scholarly journals The Impact of Induction Regimes on Immune Responses in Patients with Multiple Myeloma

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4090
Author(s):  
Michael A. Firer ◽  
Michael Y. Shapira ◽  
Galia Luboshits
Keyword(s):  
Multiple Myeloma ◽  
Immune Responses ◽  
Induction Therapy ◽  
Immune Cell ◽  
Induction Phase ◽  
Current Standard ◽  
Treatment Protocols ◽  
Cell Mortality ◽  
The Impact ◽  
Cell Functionality

Current standard frontline therapy for newly diagnosed patients with multiple myeloma (NDMM) involves induction therapy, autologous stem cell transplantation (ASCT), and maintenance therapy. Major efforts are underway to understand the biological and the clinical impacts of each stage of the treatment protocols on overall survival statistics. The most routinely used drugs in the pre-ASCT “induction” regime have different mechanisms of action and are employed either as monotherapies or in various combinations. Aside from their direct effects on cancer cell mortality, these drugs are also known to have varying effects on immune cell functionality. The question remains as to how induction therapy impacts post-ASCT immune reconstitution and anti-tumor immune responses. This review provides an update on the known immune effects of melphalan, dexamethasone, lenalidomide, and bortezomib commonly used in the induction phase of MM therapy. By analyzing the actions of each individual drug on the immune system, we suggest it might be possible to leverage their effects to rationally devise more effective induction regimes. Given the genetic heterogeneity between myeloma patients, it may also be possible to identify subgroups of patients for whom particular induction drug combinations would be more appropriate.

scholarly journals Oxidative Stress Compromises Lymphocyte Function in Neonatal Dairy Calves

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 255
Author(s):  
Wilmer Cuervo ◽  
Lorraine M. Sordillo ◽  
Angel Abuelo
Keyword(s):  
Oxidative Stress ◽  
Immune Responses ◽  
Immune Cell ◽  
Lymphocyte Activation ◽  
Dairy Calves ◽  
Lymphocyte Function ◽  
Newborn Calves ◽  
Ifn Γ ◽  
The Impact

Dairy calves are unable to mount an effective immune response during their first weeks of life, which contributes to increased disease susceptibility during this period. Oxidative stress (OS) diminishes the immune cell capabilities of humans and adult cows, and dairy calves also experience OS during their first month of life. However, the impact that OS may have on neonatal calf immunity remains unexplored. Thus, we aimed to evaluate the impact of OS on newborn calf lymphocyte functions. For this, we conducted two experiments. First, we assessed the association of OS status throughout the first month of age and the circulating concentrations of the cytokines interferon-gamma (IFN-γ) and interleukin (IL) 4, as well as the expression of cytokine-encoding genes IFNG, IL2, IL4, and IL10 in peripheral mononuclear blood cells (PBMCs) of 12 calves. Subsequently, we isolated PBMCs from another 6 neonatal calves to investigate in vitro the effect of OS on immune responses in terms of activation of lymphocytes, cytokine expression, and antibody production following stimulation with phorbol 12-myristate 13-acetate or bovine herpesvirus-1. The results were compared statistically through mixed models. Calves exposed to high OS status in their first month of age showed higher concentrations of IL-4 and expression of IL4 and IL10 and lower concentrations of IFN-γ and expression of IFNG and IL2 than calves exposed to lower OS. In vitro, OS reduced lymphocyte activation, production of antibodies, and protein and gene expression of key cytokines. Collectively, our results demonstrate that OS can compromise some immune responses of newborn calves. Hence, further studies are needed to explore the mechanisms of how OS affects the different lymphocyte subsets and the potential of ameliorating OS in newborn calves as a strategy to augment the functional capacity of calf immune cells, as well as enhance calves’ resistance to infections.

MRD-Detection by Multiparametric Flow Cytometry in Childhood Precursor B-Cell All:Predictive Impact of Early Blast Reduction Kinetics in Peripheral Blood (PB) on MRD-Level in Bone Marrow (BM) at Day 33 of the All-BFM2000 Potocol.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 987-987
Author(s):  
Richard Ratei ◽  
Mathilde Martin ◽  
Guiseppe Basso ◽  
Guiseppe Gaipa ◽  
Martin Schrappe ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Phase I ◽  
Correlation Coefficient ◽  
Induction Therapy ◽  
Lymphoblastic Leukemia ◽  
Induction Phase ◽  
Spearman Correlation ◽  
Multiparametric Flow Cytometry ◽  
Cell Counts ◽  
The Impact

Abstract Detection of minimal residual disease in childhood acute lymphoblastic leukemia (ALL) has been proven to be of crucial importance for relapse prediction. However, MRD assessment, usually performed at postinduction time points, does not allow early stratification of induction therapy. Here, we address the predictive impact of early blast reduction in pB on BM MRD-levels at the end of induction therapy phase I (d33), quantified by multiparametric flow cytometry (MFC-MRD). Absolute blast cell counts (BCC, blasts/μl) in pB at diagnosis and day 8 as well as MRD-levels in BM and pB at day 15 and 33 were determined in a series of 77 consecutive patients (pts.) enrolled in the AIEOP-BFM-FCM-MRD pilot study (BM d33:MRD+ n=29, MRD- n=48). Blast cells were detected using a two platform method and a 4-color antibody panel with three follow-up tubes:1) CD20-FITC/CD10-PE/CD34-PC5/CD19-PC7, 2) CD58-FITC/CD10-PE/ CD34-PC5/CD19-PC7, 3) CD10-FITC/CD11a-PE/CD45-PC5/CD19-PC7. Additionally, staining with the cell permeant live-cell nucleic acid fluorochrome SYTO 16 combined with CD19 or CD3 and CD45 were used to exclude residual non-nucleated erythroid cells, platelets or debris from absolute blast calculations. We found that BCC in BM and pB at d15 but not at diagnosis and after prednisone prephase at day 8 correlated with MRD-levels in BM at d33 (Spearman correlation coefficient rs=0.41, p<0.001 and rs=0,30, p<0,01). In order to further investigate the impact of early blast reduction between day 0 and day 8 we calculated the relative blast reduction rate on day 8 (BRRd8 = 1-BCCd8/BCCd0). In the group of MRD-negative patients the mean values of BRRd8 were found to be significantly higher than in the group of MRD-positive pts. (98,9% vs. 88,0%, p< 0,05). Moreover, the BRRd8 correlated with MRD-levels in BM at day 33 (Spearman correlation coefficient rs=−0.25, p<0.05). In the current series of pts. maximally selected log-rank statistics were performed for the BRRd8 and the MRD-level in BM at d33 and provided a cut-off value of 97% separating MRD-positive and MRD-negative pts. In conclusion, the assessment of the dynamics of early blast reduction with the parameter of BRRd8 is highly predictive for the outcome of induction phase I of the ALL-BFM2000 protocol.

Retrospective Comparison of Transplant Outcomes in Patients with Multiple Myeloma According to Induction Therapy with Thalidomide/Dexamethasone (TD) with or without Bortezomib (VTD).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 948-948 ◽  
Author(s):  
Sergio Giralt ◽  
Rupi Thandi ◽  
Muzaffar Qazilbash ◽  
Floralyn Mendoza ◽  
Eric Han ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Therapy ◽  
Response Rates ◽  
Induction Treatment ◽  
High Dose ◽  
Cell Transplant ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Treatment Characteristics ◽  
The Impact

Abstract Background: Thalidomide/Dexamethasone (TD) has become one of the most commonly used induction therapies for patients with symptomatic multiple myeloma (MM) eligible for high dose therapy (HDT) intensification with autologous stem cell transplant (ASCT). Bortezomib (Velcade) has been added to the combination of TD (VTD) in an effort to reduce MM tumor burden further prior to HDT.The impact of this addition on HDT outcomes has not been fully explored. Purpose: To determine the impact of the addition of bortezomib to TD induction therapy in patients with MM undergoing HDT and ASCT consolidation. Patients and Methods: Patients were eligible for this analysis if they had undergone HDT with ASCT for first remission consolidation or primary refractory disease within 12 months of diagnosis between 9/03 and 12/05 and had received either TD or VTD as induction therapy. Patients receiving VTD after TD were excluded. Patients receiving more than 1 chemo regimen other than TD or VTD were excluded. Chemomobilization was NOT considered an exclusion criteria. Results A total of 78 patients qualified for the analysis (27 VTD; 51 TD). Patient and treatment characteristics are summarized in table 1. In brief, the patients receiving VTD had a higher rate of cytogenetic abnormalities and received less cycles of chemotherapy prior to SCT. Although pre-SCT response rates were similar between patients receiving VTD or TD (95% vs 92%) there was a trend for a higher CR rate in the VTD group (15% vs 6%). Post transplants response rates assessed between 3–6 months demonstrated that 28% and 38% of VTD patients achieved near CR and CR respectively while 19% and 23% had these responses post TD induction. There was no difference in 2 year OS and PFS among patients receiving VTD or TD (91% vs 81% and 35% and 56% respectively). Conclusion: Both VTD and TD as induction treatment are associated with high response rates prior to SCT as well as 6 months post SCT. In this retrospective analysis no survival benefit was seen for induction therapy with VTD over TD, despite higher near CR and CR rates. However randomized trials need to be performed addressing type of induction as well as duration of induction therapy prior to high dose therapy consolidation. Patient and Treatment Characteristics Variables VTD TD N 27 51 Median Age 54 (34–71) 56 (34–71) %ISS> 1 76% 65% % CG Abnormal 37% 19% p=.009 B2M @ Dx 2.99 3.19 Cycles Prior to SCT 2 4 p=.00009 % Mel 200 74% 69% Post SCT Maintenance 15/27 23/51

Bortezomib (Velcade)-Melphalan-Prednisone (VMP) Versus Velcade- Thalidomide-Prednisone (VTP) in Elderly Untreated Multiple Myeloma Patients: Which Is the Best Partner for Velcade: An Alkylating or An Immunomodulator Agent?

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 651-651 ◽  
Author(s):  
Maria-Victoria Mateos ◽  
Albert Oriol ◽  
Joaquín Martínez ◽  
Ma Teresa Cibeira ◽  
Raquel de Paz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Median Time ◽  
Induction Therapy ◽  
Response Rate ◽  
Haematological Toxicity ◽  
Phase Iii ◽  
Induction Treatment ◽  
Induction Phase ◽  
Weekly Schedule ◽  
To Receive

Abstract Melphalan – Prednisone (MP) has been the Standard of care for elderly multiple myeloma patients in the past 40 years. However, bortezomib and thalidomide-based combinations have demonstrated to improve the efficacy in terms of both response rate and time to events as compared to MP. In two recent Phase II and phase III trials we have shown (Mateos et al. Blood 2006; San Miguel JF et al. EHA 2008) that the combination VMP is highly effective, but it remains to be elucidated which agent is the optimal partner for bortezomib: an alkylating or an immunomodulatory drug. In order to answer this question in April 2006, Spanish Myeloma Group (PETHEMA/GEM) activated a phase III trial comparing VMP versus VTP in untreated MM patients older than 65 years. Patients in the VMP arm received intravenous bortezomib 1.3 mg/m2 twice weekly (days 1, 4, 8, 11; 22, 25, 29 and 32) for one 6-week cycle (8 doses per cycle), followed by once weekly (days 1, 8, 15 y 22) for five 5-week cycles (4 doses per cycle) in combination with oral melphalan 9 mg/m2 and prednisone 60 mg/m2 once daily on days 1–4 of each cycle. Patients in the VTP arm received the same bortezomib and prednisone regimen, but instead of melphalan they received continuous thalidomide at dose of 100 mg daily. For both groups, treatment continued for a maximum of 6 cycles (31 weeks) unless disease progression or unacceptable treatment-related toxicity occurred. The primary endpoint was overall response rate (ORR) after induction therapy and secondary endpoints included time to progression (TTP), progression-free survival (PFS), overall survival (OS), time to and duration of response, and safety. As of July 30, 2008, 246 out of 260 planned patients have been included in the study and 167 are evaluables for response to induction therapy and adverse events (AEs). Efficacy and toxicity analyses were performed on an intention-to-treat basis. 80 patients were randomly assigned to receive VMP and 87 to receive VTP. Regarding baseline characteristics, including cytogenetic abnormalities, no significant differences were observed in both arms. No significant differences were observed in response rate: ≥ PR in 78% of patients in VMP and VTP groups respectively, with a CR rate of 18% vs 23% (p=NS) and CR/nCR of 38% vs 32% (P= NS). Only one patient prgressed under induction treatment in each arm. Median time to first response was similar in both arms (1,6 months) and there were not differences in the median time to achieve CR (4,4 vs 4,9 months). Regarding haematological toxicity, VMP resulted in higher incidence of ≥G3 neutropenia (34% vs 19%; p=0,009) and thrombocytopenia (21% vs 9%; p=0,01); in contrast, 157 related non-hematological AEs occurred in VTP arm vs 133 in VMP arm (p<0,005); and they were ≥G3 in 32% vs 25% (p=0,04). The most relevant toxicities included: ≥G3 cardiac toxicity reported in 7% of patients receiving VTP vs 0% in VMP arm; the incidence of ≥G3 thromboembolic events was 3,4% in VTP arm and <1% in VMP arm; finally, 15% of patients in VTP arm developed ≥G3 peripheral neuropathy and 9% in VMP arm. No significant differences were reported in other non-hematologic toxicities, including infections despite the higher incidence of neutropenia in VMP arm. Treatment discontinuation due to AEs was required in 8 patients in VMP arm and in 16 patients in VTP arm (p=0,08). Five patients in VMP arm and 7 in VTP group died during the induction phase due to AEs. In summary this initial analysis indicates that there are no significant differences in terms of efficacy between VMP and VTP, while the incidence of non-hematological AEs, specially cardiac events, was higher in the VTP arm, resulting in more serious AEs and treatment discontinuations.. These data suggest that thalidomide may not be the partner of choice for combination with bortezomib and other IMIDs such as lenalidomide should be explored. In addition, our data indicate that the modified VMP regimen used in this trial (weekly schedule after cycle 1 and only six cycles) is well tolerated although the CR rate is lower than in the VISTA trial.

Cytopenia at Diagnosis Impairs Stem Cell Mobilization Among Patients with Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5828-5828
Author(s):  
Selami Kocak Toprak ◽  
Atilla Uslu ◽  
Erden Atilla ◽  
Pervin Topcuoglu ◽  
Gunhan Gurman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Risk Score ◽  
Induction Therapy ◽  
Peripheral Blood ◽  
Stem Cell Mobilization ◽  
Categorical Variables ◽  
Hematological Toxicity ◽  
Cell Mobilization ◽  
The Impact

Abstract Introduction: The GIMEMA group has recently developed a risk score predicting mobilization failure (Musto et al, EHA 2014). The risk score included age, cytopenia at diagnosis, induction therapy and their toxicity. In this study we aimed to evaluate the impact of these factors on peripheral blood stem cell (PBSC) mobilization among patients with multiple myeloma (MM). Patients and methods: 125 newly diagnosed patients with MM (M: 76, F: 49) planned for autologous stem cell transplantation; median age 58 years (range, 30-67) were included in the analysis. This retrospective study examined the impact of age (> 60 years), gender of the patients, cytopenia (Hb<10 gr/dL, absolute neutrophil count < 1x109/L, thrombocyte count < 100x109/L) at diagnosis, and severe hematological toxicity during induction therapy, the type of induction and mobilization methods, the presence of neuropathy, comorbid diseases such as diabetes mellitus, hypertension and renal failure (creatinine > 2 mg/dL), and the use of beta blocker drugs. Patients with CD34+ levels of <20/μL in peripheral blood at maximum stimulation were considered to be Poor Mobilizers. The total amount of PBSC <5x106/kg after a single mobilization procedure was defined as sub-optimal collection. Poor mobilization was observed in only two patients (<2x106/kg). Statistics: Comparison of categorical variables was evaluated by chi-square test or Fisher exact test. Nominal variables were compared with non-parametrical test, Mann-Whitney U or Kruskal Wallis test. P value below as 0.05 was accepted as significance. Results: Optimal mobilization with median two apheresis (1-4) sessions for PBSC was obtained in 85.6% of the patients (n=107). Median CD34+ cells in this group were 8.33x106/kg (5-27x106/kg). The presence of cytopenia at diagnosis was the only significantly detrimental factor on mobilization (90% vs 77.1%, p=0.04). When the patients was scored in four groups as having single or combined variables (age, cytopenia at the diagnosis or during induction therapy), we were not able to develop a risk score. Conclusions: In our experience, 14.4% of the myeloma patients showed suboptimal or poor mobilization. Use of bortezomib, age, presence of neurotoxicity or hematological toxicity at mobilization did not significantly impair mobilization. We were able to confirm only cytopenia at diagnosis, from the four factors reported by Musto et al, as a detrimental factor impairing the stem cell mobilization. Disclosures No relevant conflicts of interest to declare.

scholarly journals Lipofection with Synthetic mRNA as a Simple Method for T-Cell Immunomonitoring

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1232
Author(s):  
Natalia Teresa Jarzebska ◽  
Julia Frei ◽  
Severin Lauchli ◽  
Lars E. French ◽  
Emmanuella Guenova ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Simple Method ◽  
Murine Splenocytes ◽  
T Cell Immune Responses ◽  
Synthetic Mrna ◽  
The Impact

The quantification of T-cell immune responses is crucial for the monitoring of natural and treatment-induced immunity, as well as for the validation of new immunotherapeutic approaches. The present study presents a simple method based on lipofection of synthetic mRNA in mononuclear cells as a method to determine in vitro T-cell responses. We compared several commercially available transfection reagents for their potential to transfect mRNA into human peripheral blood mononuclear cells and murine splenocytes. We also investigated the impact of RNA modifications in improving this method. Our results demonstrate that antigen-specific T-cell immunomonitoring can be easily and quickly performed by simple lipofection of antigen-coding mRNA in complex immune cell populations. Thus, our work discloses a convenient solution for the in vitro monitoring of natural or therapy-induced T-cell immune responses.

scholarly journals Subcutaneous Versus Intravenous Bortezomib in Two Different Induction Therapies for Newly Diagnosed Multiple Myeloma – Subgroup Analysis from the GMMG-MM5 Trial

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3475-3475 ◽  
Author(s):  
Maximilian Merz ◽  
Hans Salwender ◽  
Mathias Hänel ◽  
Uta Bertsch ◽  
Christina Kunz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Induction Therapy ◽  
Research Funding ◽  
Group Iv ◽  
Route Of Administration ◽  
Prolonged Treatment ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
The Impact

Abstract Background: In patients with relapsed multiple myeloma (MM), Moreau and colleagues (Lancet Oncol, 2011) demonstrated that subcutaneous (SC) administration of bortezomib (BTZ) significantly reduced rates of adverse events (AE) compared to the intravenous (IV) formulation without loss of efficacy. Prospective data on SC BTZ in newly diagnosed MM are limited. We investigated the impact of SC versus IV BTZ in two different induction therapies for patients with newly diagnosed MM treated within the multicenter, prospective randomized MM5 trial of the German Myeloma Multicenter Group (GMMG). Methods: From 06/2010 until 11/2013, 604 patients were randomly assigned to receive 3 cycles of PAd (BTZ 1.3 mg/m2, days 1, 4, 8 and 11; Doxorubicin 9 mg/m2 IV, days 1-4; Dexamethasone 20 mg/d, orally, days 1-4, 9-12 and 17-20) or 3 cycles VCD (BTZ 1.3 mg/m2, days 1, 4, 8 and 11; Cyclophosphamide 900 mg/m2IV; day 1, Dexamethasone 40 mg/d, orally, days 1-2, 4-5, 8-9 and 11-12) for induction therapy. In the MM5 trial, induction therapy is followed by stem cell mobilization and harvest, high-dose therapy and Lenalidomide-based consolidation/maintenance therapy. Primary end points of the ongoing study are response to treatment after induction therapy and progression-free survival. Due to improved AE profile of SC compared to IV BTZ reported by Moreau, the administration of BTZ was changed from IV to SC in 02/2012. Therefore, we were able to perform an explorative analysis of 598 patients who received at least one dose of trial medication (PAd: n=150 IV / 140 SC; VCD: n=154 IV / 140 SC). 14 patients were excluded from the analysis because administration of BTZ was changed after start of induction therapy. We analyzed whether the route of administration influenced the applied cumulative BTZ dose, toxicity and efficacy of PAd and VCD. Results: The cumulative applied BTZ dose was significantly higher in patients treated with SC BTZ (PAd: 28.9 mg; VCD: 28.8 mg) compared to IV-treated patients (PAd: 27.6 mg; VCD: 27.9 mg; p = 0.007). Analysis of reported AEs associated to induction therapy revealed a significantly higher rate in patients treated with IV BTZ (65.1%) compared to SC-treated patients (55.7%, p = 0.02). AE > °II were reported more frequently in the IV group (IV: 52.0%; SC: 43.9%, p = 0.004). In detail, abnormal laboratory findings including leucopenia and thrombocytopenia (IV: 23.0%; SC: 16.4%, p = 0.05), metabolism and nutrition disorders (IV: 12.5%; SC: 5.4%, p = 0.004) and gastrointestinal disorders (IV: 9.9%; SC: 3.9%, p = 0.006) occurred more often in IV-treated patients. Analysis of peripheral neuropathy (PN) ≥ °II revealed no significant differences between IV and SC BTZ during the first two cycles of induction therapy (cycle 1: IV: 1.6%; SC: 2.5%; cycle 2: IV: 2.3%; SC: 3.6%) but PN occurred more often in IV-treated patients during the third cycle of induction therapy compared to the SC group (IV: 7.6%; SC: 1.8%, p = 0.001). Overall response rates (partial response or better) were not influenced by the route of administration in patients treated with PAd (IV: 72.7%; SC: 70.7%; p = 0.79) or VCD (IV: 77.9%; SC: 82.1%; p = 0.39). Analysis of the VCD arm showed that rates of VGPR or better were significantly higher in patients treated with IV BTZ compared to SC-treated patients (IV: 41.6%; SC: 28.6%, p = 0.02). Rates of VGPR or better were also higher for IV-treated patients in the PAd arm but did not reach statistical significance (IV: 36.7%; SC: 31.4%, p=0.39). Patient characteristics including baseline creatinine levels > 2 mg/dl, obesity or age at inclusion > 65 years did not influence efficacy of IV or SC BTZ in both arms. Conclusion: Last year we reported on the favorable toxicity profile and equal efficacy of VCD compared to PAd. With the current analysis we demonstrate that toxicity is further reduced with SC BTZ compared to IV. We therefore recommend VCD as induction therapy. However, we show for the first time a possible loss of efficacy in SC-treated patients. Therefore it remains unclear whether the reduced toxicity justifies the general application of SC BTZ in newly diagnosed, transplant-eligible patients or whether a prolonged treatment (4 x VCD SC) may reduce toxicity while achieving similar efficacy. Further studies are warranted since our results are partially in contrast with the previously presented data in relapsed MM and the ongoing MM5 trial was initially not designed to prospectively investigate the effect of SC or IV BTZ. Disclosures Salwender: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Binding site: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Scheid:Celgene: Honoraria; Janssen: Honoraria. Mai:Janssen: Travel support Other. Hose:Novartis: Research Funding. Schmidt-Wolf:Janssen: Consultancy, Honoraria. Weisel:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Onyx: Consultancy, Honoraria; BMS: Consultancy; Noxxon: Consultancy. Duerig:Janssen: Consultancy, Honoraria; Celgene: Honoraria. Goldschmidt:Janssen-Cilag: Honoraria, Research Funding, Speakers Bureau; Polyphor: Research Funding; Celgene: Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; Chugai: Research Funding, Speakers Bureau; Onyx: Consultancy, Speakers Bureau; Millenium: Consultancy, Speakers Bureau.

scholarly journals Obesity Correlates With Pronounced Aberrant Innate Immune Responses in Hospitalized Aged COVID-19 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Michael Z. Zulu ◽  
Suhas Sureshchandra ◽  
Amanda N. Pinski ◽  
Brianna Doratt ◽  
Weining Shen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Host Response ◽  
Immune Cell ◽  
Severe Disease ◽  
Low Grade ◽  
Igg Antibody ◽  
Aged Patients ◽  
Prevalence Of Obesity ◽  
Antibody Titers ◽  
The Impact

Both age and obesity are leading risk factors for severe coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Specifically, although most infections occur in individuals under the age of 55 years, 95% of hospitalizations, admissions to the intensive care unit, and deaths occur in those over the age of 55 years. Moreover, hospitalized COVID-19 patients have a higher prevalence of obesity. It is generally believed that chronic low-grade inflammation and dysregulated innate and adaptive immune responses that are associated with aging and obesity are responsible for this elevated risk of severe disease. However, the impact of advanced age and obesity on the host response to SARS-CoV-2 infection remains poorly defined. In this study, we assessed changes in the concentration of soluble immune mediators, IgG antibody titers, frequency of circulating immune cells, and cytokine responses to mitogen stimulation as a function of BMI and age. We detected significant negative correlations between BMI and myeloid immune cell subsets that were more pronounced in aged patients. Similarly, inflammatory cytokine production by monocytes was also negatively correlated with BMI in aged patients. These data suggest that the BMI-dependent impact on host response to SARS-CoV-2 is more pronounced on innate responses of aged patients.

scholarly journals Long Term Survival Analysis of Multiple Myeloma Patients Receiving Induction Therapy+ Autologous STEM CELL Trasplantation, Comparing Velcade-Dexametasone to Alkylating Polichemotherapy As Induction Therapy

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5764-5764
Author(s):  
Sara Caceres ◽  
Rocio Cardesa ◽  
Carmen Cabrera ◽  
M. Helena Bañas ◽  
Fatima Ibañez ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Therapy ◽  
Conflicts Of Interest ◽  
Autologous Bone Marrow Transplantation ◽  
Young Patients ◽  
Progression Free Survival ◽  
Autologous Bone Marrow ◽  
Term Survival ◽  
The Impact

Abstract Introduction: Multiple Myeloma (MM) is an incurable disease. In young patients, autologous bone marrow transplantation (ABMT) remains a cornerstone treatment after induction therapy. Induction therapy has varied during time, from alkylating polychemotherapy (VBAD,VCMP) or VAD chemotherapy (AVAD) to Velcade-Dexametasone based regimens (VD). We present results of follow-up of a large cohort of patients treated with ABMT. We described overall survival (OS; from transplant to death by any cause) and progression free survival (PFS; from transplant to death by any case or progressive disease defined by reappearance by inmunofixation, or duplication of monoclonal peak after ABMT) , and the impact of induction therapy regiments. Patients: 183 patients transplanted from 2002 to 2017. The median age of the patients was 59 years (33-72). Before 2008 all the patients were treated in alkylating based chemotherapy (42 patients). After 2008 patients were treated with VD based regimens (141patients). Only 12 patients received maintenance therapy based in PETHEMA trials 2005 and 2012. No one patient received a planed second transplant; only 32 patients received a second transplant after relapse as consolidation therapy. Results: Median follow-up of patients still alive is 3.65 years (0.15-14.77). Median OS of all patients was 9.12 years (95% confidence interval (CI): 6.28-NR); Median PFS was 3.02 years(95% CI: 2.46-3.76). At 13 years only 2% of patients remains progression free (CI: 0.00-17%). There were significant differences between patients treated before and after VD regimens. The median OS of patients treated with APVAD was significantly shorter compared to VD (6.22 years, CI[3.39-12] vs. NR, CI[6.28-NR], p=0.025) (HR=0.49, p=0.01). Conclusions: VD schemes of induction before ABMT have improved remarkably OS inpatients with Myeloma; nonetheless, plateau is not observed in EFS. Further analysis must address if EFS could represent a strong indicator of OS, mainly due to novel effective salvage therapies after relapse/refractoriness could be a confounding factor. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

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