Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to determine the role of pre-emptive donor lymphocyte infusion (pDLI) after partial T-cell-depleted allogeneic SCT in patients with multiple myeloma (MM). A cohort of 24 MM patients was treated with partial T-cell-depleted myeloablative SCT between December 1997 and April 2002. These patients were intended to receive pDLI after SCT. The overall response rate after SCT was 83% (20 of 24 patients) with 10 patients (42%) in complete remission (CR). Transplant-related mortality within 1 year after SCT was 29%. Thirteen patients (54%) received pDLI and four patients in partial remission reached CR. GVHD>grade I after pDLI developed in 4 out of 13 patients (30%). Four patients received therapeutic DLI, without preceding pDLI. Eleven patients (46%) are alive, with a median follow-up of 67 months (range, 48-100 months). Seven of these patients (29%) are in continuous CR (CCR), which was confirmed by a negative patient-specific IgH PCR in four patients. All seven patients in CCR received pDLI. Although myeloablative SCT in MM induces high toxicity, we show that the concept of T-cell depletion followed by pDLI is promising and needs to be investigated in a reduced-intensity conditioning setting.
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PMID:Multiple myeloma patients receiving pre-emptive donor lymphocyte infusion after partial T-cell-depleted allogeneic stem cell transplantation show a long progression-free survival. 1756 32

The conditioning regimens for autologous SCT (auto-SCT) lead to impairment of the immune system and concomitant increase in susceptibility to infections. We studied the recovery of cellular immunity by in vitro analysis of T-cell proliferation and cytokine production profiles during the first 15 months after auto-SCT in patients with multiple myeloma and non-Hodgkin's lymphoma. PBMC were collected at 6, 9 and 15 months after transplantation and stimulated with a combination of CD2 and CD28 monoclonal antibodies, with PHA or with tetanus toxoid as recall antigen. A multiplex enzyme linked immunoassay was used to determine levels of Th1 cytokines IL-2, IFN-gamma and tumour-necrosis factor-alpha (TNF-alpha), Th2 cytokines IL-4, IL-5 and IL-13, the regulatory cytokine IL-10 and the proinflammatory cytokines IL-1alpha, IL-1beta, IL-6 and the chemokine IL-8. T-cell proliferation progressively increased from 6 to 15 months after auto-SCT. Overall, cytokine production increased after auto-SCT. Production of Th2 cytokines IL-5 and IL-13 was superior to production of Th1 cytokines IFN-gamma and TNF-alpha. We hypothesize that prolonged impairment of IFN-gamma production might contribute to the relatively high incidence of viral infections after auto-SCT.
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PMID:Development of T cell-mediated immunity after autologous stem cell transplantation: prolonged impairment of antigen-stimulated production of gamma-interferon. 1756 37

Allogeneic stem cell transplantation (alloSCT) has been used in the hopes of harnessing the curative potential of the graft-versus-myeloma effect. This study examines the long-term outcomes of a large cohort of patients with myeloma who were treated with myeloablative alloSCT at a single center. Comparisons are made with those who were treated with autologous stem cell transplantation (ASCT). Between January 1989 and February 2002, 158 patients age<or=55 years underwent SCT for myeloma. Seventy-two patients underwent myeloablative alloSCT (58 related; 14 unrelated), whereas 86 patients underwent ASCT. Most patients received single-agent high dose dexamethasone or VAD (vincristine, adriamycin, dexamethasone) therapy pre-SCT. Conditioning regimens were melphalan-based for all ASCT patients, whereas the alloSCT patients received melphalan-based (70%), total-body irradiation (TBI)-based (18%), or other (13%). Patients who underwent alloSCT were younger, had a higher Durie-Salmon stage disease, and a shorter median time from diagnosis to transplant. Myeloma subtypes were similar between groups. Other pre-SCT (BMT) characteristics were similar except that ASCT patients had a higher proportion of cases that received palliative radiotherapy pre-SCT. Disease response pre-SCT was similar. At last follow-up, 61 of 158 patients are alive with a median follow-up of 88.4 months (range: 35.5-208.5). The overall survival (OS) of the alloSCT cohort was 48.1% at 5 years and 39.9% at 10 years compared to 46.2% at 5 years and 30.8% at 10 years for the ASCT cohort (P=.94). The event-free survival of the alloSCT cohort was 33.3% at 5 years and 31.4% at 10 years compared to 32.9% and 15.2%for the ASCT cohort (P=.64). Treatment-related mortality (TRM) at 1 year was 22% for the alloSCT cohort and 14% in the ASCT cohort (P=.21). Cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 72% and the cumulative incidence of chronic GVHD (cGVHD) was 68% at 2 years. Neither aGVHD nor cGVHD had an influence on OS or event-free survival, although 5 of 14 patients who have received donor lymphocyte infusions (DLI) have had disease response. The risk of relapse was reduced in those who developed aGVHD (P=.02) but not cGVHD (P=.23). In conclusion, although there are patient who are alive without disease>10 years post myeloablative alloSCT, similarly there are long-term survivors post-ASCT. Myeloablative alloSCT should not be considered standard treatment, and should only be considered in the context of a clinical trial.
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PMID:Long-term outcome of myeloablative allogeneic stem cell transplantation for multiple myeloma. 1764 May 96

Here we report the first case of the development of intracranial solitary plasmacytoma in the inner ear after allogeneic stem cell transplantation (allo-SCT) in a 39-year-old Japanese female with primary plasma cell leukemia (PCL). A point to note is that this is not a case on multiple myeloma but on PCL. She was successfully treated with local irradiation and survived more than 6 years from the time of diagnosis and transplantation. This case elucidates the biology of PCL and stresses the need for an individual approach to the clinical management of patients with plasma cell neoplasm undergoing allo-SCT.
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PMID:Development of solitary plasmacytoma in the internal auditory canal and inner ear after allogeneic hematopoietic stem cell transplantation for plasma cell leukemia. 1767 74

The place of allogeneic SCT in the management of multiple myeloma remains controversial. Although it may induce long-term clinical and molecular remissions, the very high transplant-related toxicity after a myeloablative preparative regimen has limited its role to younger patients as first-line treatment option. Even with this limited indication, toxic death rate related to infections and GVHD is considered too high and this strategy has been almost abandoned. Reduced intensity conditioning (RIC) regimens look promising, as the transplant-related mortality is low even with matched unrelated donors and can be considered for older patients up to the age of 65 years. However when used in patients with a high tumor burden or with chemo-resistant disease, the immunologic effect of the graft is not sufficient to avoid relapses. Therefore, RIC allotransplantation is currently used after tumor mass reduction with high-dose therapy followed by autologous SCT. A recently published Italian study shows that this strategy induces better event-free survival than double autologous SCT due to a reduced relapse rate. The questions raised by this encouraging result are discussed in this paper.
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PMID:The allogeneic dilemma. 1768 16

Haematopoietic stem cell transplantation (HSCT) is now an established treatment fora number of non-malignant and malignant conditions. Bone marrow- or peripheral blood-derived allogeneic SCT from an HLA-identical sibling or matched unrelated donor cures more than half the patients with severe aplastic anaemia, thalassaemia major, congenital immunodeficiency diseases and genetic metabolic disorders. Among the malignant conditions, acute and chronic leukaemia, multiple myeloma, Hodgkin and non-Hodgkin lymphoma, and high risk neuroblastoma are important conditions that can be treated by HSCT. The major morbidities associated with HSCT are regimen-related toxicities, development of acute or chronic graft-versus-host disease (GVHD), failure of engraftment of the bone marrow and complications related to the immunodeficiency that occurs in the post-transplant period. Peripheral blood stem cells are now being used as an alternative to bone marrow stem cells for allogeneic HSCT and exclusively for autologous HSCT. Reduced intensity conditioning for allogeneic HSCT has resulted in a lower frequency and severity of GVHD and risk of infections. This has resulted in allogeneic HSCT being done in older patients and for those with co-morbid conditions. Patients with low grade Hodgkin and non-Hodgkin lymphoma, chronic lymphocytic leukaemia and multiple myeloma appear to benefit more with this approach. Prevention of acute GVHD while maintainingthe graft-versus-tumour effect and close monitoring of the kinetics of chimerism hold promise for improving the outcome of those receiving reduced intensity allogeneic HSCT. In recipients ofautologous HSCT, identification of patients at increased risk for relapse and use of agents (interferon, interleukin-2) post-transplant to augment the graft-versus-tumour effect are possible areas of further research.
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PMID:Haematopoietic stem cell transplantation: current status. 1786 17

Chemotherapy-susceptive multiple myeloma (MM) has an indication for high-dose melphalan (HDM) followed by autologous stem cell transplantation (auto-SCT). HDM was a most simple and convenient regimen among various preparatory regimens, because of rapid infusion divided over 2 days. In order to assess the potential of auto-SCT by HDM in a outpatient setting, we evaluated the toxicities of HDM compared with the ICE regimen generally applied to patients with refractory or relapsed lymphoma. We reviewed 27 cases of auto-SCT from April 2003 to December 2004. The preparatory regimen was HDM (melphalan 200 mg/m(2)) for 18 cases of multiple myeloma and ICE therapy (ifosfamide 12 g/m (2), carboplatin 1,200 mg/m(2), etoposide 800 mg/m2) for 9 malignant lymphomas. Gastrointestinal (GI) adverse events for a patient per hospital day were 0.93 for myeloma and 0.95 for lymphoma (no significant differences), with GI toxicity of more than grade 3, 0.08 and 0.12, respectively (p=0.07). Hematological toxicity was not significantly different between the 2 therapies. The clinical toxicity of HDM was milder compared to ICE, especially regarding the speculated GI-associated nutritional disorders. We thus concluded that outpatient auto-SCT could be validated first in myeloma patients treated by HDM with careful supportive treatments, thereby avoiding regimen-related severe adverse events.
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PMID:[Comparison of regimen-related toxicity between high-dose melphalan and ICE as a preparatory regimen for autologous stem cell transplantation]. 1794 Mar 79

There are a number of reports in literature data on the long-term outcomes of patients with multiple myeloma treated with high-dose therapy and autologous stem cell transplantation (HDT/SCT). While in general these data support the association between maximal tumor response and overall survival or progression-free survival after HDT/SCT, some trials have failed to find such correlation and there is no recent comprehensive literature analysis of this issue. We, therefore, performed a comprehensive literature review to identify prospective and retrospective studies on HDT/SCT in frontline multiple myeloma in which long-term outcomes were reported according to best tumor response observed. Following a prospectively defined search strategy we identified 21 studies (10 prospective and 11 retrospective studies) in which outcomes of 4,990 HDT/SCT patients according to their best tumor response were reported. The majority of these studies indicated a correlation between maximal response during or after HDT/SCT and long-term outcomes (overall survival and event-free/progression-free survival). The conclusions in individual studies report on the association between maximal response following induction therapy and long-term outcomes were more heterogeneous, possibly due to the low rate of complete response after standard induction therapy in each individual study. We, therefore, performed two types of meta-analyses, one based on the p-values reported for these associations in the individual studies, and one based on the primary response and outcome data provided in the individual studies. Both meta-analyses indicated highly significant associations between maximal response (complete response/near complete response/very good partial response) during or after HDT/SCT and long-term outcomes (overall survival and event-free/progression-free survival). Both meta-analyses also provided evidence of highly significant associations between maximal response following induction therapy and long-term outcomes (overall survival and event-free/progression-free survival).
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PMID:Complete response correlates with long-term survival and progression-free survival in high-dose therapy in multiple myeloma. 1802 76

The treatment of multiple myeloma (MM) is changing rapidly. During the last 10 years, higher rates of complete response (CR) and prolonged progression-free and overall survival have been seen with high-dose chemotherapy plus autologous stem-cell transplantation (HDT-ASCT). Achievement of CR and good partial response have been shown to be key prognostic factors for prolonged survival, with eradication of minimal residual disease seeming crucial to long-term disease-free survival. Until recently, high rates of CR and other major responses were primarily seen with HDT-ASCT, but insights into the biology of MM have led to the development and approval of new drugs with significant activity, and new induction regimens based on these novel agents are offering improved responses. Thalidomide, bortezomib, and lenalidomide have been combined with corticosteroids, alkylators, and anthracyclines in front-line MM treatment. Phase II studies have indicated that high rates of response and CR may be achieved. The substantial activity seen with these new drug combinations has prompted a re-examination of the role of SCT in MM treatment. Will achievement of major responses with these new regimens translate into improved survival after consolidation with transplantation? Will these improved induction regimens reduce the need for tandem transplantation, or does achievement of CR obviate the need for front-line transplantation altogether? To help address these questions, randomized trials are needed, as well as tests with improved sensitivity to better define depth of remission.
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PMID:Stem-cell transplantation for multiple myeloma in the era of novel drugs. 1805 78

We describe the results of 37 myeloma patients who received bortezomib following reduced intensity allogeneic stem cell transplantation (RIC-allo-SCT). Grade 1-2 peripheral neuropathy (35%), mild thrombocytopenia (24%) and fatigue (19%) were the most frequent adverse events, while there was no worsening of graft-vs-host disease symptoms. Twenty-seven patients (73%; 95% CI, 59-87%) achieved an objective response. With a median follow-up of 9 months from bortezomib initiation, the estimate of overall survival was 65% at 18 months while this was significantly higher (p=0.002) in the 27 patients achieving an objective response, suggesting that bortezomib is a safe and efficient option for myeloma patients after RIC-allo-SCT.
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PMID:High response rate and improved graft-versus-host disease following bortezomib as salvage therapy after reduced intensity conditioning allogeneic stem cell transplantation for multiple myeloma. 1828 32


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