Publications by authors named "Laurent Garderet"

BACKGROUND Focal segmental glomerulosclerosis (FSGS) very rarely occurs in patients with multiple myeloma. Much more common are renal impairments secondary to monoclonal light-chain tubulopathy, AL amyloidosis, light-chain deposition disease, and the so-called monoclonal gammopathy of renal significance. CASE REPORT We report the case of a 79-year-old myeloma patient without noticeable medical problems but with a long history of myeloma treatment beginning 13 years ago.

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  • Autologous peripheral blood stem cell (PBSC) transplantation is a common treatment for conditions like multiple myeloma and lymphomas, and it usually involves freezing the stem cells before transplant.* -
  • A recent systematic review of 19 transplant centers that performed non-cryopreserved PBSC transplants showed that the procedure is feasible and safe, with high stem cell viability and low rates of complications.* -
  • The study found that stem cell viability was over 90% for multiple myeloma and over 75% for lymphomas, with quick engraftment times, and only 1% transplant-related mortality within 100 days.*
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  • Autologous hematopoietic cell transplantation (AHCT) is an effective treatment for multiple myeloma, with real-world data collected from 61,725 patients revealing median overall survival of 90.2 months and median progression-free survival of 36.5 months.* -
  • Cumulative relapse incidence and non-relapse mortality rates at 24 months were found to be 33% and 2.5% respectively, with better outcomes linked to factors like younger age, certain disease subtypes, and high performance status.* -
  • Global variations were observed in patient outcomes based on registry data, influenced by differences in patient characteristics, use of maintenance treatments, and macroeconomic factors, highlighting the safety and effectiveness of AH
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  • * Both types of HCT are risky and complicated, but global collaboration among medical professionals has established it as a standard treatment for many serious blood-related illnesses, resulting in improved patient outcomes.
  • * Over 1.5 million HCT procedures were performed from 1957 to 2019, and this number continues to rise globally, supported by registries and international medical societies.
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  • CD38-targeting immunotherapy combined with lenalidomide and dexamethasone is the current best standard of care for newly diagnosed multiple myeloma patients who can't undergo transplants.
  • A phase 3 study involving 270 patients tested the effectiveness of adding weekly bortezomib to this regimen, comparing the outcomes of the combination (Isa-VRd) against the standard (IsaRd).
  • Results showed a significantly higher rate of minimal residual disease negativity at 18 months and better response rates in the Isa-VRd group, suggesting it could become the new standard of care for these patients.
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Promoting access to and excellence in hematopoietic cell transplantation (HCT) by collecting and disseminating data on global HCT activities is one of the principal activities of the Worldwide Network for Blood and Marrow Transplantation, a non-governmental organization in working relations with the World Health Organization. HCT activities are recorded annually by member societies, national registries and individual centers including indication, donor type (allogeneic/autologous), donor match and stem cell source (bone marrow/peripheral blood stem cells/cord blood). In 2018, 1,768 HCT teams in 89 countries (6 World Health Organization regions) reported 93,105 (48,680 autologous and 44,425 allogeneic) HCT.

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There is little long-term outcome data on the efficacy of autologous hematopoietic stem cell transplantation (ASCT) in light chain deposition disease (LCDD). We identified 51 LCDD patients in the European Society for Blood and Bone Marrow transplantation registry who had undergone upfront ASCT between 1995 and 2021. The median serum creatinine was 280 μmol/L and 45% required renal replacement therapy (RRT) at time of transplant.

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Recent treatment advancements in multiple myeloma have led to significant improvements in patient outcomes. Maintenance therapy following autologous haematopoietic stem cell transplantation (AHCT) is now standard of care and has been demonstrated to prolong and deepen treatment responses. Currently, lenalidomide remains the single agent that has been approved for maintenance post-AHCT in Europe and the USA which, if tolerated, is continued until disease progression.

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Bortezomib (Vel)- Melphalan 200 mg/m2 (Mel200) (Vel-Mel) has been utilised to intensify conditioning in autologous hematopoietic stem cell transplantation (AHCT) for multiple myeloma (MM). This EBMT registry-based study compared Vel-Mel with Mel200 during upfront AHCT. Between 2010 and 2017, MM patients who received Vel-Mel (n = 292) conditioning were compared with 4,096 Mel200 patients in the same 58 centres.

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  • * In a study of 50 patients with severe renal impairment, only one death occurred within the first 100 days post-transplant, with most patients showing significant improvements in hematological responses.
  • * Overall, after two years, 84% of patients were alive, 70% were free from disease progression, and 59% saw an improvement in kidney function, indicating that the procedure is both safe and effective for this population.
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Here, the International Myeloma Working Group (IMWG) updates its clinical practice recommendations for the management of multiple myeloma-related renal impairment on the basis of data published until Dec 31, 2022. All patients with multiple myeloma and renal impairment should have serum creatinine, estimated glomerular filtration rate, and free light chains (FLCs) measurements together with 24-h urine total protein, electrophoresis, and immunofixation. If non-selective proteinuria (mainly albuminuria) or involved serum FLCs value less than 500 mg/L is detected, then a renal biopsy is needed.

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Subsets of multiple myeloma (MM) and monoclonal gammopathies of undetermined significance (MGUS) present with a monoclonal immunoglobulin specific for hepatitis C virus (HCV), thus are presumably HCV-driven, and antiviral treatment can lead to the disappearance of antigen stimulation and improved control of clonal plasma cells. Here we studied the role of hepatitis B virus (HBV) in the pathogenesis of MGUS and MM in 45 HBV-infected patients with monoclonal gammopathy. We analyzed the specificity of recognition of the monoclonal immunoglobulin of these patients and validated the efficacy of antiviral treatment (AVT).

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Lenalidomide maintenance in myeloma is well established. Nevertheless, pomalidomide could provide an alternative. Myeloma patients in first relapse, initially treated in the Intergroupe Francophone du Myélome (IFM) 2009 trial, and subsequently in the IFM 2013-01 phase 2 trial, received four cycles of salvage therapy with pomalidomide plus cyclophosphamide plus dexamethasone (PCD) with transplantation plus 2 PCD consolidation or without transplantation but with 5 PCD and for all patients pomalidomide plus dexamethasone maintenance therapy.

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  • Familial forms of monoclonal gammopathy, including multiple myeloma (MM) and Monoclonal Gammopathy of Undetermined Significance (MGUS), are rare, with MGUS being more commonly observed and sometimes advancing to MM.
  • A study identified 318 families with multiple cases of monoclonal gammopathy, highlighting potential genetic links and family clusters with parent-child and sibling cases.
  • Despite some genetic similarities, familial cases generally present similarly to sporadic cases but show a better prognosis, with longer median survival rates for those with familial MM.
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Background And Purpose: Amyloid myopathy is a rare and severe manifestation of systemic light chain (AL) amyloidosis. Early diagnosis and staging are mandatory for optimal therapy, given the rapid progression of muscle weakness. Despite the efficacy of bortezomib-based treatment regimens, there is a lack of therapeutic alternatives in non-responsive patients.

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Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapeutic approach in the treatment of multiple myeloma, and the recent approval of the first two CAR T-cell products could result in improved outcomes. However, it remains a complex and expensive technology, which poses challenges to health-care systems and society in general, especially in times of crises. This potentially accelerates pre-existing inequalities as access to CAR T-cell therapy varies, both between countries, depending on the level of economic development, and within countries, due to structural disparities in access to quality health care-a parameter strongly correlated with socioeconomic status, ethnicity, and lifestyle.

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  • Primary plasma cell leukemia (pPCL) is a rare cancer with limited research on the best transplant methods; a study analyzed 751 pPCL patients from 1998-2014 to compare four transplant strategies: single autologous, single allogeneic, tandem auto-allo, and tandem auto-auto.
  • Results showed that the allo-first approach had a lower relapse rate but higher non-relapse mortality compared to the auto-first approach within 36 months; patients undergoing auto-allo had better progression-free survival without increased short-term risks.
  • This comprehensive analysis highlights the importance of disease status at transplant and suggests that tandem transplant strategies may be more effective, providing valuable insights for clinical decisions
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Background: The main goal of this post hoc analysis of the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study was to evaluate the rate of short- and long-term infectious and non-infectious complications occurring after ASCT in patients with multiple myeloma (MM). Methods: The analysis included all patients with MM from the CALM study who underwent ≥1 ASCT. The primary endpoint of the analysis was to determine the rate of infectious and non-infectious complications after ASCT and to compare them in three time periods: 0−100 days, 101 days−1 year, and >1 year after the first transplant.

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  • High-dose melphalan (HDM) combined with bortezomib (Bor-HDM) was tested in a phase 3 trial for patients with multiple myeloma to see if it was more effective than HDM alone.* -
  • The trial included 300 patients, and results showed no significant differences in complete response rates or minimum residual disease rates between the two treatment groups.* -
  • Although progression-free survival was slightly better in the Bor-HDM group (34.0 months) compared to HDM (29.6 months), the overall survival rates and serious adverse events were similar, indicating Bor-HDM did not provide a clear advantage.*
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Infection remains the leading cause of morbidity and mortality in patients with multiple myeloma because of the cumulative effect of disease, treatment, and host-related factors. Given that infectious risk is cumulative through the course of the disease, preventing infections is paramount. Optimal preventive strategies include vaccination against common pathogens, antimicrobial prophylaxis, infection control measures, and immunoglobulin replacement in a small subset of patients; however, there are no universally accepted guidelines for infection prevention.

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Primary plasma cell leukemia (PCL) has a consistently ominous prognosis, even after progress in the last decades. PCL deserves a prompt identification to start the most effective treatment for this ultra-high-risk disease. The aim of this position paper is to revisit the diagnosis of PCL according to the presence of circulating plasma cells in patients otherwise meeting diagnostic criteria of multiple myeloma.

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Monoclonal gammopathy of ocular significance (MGOS) is a rare subset of monoclonal gammopathy of clinical significance occurring secondary to plasma cell disorders and causing ocular manifestations. We identified 23 patients with paraproteinemic keratopathy (PPK) in the setting of monoclonal gammopathy of unknown significance (MGUS, 10), smoldering multiple myeloma (SMM, 3) or multiple myeloma (MM, 10). Many of these patients with PPK (11/23) presented decreased vision.

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Patients with multiple myeloma frequently present with substantial immune impairment and an increased risk for infections and infection-related mortality. The risk for infection with SARS-CoV-2 virus and resulting mortality is also increased, emphasising the importance of protecting patients by vaccination. Available data in patients with multiple myeloma suggest a suboptimal anti-SARS-CoV-2 immune response, meaning a proportion of patients are unprotected.

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Myeloma is characterized by bone lesions, which are related to both an increased osteoclast activity and a defect in the differentiation of medullary mesenchymal stem cells (MSCs) into osteoblasts. Outside the medullary environment, adipocyte-derived MSCs (ASCs) could represent a source of functional osteoblasts. However, we recently found a defect in the osteoblastic differentiation of ASCs from myeloma patients (MM-ASCs).

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Multiple myeloma (MM) is rare in young patients, especially before age 40 years at diagnosis, representing <2% of all patients with MM. Little is known about the disease characteristics and prognosis of these patients. In this study, we examined 214 patients diagnosed with MM at age ≤40 years over 15 years, in the era of modern treatments.

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