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

Autologous hematopoietic SCT (auto-HSCT) provides hematopoietic support after high-dose chemotherapy and is the standard of care for patients with multiple myeloma (MM) or chemosensitive relapsed high- or intermediate-grade non-Hodgkin's lymphoma (NHL). However, yields of hematopoietic stem cells vary greatly between patients, and the optimal strategy to mobilize hematopoietic stem cells into peripheral blood for collection has not been defined. Current mobilization strategies consist of cytokines alone or in combination with chemotherapeutic agents. Cytokine-only mobilization regimens are well tolerated, but their utility is limited by suboptimal PBSC yields. When a myelosuppressive chemotherapeutic agent is added to a cytokine mobilization regimen, PBSC collections improve two- to five-fold. This benefit is tempered by increased toxicity, morbidity and resource utilization. All current regimens fail to mobilize sufficient hematopoietic stem cells to proceed to transplantation in 5-30% of patients, necessitating additional mobilization attempts or precluding transplantation, which may negatively affect patient outcomes and survival. Improved strategies to mobilize stem cells would increase the availability of auto-HSCT and optimize engraftment and outcomes in patients with MM or NHL. Novel agents used in conjunction with cytokines have the potential to increase PBSC collections without introducing additional morbidity, thereby improving patient outcomes.
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PMID:Improving stem cell mobilization strategies: future directions. 1913 34

High-dose chemotherapy (HDT) and hematopoietic SCT are effective in patients with relapsing or refractory malignant lymphoma. Collection of sufficient numbers of stem cells is a prerequisite for such a therapy. In a pilot trial, we evaluated the feasibility of stem cell mobilization with vinorelbine/G-CSF in patients with lymphoma, a regimen allowing precise timing and harvesting of sufficient stem cells in myeloma patients. Forty-five patients with lymphoma received vinorelbine 35 mg/m(2) i.v. on day 1 and G-CSF 10 microg/kg/day s.c., divided in two daily doses from day 4 until collection. Stem cell collection was successfully performed in 43 patients (96%) with a median of 3.6 x 10(6) CD34(+) cells/kg (range: 1.4-16) in the collected product. In 28 patients (62%), the first stem cell apheresis was performed on day 8, and for 28 patients a sufficient stem cell yield was reached with one apheresis only. All 43 patients underwent high-dose chemotherapy with BEAM and auto-SCT with hematological recovery on time and without unexpected toxicity. In conclusion, vinorelbine/G-CSF allows accurate timing and safe harvesting of sufficient stem cells in patients with malignant lymphoma.
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PMID:Efficient mobilization of PBSC with vinorelbine/G-CSF in patients with malignant lymphoma. 1916 88

High-dose melphalan is considered the current standard of care among the preparative regimens used in peripheral blood autologous SCT (ASCT) for multiple myeloma (MM). We report the results of a single ASCT in 79 MM patients using the BU/CY conditioning regimen, with BU 1 mg/kg p.o. or 0.8 mg/kg i.v. every 6 h x 16 doses, and CY 60 mg/kg per day i.v. for 2 days. ASCT was carried out in first (62%) or subsequent remission/refractory disease (38%). For an overall RR of 86%, 48 and 20 patients achieved PR and CR, respectively. At a median follow-up of 41 months (range 2-132 months), the estimated median OS and PFS were 45 months (95% confidence interval (CI)=38-92) and 20 months (95% CI=15-25), respectively. The BU/CY regimen was well tolerated, and transplant-related mortality was 4%. Clinical outcomes of the BU/CY regimen are not superior to those obtained in historical controls with high-dose melphalan followed by a single ASCT. Therefore, considering even the greater complexity of administration of the BU/CY regimen compared with that of single-agent melphalan, we believe the latter should remain the conditioning regimen of choice for ASCT in MM.
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PMID:BU and CY as conditioning regimen for autologous transplant in patients with multiple myeloma. 1920 16

Treatment strategies for multiple myeloma have changed substantially over the past 10 years following the introduction of bortezomib and the immunomodulatory drugs thalidomide and lenalidomide. In the front-line setting, combination regimens incorporating these novel agents are demonstrating substantial activity, which is translating into improved outcomes compared with previous standards of care. Response rates and depth of response that were previously only seen with high-dose therapy plus stem-cell transplantation (HDT-SCT) can now be achieved with new induction regimens utilizing these novel agents. This has raised the need for trials that will determine the clinical benefit of early SCT in patients that have already achieved a high quality of response. Here, we review the improvements in response and outcome that are seen with these novel-agent regimens, both as induction therapy prior to HDT-SCT and in non-transplant patients, and highlight the latest data from key studies of various novel combinations, including regimens featuring bortezomib plus thalidomide or lenalidomide. We also review data on response and outcomes in patients with poor prognostic characteristics that indicate that the adverse impact typically seen with these factors may be overcome using novel-agent therapy.
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PMID:Emerging combination treatment strategies containing novel agents in newly diagnosed multiple myeloma. 1934 88

Deletions involving chromosome 1p are frequent events in multiple myeloma (MM). As karyotyping and single nucleotide polymorphism-based mapping analysis identify a minimal common deletion region involving the 1p21 locus, we investigated the prevalence and prognostic significance of del(1p21) in 203 MM patients undergoing high-dose therapy and autologous SCT. 1p21 status was also evaluated in 16 patients with monoclonal gammopathy of undetermined significance (MGUS) and 41 patients with plasma cell leukemia (PCL). FISH combined with cytoplasmic light chain detection (cIg-FISH) detected hemizygous 1p21 deletions in 18% of the MM, 34% of PCL but none of the MGUS cases. The presence of 1p21 deletions was correlated with 1q21(CKS1B) amplification (P=0.01), and del17p(TP53) (P=0.05) but not with del(13q), t(11;14) or t(4;14). Patients with 1p21 deletions had significantly shorter progression-free survival (PFS; median 14.2 vs 25.4 months, P<0.001) and overall survival (OS; median 39.4 vs 82.3 months, P=0.001) than those without such deletions. In multivariate analysis, del(1p21) was an independent risk factor for PFS (P= 0.003) and OS (P=0.013) after adjusting for del(13q), del(p53), t(4;14) and 1q21 amplifications. Our results indicate that del(1p21) is an independent poor prognostic factor associated with disease progression in MM.
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PMID:1p21 deletions are strongly associated with 1q21 gains and are an independent adverse prognostic factor for the outcome of high-dose chemotherapy in patients with multiple myeloma. 1944 82

This was an open-label, single-center, phase II study of 20 patients with multiple myeloma who were either proven poor mobilizers (n=10; group A) or predicted poor mobilizers (n=10; group B) and were planned for autologous hematopoietic SCT. The aim was to assess the safety and efficacy of plerixafor for stem cell mobilization and tumor cell contamination. The peripheral blood (PB) CD34+ cell count was generally very low pre- plerixafor and increased significantly post-plerixafor administration. Cumulative apheresis yields of > or =2 x 10(6) CD34+ cells/kg were observed in 7 of 10 patients (group A) and 8 of 10 patients (group B). Among the proven poor mobilizers, there was no evidence of tumor cell mobilization in the PB after G-CSF plus plerixafor treatment. Seventeen of 20 (85%) patients underwent transplantation. Neutrophil engraftment occurred at a median of 13 days for all patients. Platelet engraftment occurred at a median of 16 days and 19 days for all proven and predicted poor mobilizers, respectively. At 12 months, 12 of 17 patients had documented durable grafts, 3 of 17 patients died and 2 of 17 patients were lost to follow-up; but they had documented graft durability at the previous 3- and 6-month visit. The safety profile of plerixafor in all patients was consistent with previous reports.
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PMID:Safety and efficacy assessment of plerixafor in patients with multiple myeloma proven or predicted to be poor mobilizers, including assessment of tumor cell mobilization. 2425 74

We investigated efficacy and toxicity of lenalidomide in 24 heavily pretreated myeloma patients with a median age of 59 years (range: 37-70) and relapse after allo-SCT. Lenalidomide was given at a dose of 15 mg (n=4), or 25 mg (n=20), orally once daily on day 1 to day 1 every 28 days, with (n=20) or without (n=4) DHAP. The median number of lenalidomide cycles was five (range: 2-17). Major side effects were leukopenia (grade 4: 4%, grade 3: 21% and grade 2: 17%) and thrombocytopenia (grade 3: 17% and grade 2: 29%); infectious complications were observed in 50%. Non-hematological toxicity consisted of muscle cramps (n=9), fatigue (n=5) and constipation (n=2). Mild grade I-II GVHD was seen in three patients. Response was achieved in 66%: CR in 8%, VGPR in 8%, PR in 50% and SD in 13%. The median time to progression was 9.7 months (95% confidence interval (CI): 7.5-11.9), and median OS was 19.9 months (95% CI: 17.3-22.5). Immunomonitoring after lenalidomide showed significant increase of activated NK (NKp44(+)) and T (HLA-DR(+)) cells, as well as regulatory T cells (CD4(+), CD25(+), CD127(lo)), supporting an immunomodulating anti-myeloma effect of lenalidomide.
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PMID:Lenalidomide as salvage therapy after allo-SCT for multiple myeloma is effective and leads to an increase of activated NK (NKp44(+)) and T (HLA-DR(+)) cells. 1958 25

To describe utilization of a biosimilar product containing filgrastim (Neutromax), data of 414 myeloma or lymphoma patients subjected to autologous SCT between 1998 and 2007 were analyzed. Filgrastim was used for mobilization of progenitors (5 days at 300 microg/day) and for the recovery of neutropenia after transplantation (100 microg/day, since day +5). In 2003, the excipient mannitol was replaced by sorbitol. A mean dose of 9.47 x 10(6)CD34(+)cells/kg was infused; 100 neutrophils/mm(3) required 5-day treatment; 500 neutrophils/mm(3), 6 days and 1000 neutrophils/mm(3), 7 days. Neutromax effect in SCT is similar to reports with other brands. No difference was found between formulations.
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PMID:Utilization study of filgrastim (Neutromax) during autologous haematopoietic precursor transplantation for myeloma and lymphoma patients. 1969 52

Currently, autologous hematopoietic stem cell (SCT) transplantation is frequently used as a method of treatment for various hematologic malignant neoplasms and some solid tumors in adults and children. Autologous stem cells can be obtained in most instances from the patient's bone marrow or peripheral blood. The blood is the preferred source of stem cells because of easier collection and faster hematologic recovery post-transplantation. Prospective clinical trials confirmed the role of autologous SCT in the treatment of chemosensitive non-Hodgkin's lymphomas and Hodgkin's disease after first relapse, and probably in selected high-risk patients in earlier stage of the disease. In multiple myeloma, autologous SCT is a standard treatment approach for all patients younger than 65, either as a single transplant or as a tandem transplant in patients that failed to achieve complete or very good response after first transplant. In acute leukemia, the role of autologous SCT is less well defined although in acute myeloid leukemia several studies resulted in statistically superior patient outcome in comparison to chemotherapy. Advances in supportive therapy and use of peripheral blood stem cells have made autologous SCT a relatively safe treatment modality with attributable mortality mainly less than 5%. Yet, the relatively high incidence of relapse after transplantation remains a major problem. A variety of methods have been under investigation before and after transplantation to reduce the risk of relapse and improve the results of treatment.
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PMID:[Autologous hematopoietic stem cell transplantation]. 1982 49

From 2002 to 2007, 49 myeloma patients who relapsed following autologous SCT were included in a prospective multicenter trial to determine the efficacy of a reduced melphalan/fludarabine regimen followed by allogeneic SCT from unrelated donors. All patients showed leucocyte and platelet engraftment after a median of 15 and 19 d, respectively. Grade II-IV acute graft-versus-host disease (GvHD) occurred in 25% of patients and 35% had chronic GvHD. Overall response rate at day 100 was 95% including 46% complete remission (CR). Cumulative incidence of non-relapse mortality at 1 year was 25% [95% confidence interval (CI): 13-37%] and was significantly lower for human leucocyte antigen (HLA)-matched compared to -mismatched SCT (10% vs. 53%, P = 0.001). The cumulative incidence of relapse at 3 years was 55% (95% CI: 40-70%). After a median follow up of 43 months, the estimated 5-year progression-free and overall survival rates were 20% and 26% respectively and were significantly better for matched in CR at day 100 (41% vs. 7%, P = 0.04 and 56% vs. 16%, P = 0.02). We conclude that optimal donor selection is mandatory for a low non-relapse mortality and high relapse incidence, which remains a major concern, should be improved by including post-transplant strategies to upgrade remission status.
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PMID:Unrelated stem cell transplantation after reduced intensity conditioning for patients with multiple myeloma relapsing after autologous transplantation. 1991 15


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