Disease Monitoring In Patients Research Articles

Clinical significance of baseline Pan-Immune-Inflammation Value and its dynamics in metastatic colorectal cancer patients under first-line chemotherapy

Pan-Immune-Inflammation Value (PIV) has been recently proposed as a new blood-based prognostic biomarker in metastatic colorectal cancer (mCRC). Herein we aimed to validate its prognostic significance and to evaluate its utility for disease monitoring in patients with mCRC receiving first-line chemotherapy. We conducted a single-centre retrospective study involving 130 previously untreated mCRC patients under first-line standard chemotherapy in a real-world scenario. PIV was calculated as (neutrophil count × platelet count × monocyte count)/lymphocyte count at three different time-points: baseline, week 4 after therapy initiation, and at disease progression. We analyzed the influence of baseline PIV on overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and overall response rate (ORR). We also explored the utility of PIV dynamics for disease monitoring. Baseline PIV high was significantly associated with worse OS in univariate [hazard ratio (HR) = 2.10, 95% CI, 1.41–3.15; p = 0.000299] and multivariate (HR = 1.82, 95% CI, 1.15–2.90; p = 0.011) analyses. Baseline PIV was also associated with worse PFS in univariate (HR = 2.04, 95% CI, 1.40–2.97; p = 0.000187) and multivariate (HR = 1.56, 95% CI, 1.05–2.31; p = 0.026) analyses. Baseline PIV was not correlated either with DCR or ORR. Regarding PIV dynamics, there was a statistically significant increase from week 4 to disease progression (p = 0.0003), which was at the expense of cases with disease control as best response (p < 0.0001). In conclusion, this study validates the prognostic significance of baseline PIV in patients with mCRC receiving first-line standard chemotherapy in a real-world scenario. Moreover, it suggests the potential utility of PIV monitoring to anticipate the disease progression among those patients who achieve initial disease control.

A Wearable Respiration Sensor for Real-Time Monitoring of Chronic Kidney Disease.

Human respiration is accompanied with abundant physiological and pathological information, such as the change in ammonia (NH3) content, which is related to chronic kidney disease (CKD); hence, monitoring the breathing behavior helps in health assessment and illness prediction. In this work, a wearable respiration sensor based on CeO2@polyaniline (CeO2@PANI) nanocomposites that underwent a hydrogen plasma treatment is developed. The results unambiguously show that the response of the corresponding nanocomposites is significantly enhanced from 165 to 670% to 100 ppm NH3 compared to the counterpart that did not undergo hydrogen plasma treatment and even reaches 24% to 50 ppb NH3, suggesting its fascinating capability of detecting the trace level of NH3 in human breathing. The superior response for NH3 is ascribed to the stable oxygen vacancies produced by the hydrogen plasma treatment. Furthermore, the clinical tests for patients with uremia suggest that the as-designed sensor has potential applications in clinical monitoring for CKD. Herein, this work offers a new strategy to obtain respiration sensors with high performance and provides a feasible approach for health evaluation and disease monitoring of patients with CKD.

Value of measurable residual disease monitoring in patients with acute promyelocytic leukemia in the era of frontline ‘chemotherapy-free’ therapy

Acute promyelocytic leukemia (APL) is characterized by the chromosomal translocation t(15;17) and the resulting gene PML-RARA, used for measurable residual disease (MRD) monitoring. Despite highly effective therapy for APL, MRD monitoring practices are not fully established. We aimed to assess the value of MRD monitoring by RT-qPCR in patients with APL treated with ATRA and arsenic trioxide +/– GO. We reviewed 223 patients with APL treated with this regimen. RT-qPCR for PML-RARA was measured every 3 months, and at 12, 18, and 24 months after therapy. Seven patients relapsed. Time to relapse was 7.9–12.4 months in 6 patients, and one patient relapsed after 79.5 months. These data show that MRD monitoring may be important for the detection of relapse in patients treated with this regimen within one year after completing therapy, however, since late molecular relapse is rare, our data suggest a low value of MRD monitoring beyond that first year.

Targeted Next Generation Sequencing of Circulating Tumor DNA in Multiple Myeloma

Introduction: Immunophenotypic and chromosomal analysis among patients with multiple myeloma (MM) has traditionally been performed on plasma cells enriched from bone marrow aspirates. However, due to the patchy nature of MM, a bone marrow aspirate may not accurately represent the total body burden of disease nor does it reflect the true heterogeneity of the cancer cells. Additionally, since it is an invasive procedure, frequent resampling to monitor clonal evolution is infeasible. Next generation sequencing of circulating tumor DNA is a promising new approach that may address these shortcomings. Circulating tumor DNA, either from cell-free DNA or circulating tumor cells, originates from multiple different sites of disease and may be obtained from a single blood sample. This non-invasive approach may enable clinicians to detect early signs of resistance, monitor minimal residual disease, identify therapeutic targets, and provide prognostic information to help guide treatment decisions.Methods: Bone marrow mononuclear cells (BMMC), peripheral blood mononuclear cells (PBMC), and plasma samples were obtained from 45 patients treated at our center at the time of MM diagnosis, remission, or disease relapse. All samples were obtained through an Institutional Review Board approved protocol. DNA was extracted and library preparation for next generation sequencing was performed using unique molecular identifiers (UMI). The incorporation of UMIs allows for the identification and removal of errant base calls introduced during PCR amplification and Illumina sequencing thereby increasing the sensitivity of the assay to detect rare mutations. Target enrichment was performed using a panel of primers specific to exons of genes known to be significantly, recurrently mutated in MM as well as genes with predictive or prognostic value. Illumina sequencing was performed to a depth of 10,000X. Comparison of single nucleotide variants (SNV) and indels between matched BMMC, PBMC and plasma samples was determined. Correlation of clinical outcomes with mutation status and variant allele frequency was performed.Results: While good concordance was found between BMMC, PBMC, and plasma samples among the SNVs and indels detected, distinct variants unique to each tissue compartment were also identified. Indicating the assay may have utility for disease monitoring, variants detected in the blood pre-treatment were no longer detectable in post-treatment remission samples. Additionally, new variants in blood samples not present prior to initiation of therapy were detected at later time points providing evidence for clonal evolution. Finally, driver mutations were found in genes for which known targeted therapy is available or in genes that may theoretically confer drug resistance such as CUL4A that binds to Cereblon, a target of the immunomodulatory drug lenalidomide.Conclusions: While bone marrow biopsy represents the standard of care for diagnosis and disease monitoring in patients with multiple myeloma, the procedure is subject to sampling bias and frequent serial biopsies are impractical. A noninvasive approach using targeted next generation sequencing of circulating tumor cells is an appealing alternative. We demonstrate the feasibility of this technique in MM PBMC and plasma samples and find evidence that the assay may support clinical decision making. DisclosuresNo relevant conflicts of interest to declare.

One-Step Multiplexed Droplet Digital Polymerase Chain Reaction for Quantification of p190 BCR-ABL1 Fusion Transcript in B-Lymphoblastic Leukemia.

Quantification and detection of the t(9;22) (BCR-ABL1) translocation in chronic myelogenous leukemia and B-lymphoblastic leukemia are important for directing treatment protocols and monitoring disease relapse. However, quantification using traditional reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) is dependent on a calibration curve and is prone to laboratory-to-laboratory variation. Droplet digital polymerase chain reaction (ddPCR) is a novel method that allows for highly sensitive absolute quantification of transcript copy number. As such, ddPCR is a good candidate for disease monitoring, an assay requiring reproducible measurements with high specificity and sensitivity. To compare results of ddPCR and RT-qPCR BCR-ABL1 fusion transcript measurements of patient samples and determine if either method is superior. We optimized and standardized a 1-step multiplexed ddPCR assay to detect BCR-ABL1 p190 and ABL1 e10 transcripts. The ddPCR optimization included varying cycle number and primer concentration with standardization of droplet generation and droplet number and analyses to improve data sensitivity. Following optimization, ddPCR measurements were performed on clinical samples and compared with traditional RT-qPCR results. Droplet digital polymerase chain reaction was able to detect the BCR-ABL1 p190 transcript to 0.001% (1:10-5) with a calculated limit of detection and limit of quantitation of 4.1 and 5.3 transcripts, respectively. When tested on patient samples, ddPCR was able to identify 20% more positives than a laboratory-developed 2-step RT-qPCR assay. Droplet digital polymerase chain reaction demonstrated increased detection of BCR-ABL1 compared with RT-qPCR. Improved detection of BCR-ABL1 p190 and the potential for improved standardization across multiple laboratories makes ddPCR a suitable method for disease monitoring in patients with acute B-lymphoblastic leukemia.

Study on Integrated Workflow Development and Presentation of Fangcang Shelter Hospitals in COVID-19 Pandemic

Fangcang shelter hospital, which serves as hospital for isolation, treatment and disease monitoring of patients with mild symptoms, has made significant achievements in the prevention and control of COVID-19 pandemic. Meanwhile, due to the urgency and innovation of the task, managers lack clear management of the operation task flow. This paper presents some experiences learnt from the management of Fangcang shelter hospitals, which adopted the LEAN methodology to develop an integrated workflow system with clear responsibilities and process standards as a framework for performance improvement, involving nurses, patient, physicians, clerical staff, logistics staff, and other inter professional staff as well as managers and support staff.

1198P Digital droplet PCR-based detection of TP53 mutations in circulating DNA for the disease monitoring in patients with hereditary ovarian or breast cancer

1198P Digital droplet PCR-based detection of TP53 mutations in circulating DNA for the disease monitoring in patients with hereditary ovarian or breast cancer

Conformational anti–desmoglein 3 enzyme-linked immunosorbent assay is not superior to conventional anti–desmoglein 3 enzyme-linked immunosorbent assay for disease monitoring in patients with pemphigus vulgaris—A longitudinal study

Conformational anti–desmoglein 3 enzyme-linked immunosorbent assay is not superior to conventional anti–desmoglein 3 enzyme-linked immunosorbent assay for disease monitoring in patients with pemphigus vulgaris—A longitudinal study

The role of interleukin-6 in monitoring severe case of coronavirus disease 2019.

Progression to severe disease is a difficult problem in treating coronavirus disease 2019 (COVID‐19). The purpose of this study is to explore changes in markers of severe disease in COVID‐19 patients. Sixty‐nine severe COVID‐19 patients were included. Patients with severe disease showed significant lymphocytopenia. Elevated level of lactate dehydrogenase (LDH), C‐reactive protein (CRP), ferritin, and D‐dimer was found in most severe cases. Baseline interleukin‐6 (IL‐6) was found to be associated with COVID‐19 severity. Indeed, the significant increase of baseline IL‐6 was positively correlated with the maximal body temperature during hospitalization and with the increased baseline of CRP, LDH, ferritin, and D‐dimer. High baseline IL‐6 was also associated with more progressed chest computed tomography (CT) findings. Significant decrease in IL‐6 and improved CT assessment was found in patients during recovery, while IL‐6 was further increased in exacerbated patients. Collectively, our results suggest that the dynamic change in IL‐6 can be used as a marker for disease monitoring in patients with severe COVID‐19.

Identification of Serum miRNA Signature and Establishment of a Nomogram for Risk Stratification in Patients With Pancreatic Ductal Adenocarcinoma.

The aim of the study was to perform mRNA-miRNA regulatory network analyses to identify a miRNA panel for molecular subtype identification and stratification of high-risk patients with pancreatic ductal adenocarcinoma (PDAC). Recent transcriptional profiling effort in PDAC has led to the identification of molecular subtypes that associate with poor survival; however, their clinical significance for risk stratification in patients with PDAC has been challenging. By performing a systematic analysis in The Cancer Genome Atlas and International Cancer Genome Consortium cohorts, we discovered a panel of miRNAs that associated with squamous and other poor molecular subtypes in PDAC. Subsequently, we used logistic regression analysis to develop models for risk stratification and Cox proportional hazard analysis to determine survival prediction probability of this signature in multiple cohorts of 433 patients with PDAC, including a tissue cohort (n = 199) and a preoperative serum cohort (n = 51). We identified a panel of 9 miRNAs that were significantly upregulated (miR-205-5p and -934) or downregulated (miR-192-5p, 194-5p, 194-3p, 215-5p, 375-3p, 552-3p, and 1251-5p) in PDAC molecular subtypes with poor survival [squamous, area under the receiver operating characteristic curve (AUC) = 0.90; basal, AUC = 0.89; and quasimesenchymal, AUC = 0.83]. The validation of this miRNA panel in a tissue clinical cohort was a significant predictor of overall survival (hazard ratio = 2.48, P < 0.0001), and this predictive accuracy improved further in a risk nomogram which included key clinicopathological factors. Finally, we were able to successfully translate this miRNA predictive signature into a liquid biopsy-based assay in preoperative serum specimens from PDAC patients (hazard ratio: 2.85, P = 0.02). We report a novel miRNA risk-stratification signature that can be used as a noninvasive assay for the identification of high-risk patients and potential disease monitoring in patients with PDAC.

Hypermethylated RASSF1A as Circulating Tumor DNA Marker for Disease Monitoring in Neuroblastoma.

PURPOSECirculating tumor DNA (ctDNA) has been used for disease monitoring in several types of cancer. The aim of our study was to investigate whether ctDNA can be used for response monitoring in neuroblastoma.METHODSOne hundred forty-nine plasma samples from 56 patients were analyzed by quantitative polymerase chain reaction (qPCR) for total cell free DNA (cfDNA; albumin and β-actin) and ctDNA (hypermethylated RASSF1A). ctDNA results were compared with mRNA-based minimal residual disease (qPCR) in bone marrow (BM) and blood and clinical patient characteristics.RESULTSctDNA was detected at diagnosis in all patients with high-risk and stage M neuroblastoma and in 3 of 7 patients with localized disease. The levels of ctDNA were highest at diagnosis, decreased during induction therapy, and not detected before or after autologous stem-cell transplantation. At relapse, the amount of ctDNA was comparable to levels at diagnosis. There was an association between ctDNA and blood or BM mRNA, with concordant results when tumor burden was high or no tumor was detected. The discrepancies indicated either low-level BM infiltration (ctDNA negative/mRNA positive) or primary tumor/soft tissue lesions with no BM involvement (ctDNA positive/mRNA negative).CONCLUSIONctDNA can be used for monitoring disease in patients with neuroblastoma. In high-risk patients and all patients with stage M at diagnosis, ctDNA is present. Our data indicate that at low tumor load, testing of both ctDNA and mRNA increases the sensitivity of molecular disease monitoring. It is likely that ctDNA can originate from both primary tumor and metastases and may be of special interest for disease monitoring in patients who experience relapse in other organs than BM.

The Potential Role of IL-6 in Monitoring Coronavirus Disease 2019

Background: The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan City, China spreads rapidly since December, 2019. Most patients show mild symptoms, but some of them develop into severe disease. There is currently no specific medication. The purpose of this study is to explore changes of markers in peripheral blood of severe COVID-19 patients, which may be of value in disease monitoring. Methods: Clinical data of patients with nonsevere and severe type COVID-19 diagnosed by laboratory test in our institution were collected. The relationship between peripheral blood cells and cytokines, clinical manifestation and outcome was analyzed. Results: A total of 69 severe type COVID-19 patients were included. On admission, the median age of severe cases was 56-year old, with 52.17% of female patient. The most common symptoms were fever (79.72%), coughing (63.77%), shortness of breath (57.97%) and fatigue (50.72%). Diarrhea is less common. The most common comorbidity is hypertension. Upon admission, the proportion of bilateral pulmonary involvement or interstitial pneumonia evidenced by CT imaging in severe cases was 60.87% and 27.54%, respectively. Compared with patients with nonsevere disease, those with severe disease showed lymphocytopenia. Elevated level of lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin and D-dimer was found in most cases. Two patients (2.9%) needed transfer to the intensive care unit. Baseline immunological parameters and most of the inflammatory parameters were basically within the normal range. However, baseline IL-6 was significantly increased in severe type which is closely related to the maximal body temperature during hospitalization and CT findings. Baseline IL-6 was also significantly related to the increase of baseline level of CRP, LDH, ferritin and D-dimer. The increase of baseline IL-6 level suggests that it may positively correlate with the severity of COVID-19. Among the 30 severe type patient whose level of IL-6 was assessed before and after treatment, significant decrease in IL-6 and improved CT assessment was found in 25 patients after treatment. Whereas the IL-6 level was further increased in 3 cases, which was closely related to the progression of pneumonia. It is suggested that IL-6 may be used as a biomarker for disease monitoring in severe COVID-19 patients. Conclusion: On admission, the baseline level of IL-6, CRP, LDH and ferritin was closely related to the severity of COVID-19, and the high level of IL-6 was significantly related to the clinical manifestation of severe type patients. The decrease of IL-6 was closely related to treatment effectiveness, while the increase of IL-6 indicated disease progression. Collectively, the dynamic change of IL-6 level can be used as a marker for disease monitoring in patients with severe COVID-19. Funding Statement: This work was supported by the National Natural Science Foundation of China (No. 81602696 to TL) and Science and Technology Major Project of China (No.2018ZX10302204-002-003). Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: This study was approved by the Research Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology. Written consent was obtained from patients before the enrollment.

QUANTIFICATION OF RETINAL CAPILLARY NONPERFUSION IN DIABETICS USING WIDE-FIELD OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

To combine advances in high-speed, wide-field optical coherence tomography angiography (OCTA) with image processing methods for semiautomatic quantitative analysis of capillary nonperfusion in patients with diabetic retinopathy (DR). Sixty-eight diabetic patients (73 eyes), either without retinopathy or with different degrees of retinopathy, were prospectively recruited for volumetric swept-source OCTA imaging using 12 mm × 12 mm fields centered at the fovea. A custom, semiautomatic software algorithm was used to quantify areas of capillary nonperfusion. The mean percentage of nonperfused area was 0.1% (95% confidence interval: 0.0-0.4) in the eyes without DR; 2.1% (95% confidence interval: 1.2-3.7) in the nonproliferative DR eyes (mild, moderate, and severe), and 8.5% (95% confidence interval: 5.0-14.3) in the proliferative DR eyes. The percentage of nonperfused area increased in a statistically significant manner from eyes without DR, to eyes with nonproliferative DR, to eyes with proliferative DR. Capillary nonperfusion area in the posterior retina increases with increasing DR severity as measured by swept-source OCTA. Quantitative analysis of retinal nonperfusion on wide-field OCTA may be useful for early detection and monitoring of disease in patients with diabetes and DR.

Measurement of Salivary Adrenal-Specific Androgens as Biomarkers of Therapy Control in 21-Hydroxylase Deficiency.

Monitoring of hormonal control represents a key part of the management of congenital adrenal hyperplasia (CAH). Monitoring strategies remain suboptimal because they rely on frequent blood tests and are not specific for adrenal-derived hormones. Recent evidence suggests the crucial role of adrenal-specific 11-oxygenated-C19 androgens in the pathogenesis of CAH. To establish a correlation between plasma and salivary adrenal-specific androgens in CAH as a noninvasive monitoring strategy. This prospective cross-sectional study recruited patients between 2015 and 2018. Multicenter study including 13 tertiary centers in the United Kingdom. Seventy-eight children with CAH and 62 matched healthy controls. Using liquid chromatography-tandem mass spectrometry, plasma and salivary concentrations of five steroids were measured: 17-hydroxyprogesterone (17OHP), androstenedione (A4), testosterone (T), 11-hydroxyandrostenedione (11OHA4), and 11-ketotestosterone (11KT). The correlation between plasma and salivary steroids was analyzed to assess their use in clinical practice. Strong correlations between plasma and salivary steroid concentrations in patients with CAH were detected: 17OHP (rs = 0.871; P < 0.001), A4 (rs = 0.931; P < 0.001), T (rs = 0.867; P < 0.001), 11OH4A (rs = 0.876; P < 0.001), and 11KT (rs = 0.944; P < 0.001). These results were consistent for patient subgroups based on sex and age. Analysis of patient subgroups based on 17OHP concentrations established clear correlations between plasma and salivary concentrations of the adrenal-specific androgen 11KT. The current study identified tight correlations between plasma and saliva for the adrenal-derived 11-oxygenated C19 androgen 11KT, as well as 17OHP and A4, which are widely used for monitoring treatment in CAH. This combination of steroid hormones will serve as an improved noninvasive salivary test for disease monitoring in patients with CAH.

Metabolic MRI for In Vivo Detection of Graft-Versus-Host Disease in a Pre-Clinical Model

Chronic graft-versus-host disease (cGVHD) remains a prominent barrier preventing successful allogeneic hematopoietic stem cell transplantation (AHSCT). Diagnosis of cGVHD is challenging since biopsies of the involved tissues are associated with bleeding and infection risks. In the absence of biopsy specimens, clinicians rely on subjective clinical scoring for cGVHD diagnosis and monitoring of therapeutic responses. Our previous studies in the pre-clinical cGVHD mouse model demonstrated that the primary cellular mediators of cGVHD, alloreactive donor-derived CD4+ T cells, are distributed to target rather than lymphoid organs. This is in direct contrast to syngeneic HSCT recipients (matched host and donor pairings) where T cells are primarily localized to lymphoid organs. Our prospective metabolic screening and ex vivo metabolic profiling of CD4+ T cell subsets indicated that effector memory T cells (Tem) preferentially utilize aerobic glycolysis. Thus, we hypothesized that visualization of tissues exhibiting high rates of glycolysis could allow in vivo detection of cGVHD in the affected organs since they are infiltrated by alloreactive glycolytic Tem cells. In order to test this, we initiated metabolic magnetic resonance imaging (MRI) in the minor antigen mismatched HSCT mouse model. Following administration of 13C-pyruvate, we measured the conversion of the glycolytic end product, pyruvate, into lactate as a means of evaluating glycolytic rates in target organs. Indeed, hyperpolarized 13C-pyruvate MRI of the liver and gut distinguished allogeneic versus syngeneic HSCT recipients, prior to the development of clinically evident cGVHD. This imaging approach is amenable to clinical translation to potentially allow for cGVHD diagnosis and disease monitoring in patients.

PP186 Telemonitoring With Pacemakers For Patients With Heart Failure

IntroductionEvidence supporting the use of pacemakers is well established. However, evidence about the optimal use of pacemaker telemonitoring for disease management in heart failure is not. Health Technology Wales (HTW) held a national adoption event to encourage implementation and best practice in use of pacemaker telemonitoring in the National Health Service (NHS) Wales to improve patient outcomes in heart failure.MethodsMulti-stakeholder national adoption workshop using a mixture of expert presentations, case studies and interdisciplinary group and panel discussions to agree key actions to understand the value and promote optimal use of pacemakers for remote disease monitoring in patients with heart failure in Wales.ResultsThe workshop was attended by forty-five senior professionals with an interest in improving care of patients with heart failure. Actions to progress included: providing a centralized Welsh system to support technical issues that arise with telemonitoring; considering interoperability with other NHS Wales systems; encouraging value-based procurement with collection of a core outcome set; agreeing implementation issues with both professionals and patients; audit to understand experience, resource use and outcomes; and sharing manufacturer evidence on the accuracy of telemanagement algorithms. It was suggested that these actions be progressed via an All-Wales multi-stakeholder approach, led by the Welsh Cardiac Network.ConclusionsDeveloping a more agile, lifecycle approach to technology appraisal is currently advocated; recalibrating the focus from technology assessment to technology management across the complete technology lifecycle. HTW will endeavour through regular adoption events to facilitate such a paradigm shift that aims to understand value and optimise use of evidence-based technologies.

Clinical and Radiological Assessment in Axial Spondyloarthritis

Abstract The Assessment of SpondyloArthritis International Society (ASAS) has developed the concept of axial spondyloarthritis (SpA) in 2009. The symptoms and burden of disease of nonradiographic axial SpA and Ankylosing Spondylitis (AS) are similar and both can affect multiple organs and systems. Assessment and monitoring in SpA are, therefore, crucial. Different instruments have been developed for assessing and monitoring the wide variety of presentations in SpA. Generally, disease monitoring of patients can include patient reported outcome, clinical findings, laboratory tests, imaging, and disease activity composite scores.

Efficacy of Bortezomib Based Regimens and Disease Monitoring in Light Chain Multiple Myeloma: A Review of Literature

IntroductionLight chain multiple myeloma (LCMM) constitutes approximately 15% of patients with multiple myeloma (MM). It has an earlier average age of onset (54 years) and appears to have a poorer prognosis when compared to IgG or IgA variant. The main aim of our analysis is to study the published literature on the efficacy of bortezomib (V) based regimens and disease monitoring in patients with LCMM.MethodsWe performed a literature search of articles published after 2012 using following four databases (PubMed, Embase, Cochrane Library and Web of Science). We included only English language studies and summarized our data using medians, absolute values, and percentages.ResultsThe literature search identified a total of 390 articles on LCMM. After detailed scrutiny, 6 studies involving a total of 1054 LCMM patients (pts) were included. In a study by Zhang et al. (2014) including 96 pts, 66 pts received 4 cycles of V (1 mg/m2) with dexamethasone (D) (20 mg) while 30 pts received non-V regimens. In bortezomib group, the overall response rate (ORR) was 95.5%. Complete response (CR) was seen in 56.1% pts while 39.4% pts showed partial response (PR). In non-bortezomib group, the ORR was 60%. CR was seen in 10% pts while 50% pts showed PR. The overall survival (OS) at 3 and 5 years in bortezomib group was 33% and 24% respectively while the OS in non-bortezomib group was 28% and 9% respectively (p=0.335). The progression free survival (PFS) at 1, 2 and 3 years in bortezomib group was 37%, 25% and 8% respectively while the PFS at 1 and 2 years in non-bortezomib group was 27% and 9% respectively (p=0.036) (Table 1). In two different studies by Mrachacz et al. (2015) and Tessenow et al. (2017), a total of 45 pts were treated with V (1.3 mg/m2) in combination with bendamustine (B) (60 mg/m2) and prednisone (P) (100 mg). ORR was 95.5% including 37.7% pts with CR, 22.2% pts with very good partial response (VGPR) and 35.5% pts with PR. Median OS at 24 and 30 months was 95% and 96 % respectively while PFS at 24 and 30 months was 90% and 68% respectively. In another study by Heaney et al. (2017) including 576 pts, 567 (98.4%) pts were identified by serum free light chain (sFLC) level compared to 460 (79.8%) pts which were identified by urine free light chain (uFLC) level. Hundred thirty-two pts were evaluated at maximum response to therapy with V. ORR was 98.4% including 43.1% pts with CR, 44.6% pts with VGPR, 10.6% pts with PR and 1.5 % pts had stable disease (SD).In a study by Dejoie et al. PFS (2016) including 113 pts, Urine Protein Electrophoresis (UPEP) was positive in 87 (78.3%) out of 111 evaluable pts while serum involved free light chain (iFLC) was positive in all (113) pts. Seventy eight %, 37% and 18% pts showed abnormal UPEP at baseline (diagnosis), treatment cycle 1 and treatment cycle 3 respectively while 100%, 71% and 46% of pts showed abnormal iFLC at baseline, treatment cycle 1 and treatment cycle 3 respectively, indicating sFLC as more sensitive indicator of the disease than UPEP. Abnormal iFLC level at the end of consolidation therapy showed a statistically significant shorter PFS than pts with normal iFLC level [p= 0.004; Hazard ratio (HR) = 2.7; 95% CI = 1.4-5.4]. UPEP did not reach any statistical significance in determining PFS [p = 0.178; HR= 1.6; 95% CI= 0.8-3.3]. No statistically significant data was found for abnormal iFLC and abnormal UPEP in determining OS [(p= 0.164; HR= 2.2; 95% CI= 0.7-6.6) and (p= 0.891; HR= 0.9; 95% CI= 0.2-4.0) respectively]. However, abnormal sFLC ratio at the end of consolidation therapy showed a statistically significant shorter PFS (p= 0.006; HR= 3.1; 95% CI= 1.4-6.8) as well as OS (p=0.047; HR=7.8; 95% CI= 1.0-58.5). In a similiar study by Bradwell et al. including 224 pts, 82 pts were evaluated at follow up after chemotherapy with vincristine, doxorubicin and melphalan. CR was seen in 26 (31.7%) pts as indicated by normal uFLC levels compared with only 9 (10.9%) pts by their normal sFLC levels, indicating false negative results with uFLC compared to sFLC.ConclusionThere is a paucity of data on LCMM in the literature. V has shown superior efficacy in LCMM patients over non-V regimens with ORR > 95%. Moreover, V showed better PFS at 2 years when used with bendamustin compared to VD (95% vs. 25%). Similarly, V with B showed better OS i.e. 90% at 2 years. Moreover, sFLC levels were more sensitive in indicating the disease and predicting PFS and OS compared to uFLC levels, hence monitoring of LCMM patients should include serum assays. DisclosuresNo relevant conflicts of interest to declare.

Next-generation sequencing-based minimal residual disease monitoring in patients receiving allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia or myelodysplastic syndrome.

The monitoring of minimal residual disease (MRD) has important clinical implications in both the pre and postallogeneic stem cell transplant (SCT) setting in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Next-generation sequencing (NGS) is a rapidly improving technology whose application to the monitoring of MRD is an active area of research. We aim to describe existing methods of MRD in AML and MDS, with a focus on the utility of NGS in patients undergoing SCT. Flow cytometry and quantitative PCR have been recommended by the European Leukemia Net as the preferred methods of MRD in AML and MDS, but these methods have limitations in cases without a disease-defining phenotype and genotype. Clinical trials are currently ongoing to assess the use of NGS in the setting of SCT for MDS and AML. Few studies have so far assessed the optimal method of MRD monitoring in the posttransplant setting. The optimal method for the monitoring of MRD in AML and MDS both pre and post transplant may require more than one technology. NGS holds great promise for the monitoring of MRD, with prospective trials currently ongoing to evaluate its efficacy in this regard.

An Overview of Light Chain Multiple Myeloma: Clinical Characteristics and Rarities, Management Strategies, and Disease Monitoring.

Light chain multiple myeloma (LCMM) constitutes approximately 15% of patients with multiple myeloma (MM). It has a poorer prognosis when compared to immunoglobulin (Ig) G or IgA variant. We performed a comprehensive literature search on LCMM and identified a total of 390 articles. After a detailed screening, six studies involving a total of 1054 LCMM patients were included. A literature review revealed bone pain and renal failure as the most common initial sign and symptoms while extramedullary disease (EMD) was acquired later during the progression of the disease. Bortezomib has shown superior efficacy in LCMM patients over nonbortezomib regimens as demonstrated by better overall response rate (95.5% vs. 60%), progression-free survival (PFS) (25% vs. 9% at two years), and overall survival (OS) (24% vs. 9% at five years). Moreover, better PFS was seen, when bortezomib was used in combination with bendamustine compared to dexamethasone (95% vs. 25% at two years). Similarly, better OS (90% at two years) was observed with bortezomib in combination with bendamustine. Monitoring of disease should include serum free light chain levels, as literature review revealed that serum assays were more sensitive in indicating the disease and predicting PFS and OS as compared to urine assays. We provide presentation patterns, clinical rarities, management strategies including their efficacy, and disease monitoring in patients with LCMM in our review paper.