ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • 1
    Publication Date: 2019-11-13
    Description: Background: triplet combinations comprising a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) are current standard induction and consolidation regimens in NDMM. The all-oral combination of weekly ixazomib plus lenalidomide-dexamethasone (IRd) has been evaluated by several groups in NDMM and is approved in relapsed-refractory MM. The IFM 2014-01 phase 2 trial previously studied the weekly IRd regimen as induction and extended consolidation followed by single-agent ixazomib maintenance in frontline transplant eligible patients (Moreau et al ASH meeting 2016): IRd was well tolerated and overall response rate was 81%, including 38% very good partial response or better (≥VGPR) at the completion of induction (3 cycles). Responses further increased at each step of the program and 76% of patients (per protocole analysis) achieved ≥VGPR before maintenance with 6% CR and 38% sCR. To stay in line with current RVd regimen, and to increase dose intensity, we examined the efficacy and safety of twice-weekly ixazomib +Rd as induction prior to transplant, followed by weekly IRd consolidation and single-agent lenalidomide maintenance (NCT02897830). Methods: This is a phase II, single-arm, open-label, multicenter study. During induction, patients received three 21-day cycles of twice-weekly oral IRd: ixazomib (3 mg on days 1, 4, 8 and 11), lenalidomide (25 mg daily, days 1-14), and dexamethasone (40 mg on days 1, 4, 8 and 11) followed by transplant. Patients then received two 28-day cycles of weekly IRd early consolidation followed by 6 additional cycles of IR (no dexamethasone) as late consolidation (ixazomib 4mg on days 1-8 and 15; lenalidomide 25mg daily, days 1-21). Single-agent lenalidomide maintenance was administered for up to 1 year (10 mg daily, days 1-21). The primary endpoint was the stringent complete response (sCR) rate at the completion of consolidation. The secondary endpoints included assessments of overall response rate (ORR) and rates of response categories at each step of the program, progression-free survival (PFS), feasibility and safety. Responses were assessed in accordance with the IMWG uniform criteria. Toxicity was evaluated according to NCI CTCAE, version 4.03. Results Between 07/2016 and 08/2017, 50 patients with NDMM were screened at 10 IFM centers, 46 were enrolled with a median age of 59 years, and 59% were male. The percentages of patients with ISS stage I, II, and III were 41.5%, 41.5%, and 17%, respectively. High-risk cytogenetics, defined as t (4; 14), or del17p (central Lab, H. Avet-Loiseau), was observed in 9% of patients (6.5% FISH failure). As of July 1st 2019 (data cut-off), 10 patients prematurely discontinued therapy. Considering efficacy, 43/46 patients (94%) completed consolidation and 9 achieved sCR (20.9%; 90% CI [11.4 to 33.7]). This result did not meet the minimum efficacy threshold (40%) for the primary efficacy endpoint (p=0.998). Overall, at the completion of consolidation, ORR was 91% including 21% sCR, 30% ≥CR and 58%≥VGPR. Responses at each step of the program are described in the table 1. If we focus on twice-weekly IRd induction, at the completion of 3 cycles, ORR was 74%, including 33% ≥VGPR. The feasibility of the program was good and overall, 39/46 patients (85%) were able to receive maintenance therapy with single-agent lenalidomide. After a median follow-up of 22 months, 7 patients progressed and 3 patients died. Concerning safety: 31 serious treatment emergent AEs were reported in 20 patients (43.5%) comprising infections (8 patients), cardiac disorders (2 patients: ischemic heart disease and aortic valve incompetence), psychiatric, renal and respiratory disorders (2 cases each). No grade 3-4 peripheral neuropathy was described. Conclusions The all-oral Ixazomib-Lenalidomide-Dexamethasone (IRd) induction/consolidation regimen in the transplant setting is convenient, well tolerated, leading to 21% sCR before maintenance. Twice-weekly IRd induction does not seem superior to weekly IRd induction Results on response rates following maintenance and MRD data will be presented during the meeting. Table Disclosures Roussel: Celgene Corporation: Consultancy, Other: travel fees, lecture fees, Research Funding; takeda: Other: travel fees, lecture fees, Research Funding; Amgen: Other: travel fees, lecture fees, Research Funding; Janssen: Honoraria, Other: travel fees, lecture fees, Research Funding. Hebraud:celgene: Other: travel fees, lecture fees; takeda: Other: travel fees, lecture fees. Hulin:Janssen, AbbVie, Celgene, Amgen: Honoraria; celgene: Consultancy, Honoraria. Leleu:Oncopeptide: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Karyopharm: Honoraria; Amgen: Honoraria; Carsgen: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria; Merck: Honoraria. Facon:Amgen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Touzeau:celgene: Other: travel fees, lecture fees, Research Funding; takeda: Other: travel fees, lecture fees. Perrot:jannsen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; takeda: Honoraria. Stoppa:celgene: Other: travel fees, lecture fees; takeda: Other: travel fees. Moreau:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Avet-Loiseau:takeda: Consultancy, Other: travel fees, lecture fees, Research Funding; celgene: Consultancy, Other: travel fees, lecture fees, Research Funding. Attal:celgene: Consultancy, Other: travel fees, lecture fees, Research Funding; takeda: Consultancy, Other: travel fees, lecture fees, Research Funding. OffLabel Disclosure: Ixazomib is indicated in RRMM in association with Rd
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2015-12-03
    Description: Background. Lenalidomide plus Dexamethasone is approved at first relapse and beyond in Europe, and has transformed the prognosis of Myeloma in the relapse setting. Lenalidomide plus Dexamethasone is approved until progression, that could last for years, the median PFS in phase 3 studies being at 17 months at first relapse, but many patients eventually reach 5 to 7 years these days. Dexamethasone was showed to enhance lenalidomide-antitumor efficacy and to prolong the progression-free survival. However, long term exposure to dexamethasone is also known to be associated to an array of adverse events. Finally, IMiDs are known to act through immunomodulation a class-based mechanism. It is possible that lenalidomide might show efficacy on the long run without need to dexamethasone use, at least for some patients with myeloma. We sought to study the impact of dexamethasone discontinuation beyond six months and one year, and compare this analysis to patients treated on lenalidomide plus dexamethasone. Method. We have recruited 200 relapse refractory myeloma patients for this study from various IFM centers. The patients were to be older than 18 years old and treated with lenalidomide plus dexamethasone. We sought to study the impact of the various ways to use dexamethasone in the real life, and therefore dexamethasone was given according to physician decision. We identified groups according to dexamethasone given high dose (4 days 160mg total in a raw), given once a week at 40mg (considered standard dose), given at lower dose (considered low dose) and a group that had dexamethasone discontinued. Patients were not allowed to have other type of combination but lenalidomide plus dexamethasone. Result. A total of 200 patients were analyzed, median age of 57 years old (range 25-76). 17,5% patients had renal dysfunction at diagnosis. ISS was 2 for 20% and 3 for 20%. Approximately 10% had either del17p or t(4;14). 7% of patients had previous history of venous thrombosis before the treatment. Response rate, survival, including TTP, PFS, EFS and overall survival will be presented at ASH with updated follow-up. Conclusion. This study aims to investigate the importance of long run and exposure to Dexamethasone in the Lenalidomide-Dexamethasone regimen. We also wished to assess the optimal dose of dexamethasone that could be given to patients with prolonged exposure to lenalidomide plus dexamethasone. Disclosures Arnulf: Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. MACRO:millenium: Membership on an entity's Board of Directors or advisory committees; jansen: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees. Facon:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Pierre Fabre: Membership on an entity's Board of Directors or advisory committees. Leleu:LeoPharma: Honoraria; Pierre Fabre: Honoraria; BMS: Honoraria; Novartis: Honoraria; TEVA: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Chugai: Honoraria.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 3
    Publication Date: 2010-11-19
    Description: Abstract 2979 Introduction: Multiple myeloma (MM) is a B-cell neoplasia characterized by the accumulation of malignant plasma cells in the bone marrow (BM) patients causing severe bone disease (with osteolytic lesions, pain, pathological fractures) and cytopenias. These lesions are irreversible, even for patients in complete response to treatment. We have proposed to treat those lesions with mesenchymal stem cells (MSC) of the BM using their ability to differentiate into osteoblasts and to support haematopoiesis. But our previous results demonstrated that MM MSC are abnormal. We thus studied cells from adipose tissue (AT) with similar properties than MSC; the Adipose derived Stromal Cells (ASC). The aim of this study is to demonstrate the normality of ASC in MM context for a potential use in autologous stem cell transplantation. Here we propose the first study comparing ASC issue from MM patients and healthy donors (HD). Patients and Methods: We studied ASC from 15 patients with newly diagnosed MM and 15 HD between 18 and 65 years. All gave their informed consent. The stromal vascular fraction was isolated from subcutaneous AT by and centrifugation. The ASC were sorted by adhesion to the plastic flask and expanded for 3 passages. We then performed the following assays to compare ASC from MM and HD: Results: The cell culture assay of ASC didn't show any difference between MM and HD for all the studied parameters: expansion capacity (HD 470± 45, MM 208±194; p=0.13), cell population doubling (HD 16.0±0.3, MM 15.0±1.3; p=0.17) and progenitor frequency (HD 3.4%±3, MM 3.7%±5.5; p=0.165). ASC phenotype didn't show any significant difference for all the checked markers and confirm their stromal feature: positive for CD90, CD73 and CD105, and negative for CD14 and CD45. The differentiation assay was evaluated for osteogenic, chondrogenic and adipogenic lineages. We did not underline any difference comparing ASC from MM or HD (Table 1). We previously showed that MM MSC secreted increased amount of IL-6, GDF15 and DKK-1 when compared with HD MSC. Interestingly, no difference was observed between MM ASC and HD ASC (Table 2). In the same way, contrary to MM MSC, MM ASC didn't promote the proliferation of MOLP-6 cell line better than HD ASC (proliferation rate: 1.49±0.34 for HD and 1.66±0.80 for MM; p=0.33). Conclusion: To our knowledge, this is the first study to compare ASC from MM patient and HD. These preliminary data suggest that ASC from MM patients are normal and could potentially be used in autologous stem cell transplantation for MM patients. We are currently completing this study by performing haematopoiesis support and microarrays assays. Disclosures: No relevant conflicts of interest to declare.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 4
    Publication Date: 2014-12-06
    Description: In multiple myeloma, cytogenetic changes display important value for patients’ outcome. In this setting, the most important changes are the del(17p), and the t(4;14), conferring a poor outcome. However, a certain heterogeneity is observed in survival of these high-risk patients. We hypothesized that other chromosomal changes may impact the outcome. We retrospectively analyzed a large series of 242 patients displaying either the t(4;14) (157 patients), or the del(17p) (110 patients), 25 patients presenting both abnormalities, using SNP-array. The main advantage of SNParray analyses is that all the unbalanced chromosomal changes are analyzed, in contrast to FISH which informs only for the chosed probes. For t(4;14), 144 patients have relapsed, and 103 have died. The median PFS was 1.4 year, and the median OS was 3.5 years. The median beta2-microglobulin (b2m) level was 4.0 mg/L (range, 1.2-38.3). The distribution of ISS stages 1, 2, and 3 was 35.4%, 26.4%, and 38.2%, respectively. Based on FISH results, 31.2% of the patients presented the abnormal configuration with only one fused signal. In all these patients, SNP-array analysis showed a loss of the telomeric part of one chromosome 4. In contrast to previous reports on this particularity in which the explanation was a loss of the derivative chromosome 14,17,18 we clearly show here that this configuration results from an unbalanced translocation. In patients with t(4;14), del(1p32) (p
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 5
    Publication Date: 2012-11-16
    Description: Abstract 3096 Background. Several studies have demonstrated the impact of VTd on response rates and PFS either as induction or consolidation regimen. However there are limitations to these studies, especially that no data is available regarding the role of VTd consolidation in the context of bortezomib-triple based VTd induction regimen followed by a single auto. At completion of therapy, the response rate (ORR, PR and better) was 89%, VGPR+CR rate 74%, CR rate 29%, relapse rate and median PFS was 53% and 26 months (median F-up 32 months) in the VTd arm of the phase 3 IFM2007-02 trial conducted for newly diagnosed MM (Moreau et al, Blood 2012). In this study, only a minority of patients had received a consolidation or maintenance. On the other hand, Cavo et al. (Blood 2012) reported 97.5%, 92%, 61%, 39% 3-year progression and 62% estimated 5-year PFS (F-up 43 months) respectively in the VTd arm. VTd was given as induction before and consolidation after double auto in this upfront GIMEMA phase 3 trial (Cavo et al, Lancet 2010). We aimed to assess the efficacy and safety of VTd as consolidation therapy in the context of VTd as induction regimen followed by a single auto (VTd-auto-VTd regimen). Method. This study has included a first group of 121 newly diagnosed MM from 2009 to 2011 across 9 IFM centers. Patients were to be eligible for auto upfront, aged less than 65 and treated with VTd-auto-VTd regimen. The second cohort included MM treated with VTd-auto without consolidation from the IFM2007-02 trial (n=76). A third cohort comprised MM that received upfront a triplet Vd-based combination induction (VCd, VRd) -auto without consolidation (n = 40). Results. In the whole study, the median age was 56 years, the sex ratio was 1,49, 50% had ISS 2 and 3, 22% had adverse FISH [t(4;14); del17p] (similar in the 3 groups). Overall, the ORR was identical in the 3 cohorts at completion of therapy, 104 (86%), 72 (94%) and 32 (80%) for the cohort 1 to 3, respectively. Nevertheless, the CR rate was significantly greater in patients that received a consolidation (cohort 1), as compared to the cohorts 2 and 3 that did not receive any consolidation, 59 (53%) vs. 26 (34%) and 13 (32.5%), respectively (p=0.0001). Interestingly, the CR rates were identical at the end of the induction in the 3 cohorts, 13%, 15% and 22.5%, respectively. With a median follow-up of 25 months, the incidence rate of relapse was significantly greater in the cohort 2 and 3 versus 1, further demonstrating the importance of the consolidation, 25 (21%), 42 (55%) and 13 (32.5%) patients (p=0.0001), respectively; and 9 (8%), 6 (8%) and 8 (20%) had died in cohorts 1 to 3 (p=0.07). The median (95%CI) PFS was not reached in cohort 1, and was 32 (28;36) months and 30 (26;33) months in cohort 2 and 3, respectively. Importantly, 54.5%, 32% and 32% of patients were free of relapse at 32 months in the 3 cohorts, respectively. Similar data were obtained for TTP. The median (95%CI) OS was not significantly different in cohorts 1 to 3, although not reached for the first 2 cohorts and 38 (33;43) months for the 3rdcohort. The 3-year survival was 84%, 91% and 76%, respectively (p=ns). A longer follow up will certainly demonstrate greater survival end points benefit in favor for consolidation. The safety profile of the cohort that contained a consolidation was superimposable to that of the remaining 2 cohorts without consolidation. The incidence rate of hematological EIs of grade 3 and 4 was 4%, 6% and 8% in the 3 cohorts (p=ns), respectively. The incidence rate of neuropathy grade 1–2 and 3–4 was 5% and 2% in the cohort 1 with consolidation, but only 1% occurred during the consolidation. This data compares favorably to the 3% reported in the cohort 2 (Moreau et al. Blood 2012). We have also observed 9 (9%) thromboembolic events (TE), 8 of venous type and 1 arterial. None of them happened during the consolidation, and again, this incidence rate if superimposable to that reported in the IFM2007-02 vTd cohort. Conclusion. This study showed an impressive increase in CR rate in relation to the consolidation that translated into a lower relapse rate. This study also demonstrated that the VTd regimen, used both as induction and consolidation, in the context of a single auto upfront in MM, significantly contributed to improve clinical outcomes with an acceptable toxicity profile. VTd-auto-VTd compared very favorably to the other upfront protocols, and may become in the near future a standard of care in newly diagnosed patients with Myeloma. Disclosures: Leleu: Celgene: Honoraria, Research Funding, Speakers Bureau; Janssen: Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Sanofi: Honoraria; Onyx: Honoraria, Speakers Bureau; LeoPharma: Honoraria, Speakers Bureau. Off Label Use: Pomalidomide. Roussel:celgene: Honoraria; janssen: Honoraria. Facon:onyx: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees; janssen: Membership on an entity's Board of Directors or advisory committees; millenium: Membership on an entity's Board of Directors or advisory committees. Attal:celgene: Membership on an entity's Board of Directors or advisory committees; janssen: Membership on an entity's Board of Directors or advisory committees.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 6
    Publication Date: 2015-03-26
    Description: Key Points Additional chromosomal changes modulate the outcome of patients with high-risk multiple myeloma.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 7
    Publication Date: 2016-12-02
    Description: Background. Peripheral blood stem cell (PBSC) collection prior to high dose chemotherapy for autologous transplantation (ASCT) is a standard of care, and an attractive alternative to the use of bone marrow cells, for transplantation in Multiple Myeloma (MM). The optimal methodology for mobilizing PBSC has yet to be defined, both G-CSF and GM-CSF can be used; although, the stimulatory effect may be more pronounced when given after high dose cyclophosphamide (usually administered at a dose of 1.5 to 6g/m2 IV for one to two days) and use of Plerixafor, a CXCR4 antagonist (Mozobil®). The latter 2 options are preferred, overall, in France. Indeed, it was shown that the most recent combined bortezomib and IMids-based induction regimens used prior to ASCT in MM upfront yielded poorly or required multiple days of collection with steady state method. Because of the intense competition for hospital resources and the staff required to evaluate and manage patients preparing for stem cell mobilization and transplantation, it is reasonable to attempt to quantify the total impact of stem cell mobilization on available staff resources and cost to the hospital, especially when newer therapies, i.e. plerixafor is available and may be more suitable for some of these patients. We aimed at better evaluate the burden of stem cell mobilization on the hospital of the 2 techniques of mobilization, either high dose endoxan (n=57) versus plerixafor (n=55); this study will not, however, evaluate the suitability or advisability of one therapy versus another. Method and Results . This is a retrospective observational cohort database analysis of 112 consecutive patients with MM treated upfront with ASCT between 2009 and 2013 and that had been mobilized with either high dose endoxan or plerixafor from 15 IFM centers. We planned to determine the cost versus benefit of either technique taking in consideration a number of key markers that influence the mobilization process. A cost-consequences analysis of the different regimens of mobilization will be performed. Cost will be quantified using "microcosting" approach. Only direct medical costs are included in this economic analysis. Hospital resources will be calculated using two different approaches: per diem hospitalization costs (excluding direct medical costs) versus French public diagnosis-related group (DRG). The point of view of the French Public Health System is adopted for this study. Monetary values for 2012 euros prices will be used for all components. Median (range) age was 59.5 (24-72), sex ratio was 1.5, ISS 3 was 26% in either group, all patients were collected to allow the number of graft requested by the hematologist of reference. The median CD34 collected was 8.9 (4-30) for HD cyclophosphamide and 5.8 (2-15) for plerixafor. All data will be updated at ASH 2016 including cost comparison. Conclusion. Because of the intense competition for hospital resources and the staff required to evaluate and manage patients preparing for stem cell mobilization and transplantation, it is reasonable to attempt to quantify the total impact of stem cell mobilization on available staff resources and cost to the hospital, especially when newer therapies, i.e. plerixafor is available and may be more suitable for some of these patients. Disclosures Macro: Janssen: Consultancy, Honoraria; Bristol: Consultancy; Celgen: Consultancy, Honoraria; Novartis: Honoraria; sanofi: Consultancy; Amgen: Consultancy, Honoraria. Hulin:celgene: Honoraria; janssen: Honoraria; takeda: Honoraria. Attal:sanofi: Consultancy; celgene: Consultancy, Research Funding; janssen: Consultancy, Research Funding; amgen: Consultancy, Research Funding. Moreau:Novartis: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria, Speakers Bureau; Celgene: Honoraria. Leleu:TEVA: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; LeoPharma: Honoraria; Pierre Fabre: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 8
    Publication Date: 2012-11-16
    Description: Abstract 3993 Introduction: One of the main feature of MM is bone disease resulting from an increased osteoclastic activity and inhibition of osteoblast function; this imbalance also promotes MM growth leading to a vicious circle. Interestingly mature osteoblasts reduce osteoclastogenesis via high levels of OPG and reduced levels of RANKL and have anti-MM effect too, especially via decorin causing MM cells apoptosis. Hence, therapeutic approaches restoring osteoblast function could reduce osteoclastogenesis and MM growth. Mature osteoblasts originate from bone marrow mesenchymal stromal cells (MSC) that are key component of MM microenvironment. We and others showed that MSC from patients with MM are abnormal. In particular, they have an impaired capacity to diffentiate into osteoblasts. Hence we studied mesenchymal stromal cells from adipose tissue (AT) called the Adipose derived Stromal Cells (ASC). They have very similar properties than MSC, in particular osteoblastic differentiation capacity. The aim of our work is to demonstrate that ASC from patients with MM are normal, contrary to their MSC; we propose the first study comparing ASC from MM patients and ASC from Healthy Donor (HD) with functional and genomics tests. Patients and Methods: We studied ASC from 15 patients with newly diagnosed MM (MM ASC) and CRAB symptoms and from 15 HD (HD ASC) between 18 and 65 years. The stromal vascular fraction was isolated from subcutaneous AT by centrifugation and enzymatic digestion. The ASC were sorted by adhesion to the plastic flask and expanded for 3 passages of 21 days in culture medium MEMa containing 10% FBS and ciprofloxacine. We perform: Results: Our data confirm the stromal nature of MM and HD ASC. The cells were adherent and proliferate into plastic flasks; able to differentiate into osteogenic, chondrogenic and adipogenic lineage; positive for CD90, CD73, CD105 and negative for CD14, CD45. We next found that MM and HD ASC have the same expansion capacity (HD 470±45, MM 208±194, p=0.13), cell population doubling (HD 16.0±0.3, MM 15.0±1.3 p=0,17), and progenitor frequency (HD 3.4%±3, MM 3.7±5,5%, p=0.166). Phenotype didn't show any significant difference except for CD200. Osteogenic, chondrogenic and adipogenic differentiation assays didn't show any difference according to the origin of ASC; alizarin (mmol/l): HD 2.66±0.6, MM 2.15±2.1 p=0.15, chondroitin sulfate (ng/ml): HD 0.5±0.17, MM 0.58±0.58 p=0.2, glycerol (mg/well): HD 2.7±1.6, MM 3.28±1.2 p=0.26. Measurement of IL-6 (HD 7143±10029, MM 10192±6379 pg/ml p=0.15), DKK1 (HD 16698±2432, MM 15948±6558 pg/ml p=0.98), and GDF15 (HD 0.29±0.3, MM 0.43±0.37 ng/ml p=0.13) shows similar levels in both population. We then analysed proliferation rate of MOLP-6 in co-culture with ASC and observed no difference (proliferation rate HD 1.49±0.34, MM 1.66±0.80 p=0,33). MM ASC and HD ASC had the same capacity to support haematopoiesis. Finally, genomic analysis performed by GEP did not identify any difference between the two groups. miRNA analysis tested 1036 targets and found only one, HSA-MIR-196A, differentially expressed between HD and MM ASC(p=0,014). Conclusion: To our knowledge, this is the first exhaustive study that compare ASC from MM patients and HD. Our results strongly suggest that MM ASC are normal and could potentially be used in autologous stem cell transplantation in order to restore the patients' osteoblastic function. Disclosures: Roussel: celgene: Honoraria; janssen: Honoraria. Attal:celgene: Membership on an entity's Board of Directors or advisory committees; janssen: Membership on an entity's Board of Directors or advisory committees.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 9
    Publication Date: 2014-12-06
    Description: Impact on Survival Outcomes of Bone Marrow Plasma Cells Percentage and Morphology Evaluation by Conventional Microscopy in Multiple Myeloma after High Dose Therapy. Background: The achievement of at least CR is a crucial step for a long-lasting response and prolonged survival after autologous stem cell transplantation (ASCT) in patients (pts) with multiple myeloma (MM). The current definition of complete remission (CR) or better in MM requires a negative serum and urine immunofixation (IF) and
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 10
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...