Specific TCR gene rearrangements in mycosis fungoides: does advanced clinical stage show a preference?

2018 ◽  
Vol 71 (12) ◽  
pp. 1072-1077
Author(s):  
Etan Marks ◽  
Yanhua Wang ◽  
Yang Shi ◽  
Joseph Susa ◽  
Mark Jacobson ◽  
...  
Keyword(s):  
Mycosis Fungoides ◽  
Late Stage ◽  
Gene Rearrangement ◽  
Early Stage ◽  
Clinical Stage ◽  
Disease Stage ◽  
Gene Rearrangements ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Late Stage Disease

AimsThe relationship between the presence of specific T-cell receptor (TCR) gene rearrangements and clinical stage in mycosis fungoides (MF) has not been studied. We analysed a cohort of patients with a diagnosis of MF to determine the different types of specific TCR gene rearrangements present and their relationship to disease stage.MethodsA retrospective chart review was used to select patients with a diagnosis of MF who had a skin biopsy and a positive TCR gene rearrangement study in either blood or tissue and at least 2 years of clinical follow-up.Results43 patients were identified and divided into two groups. The first group consisted of 23 patients with early stage disease (IA-IIA) that was either stable or went into partial or complete remission with minimal intervention. None of these patients advanced to late stage disease. The second group consisted of 20 patients who had either late stage disease at diagnosis or progressed to late stage disease at some point in time. In the first group, only 4/23 (17%) patients had a single TCR gene rearrangement in the Vɣ1–8 region. In contrast, the second group had 13/20 (65%) patients with a single TCR gene rearrangement in the Vɣ1–8 region (p=0.002).ConclusionThe presence of a single TCR gene rearrangement in the Vɣ1–8 region could possibly be related to a more advanced stage of MF. However, more comprehensive studies, such as next generation sequencing, with a larger cohort is necessary for a more definitive conclusion.

Causes of death in nodular lymphocyte predominant Hodgkin's lymphoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20016-e20016
Author(s):  
Anas M Saad ◽  
Ahmed Afifi ◽  
Mohamed Gad ◽  
Muneer J. Al-Husseini ◽  
Firas Baidoun ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Late Stage ◽  
Hodgkin’S Lymphoma ◽  
Causes Of Death ◽  
Early Stage ◽  
Hodgkin's Lymphoma ◽  
Disease Stage ◽  
Advanced Stage ◽  
Stage Disease ◽  
Late Stage Disease

e20016 Background: Nodular lymphocyte-predominant Hodgkin’s lymphoma (NLPHL) accounts for 5% of all cases of HL. The outcomes of patients with NLPHL is generally regarded as better than those with classical HL. However, causes of death (COD) of patients with NLPHL have not been previously described. Methods: The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program was used to identify all patients with NLPHL diagnosed between 1990 and 2015. Patient characteristics and disease stage, using the Ann-Arbor system, was extracted and tabulated. COD were identified and proportions were calculated for deaths within 5 years and after 5 years of diagnosis for patients with early and late stage NLPHL. Results: We identified 1,937 cases of NLPHL. The majority were younger than 65 years (86%), white (70%), male (67%), and diagnosed between 2001-2015 (85%), when rituximab was introduced. Of all cases, 1336 (69%) were classified as early stage. At a median follow-up of 91 months (IQR 41, 152) for early stage disease, and 73 months (IQR 30-123) for late stage disease, the median cancer-specific or overall survival were not reached. The estimated 5-year survival was 92% and 81% for early stage and late stage disease, respectively. Of all patients with early stage NLPHL, 186 (14%) died by the end of 2015, and 87 (46%) deaths occurred within 5 years of diagnosis. During the first 5 years after diagnosis, COD was NLPHL in 30 (35%). Beyond 5 years from diagnosis, NLPHL was the COD in 27% followed by other cancers (23%), and cardiovascular disease (18%). Of all patients with late stage NLPHL, 107 (21%) died, and 75 (70%) of deaths occurred within 5 years of diagnosis. During the first 5 years after diagnosis, COD was NLPHL in 44 (59%). Beyond 5 years from diagnosis, cardiovascular disease was the COD in 25%, followed by NLPHL (22%). Conclusions: The prognosis of NLPHL is excellent. Of all patients with NLPHL, those with advanced stage disease are more likely to die of their disease within 5 years of diagnosis. Patients with early and advanced stage disease beyond 5 years of diagnosis are more likely to die of causes other than NLPHL.

Matching for 12 HLA Alleles Is Associated with a Significantly Superior Survival Due to a Lower Mortality in Recipients of Unrelated Donor Haematopoietic Cell Transplants for Early but Not Late Stage Leukaemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3056-3056
Author(s):  
B.E. Shaw ◽  
N.P. Mayor ◽  
A.-M. Little ◽  
Nigel H. Russell ◽  
A. Pagliuca ◽  
...  
Keyword(s):  
Late Stage ◽  
Early Stage ◽  
Disease Stage ◽  
Unrelated Donor ◽  
Disease Relapse ◽  
Early Stage Disease ◽  
Hla Alleles ◽  
Graft Versus Host ◽  
Multiple Loci ◽  
Stage Disease

Abstract Recipient/donor HLA matching is an important determinant of outcome in transplantation using volunteer unrelated donor (VUD). The degree of matching remains controversial. Some data suggest that disease stage is an important factor to consider when assessing the need for a well-matched donor. We analysed the impact of matching for 12 HLA alleles at six loci (HLA-A, -B, -C, -DRB1, -DQB1, -DPB1) in a cohort of 458 patients receiving VUD transplants for leukaemia (142 CML, 170 AML, 146 ALL). Of the pairs, 84 were matched for 12/12 alleles, 250 and 124 were mismatched for one locus or more than one locus respectively (graft versus host vector). Most single locus mismatches were at DPB1 (218/250, 87%). In multiply mismatched pairs the loci were: DPB1 plus one other locus (81), 2 other loci excluding DPB1 (10) and more than 2 loci (33). Patients receiving 12/12 matched grafts had a significantly better survival than those who had mismatched grafts (7 years: 45% vs 30%, p=0.022) and those matched for 10/10 alleles (p=0.050). The outcome was not significantly different dependent on whether the mismatch was at single or multiple loci, nor whether the single mismatch was at DPB1 compared to any other HLA locus. Disease stage was a significant determinant of outcome, with patients transplanted in early stage disease (defined as CR1 or CP1, N=222) having a superior outcome to those with late stage disease (N=236) (7 year: 42% vs 28%; p=0.002) In patients with early stage disease, the survival was significantly better if 12/12 matched compared to the mismatched group (7 years: 62% vs 36%; p=0.005). Other factors associated with a significantly improved survival in this cohort were: patient age below the median (32 years), patient CMV seronegativity and CML (rather than acute leukaemia). In multivariate analysis, pairs matched for less than 12/12 HLA alleles (HR=1.8; CI 1.0–3.0; p=0.034) and acute leukaemia (HR=1.8; CI 1.2–2.6; p=0.003) had a significantly worse survival. The reason for the inferior outcome was a significantly worse transplant related mortality (TRM) in the mismatched pairs (p=0.006). This was 16%, 32% and 48% at 100 days, 1 and 7 years in the mismatched group, compared to 9%, 13% and 21% in the matched group. While the incidence of acute graft versus host disease (GvHD) overall was not increased in the mismatched group, the incidence of grade III/IV GvHD was higher (12/12 match = 0%, single locus mismatch = 2%, multiple loci=13%; p=0.002) and this was associated with a higher TRM (p=0.002). There was no significant impact of mismatching on chronic GvHD or disease relapse. Unlike these data, in the late disease stage cohort there was no effect of 12/12 matching status on survival (7 years: 25% vs 28%, NS) or TRM. However, there was an increase in GvHD in HLA mismatched pairs (acute, p=0.012; chronic, p=0.015) and the presence of cGvHD was protective against disease relapse (p=0.044). These data suggest that in patients transplanted at an early disease stage, matching for 12 HLA alleles is important to improve survival. In later stage disease the presence of an HLA mismatch may increase the incidence of GvHD and consequently of the graft versus leukaemia effect and hence be tolerated overall.

scholarly journals Molecular estimation of neurodegeneration pseudotime in older brains

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Sumit Mukherjee ◽  
Laura Heath ◽  
Christoph Preuss ◽  
Suman Jayadev ◽  
Gwenn A. Garden ◽  
...  
Keyword(s):  
Late Stage ◽  
Late Onset ◽  
Early Stage ◽  
Disease Onset ◽  
Postmortem Brain ◽  
Disease Stage ◽  
Rna Seq ◽  
Early Stage Disease ◽  
Molecular Changes ◽  
Stage Disease

AbstractThe temporal molecular changes that lead to disease onset and progression in Alzheimer’s disease (AD) are still unknown. Here we develop a temporal model for these unobserved molecular changes with a manifold learning method applied to RNA-Seq data collected from human postmortem brain samples collected within the ROS/MAP and Mayo Clinic RNA-Seq studies. We define an ordering across samples based on their similarity in gene expression and use this ordering to estimate the molecular disease stage–or disease pseudotime-for each sample. Disease pseudotime is strongly concordant with the burden of tau (Braak score, P = 1.0 × 10−5), Aβ (CERAD score, P = 1.8 × 10−5), and cognitive diagnosis (P = 3.5 × 10−7) of late-onset (LO) AD. Early stage disease pseudotime samples are enriched for controls and show changes in basic cellular functions. Late stage disease pseudotime samples are enriched for late stage AD cases and show changes in neuroinflammation and amyloid pathologic processes. We also identify a set of late stage pseudotime samples that are controls and show changes in genes enriched for protein trafficking, splicing, regulation of apoptosis, and prevention of amyloid cleavage pathways. In summary, we present a method for ordering patients along a trajectory of LOAD disease progression from brain transcriptomic data.

The Effect of Increasing Two-Week Wait Referrals for Head and Neck Cancer in East Kent

2011 ◽  
Vol 93 (6) ◽  
pp. 217-220 ◽  
Author(s):  
S Haikel ◽  
N Dawe ◽  
G Lekakis ◽  
M Black ◽  
D Mitchell
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Late Stage ◽  
Early Stage ◽  
White Paper ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Late Stage Disease ◽  
The Uk

In 1998 the UK government published its white paper The New NHS: Modern and Dependable, in which it first suggested that patients being referred with a suspicion of cancer should have a maximum wait of two weeks to see a specialist. The rationale for this was that outcomes for late-stage disease are significantly worse when compared with outcomes for early-stage disease (Table 1). It was assumed that reducing the wait to see a specialist would reduce the stage of disease at presentation.

scholarly journals Treatment and Outcome of Patients with Uterine Carcinosarcoma in a Comprehensive Cancer Network

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
K. Hapsari ◽  
C. Bhugwandass ◽  
G. W. J. van Rijn ◽  
A. A. M. van der Wurff ◽  
M. van ‘t Veer ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Adjuvant Chemotherapy ◽  
Late Stage ◽  
Adjuvant Radiotherapy ◽  
Early Stage ◽  
Uterine Carcinosarcoma ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Late Stage Disease ◽  
Cancer Network

Abstract Aim To determine clinical characteristics, treatment modalities and survival of uterine carcinosarcoma (UCS). Methods Data on treatment of UCS patients in the Comprehensive Cancer Network south region in the Netherlands between 2004 and 2014 were retrospectively evaluated. Results Data of 62 patients with UCS were retrieved. Mean age at diagnosis was 69.2 years (45–95 years). Data of six patients were excluded because they did not receive any treatment. Of the 56 patients included in this study, 57.1% presented with early-stage (FIGO I–II) disease and 42.9% with late-stage (FIGO III–IV) disease. 46.9% of the patients with FIGO early-stage disease received only surgical treatment, whereas 9.4% received adjuvant chemotherapy and 43.8% received adjuvant radiotherapy. Median DFS in patients with early-stage disease was 47.0 months (17.5–72.0). Adjuvant therapy did not seem to alter prognosis (p = 0.261). 16.7% of the patients with late-stage disease received only surgical treatment, 12.5% received only chemotherapy, whereas 50% received adjuvant chemotherapy and 20.8% adjuvant radiotherapy after surgery. Median DFS in late-stage disease was 8.5 months (2.5–23.5). Adjuvant therapy did not seem to alter prognosis (p = 0.30). Conclusion UCS with both FIGO stages I–II and III–IV has a dismal prognosis. The addition of adjuvant treatment did not seem to increase survival.

scholarly journals SURVIVAL AND TREATMENT OUTCOMES OF PEDIATRIC SOFT TISSUE AND BONE SARCOMAS IN TANZANIA

2019 ◽  
Author(s):  
Zephania Saitabau Abraham ◽  
Siwillis Elizabeth Mithe ◽  
Nazima Dharsee ◽  
Trish Scanlan ◽  
Mamsau Ngoma ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Soft Tissue ◽  
Early Stage ◽  
Complete Response ◽  
Disease Stage ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Pediatric Sarcomas ◽  
Late Stage Disease ◽  
Bone Sarcomas

Abstract Background Pediatric sarcomas represent an important group of childhood tumors who require treatment at Muhimbili National Hospital (MNH), the largest pediatric oncology center in Tanzania. Treatment is often adapted from established childhood protocols validated in clinical trials from the United States and United Kingdom. There are no studies describing the outcomes of treatment in Tanzania to understand similarities and disparities with other countries. The objective of this study was to describe the treatment outcomes including the overall survival for children seen at MNH. Methods Data on treatment outcome was collected on all children seen at MNH pediatric oncology unit between 2011 and 2016 with a confirmed histological diagnosis of either bone or soft tissue sarcoma. Results A total of 135 cases were analyzed; 89 (66%) were Soft tissue sarcoma (STS) and 46 (34%) were bone sarcomas. In the STS group, 37 (41.6%) achieved a complete response, 12 (13.5%) achieved a partial response and 40 (44.9%) had no response. Factors found to be significantly associated with a higher complete response rate included early stage disease (stage I or II), embryonal histology, tumor in favorable sites and tumor size of <5cm for STS and <8cm for the bone sarcomas. There was a trend for better 2-year overall survival for STS in early stage disease (74.5%) compared to late stage disease (20.6%), p<0.001. A similar trend was noted for the bone sarcomas; 91.7% versus 25.3% for early stage and late stage disease respectively, p=0.001. Conclusions This report is the first study documenting the treatment outcome for pediatric sarcomas seen in Tanzania. Disease stage is strongly related to treatment outcome with later stages of the disease having an overall poor prognosis.

scholarly journals Molecular estimation of neurodegeneration pseudotime in older brains

2019 ◽  
Author(s):  
Sumit Mukherjee ◽  
Laura Heath ◽  
Christoph Preuss ◽  
Suman Jayadev ◽  
Gwenn A. Garden ◽  
...  
Keyword(s):  
Late Stage ◽  
Protein Trafficking ◽  
Early Stage ◽  
Disease Onset ◽  
Postmortem Brain ◽  
Disease Stage ◽  
Rna Seq ◽  
Early Stage Disease ◽  
Molecular Changes ◽  
Stage Disease

AbstractThe temporal molecular changes that lead to disease onset and progression in Alzheimer’s disease are still unknown. Here we develop a temporal model for these unobserved molecular changes with a manifold learning method applied to RNA-Seq data collected from human postmortem brain samples collected within the ROS/MAP and Mayo Clinic RNA-Seq studies. We define an ordering across samples based on their similarity in gene expression and use this ordering to estimate the molecular disease stage – or disease pseudotime - for each sample. Disease pseudotime is strongly concordant with the burden of tau (Braak score, P = 1.0×10−5), Aβ (CERAD score, P = 1.8×10−5), and cognitive diagnosis (P = 3.5×10−7) of LOAD. Early stage disease pseudotime samples are enriched for controls and show changes in basic cellular functions. Late stage disease pseudotime samples are enriched for late stage AD cases and show changes in neuroinflammation and amyloid pathologic processes. We also identify a set of late stage pseudotime samples that are controls and show changes in genes enriched for protein trafficking, splicing, regulation of apoptosis, and prevention of amyloid cleavage pathways. In summary, we present a method for ordering patients along a trajectory of LOAD disease progression from brain transcriptomic data.

scholarly journals Timing of Antiretroviral Therapy and Systemic Inflammation in Sub-Saharan Africa: Results From the META Longitudinal Cohort Study

2019 ◽  
Vol 220 (7) ◽  
pp. 1172-1177 ◽  
Author(s):  
Mark J Siedner ◽  
Mwebesa Bosco Bwana ◽  
Stephen Asiimwe ◽  
Gideon Amanyire ◽  
Nicholas Musinguzi ◽  
...  
Keyword(s):  
T Cell ◽  
Antiretroviral Therapy ◽  
Cell Count ◽  
Late Stage ◽  
Sub Saharan Africa ◽  
Cd4 T Cell ◽  
Disease Stage ◽  
Stage Disease ◽  
Late Stage Disease ◽  
Cd4 T Cell Count

Abstract Chronic inflammation predicts complications in persons with human immunodeficiency virus infection. We compared D-dimer, soluble CD14, and interleukin 6 levels before and 12 months after antiretroviral therapy (ART) initiation, among individuals starting ART during earlier-stage (CD4 T-cell count >350/µL) or late-stage disease (CD4 T-cell count <200/µL). Female sex, older age, viral load, and late-stage disease were associated with pre-ART biomarkers (n = 661; P < .05). However, there were no differences in biomarkers by disease stage after 12 months of ART (n = 438; P > .05), owing to loss from observation and greater declines in biomarkers in late-stage initiators (P < .001). Earlier initiation of ART is associated with decreased inflammation, but levels seem to converge between earlier and later initiators surviving to 12 months.

Vaginal sarcoma: the Royal Marsden experience

1994 ◽  
Vol 4 (5) ◽  
pp. 337-341 ◽  
Author(s):  
H. Y.S. Ngan ◽  
J. H. Shepherd ◽  
C. Fisher ◽  
P. Blake
Keyword(s):  
Late Stage ◽  
Poor Prognosis ◽  
Recurrent Disease ◽  
Early Stage ◽  
Tumor Grade ◽  
Intermediate Grade ◽  
Early Stage Disease ◽  
The Poor ◽  
Stage Disease ◽  
Prognostic Importance

Six patients with vaginal sarcoma are reported here. This clinicopathologic review confirms the poor prognosis of this disease. However, there were three 5-year survivors, all of whom had early stage disease and low to intermediate grade tumors. Apart from tumor grade, stage was of prognostic importance. Late recurrences at 5 and 21 years were noted in two of the three 5-year survivors. Neither chemotherapy nor radiotherapy were of use in the treatment of late stage or recurrent disease.

Expression of the Cancer-Testis Antigens, SEMG 1 and Protamine 1, in Early CLL: Their Relationship to Disease Stage and Zap 70 Expression.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4680-4680
Author(s):  
Farouk Meklat ◽  
Yana Zhang ◽  
Zhiqing Wang ◽  
Jian Zhang ◽  
Sukhrob Mustalov ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Tumor Vaccine ◽  
Early Stage ◽  
Disease Stage ◽  
Early Disease ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Ct Antigen ◽  
Cancer Testis ◽  
Protamine 1

Abstract Despite advances in modern chemotherapy, CLL remains incurable. CLL is an indolent disease. It expresses a panel of Cancer-Testis (CT) antigens. CLL leukemia cells are susceptible to the cytotoxicity of T cells. CLL is, therefore, an ideal disease for immunotherapeutic approaches. Immunotherapy, in addition to being less toxic and more specific than chemotherapy, provides a different mode of cytotoxicity that may synergize with that induced by chemotherapeutic agents. Immunotherapy also offers the prospect of inducing immune memory that may be important for long term disease-free survival of patients with CLL. However, there are obstacles that may prevent successful immunotherapy. CLL patients are generally immunosuppressed even before any therapy is given and the immunosuppression increases as the disease progresses. Therefore, any immunotherapeutic approaches for CLL should be aplied in early disease when immunosuppression is least encountered. We previously demonstrated the expression of a CT antigen, SEMG 1, in 3/9 patients with CLL. Furthermore, we also demonstrated that the presence of high titer IgG in the serum of patients expressing SEMG 1, suggesting the in vivo immunogenicity of SEMG 1 in the cancer-bearing autologous host. We have also recently used SEMG 1 as the bait in a yeast two-hybrid system of testicular cDNA library and identified that Protamine 1 is the interacting ligand of SEMG 1 and that Protamine 1 is also a novel CT antigen, suggesting that both SEMG 1 and Protamine 1 may be suitable antigens for tumor vaccine development. However, the expression of SEMG 1 and Protamine 1 in early CLL is unknown. We have in this study set out to determine whether or not SEMG 1 and/or Protamine 1 could be used for the design of tumor vaccine for the targeting of patients with early CLL, in particular, those with poor risk disease, as predicted by Zap 70 expression. Using pairs of sequence-specific primers in RT-PCR on a cohort of CLL (41 Stage 0/I and 6 Stage II/III), we found that SEMG 1 gene is expressed in 24/47 (51%) and Protamine 1 in 16/47 (34%) of CLL patients. Gene expression in most cases was associated with the detection by immunocytochemistry of SEMG 1 and/or Protamine 1 in the CLL cells. The expression frequency of SEMG1 and Protamine 1 in CLL did not appear to differ between early and late stage disease. 19/41 of patients with early stage disease and 5/6 of patients with late disease expressed SEMG 1; 12/41 of patients with early stage disease and 4/6 patients with late disease expressed Protamine 1. Furthermore, the expression of these antigens was equally distributed between Zap 70+ and Zap 70− CLL. SEMG 1 was expressed in 4/6 of Zap 70+ CLL (all 6 had early disease) and 2/9 of Zap 70− CLL (1/8 early disease and 1/1 late disease). Interestingly, although Protamine 1 expression in CLL predicted for SEMG 1 co-expression, only 67% of SEMG 1+ CLL expressed Protamine 1. Our results, therefore, suggest that both SEMG 1 and Protamine 1 are suitable targets for tumor vaccine development for some patients with early CLL, especially those with high risk disease, as predicted by Zap 70 expression.

Sign in / Sign up

Export Citation Format

Share Document