early progression
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Author(s):  
Ta-Chuan Yu ◽  
Shan-Chi Yu ◽  
Ren-Ching Wang ◽  
Shih-Fan Lai ◽  
Chieh-Lin Jerry Teng ◽  
...  

Haematologica ◽  
2022 ◽  
Vol 107 (1) ◽  
pp. 7-18 ◽  
Author(s):  
Guillaume Cartron ◽  
Judith Trotman

Follicular lymphoma is a heterogeneous B-cell lymphoma both in presentation and at progression. For most patients it is a chronic, relapsing indolent disease with overall survival expectations now potentially beyond 20 years. However, in a significant minority (~20%) who experience early progression or histological transformation after treatment, the disease no longer has an indolent behavior. This review looks at the development of prognostic indices, staging and therapies for follicular lymphoma, identifying where the data can, and cannot, guide the multidisciplinary team to determine an individualized approach to first-line therapy. A nuanced patient- and disease-specific approach is necessary to maximize disease response and survival while minimizing therapeutic toxicity.


2021 ◽  
Vol 12 ◽  
Author(s):  
Zhonghong Yan ◽  
Guanran Wang ◽  
Xingyang Shi

Chronic kidney disease (CKD) is one of the increasingly serious public health concerns worldwide; the global burden of CKD is increasingly due to high morbidity and mortality. At present, there are three key problems in the clinical treatment and management of CKD. First, the current diagnostic indicators, such as proteinuria and serum creatinine, are greatly interfered by the physiological conditions of patients, and the changes in the indicator level are not synchronized with renal damage. Second, the established diagnosis of suspected CKD still depends on biopsy, which is not suitable for contraindication patients, is also traumatic, and is not sensitive to early progression. Finally, the prognosis of CKD is affected by many factors; hence, it is ineviatble to develop effective biomarkers to predict CKD prognosis and improve the prognosis through early intervention. Accurate progression monitoring and prognosis improvement of CKD are extremely significant for improving the clinical treatment and management of CKD and reducing the social burden. Therefore, biomarkers reported in recent years, which could play important roles in accurate progression monitoring and prognosis improvement of CKD, were concluded and highlighted in this review article that aims to provide a reference for both the construction of CKD precision therapy system and the pharmaceutical research and development.


2021 ◽  
pp. 1-11
Author(s):  
Deniz Can Guven ◽  
Oktay Halit Aktepe ◽  
Melek Seren Aksun ◽  
Taha Koray Sahin ◽  
Gozde Kavgaci ◽  
...  

BACKGROUND: The albumin-globulin ratio (AGR) could be a prognostic biomarker in patients with cancer, although the data is limited in patients treated with immune-checkpoint inhibitors (ICIs). OBJECTIVES: We aimed to evaluate the association between AGR and survival in ICI-treated patients. METHODS: The data of 212 advanced-stage patients were retrospectively evaluated in this cohort study. The association between AGR with overall (OS) and progression-free survival (PFS) were evaluated with multivariate analyses. Additionally, receptor operating curve (ROC) analysis was conducted to assess the AGR’s predictive power in the very early progression (progression within two months) and long-term benefit (more than twelve months survival). RESULTS: The median AGR was calculated as 1.21, and patients were classified into AGR-low and high subgroups according to the median. In the multivariate analyses, patients with lower AGR (< 1.21) had decreased OS (HR: 1.530, 95% CI: 1.100–2.127, p= 0.011) and PFS (HR: 1.390, 95% CI: 1.020–1.895, p= 0.037). The area under curve of AGR to detect early progression and long-term benefit were 0.654 (95% CI: 0.562–0.747, p= 0.001) and 0.671 (95% CI: 0.598–0.744, p< 0.001), respectively. CONCLUSIONS: In our experience, survival with ICIs was impaired in patients with lower AGR. Additionally, the AGR values could detect the very early progression and long-term benefit ICIs.


2021 ◽  
Vol 12 ◽  
Author(s):  
Andrea K. Brown ◽  
Alyssa Nichols ◽  
Chantell A. Coley ◽  
Ubong S. Ekperikpe ◽  
Kasi C. McPherson ◽  
...  

Recently, we reported that obese Dahl salt-sensitive leptin receptor mutant (SSLepRmutant) rats develop glomerular injury and progressive proteinuria prior to puberty. Moreover, this early progression of proteinuria was associated with elevations in GFR. Therefore, the current study examined whether treatment with lisinopril to reduce GFR slows the early progression of proteinuria in SSLepRmutant rats prior to puberty. Experiments were performed on 4-week-old SS and SSLepRmutant rats that were either treated with vehicle or lisinopril (20 mg/kg/day, drinking water) for 4 weeks. We did not observe any differences in MAP between SS and SSLepRmutant rats treated with vehicle (148 ± 5 vs. 163 ± 6 mmHg, respectively). Interestingly, chronic treatment with lisinopril markedly reduced MAP in SS rats (111 ± 3 mmHg) but had no effect on MAP in SSLepRmutant rats (155 ± 4 mmHg). Treatment with lisinopril significantly reduced proteinuria in SS and SSLepRmutant rats compared to their vehicle counterparts (19 ± 5 and 258 ± 34 vs. 71 ± 12 and 498 ± 66 mg/day, respectively). Additionally, nephrin excretion was significantly elevated in SSLepRmutant rats versus SS rats, and lisinopril reduced nephrin excretion in both strains. GFR was significantly elevated in SSLepRmutant rats compared to SS rats, and lisinopril treatment reduced GFR in SSLepRmutant rats by 30%. The kidneys from SSLepRmutant rats displayed glomerular injury with increased mesangial expansion and renal inflammation versus SS rats. Chronic treatment with lisinopril significantly decreased glomerular injury and renal inflammation in the SSLepRmutant rats. Overall, these data indicate that inhibiting renal hyperfiltration associated with obesity is beneficial in slowing the early development of glomerular injury and renal inflammation.


2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi24-vi24
Author(s):  
Sho Onodera ◽  
Jiro Akimoto

Abstract Tirabrutinib (TIR), a Burton’s tyrosine kinase inhibitory drug, has been approved in Japan for treating relapsed/refractory primary central nervous system lymphoma (PCNSL). The authors recently encountered three patients with newly diagnosed refractory PCNSL using TIR. Three patients, 48, 78 and 88 years-old males, diagnosed with PCNSL by histologically verification were firstly treated with high dose Methotrexate based chemotherapy (HD-MTX) and/or radiotherapy, however these cases were refractory for these standard treatments, demonstrated early cerebrospinal fluid dissemination or accompanied with severe adverse event. The authors decided to administrate TIR to these patients with a full informed consent. TIR demonstrated dramatic reduction of the volume of tumor on MRI within one month after administration of TIR, and improved the patient’s performance status. However, one case demonstrated liver dysfunction and multiple brain abscess due to aspergillus infection, and one case demonstrated early progression of the tumor 49 days after starting TIR. Administration of TIR for the patients with newly diagnosed refractory PCNSL demonstrated a rapid and dramatic clinical response, and presented with several clinical implications for this complicated condition.


2021 ◽  
Author(s):  
Alipi Bonm ◽  
Anthony Menghini ◽  
Jerome J. Graber

Abstract Introduction: Primary CNS lymphoma (PCNSL) outcomes diverge between a majority of patients who achieve long term remission and a smaller minority who have aggressive disease course and die in the first year. Sarcopenia is increasingly recognized as a powerful predictor of mortality in brain and systemic cancers. Temporalis muscle thickness (TMT) is a validated radiographic measure of sarcopenia. We hypothesized that patients with TMT less than one standard deviation below the mean (“very thin TMT”) would go on to have shorter survival. Methods: Two blinded operators retrospectively measured TMT in 99 consecutive pretreatment brain MRIs from patients that were subsequently diagnosed with PCNSL. Results: On univariate analysis TMT predicted early progression (HR 4.25, 95% CI 1.95 – 9.29, p<0.001) and early mortality (HR 4.38, 95% CI 2.25 – 8.53, p<0.001), and these effects were maintained in subgroups of patients both <65 and ³65 years of age. Very thin TMT predicted mortality more robustly than IELSG or MSKCC scores. Patients with very thin TMT received fewer cycles of high-dose methotrexate (HD-MTX) and were less likely to receive consolidation. On multivariate analysis which included the covariates age, sex, TMT, ECOG, BMI, lifetime doses of HD-MTX, and consolidation, very thin TMT was independently associated with both early progression (HR = 7.87, 95% CI = 3.55 – 17.45, p<0.001) and short survival (HR 4.49, 95% CI = 1.94 – 10.40, p<0.001). Conclusions: We conclude that PCNSL patients with very thin TMT are at high risk for relapse and early mortality. Future trials should stratify patients by TMT to avoid potential confounding.


Author(s):  
Ariel A. Salas ◽  
Kent A. Willis ◽  
Waldemar A. Carlo ◽  
Nengjun Yi ◽  
Li Zhang ◽  
...  

Abstract Background Early progression of feeding could influence the development of the gut microbiome. Methods We collected fecal samples from extremely preterm infants randomized to receive either early (feeding day 2) or delayed (feeding day 5) feeding progression. After study completion, we compared samples obtained at three different time points (week 1, week 2, and week 3) to determine longitudinal differences in specific taxa between the study groups using unadjusted and adjusted negative binomial and zero-inflated mixed models. Analyses were adjusted for a mode of delivery, breastmilk intake, and exposure to antibiotics. Results We analyzed 137 fecal samples from 51 infants. In unadjusted and adjusted analyses, we did not observe an early transition to higher microbial diversity within samples (i.e., alpha diversity) or significant differences in microbial diversity between samples (i.e., beta diversity) in the early feeding group. Our longitudinal, single-taxon analysis found consistent differences in the genera Lactococcus, Veillonella, and Bilophila between groups. Conclusions Differences in single-taxon analyses independent of the mode of delivery, exposure to antibiotics, and breastmilk feeding suggest potential benefits of early progression of enteral feeding volumes. However, this dietary intervention does not appear to increase the diversity of the gut microbiome in the first 28 days after birth. Trial Registration ClinicalTrials.gov identifier: NCT02915549. Impact Early progression of enteral feeding volumes with human milk reduces the duration of parenteral nutrition and the need for central venous access among extremely preterm infants. Early progression of enteral feeding leads to single-taxon differences in longitudinal analyses of the gut microbiome, but it does not appear to increase the diversity of the gut microbiome in the first 28 days after birth. Randomization in enteral feeding trials creates appealing opportunities to evaluate the effects of human milk diets on the gut microbiome.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1353-1353
Author(s):  
Jowon Laura Kim ◽  
Alina S. Gerrie ◽  
Kerry J. Savage ◽  
Diego Villa ◽  
David W. Scott ◽  
...  

Abstract Background: Waldenström macroglobulinemia (WM) is a rare, indolent B-cell lymphoproliferative disorder. After the STiL-1 trial (Rummel MJ. Lancet. 2013;381(9873):1203-1210) demonstrated significant benefit in a subgroup analysis as well as reduced toxicity using bendamustine and rituximab (BR) compared to R-CHOP (N=41 enrolled WM patients), BR became the preferred immunochemotherapy (IC) regimen for all patients with symptomatic treatment naïve (TN) WM in British Columbia (BC) since 2014. Prior to the introduction of BR, the combination of rituximab, cyclophosphamide, vincristine, and prednisone (RCVP), was the standard of care in BC for this population since 2004, given its widespread use across a broad range of indolent B-cell lymphomas. We report a population-based analysis evaluating outcomes in TN-WM patients comparing BR with RCVP. Methods: The BC Cancer Centre for Lymphoid Cancer Database was used to identify TN-WM patients treated with BR or RCVP as their first systemic therapy between August 1, 2004 - August 1, 2020. A period of observation but no prior to systemic therapy was permitted. All patients had clinicopathologically confirmed lymphoplasmacytic lymphoma and measurable monoclonal IgM. Event-free survival (EFS) was defined as time from start of IC to progression, relapse, initiation of alternative therapy, histologic transformation, or death due to any cause. Early progression (POD24) was defined as relapse or progression, death from lymphoma, or treatment toxicity within 24 months of initiation of systemic therapy. Outcomes were compared with a historical cohort of patients treated with frontline RCVP. Responding patients were eligible to receive maintenance rituximab (MR) every 3 months for 2 years since 2006; however this was discontinued in 2020 when a subgroup analysis of the MAINTAIN trial (Rummel MJ. Blood 2019; 134 (Supplement_1): 343), showed a lack of PFS benefit after BR, coupled with safety and vaccine response concerns during the COVID-19 pandemic. Results: A total of 111 patients with WM were identified; 57 treated with BR, 54 treated with RCVP. Median age was 69 years (range 33-89) and baseline characteristics (Table 1), were well-balanced. A higher proportion of RCVP-treated patients received &gt;4 cycles of chemotherapy (81% vs 65%, p=0.049). After IC, 75 (68%) received MR, with 36 (63%) and 39 (72%) in the BR and RCVP groups respectively (p=0.3). Median follow-up from diagnosis for all living patients was 5.9 years (range 0.8-19.2), with median 4.4y vs 9.8y for BR and RCVP respectively. EFS estimates at 4-years achieved with BR were 57% (95% CI 40-71%) compared to RCVP 60% (95% CI 45-72%), p=0.5 (Figure 1). Median EFS was established for RCVP due to longer duration of follow up at 6.3 years (95% CI 3.6-11.8y). Overall survival (OS) estimates at 4-years were 74% (95% CI 57-85%) and 81% (95% CI 67-89%) for BR and RCVP patients respectively, p=0.6. Worse performance status (≥2) was the only pre-treatment factor identified as significant for inferior EFS. A sub-analysis limited to patients that received &gt;4 cycles of IC also showed no clear difference in outcomes between BR and RCVP. Median time to transformation was 6.5y (5.5-13y), with only 3 late biopsy-proven events. Early progression (POD24) has occurred in 19 (18%) patients, with inferior survival observed in patients that had an early event compared with a reference cohort (2-years event free), however this did not reach statistical significance (p=0.3) (Figure 1). Conclusion: This population-based analysis of TN-WM patients treated with upfront IC confirms the excellent outcomes that can be achieved with a finite course of therapy. In contrast to prior studies, similar outcomes were observed with RCVP and BR. Further, regardless of front-line therapy, POD24 may be associated with inferior outcome but larger studies are needed. To our knowledge, this study is the first to make a direct comparison between BR and RCVP, and one of the largest restricted to IC-treated TN-WM. This data supports RCVP as a viable option, and should serve to inform clinicians, patients, and policy makers in decision-making when considering upfront therapeutic options, and when considering indefinite alternative regimens such as BTK inhibitors. Figure 1 Figure 1. Disclosures Gerrie: AbbVie: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Astrazeneca: Honoraria, Research Funding; Sandoz: Honoraria; Roche: Research Funding. Savage: Servier: Consultancy, Honoraria; Astra-Zeneca: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Other: Institutional clinical trial funding; Seattle Genetics: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Other: Institutional clinical trial funding; Takeda: Other: Institutional clinical trial funding; AbbVie: Consultancy, Honoraria; Roche: Research Funding; Beigene: Other: Institutional clinical trial funding; Genentech: Research Funding. Villa: Roche: Honoraria; Janssen: Honoraria; Lundbeck: Honoraria; Celgene: Honoraria; Seattle Genetics: Honoraria; AbbVie: Honoraria; AstraZeneca: Honoraria; Gilead: Honoraria; NanoString Technologies: Honoraria. Scott: BC Cancer: Patents & Royalties: Patent describing assigning DLBCL COO by gene expression profiling--licensed to NanoString Technologies. Patent describing measuring the proliferation signature in MCL using gene expression profiling. ; Abbvie: Consultancy; Janssen: Consultancy, Research Funding; AstraZeneca: Consultancy; Rich/Genentech: Research Funding; Celgene: Consultancy; Incyte: Consultancy; NanoString Technologies: Patents & Royalties: Patent describing measuring the proliferation signature in MCL using gene expression profiling.. Craig: Bayer: Consultancy. Slack: Seagen: Consultancy, Honoraria. Sehn: Debiopharm: Consultancy; Novartis: Consultancy; Genmab: Consultancy. Freeman: Amgen: Honoraria; Celgene: Honoraria; Sanofi: Honoraria, Speakers Bureau; Incyte: Honoraria; Abbvie: Honoraria; Teva: Research Funding; Roche: Research Funding; Bristol Myers Squibb: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Seattle Genetics: Honoraria.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1761-1761
Author(s):  
Mariana Bastos Oreiro ◽  
Laura Sanz-Villanueva ◽  
Francisco Diaz Crespo ◽  
Rebeca Bailén ◽  
Gillen Oarbeascoa ◽  
...  

Abstract Introduction: Chimeric antigen receptor (CAR) T-Cell therapy is approved for relapse/refractory diffuse large B cell lymphoma (DLBCL) patients after two lines of therapy. Although it is an effective treatment, approximately 20-30% of patients have an early relapse. In this context, biomarkers that helps to identify those patients who will be refractory to this therapy are relevant. Cell-free DNA (cfDNA) has emerged as a new tool for non-invasive monitoring of patients with lymphoma, therefore the aim of this study was to evaluate dynamic cfDNA concentration in addition to other biomarkers (LDH, CRP, ferritin) before CAR T-cell infusion to detect early progressors. Methods: We selected 44 r/r DLBCL patients treated with CAR T-cell in our centre. Plasma samples were collected pre-apheresis (PA) and pre-infusion (PI)(∆cfDNA). Other biomarkers (LDH, CRP, Ferritin) were studied PA, pre-lymphodepletion (PL) and PI, tumour volume metabolic (TMV) are also studied. CfDNA were obtained from plasma using QIAamp® Circulating Nucleic Acid (Qiagen) and quantified by QuantiFluor dsDNA System (Promega). The Mann-Whitney test was used to compare differences between two independent quantitative variables . ROC analysis was conducted to determine the cut-off value of biomarkers. Cumulative incidence of progression (1 and 3 months) was calculated from the date of CAR T-cell infusion. Data analysis was performed using Stata. Results: Cumulative incidence of relapse at 1 month and 3 months was 20% and 30% respectively. The correlation between the progression (1 month, 3 months) and the different biomarkers is shown in Table 1. The CRP PL, CRP PI, LDH PI and ∆cfDNA (PI-PA, median time 41.5 days [range:31-107]) was correlated with early progression (1 month). No differences were found with progression at 3 months. The different cut-off for the biomarkers selected was 9 ng/mL for ∆cfDNA, 225 U/L for LDH and 1.35 mg/dL for CRP. Cumulative incidence of progression at 1 month was calculated for these biomarkers (figure 1): ∆cfDNA, HR: 4.3 (1.05-17), p=0.042; CRP PL: HR: 6.9 (1.5-31.1), p=0.012; CRP PI, HR: 11.2 (1.5-83), p=0.019 and LDH PI, HR: 3.4 (1-17) p=0.11. It should be noted that 83.3% (10/12) of the patients who progressed during the first month had at least one of the above variables. Conclusions: Our results highlight that increase in cfDNA higher than 9 ng/mL, CRP PL and PI &gt;1.35 mg/dL and LDH PI &gt; 225 U/L before CAR T-cell therapy may detect early progressors within the first month after treatment. Therefore, ∆cfDNA, CRP and LDH could be useful to identify patients who highly probable will not benefit from the CAR T infusion, in which another prior strategy could be considered in an attempt to control the disease. These results need to be confirmed with a larger cohort. Figure 1 Figure 1. Disclosures Bailén: Pfizer: Honoraria; Kite-Gilead: Honoraria; Gilead: Honoraria. Kwon: Gilead: Honoraria.


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