represents a potentially deadly threat often requiring strong prophylactic (and sometimes therapeutic) immunosuppression  . "
[Show abstract][Hide abstract] ABSTRACT: Multiple myeloma (MM) and its therapies may induce a severely compromised humoral immunity. We have performed a longitudinal analysis of IgG-antibody responses against influenza virus (FLU) and tetanus toxoid (TT) as surrogate markers for the B cell-mediated immunity in MM patients.
1094 serum samples of 190 MM patients and samples from 100 healthy donors were analyzed by ELISA for FLU- and TT-specific antibodies.
MM patients evidenced lower levels of FLU- and TT-specific antibodies than healthy controls (P < 0.001). Immunoreactivity decreased with progressing disease and worsening clinical status. Levels of FLU- and TT-specific antibodies increased shortly (0-6 months) after alloSCT (P < 0.001), a time-period during which intravenous immunoglobulin (IVIG) is routinely applied. Thereafter, antibody concentrations declined and remained suppressed for 3 years in the case of FLU-specific and for more than 5 years in the case of TT-specific antibodies.
We found that MM is associated with a profound disease- and therapy-related immunosuppression, which is compensated for a few months after alloSCT, most likely by application of IVIG. This and the differences regarding the recovery of anti-FLU and anti-TT antibody titers during the following years need to be taken into account for optimizing IVIG application and immunization after alloSCT.
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