Evidence Of Clinical Relapse Research Articles

Liquid biopsy with plasma Epstein-Barr virus DNA characterizes biological relapse for the prediction of cancer recurrence in non-disseminated nasopharyngeal carcinoma

PurposeTo investigate whether a bounce in plasma Epstein-Barr virus (EBV) DNA during posttreatment surveillance of nasopharyngeal carcinoma (NPC) informs the risk of clinical recurrence and its implication for early therapeutic intervention. Methods950 non-disseminated NPC patients with completed remission in 3 months after treatment were retrospectively screened. Detectable EBV DNA with no evidence of clinical relapse during follow-up was deemed as DNA bounce. The diagnostic and prognostic performance of EBV DNA bounce was assessed for subsequent failures. ResultsTumor recurrence occurred in 6.6 %, 10.1 % and 65.8 % in the group with persistently negative EBV DNA, single positive test and ≥ 2 positive tests, respectively. EBV DNA bounce over twice was associated with worse disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) than the other two groups. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for the prediction of recurrence were 0.56, 0.95, 0.66, 0.93 and 0.90 using two positive tests, which were hence deemed as biological relapse. Serial cutoffs (EBV DNA 1 ≥ 40 copies/ml or EBV DNA 2 ≥100 copies/ml) further defined a high-risk subgroup with an eventual recurrence rate of 77.9 % and 3-year DFS of merely 20.5 %. Prophylactic medical intervention with capecitabine or S1 significantly improved the 3-year DFS when compared to those with observation. ConclusionsThe earliest two positive tests of EBV DNA represent a biomarker of biological relapse that allows early detection of clinical recurrence in EBV-related NPC. For high-risk biological relapse, preemptive intervention provides potential survival benefits.

Fasciitis by Lactococcus garvieae on an immunosuppressed patient by Diabetes Mellitus

Lactococcus garvieae, a gram-positive anaerobe facultative coccus, is a well-known pathogen in the aquaculture and cattle sector, being extremely rare for human beings. There are some case reports of infections caused by this microorganism, however, there are no fasciitis cases up to date. This is a case of a 24-year-old patient with uncontrolled diabetes mellitus and previous COVID-19 pneumonia without sequelae, admitted to the emergency room for a case compatible with fasciitis. Three cultures for L. garvieae were obtained from surgical debridement and microbiological studies were performed using automated VITEK-2 equipment. No posterior complications were documented. The patient went through a skin graft with a favorable response without evidence of clinical relapse.

Chimerism Analysis of Cell-Free DNA in Patients Treated with Hematopoietic Stem Cell Transplantation May Predict Early Relapse in Patients with Hematologic Malignancies.

Background. We studied DNA chimerism in cell-free DNA (cfDNA) in patients treated with HSCT. Methods. Chimerism analysis was performed on CD3+ cells, polymorphonuclear (PMN) cells, and cfDNA using 16 small tandem repeat loci. The resulting labeled PCR-products were size-fractionated and quantified. Results. Analyzing samples from 191 patients treated with HSCT for nonneoplastic hematologic disorders demonstrated that the cfDNA chimerism is comparable to that seen in PMN cells. Analyzing leukemia patients (N = 126) showed that, of 84 patients with 100% donor DNA in PMN, 16 (19%) had evidence of clinical relapse and >10% recipient DNA in the plasma. Additional 16 patients of the 84 (19%) showed >10% recipient DNA in plasma, but without evidence of relapse. Eight patients had mixed chimerism in granulocytes, lymphocytes, and plasma, but three of these patients had >10% recipient DNA in plasma compared to PMN cells and these three patients had clinical evidence of relapse. The remaining 34 patients showed 100% donor DNA in both PMN and lymphocytes, but cfDNA showed various levels of chimerism. Of these patients 14 (41%) showed laboratory or clinical evidence of relapse and all had >10% recipient DNA in cfDNA. Conclusion. Monitoring patients after HSCT using cfDNA might be more reliable than cellular DNA in predicting early relapse.

Biological and histological parameters as predictors of relapse in ulcerative colitis: A prospective study

Background/Aim:Ulcerative colitis is a chronic inflammatory disease of unknown etiology characterized by periods of remission and relapses. This study has been carried out in a group of North Indian patients, where the disease has shown an increasing prevalence and frequent relapses. Hence, there is a need to predict relapse for better management and to reduce morbidity. To assess the importance of biological and histological parameters in predicting relapse when the disease is in quiescent phase.Materials and Methods:A prospective study of twenty-six patients with quiescent ulcerative colitis was carried out in Dayanand Medical College and Hospital, Punjab. Only patients with clinical and endoscopic remission at the time of screening visit were included. Hemoglobin, erythrocyte sedimentation rate (ESR), C- reactive protein (CRP) and serum Interleukin-6 (IL-6) levels were measured. The baseline colonoscopic mucosal biopsies were retrieved and studied. Follow-up was conducted for one year at monthly interval or earlier if relapse occurred.Results:Fifteen out of twenty-six patients (57.69%) had evidence of clinical relapse during the follow-up. Hemoglobin, ESR, CRP and IL-6 levels were not found to be significant predictors of relapse. Increased number of eosinophils and neutrophils in the lamina propria were observed to be associated with significantly higher relapse rate.Conclusion:A higher risk of relapse in patients with quiescent colitis can be predicted by the presence of increased number of eosinophils and neutrophils in the lamina propria.

Treatment Relapsed Subcutaneous Panniculitis-like T-Cell Lymphoma together HPS by Cyclosporin A

A 25-year-old man was diagnosised subcutaneous panniculitis-like T-cell lymphoma (SPTCL) through biopsy of a nodule from the anterior chest. After the treatment with prednisone 90 mg 3 weeks and tapered off in 1 month, the disease released, but relapsed together with symptions of hemophagocytic syndrome eight months after the termination of prednisone. CHOEP recipe was given but with unsatisfactory result until cyclosporine was prescribed. Cyclosporine was removed 6 months later. There is no evidence of clinical relapse 1 year later. This case suggest that cyclosporine could be a selectable treatment even in relapsed SPTCL.

Phase II Study of the Human Anti-Epithelial Cell Adhesion Molecule Antibody Adecatumumab in Prostate Cancer Patients with Increasing Serum Levels of Prostate-Specific Antigen after Radical Prostatectomy

Background: Rising serum levels of prostate-specific antigen (PSA) after radical prostatectomy are indicative of recurrent prostate cancer. This double-blind, placebo-controlled phase II study evaluated the anti-tumour activity of the anti-epithelial cell adhesion molecule (EpCAM) antibody adecatumumab in delaying biochemical disease progression. Patients and Methods: Prostate cancer patients with increasing serum PSA levels following radical prostatectomy were randomized to low- (2 mg/kg) or high-dose adecatumumab (6 mg/kg) or placebo. The primary efficacy endpoint was the mean change from baseline in total serum PSA at week 24. Secondary endpoints included PSA response rate, prolongation of serum PSA doubling time and time to biochemical disease progression. Results: The primary and secondary endpoints of the study were not met in the predefined analyses. In a retrospective analysis of patients with baseline PSA ≤1 ng/ml and a high EpCAM expression, both the mean increase in PSA from baseline to week 24 and the PSA doubling time at week 15 were significantly improved in the high-dose adecatumumab group compared with the placebo group. Most frequent treatment-related clinical adverse events were gastrointestinal (diarrhoea and nausea) or general events (chills), showing a dose dependency but no grade 3/4 intensity in any patient. Conclusion: In men with rising PSA levels after radical prostatectomy and no evidence of clinical relapse, adecatumumab delayed disease progression in a subgroup of patients with baseline PSA levels ≤1 ng/ml and high EpCAM-expressing tumours.

We Should Use Magnetic Resonance Imaging to Classify and Monitor the Course of Multiple Sclerosis

D ISEASE ACTIVITY IN multiple sclerosis (MS) consists of acute exacerbations that can be either clinical or subclinical (seen on magnetic resonance imaging [MRI]) and incremental increases in disability that can be related to relapses or occur independently of them. In 1996, Lublin and Reingold developed a consensus disease course classification for MS that is now widely used. Persons who demonstrate an acute or subacute clinical exacerbation associated with transient or persistent neurological deficits are assigned into a “relapsing” form while those who accrue disability either without documented exacerbations or superimposed on clinical exacerbations fall into a more “progressive” category. While quite useful, a potential deficiency of this classification is the lack of formally incorporating MRI measures of disease activity. Serial studies of individual patients with MS have clearly shown that the inflammatory lesions of MS occur with considerably greater frequency than is evident clinically. Active inflammation has been detected 5 to 10 times more frequently by conventional MRI and up to 30fold more frequently by using sensitive MRI technology (interferon beta-1b vs glatiramer acetate in MS with triple-dose gadolinium and 3-T MRI end points [D.C., L. J. Wolansky, MD, J. Skurnick, PhD, et al, unpublished data]) than by clinical criteria alone. It has been previously shown that persistent MRI activity (inflammation) may result in axonal loss and irreversible cerebral atrophy. Evidence of axon pathology has also been described within T2 lesions, as has a strong correlation between overall T2 lesion volume, in the first 5 years after diagnosis with clinically isolated syndrome and long-term MS disability. Recently, Fazekas et al suggested that the occurrence of new/enlarging T2 lesions or gadolinium-enhancing lesions supports the idea of insufficient suppression of the inflammatory/demyelinating process. Although the association between MRI activity, using generally available technology, and prognosis is not robust, it is clear that MRI is more sensitive than clinical assessment of disease activity. Indeed, radiographic worsening may prove to be the most sensitive and important laboratory tool currently available for evaluating MS disease course. In contrast to clinical course alone, diagnostic criteria have appropriately evolved to incorporate MRI evidence of disease activity when evidence of clinical relapse is unavailable. The revised McDonald criteria allow MS to be diagnosed when a new lesion is found on an appropriate follow-up MRI. We argue that using this robust tool to monitor the course of MS once diagnosed could also potentially allow for earlier detection of inflammation and ongoing disease activity, even in the absence of clinical symptoms.

Gluten-Free Diets in Celiac Disease: Does Life Mean Life?

Gluten-Free Diets in Celiac Disease: Does Life Mean Life?

Subcutaneous Panniculitis‐Like T‐Cell Lymphoma With Hemophagocytic Syndrome Successfully Treated With Cyclosporin A

A 17-year-old girl previously in good health presented with a 2-month history of recurrent, high-grade fever; general fatigue; anorexia; a 10-kg weight loss; and multiple, painful, reddish skin lesions on the lower abdomen. Some lesions were ulcerated, with an oily yellowish brown discharge. A systemic review was unremarkable other than bleeding from the nose. Her medical and family histories were unremarkable. On examination, the patient was pale, jaundiced, and febrile (temperature of 39 degrees C). She had enlarged lymph nodes in the axillary and inguinal areas. There was moderate hepatosplenomegaly. Local skin examination revealed multiple erythematous, tender, and firm subcutaneous nodules of variable size (1-2 cm) on the lower abdomen. Some nodules were ulcerated, with oily yellowish brown discharge and overlying ecchymosis (Figures 1 and 2). Mucous membranes were free of lesions. Laboratory investigations showed pancytopenia, an elevated erythrocyte sedimentation rate (>80 mm/h), normal renal function tests, abnormal hepatic function tests (alanine aminotransferase 172 U/L, aspartate aminotransferase 229 U/L, alkaline phosphatase 725 U/L, and total bilirubin 100 mmol/L [normal range 0-18 mmol/L]), conjugated bilirubin 45 mmol/L (normal range 0-5 mmol/L), and high triglycerides 855 mg/dL (normal range 20-200 mg/dL). Prolonged prothrombin time, 26 seconds (normal range 13-16 seconds); prolonged activated partial thromboplastin time, 61 seconds (normal range 26-38 seconds); positive disseminated intravascular coagulation studies evidenced by low fibrinogen, 74 mg/dL (normal range 160-350 mg/dL); and positive fibrinogen degradation products were also noted. Throat, midstream urine, and blood culture results were negative. Serologic tests for syphilis, HIV, and hepatitis B and C viruses were negative. Epstein-Barr virus and cytomegalovirus serologic values revealed evidence of past infection. Tuberculin and Coombs tests were negative. The alpha1-antitrypsin level was normal. Antinuclear and anti-smith antibodies, rheumatoid factor, and cryoglobulins were negative. CT showed enlarged lymph nodes in the axillary and inguinal areas, bilateral small pleural effusion, moderate hepatosplenomegaly, severe fatty infiltration of the liver, and thickening of lower abdominal subcutaneous tissue. A liver biopsy showed steatohepatitis. Bone marrow aspirate and trephine were normal. A deep punch biopsy of a nodule from the right lower abdomen revealed lobular panniculitis with atypical lymphocytes and large macrophages with cytophagocytosis ("beanbag" cells) (Figures 3 and 4). Immunohistochemistry showed that these atypical cells were positive for CD3, CD8, granzyme B, and perforin, and negative for CD56. T-cell gene rearrangement studies on skin lesions revealed a monoclonal T-cell receptor (gamma-chain) gene rearrangement, supporting the diagnosis of subcutaneous panniculitis-like T-cell lymphoma. On presentation, the initial treatment included 6 U of fresh frozen plasma, 2 U of packed red blood cells, and 2 g IV fibrinogen for 3 consecutive days. The patient was started on prednisolone 60 mg orally once daily and cyclosporine A 5 mg/kg/d orally in two divided doses. The fever and other systemic symptoms and skin lesions resolved within 2 weeks after the treatment. The prednisolone dose was tapered gradually, and a maintenance dose of cyclosporine A was continued. The patient's condition remained in remission at 12-month follow-up; there was no evidence of clinical relapse.

The Use of PET Scans To Direct Immunotherapy Following Reduced Intensity Stem Cell Transplants in Adults with Lymphoid Malignancies.

FDG PET scanning is increasingly being used to establish poor response and early relapse in patients with lymphoid malignancies in order to direct early intensification of treatment. We have performed a prospective study to assess the role of PET scans in directing immune manipulation (withdrawal of immune suppression and donor lymphocyte infusions (DLI)) following reduced intensity transplants (RIT) in patients with lymphoid malignancies. 34 patients (8 Hodgkin's lymphoma, 3 Mantle cell lymphoma, 23 Non-Hodgkin's Lymphoma), median age 44 years (range 20 to 64 years) have been entered since May 2002 and have > 3months follow up. PET and CT scans were performed pre-RIT and at 3, 6, 9, 15 and 24 months post RIT. Patients were conditioned with fludarabine (30mg/m2x5) and melphalan (140mg/m2x1) and in vivo alemtuzumab. Cyclosporin (CSA) was given day −1 to 3 months after RIT. Progression was defined as persistent and/or increasing PET positivity. Relapse was defined as either new PET positive imaging (PET+), progression on CT scan (CT+) or clinical progression. DLI was subsequently given to patients who progressed or relapsed at escalating doses of 1 x 106/kg T cells up to 1 x 108/kg. Patients with active GVHD were excluded from DLI.Results: 17 patients had positive PETs pre-treatment. 9 of these became PET negative, showing an anti-lymphoma effect of the conditioning regime. There were 7 TRMs, leaving 27 of 34 patients evaluable to assess the role of PET in post-transplant management. Of these 27 patients, 6 have had positive CT scans (CT+) with negative PET scans (PET-), with no evidence of clinical relapse. 10/27 patients have subsequently progressed on PET scan (PET+): 2 with PET+ and CT+ disease were not eligible for DLI (GVHD). Both progressed and died at 9 months. One patient is too early to evaluate. The remaining 7 patients received immunotherapy: 4/7 had CT negative (−) disease at PET+ relapse. One patient responded to CSA withdrawal, 6 responded to escalating DLI +/− rituximab (n=3): 3/7 having never developed CT+ disease. 2 patients have subsequently relapsed at 18 and 30 months and are being re-treated. In summary, negative PET scans prevented 6 patients from either undergoing invasive investigations or receiving potentially harmful DLI because of persistently abnormal CT scans. PET scans became positive before CT scans in 4 of 7 patients who relapsed, allowing earlier treatment with immunotherapy, resulting in PET remissions all 7 patients, 3 without CT or clinical relapse. There were no cases of CT relapse before PET relapse. The use of regular PET scanning therefore altered therapy (either delayed or initiated immunotherapy) in 10/27 (37%) evaluable patients in this study. The use of PET scans in identifying early relapse in patients undergoing RIT for lymphoid malignancies, where early DLI can be beneficial is very promising and needs further evaluation, with larger event numbers and longer follow-up.

Prostate-specific antigen: Monitoring the response of carcinoma of the prostate to radiotherapy with a new tumor marker

The role of prostate-specific antigen (PSA), a sensitive tumor marker for cancer of the prostate, has yet to be defined in patients treated with radiotherapy. To evaluate this, PSA and acid phosphatase (AP) were measured prospectively in 110 sequential patients who presented with locoregional carcinoma of the prostate and in whom radiotherapy was to be definitive treatment. Therapy was divided into the following treatment groups: external-beam radiotherapy alone (EBRT), EBRT with brachytherapy (EBRT + B), and hormone therapy either pre-EBRT or post-EBRT (EBRT + H). All patients have been followed for 1 to 17 months and a total of 521 posttreatment PSA determinations have been made. In 91 of 110 patients (83%) PSA was elevated pretreatment and correlated with clinical stage and subsequent relapse. There was no association with Gleason grade, assigned treatment group, or lymph node involvement. Acid phosphatase was elevated in only 31% of the patients initially and had no predictive value in subsequent failure. Nine patients have developed local and/or distant recurrence. None of the patients who failed had their PSA return to normal whereas 74 of 101 (73%) of the remainder have done so. Levels of PSA that do not return to normal during follow-up probably indicate active disease, often without evidence of clinical relapse. The authors conclude that PSA is a useful tumor marker for monitoring response to radiotherapy and may be a predictor of eventual failure thus identifying patients eligible for early intervention therapy as and when it becomes available.