High-Dose Treatment With Autologous Stem Cell Transplantation in Multiple Myeloma: Past, Present, and Future
Section snippets
Prognostic Factors and Risk Factors
The EBMT myeloma registry has performed several analyses on factors of importance for the outcome after ASCT. In the most recent analysis of 4,322 patients transplanted from 1986 through 2000, favorable prognostic factors were lower age, response to chemotherapy before transplantation, only one line of primary induction treatment, Durie and Salmon stage I or II, and a low β2-microglobulin value at diagnosis.3 However, despite the statistical significance, the actual difference in survival
ASCT Versus Standard Chemotherapy
Since the early 1990s, several studies have compared first-line treatment including ASCT versus standard combination chemotherapy (Table 1). Most trials have comprised patients of a younger age category, essentially up to the age of 65 years. The first randomized study to demonstrate the superiority of ASCT was the French IFM90 study on 200 patients, published in 1996: median OS and event-free survival (EFS) were 57 and 44 months, respectively, for patients who underwent ASCT, compared with 44
Tandem Transplants
The idea of further dose intensification by sequential cycles of high-dose treatment with ASCT emerged in the late 1980s, and its feasibility was demonstrated.30 Double or tandem autotransplant programs as part of front-line therapy were then pursued during the 1990s in different centers,31, 32 in particular the “Total Therapy” program at the University of Little Rock, AR. In a retrospective case control study of 116 matched pairs, “Total Therapy” was superior to standard chemotherapy.25 Single
ASCT in Elderly Patients
The initial study and most of the randomized studies on ASCT have consisted of myeloma patients in a younger age category, mainly up to the age of 60 to 65 years. The exception is the Italian study, which enrolled patients between 50 and 70 years.24 The younger patient group is a minority within the myeloma patient community, since only about 15% of patients are under the age of 60.38 The benefit of ASCT to older patients has been questioned: the treatment is less well tolerated by more elderly
Graft Purging in Multiple Myeloma
There is no doubt that autologous hematopoietic stem cell grafts from patients with multiple myeloma are always more or less contaminated with clonal myeloma cells in various steps of maturation,44, 45 and this forms the theoretical basis for graft purging to avoid or minimize the reinfusion of clonal malignant cells in the patient. The purging technique most widely used in clinical practice has been immunological separation of CD34-positive hematopoietic progenitor cells, which can reduce the
High-Dose Treatment Protocols
During recent years, melphalan at a dose of 200 mg/m2 has been considered to be the standard high-dose preparative regimen before ASCT in multiple myeloma.22 In the 1980s and early 1990s, combinations with melphalan, usually at a dose of 140 mg/m2, and total body irradiation (TBI) were frequently used, probably because of adoption from allogeneic transplant preparative protocols, and the fact that multiple myeloma is a radiosensitive disease. However, a retrospective EBMT registry study
Maintenance and Consolidation Treatment
Since HDT with ASCT does not cure multiple myeloma, and the disease in the vast majority of patients will progress with time, one obvious idea has been to augment the effect by some type of post-transplant maintenance or consolidation treatment, in order to prolong the duration of response. Alpha-interferon maintenance treatment, with doses of 9 to 15 million units weekly, has been demonstrated to be effective. In a randomized study of 84 patients, there was an initial survival advantage in the
Autologous Transplantation and Allogeneic Transplantation
In 1996, the EBMT published a retrospective case-matched registry study comparing ASCT with allogeneic bone marrow transplantation with full-dose, myeloablative conditioning, with 189 patients in each group.59 Outcome was significantly better in the ASCT group, mainly because of a very high TRM of more than 40% in the allotransplant group. This TRM rate was improved in a later survey of allotransplant patients who were treated more recently, but was still high at more than 30%.60 Therefore, the
Conclusions
Can HDT including ASCT cure multiple myeloma? The general opinion is probably no. However, in retrospective analyses of more than 10,000 transplanted patients from the EBMT myeloma registry3 and the University of Arkansas Total Therapy Program,62 the PFS curve forms a plateau on a 5% to 10% level from 7 to 8 years after transplantation and onwards. Furthermore, in the latter study, the analysis of the 515 patients who were followed for at least 5 years after transplantation showed no further
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Cited by (27)
Multiple myeloma cells adapted to long-exposure of hypoxia exhibit stem cell characters with TGF-β/Smad pathway activation
2018, Biochemical and Biophysical Research CommunicationsCitation Excerpt :Multiple myeloma (MM) is a malignant neoplasm of plasma cells that is characterized by clonal proliferation of neoplastic plasma cells, production of M-proteins, and associated organ damage including bone fractures, renal failure, anemia, and hypercalcemia. The recent introduction of new molecular targeting agents such as proteasome inhibitors and immunomodulatory drugs, and autologous stem cell transplantation has improved the outcomes of MM patients [1,2]. However, MM remains incurable, and new molecular targeting agents are continually being developed as understanding of the pathogenesis of this disease increases [3–5].
CG13250, a novel bromodomain inhibitor, suppresses proliferation of multiple myeloma cells in an orthotopic mouse model
2017, Biochemical and Biophysical Research CommunicationsCitation Excerpt :Multiple myeloma (MM) is a malignant neoplasm of plasma cells that is characterized by clonal proliferation of neoplastic plasma cells, production of M-proteins, and associated organ damage including bone fractures, renal failure, anemia, and hypercalcemia. Due to the availability of new molecular targeting agents such as proteasome inhibitors and immunomodulatory drugs, and the introduction of autologous stem cell transplantation, the outcomes for MM patients have recently improved [1–3]. However, it remains incurable at present [1], and new molecular targeting agents are continually being sought and developed in step with better understanding of the pathogenesis underlying MM [1,4–6].
The effects of cold atmospheric plasma on cell adhesion, differentiation, migration, apoptosis and drug sensitivity of multiple myeloma
2016, Biochemical and Biophysical Research CommunicationsEfficacy and Outcome of Allogeneic Transplantation in IgD and Nonsecretory Myeloma. A Report on Behalf of the Myeloma Subcommittee of the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation
2015, Biology of Blood and Marrow TransplantationCitation Excerpt :The number of patients who could be evaluated for each parameter was noted and the proportions of evaluable patients are included in the results. Factors known to affect transplantation outcomes from previous EBMT studies were also analyzed [5]. Response criteria were those used by the centers that were in current use at the time of reporting.
Second Autologous Stem Cell Transplant: An Effective Therapy for Relapsed Multiple Myeloma
2015, Biology of Blood and Marrow TransplantationSelective Purging of Human Multiple Myeloma Cells from Autologous Stem Cell Transplantation Grafts using Oncolytic Myxoma Virus
2012, Biology of Blood and Marrow TransplantationCitation Excerpt :In North America alone, ASCT is used to treat approximately 5,000 patients with MM annually. This treatment results in improved rates of disease remission as well as significantly prolonged event-free survival time compared with patients treated with conventional chemotherapy [4,5]. However, despite the improved prognosis associated with myeloablative chemotherapy followed by ASCT, the treatment is generally not curative, and a large majority of all patients with MM will suffer from relapsed disease.
Supported by the Swedish Cancer Society and the Stockholm Cancer Society.