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  • Jefferson Adams
    Jefferson Adams

    Enteropathy-Associated T-Cell Lymphoma Type I Strongly Expresses CD30

      A new understanding of CD30 expression in EATL could mean new treatments.

    Caption: Photo: CC--helices_colors--cc--The Wandering Angel.

    Celiac.com 10/25/2016 - Some potentially big news for people who suffer from enteropathy-associated T-cell lymphoma (EATL), an intestinal tumor that targets intraepithelial T lymphocytes. EATL may be preceded by refractory celiac disease (RCD), which resists treatment with gluten-free diet. In almost all cases, a range of the tumor cells express CD30.

    RCD occurs in two types based on the absence (type I) or presence (type II) of abnormal intraepithelial lymphocytes (IEL) showing down-regulation of CD8 and often TCR gamma genes rearrangement. RCD II is now considered as a small cell intraepithelial T-cell lymphoma that could be an intermediate stage between celiac disease and EATL.

    A team of researchers recently set out to establish the pattern of CD30 expression in EATL, which help to improve therapies with the use of anti-CD30 monoclonal antibody like brentuximab vedotin (BV). The research team included David Sibon, Georgia Malamut, Virginie Verkarre, Coralie Derrieux, Isabelle Radford, Bertrand Meresse, Elizabeth Macintyre, Christophe Cellier, Nadine Cerf-Bensussan, Nicole Brousse, and Olivier Hermine.

    For their study, the team enrolled consecutive adult patients diagnosed with EATL between 2007 and 2013 in Necker University Hospital and Georges Pompidou European Hospital. The team confirmed celiac diagnosis using histopathologic and immunohistochemical review. For the purpose of the present study, two expert hematopathologists reviewed all EATL and extended the phenotypic analysis to reclassify them according to the 2008 WHO classification.

    The team used a panel of antibodies directed against CD20, CD3, CD4, CD5, CD8, CD56, granzyme B and ALK1. They also performed CD30 staining with Monoclonal Mouse Anti-Human CD30, Clone Ber-H2 (Dako). As a control group, they used consecutive RCDI and RCDII cases with complete phenotype and clonality analyses diagnosed in the same period. They based celiac disease diagnosis on HLA-DQ2/8 typing, detection of celiac specific antibodies, and of villous atrophy with increased counts of IEL on normal diet. They classified patients RCDI or II, depending on their clinical and histological response to a gluten-free diet, and the presence of abnormal IEL.

    In all 25 cases of EATL, large tumor cells strongly expressed CD30. In RCDI and II, CD30 was negative in most cases (∼90%), and was rarely expressed by dispersed atypical lymphocytes, whether in IEL or in lamina propria. TCR gamma genes were clonally rearranged in 11/14 (79%) EATL, 3/25 (12%) RCDI and 18/20 (90%) RCDII.

    Based on their findings, the team began a pilot study in 2012. The pilot study combines BV with chemotherapy followed by autologous stem-cell transplantation (ASCT) as frontline treatment for EATL. The team has treated five patients to date. For chemotherapy, the the first two patients received IVE/MTX. After presenting their initial results at ASH 2012 Annual Meeting, the team replaced IVE/MTX with CHP regimen, and treated 3 more patients. Both treatments were well tolerated, and all 5 patients reached clinical remission, and underwent ASCT.

    EATL type I strongly expresses CD30. Promising results from combining BV with CHP led the team to plan a phase 2 study of BV and CHP, followed by ASCT, as frontline treatment of EATL.

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  • About Me

    Jefferson Adams earned his B.A. and M.F.A. at Arizona State University, and has authored more than 2,000 articles on celiac disease. His coursework includes studies in biology, anatomy, medicine, science, and advanced research, and scientific methods. He previously served as Health News Examiner for Examiner.com, and devised health and medical content for Sharecare.com. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of the book "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.

  • Related Articles

    Jefferson Adams
    Celiac.com 07/30/2012 - A number of studies have found higher rates of lymphoma in people with celiac disease. However, few studies make any distinction between lymphoproliferative disorders (LPDs).
    A team of researchers recently investigated rates of various lymphoproliferative disorders in patients with celiac disease.
    The research team included L.A. Leslie, B. Lebwohl, A.I. Neugut, J. Gregory Mears, G. Bhagat, and P.H. Green. They are affiliated with the Department of Medicine at Columbia University Medical Center in New York, NY.
    The team wanted to assess rates of LPD subtypes in celiac disease patients, describe patterns of celiac disease presentation in patients who develop LPD, and compare survival in patients with various LPD subtypes.
    To do so, they carried out a retrospective cohort study of adults with biopsy-proven celiac disease seen at a US referral center from 1981 to 2010. They also identified patients with comorbid LPD, and calculated standardized incidence ratios (SIR) for each LPD subtype.
    They began with a study group of 1,285 patients with celiac disease. The group contained 40 patients with LPD [sIR = 6.48, 95% confidence interval (CI) = 4.62-8.64] including 33 with non-Hodgkin lymphoma (NHL, SIR = 6.91, 95% CI = 4.26-8.28).
    Rates of NHL subtypes including enteropathy-associated T-cell (EATL, n = 12), non-EATL T-cell (SIR = 22.43, 95% CI = 7.08-46.41), diffuse large B-cell (SIR = 5.37, 95% CI = 1.93-10.52), mantle cell (SIR = 32.21, 95% CI = 6.07-78.97), and marginal zone (SIR = 37.17, 11.73-76.89), lymphoma were substantially higher
    among patients diagnosed with celiac before LPD (n = 24, NHL SIR = 4.47, 95% CI = 2.86-6.44).
    Patients who developed LPD were usually older at time of celiac diagnosis (57.9 ± 15.5 versus 42.5 ± 17.4 years, P < 0.0001) and more likely to present with diarrhea (60.0% versus 39.8% P = 0.016), abdominal pain (17.5% versus 5.5% P = 0.0046), and/or weight loss (12.5% versus 4.0%, P = 0.028).
    EATL patients had a shorter average survival than non-EATL NHL patients (3.2 versus 15.0 years, P = 0.016).
    Overall, rates of LPD are higher in celiac disease patients, and those diagnosed at an older age, who present with symptoms of malabsorption, are more likely to be diagnosed with LPD.
    Source:
    Am J Hematol. 2012 Apr 26. doi: 10.1002/ajh.23237.

    Jefferson Adams
    Celiac.com 11/08/2012 - T-cell lymphoma is a deadly type of cancer that is more common in people with celiac disease than in the general population. Currently, there is no cure for T-cell lymphoma, and no promising treatment exists for people who suffer from this condition.
    However, that may be set to change, as the results of a new study suggest that new treatments for T-cell lymphoma my be on the horizon. The study appears in the journal Clinical Lymphoma Myeloma and Leukemia.
    The study team included J.R. Bertino, M. Lubin, N. Johnson-Farley, W.C. Chan, L. Goodell, and S. Bhagavathi. They are affiliated with the Departments of Medicine, Pharmacology, and Pathology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ.
    The team was attempting to address the fact that doctors treating T-cell lymphomas, especially types of T-cell lymphoma known as peripheral T-cell lymphoma (PTCL), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large cell lymphoma (ALCL) have limited treatment options and cannot cure the condition.
    Their study noted that a high percentage of PTCL, AITL, and ALCL, along with T-cell leukemia and T-cell lymphoblastic leukemia lack the enzyme methylthioadenosine phosphorylase (MTAP).
    Their published results also note that MTAP-deficient cells cannot cleave endogenous methylthioadenosine to adenine and 5-methylthioribose-1-phosphate, a precursor of methionine, and as a result have enhanced sensitivity to inhibitors of de novo purine biosynthesis.
    A recently introduced antifolate, pralatrexate, which has been shown to inhibit de novo purine biosynthesis, has been approved for treatment of PTCL and may have an increasing role in therapy. An alternative strategy involving coadministration of methylthioadenosine and high-dose 6-thioguanine has been proposed and may prove to be selectively toxic to MTAP-deficient uncommon lymphomas.
    As a result of these MTAP results, the team suggests that new therapies and treatments for T-cell lymphoma may be possible going forward.
    Source:
    Clin Lymphoma Myeloma Leuk. 2012 Oct;12(5):306-9. doi: 10.1016/j.clml.2012.07.001.

    Jefferson Adams
    Celiac.com 04/15/2013 - Enteropathy-associated T cell lymphoma (EATL) is a gut cancer that often ends in death. Currently, doctors have very little idea what factors might help patients survive.
    The manner in which clinical presentation, pathological features and therapies influence EATL outcome was the subject of a recent study by a team of researchers.
    The research team included: G. Malamut; O. Chandesris; V. Verkarre; B.Meresse, C. Callens, E. Macintyre, Y. Bouhnik, J.M. Gornet; M. Allez; R. Jian; A. Berger; G. Châtellier; N. Brousse, O. Hermine, N. Cerf-Bensussan, and C. Cellier.
    They are variously affiliated with the Université Paris Descartes, the Gastroenterology Department of Hôpital Européen Georges Pompidou, APHP, and Inserm U989 in Paris, France.
    For their study, the team evaluated the medical files of 37 well-documented patients with celiac disease and T-cell lymphoma. They then analyzed lymphoma and intestinal mucosa by histopathology, multiplex PCR and intestinal intraepithelial lymphocytes phenotyping.
    Using Kaplan-Meier curves with Logrank test and Cox Model they then analyzed patient survival and prognostic factors. They found 15 patients with lymphoma-complicated non-clonal enteropathy, celiac disease, two patients with type I refractory celiac disease, and 20 patients with clonal type II refractory celiac disease. Twenty-five patients underwent surgery with resection of the main tumor mass in 22 cases.
    Univariate analysis showed that non-clonal celiac disease, serum albumin levels under 21.6g/L at diagnosis, chemotherapy and surgical resection predicted good survival (p=0.0007, p
    Multivariate analysis showed that serum albumin level>21.6g/L, chemotherapy and reductive surgery were all significantly associated with increased survival rates (p
    The results reinforce the value of assessing celiac disease type in patients with T-cell lymphoma, and suggest that a combination of nutritional, chemotherapy and reductive surgery may improve survival rates in cases of EATL.
    Source:
     Dig Liver Dis. 2013 Jan 9. pii: S1590-8658(12)00438-0. doi: 10.1016/j.dld.2012.12.001.

    Jefferson Adams
    Celiac.com 08/24/2015 - A new study reveals that U.S. Asians experience higher rates of deadlier cases of Enteropathy-associated T-cell lymphoma EATL.
    Enteropathy-associated T-cell lymphoma is a rare primary intestinal non-Hodgkin lymphoma (NHL) strongly associated with celiac disease. It is an aggressive disease with a median survival of approximately 10 months (Ferreri et al, 2011).
    Previous studies suggest that EATL may be more common in Europe and among Whites, among whom celiac disease is prevalent (Delabie et al, 2011; Ferreri et al, 2011). However, a second type of EATL (Type II) not associated with celiac disease is increasingly reported in Asia (Lee et al, 2005; Sun et al, 2011; Tan et al, 2013).
    To date, there have been no comparative epidemiological study in a racially diverse large population. A team of researchers recently set out to conduct such a study. The research team included Pawan K. Karanam, Mohammed Al-Hamadani, and Ronald S. Go. They are variously associated with the Departments of Medical Education and Medical Research at the Gundersen Medical Foundation in La Crosse, USA, and with the Division of Hematology at the Mayo Clinic, and the Mayo Clinic's Robert D, and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, MN, USA.
    The team turned to the two largest public cancer databases in the US: the Surveillance, Epidemiology, and End Results (SEER) database (http://www.seer.cancer.gov); and the National Cancer Data Base (NCDB; http://www.facs.org/quality-programs/cancer/ncdb).
    Using these databases, the research team was able to find and compare the cases of EATL by race. They were also able to describe the clinical features and overall survival (OS) for these cases. 
    The team's study included all patients with an EATL diagnosis according to International Classification of Diseases for Oncology (ICD-O: 9717). The team used SEER-18 registries from 2000 to 2011 to calculate incidence.
    To describe clinical outcomes, they used the NCDB NHL-PUF with patients diagnosed between 1998 and 2012 for clinical characteristics and those diagnosed between 1998 and 2006 for OS. Because CoC-accredited programs report survival data only once every 5 years, OS analysis was possible only for patients diagnosed between 1998 and 2006.
    From the data, the team calculated the incidence rate (case/1 000 000), age-adjusted to the 2000 standard US population, according to race (White, Black, Asian/Pacific Islander, American Indian/Alaska native) using seer*stat software version 8.1.5 (National Cancer Institute, Bethesda, MD, USA) and performed risk ratio comparisons using Poisson regression.
    They analyzed OS using the Kaplan–Meier method and used log-rank tests to compare survival distributions between race cohorts. The prognostic effect of pertinent clinical variables were studied using multivariate Cox proportional hazards models.
    They found that, for the years 2000–2010, the overall age-adjusted incidence rate of EATL in the US was 0·111 per 1,000,000. Asians/Pacific Islanders had a higher incidence rate (0·236) compared with other races [White (0·101), Black (0·107), American Indian/Alaska native (0·128)].
    The risk ratio of Asians/Pacific Islanders compared with non–Asians/Pacific Islanders was 2·32 [95% confidence interval (CI) 1·39–3·69; P = 0·002].
    The incidences for Asians and Pacific Islanders were combined in seer*stat, therefore we could not provide separate incidences for Asians and Pacific Islanders.
    All tests of statistical significance were two-sided and P < 0·05 was considered significant.
    Source:
    British Journal of Haematology, Vol. 170 Issue 3. DOI: 10.1111/bjh.13555

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    You can say that again! Part of my disdain for doctors, and the medical (I refuse to say "health care") industry more generally, is due to having suffered (and had repeatedly been misdiagnosed, if not treated by doctors with complete disbelief and contempt) in my later teens and early 20s from a rare condition called aquagenic urticaria, in which my entire body would break out in nasty, ugly, intense hives upon merely GETTING WET!  Yes, that included bathing.  It was the only thing I have e
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