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Stuver R, Epstein-Peterson ZD, Horwitz SM. Few and far between: clinical management of rare extranodal subtypes of mature T-cell and NK-cell lymphomas. Haematologica 2023; 108:3244-3260. [PMID: 38037801 PMCID: PMC10690914 DOI: 10.3324/haematol.2023.282717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Accepted: 07/03/2023] [Indexed: 12/02/2023] Open
Abstract
While all peripheral T-cell lymphomas are uncommon, certain subtypes are truly rare, with less than a few hundred cases per year in the USA. There are often no dedicated clinical trials in these rare subtypes, and data are generally limited to case reports and retrospective case series. Therefore, clinical management is often based on this limited literature and extrapolation of data from the more common, nodal T-cell lymphomas in conjunction with personal experience. Nevertheless, thanks to tremendous pre-clinical efforts to understand these rare diseases, an increasing appreciation of the biological changes that underlie these entities is forming. In this review, we attempt to summarize the relevant literature regarding the initial management of certain rare subtypes, specifically subcutaneous panniculitis-like T-cell lymphoma, hepatosplenic T-cell lymphoma, intestinal T-cell lymphomas, and extranodal NK/T-cell lymphoma. While unequivocally established approaches in these diseases do not exist, we make cautious efforts to provide our approaches to clinical management when possible.
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Affiliation(s)
- Robert Stuver
- Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center.
| | - Zachary D Epstein-Peterson
- Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center; Department of Medicine, Weill Cornell Medical College
| | - Steven M Horwitz
- Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center; Department of Medicine, Weill Cornell Medical College; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
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Pelizzaro F, Marsilio I, Fassan M, Piazza F, Barberio B, D’Odorico A, Savarino EV, Farinati F, Zingone F. The Risk of Malignancies in Celiac Disease-A Literature Review. Cancers (Basel) 2021; 13:cancers13215288. [PMID: 34771450 PMCID: PMC8582432 DOI: 10.3390/cancers13215288] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 10/15/2021] [Accepted: 10/19/2021] [Indexed: 12/14/2022] Open
Abstract
Celiac disease (CeD) is an immune-mediated enteropathy precipitated by ingestion of gluten in genetically predisposed individuals. Considering that CeD affects approximately 1% of the Western population, it may be considered a global health problem. In the large majority of cases, CeD has a benign course, characterized by the complete resolution of symptoms and a normal life expectancy after the beginning of a gluten-free-diet (GFD); however, an increased risk of developing malignancies, such as lymphomas and small bowel carcinoma (SBC), has been reported. In particular, enteropathy-associated T-cell lymphoma (EATL), a peculiar type of T-cell lymphoma, is characteristically associated with CeD. Moreover, the possible association between CeD and several other malignancies has been also investigated in a considerable number of studies. In this paper, we aim to provide a comprehensive review of the current knowledge about the associations between CeD and cancer, focusing in particular on EATL and SBC, two rare but aggressive malignancies.
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Affiliation(s)
- Filippo Pelizzaro
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Ilaria Marsilio
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Matteo Fassan
- Surgical Pathology and Cytopathology Unit, Department of Medicine (DIMED), University Hospital of Padova, 35128 Padova, Italy;
- Veneto Oncology Institute, IOV-IRCCS, 35128 Padova, Italy
| | - Francesco Piazza
- Department of Medicine, Hematology, University Hospital of Padova, 35128 Padova, Italy;
| | - Brigida Barberio
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Anna D’Odorico
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Edoardo V. Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Fabio Farinati
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Fabiana Zingone
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
- Correspondence:
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Abstract
There are a number of rare T-cell lymphoma subtypes that may be encountered in clinical practice. In recent years, improved immunohistochemical techniques and molecular tumor profiling have permitted refinement of some of the diagnostic categories in this group, as well as the recognition of distinct conditions not previously well elucidated. In this chapter, we cover the diagnostic and clinical features of some of the more common of these conditions, including subcutaneous panniculitis-like T-cell lymphoma, cutaneous gamma-delta T-cell lymphoma, enteropathy-associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma, primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma, CD4-positive small/medium T-cell lymphoproliferative disorder, and acral CD8-positive T-cell lymphoma. Given the rarity of these conditions, optimal treatments approaches are not always well established, not least as data from large-scale clinical trials are lacking. In this chapter, we aim to provide a summation of current thinking around best treatment, as well as highlighting some controversies in the management of these diagnoses.
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Affiliation(s)
- C van der Weyden
- Department of Haematology, Peter MacCallum Cancer Centre, Melbourne, Australia.
| | - C McCormack
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
- Department of Dermatology, St Vincent's Hospital, Fitzroy, Australia
- Department of Oncology, Sir Peter MacCallum, The University of Melbourne, Parkville, Australia
| | - S Lade
- Department of Oncology, Sir Peter MacCallum, The University of Melbourne, Parkville, Australia
- Department of Anatomical Pathology, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - R W Johnstone
- Department of Oncology, Sir Peter MacCallum, The University of Melbourne, Parkville, Australia
- Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - H M Prince
- Department of Haematology, Peter MacCallum Cancer Centre, Melbourne, Australia
- Department of Oncology, Sir Peter MacCallum, The University of Melbourne, Parkville, Australia
- Epworth Healthcare, Melbourne, Australia
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Gentille C, Qin Q, Barbieri A, Ravi PS, Iyer S. Use of PEG-asparaginase in monomorphic epitheliotropic intestinal T-cell lymphoma, a disease with diagnostic and therapeutic challenges. Ecancermedicalscience 2017; 11:771. [PMID: 29062389 PMCID: PMC5636209 DOI: 10.3332/ecancer.2017.771] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Indexed: 12/14/2022] Open
Abstract
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), previously known as enteropathy associated T-cell lymphoma (EATL) type II, is a rare haematological malignancy with a difficult and delayed diagnosis. Symptoms can include abdominal pain, weight loss, and chronic diarrhoea. However, most patients are only diagnosed after complications, such as perforation or obstruction, have developed. There is no standard treatment for MEITL; most accepted regimens consist of surgical resection and anthracycline-based chemotherapy. Prognosis is poor with an approximate survival of less than a year. Even though other therapies, such as autologous stem cell transplant, has shown promising results, not all patients can tolerate this course of treatment especially if they are elderly, have several comorbidities or are malnourished. Innovative therapies that improve survival and can be used as an alternative for more intensive treatment are needed. We report the use of PEG-asparaginase along with conventional anthracycline therapy in a 70-year-old woman diagnosed with MEITL, who went into remission and survived for more than one year before succumbing to relapsed disease.
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Affiliation(s)
- Cesar Gentille
- Department of Internal Medicine, Houston Methodist Hospital, Houston, Texas 77030, USA
| | - Qian Qin
- Department of Internal Medicine, Houston Methodist Hospital, Houston, Texas 77030, USA
| | - Andreia Barbieri
- Department of Pathology, Houston Methodist Hospital, Houston, Texas 77030, USA
| | - Pingali Sai Ravi
- Houston Methodist Cancer Center, Houston Methodist Hospital, Houston, Texas 77030, USA
| | - Swaminathan Iyer
- Houston Methodist Cancer Center, Houston Methodist Hospital, Houston, Texas 77030, USA
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Rezania D, Cualing HD, Ayala E. The Diagnosis, Management, and Role of Hematopoietic Stem Cell Transplantation in Aggressive Peripheral T-Cell Neoplasms. Cancer Control 2017; 14:151-9. [PMID: 17387300 DOI: 10.1177/107327480701400208] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background Peripheral T-cell neoplasms (PTCNs) comprise a group of uncommon and heterogeneous lymphoid malignancies. They are more difficult to diagnose and treat and have a worse prognosis than B-cell lymphomas. Although PTCNs initially show a significant degree of chemosensitivity, the outcome of treatment with conventional dose chemotherapy remains poor. Methods We reviewed the literature on the diagnosis, treatment, and collective transplant reports regarding PTCNs. Results The correct diagnosis of peripheral T-cell lymphoma requires a combination of clinical presentation, morphology, immunophenotype, and molecular study. While no specific treatment other than conventional dose chemotherapy is currently available for aggressive PTCN, histone acetylase inhibitors and monoclonal antibodies such as anti-CD7 and anti-CD52 are being studied in T-cell malignancies. The role of autologous and allogeneic transplantation is being investigated for high-risk, relapsed, and refractory PTCNs with some promising results. Conclusions Access to hematopathology expertise in a tertiary care setting may lead to earlier and more accurate diagnoses of these diseases. PTCNs comprise a heterogeneous group of diseases with no widely accepted standard of care, and accurate determination of their histologic subtypes correlates with prognosis. Patients in first complete remission with poor risk features and patients with relapsed and refractory disease should be considered for bone marrow transplant due to the poor outcomes obtained with conventional chemotherapy.
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Affiliation(s)
- Dorna Rezania
- Blood and Marrow Transplant Program, H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA
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Varghese D, Haseer Koya H, Cherian SV, Mead K, Sharma A, Sharma N, Knohl SJ, Benjamin S. Hemophagocytic lymphohistiocytosis: an uncommon presentation of enteropathy-associated T-cell lymphoma. J Clin Oncol 2013; 31:e226-30. [PMID: 23530098 DOI: 10.1200/jco.2012.43.4944] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Affiliation(s)
- Dona Varghese
- State University of New York Upstate Medical University, Syracuse, NY 13210, USA.
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Autologous stem cell transplantation for enteropathy-associated T-cell lymphoma: a retrospective study by the EBMT. Blood 2013; 121:2529-32. [PMID: 23361910 DOI: 10.1182/blood-2012-11-466839] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Enteropathy-associated T-cell lymphoma (EATL) is a rare subtype of peripheral T-cell lymphomas with a poor prognosis. Autologous stem cell transplantation (ASCT) was retrospectively evaluated as a consolidation or salvage strategy for EATL. The analysis included 44 patients who received ASCT for EATL between 2000 and 2010. Thirty-one patients (70%) were in first complete or partial remission at the time of the ASCT. With a median follow-up of 46 months, relapse incidence, progression-free survival, and overall survival were 39%, 54%, and 59% at 4 years, respectively, with only one relapse occurring beyond 18 months posttransplant. There was a trend for better survival in patients transplanted in first complete or partial remission at 4 years (66% vs 36%; P = .062). ASCT is feasible in selected patients with EATL and can yield durable disease control in a significant proportion of the patients.
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Abstract
Enteropathy-associated T-cell lymphoma (EATL) is a complication of celiac disease (CD). This tumor derives from the neoplastic transformation of aberrant intraepithelial T lymphocytes emerging in celiac patients unresponsive to a gluten-free diet. Poor adherence to a gluten-free diet, HLA-DQ2 homozygosity, and late diagnosis of CD are recognized as risk factors for malignant evolution of CD. Recurrence of diarrhea, unexplained weight loss, abdominal pain, fever, and night sweating should alert physicians to this complication. The suspicion of EATL should lead to an extensive diagnostic workup in which magnetic resonance enteroclysis, positron emission tomography scan, and histologic identification of lesions represent the best options. Treatment includes high-dose chemotherapy preceded by surgical resection and followed by autologous stem cell transplantation, although biologic therapies seem to be promising. Strict adherence to a gluten-free diet remains the only way to prevent EATL.
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Jantunen E, Sureda A. The evolving role of stem cell transplants in lymphomas. Biol Blood Marrow Transplant 2011; 18:660-73. [PMID: 21963876 DOI: 10.1016/j.bbmt.2011.09.009] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2011] [Accepted: 09/10/2011] [Indexed: 10/17/2022]
Abstract
Autologous stem cell transplantation (ASCT) is an established therapeutic modality in the treatment of lymphomas, especially in the relapse setting. It is also under investigation after first-line therapy, for example, in patients with mantle cell or T cell lymphomas. Each year more than 6000 autotransplants for lymphomas are reported to the European Blood and Marrow Transplantation (EBMT) registry. The number of allogeneic stem cell transplantations (alloSCT) in lymphoma patients has increased over the last decade, with about 1200 transplanted lymphoma patients annually reported to the registry. Optimal timing and indications for alloSCT are not well defined because of absence of randomized trials. Developments in the treatment of lymphomas including immunotherapy have changed the clinical scenarios in regard to ASCT, and many published studies are now outdated. On the other hand, patients relapsing after immunochemotherapy may derive less benefit from ASCT. Consequently, there is an increasing interest in using alloSCT not only in lymphoma patients relapsing after ASCT but also in earlier phases in specific circumstances. Although curative potential is higher with alloSCT compared with ASCT, its wider use has been hindered by excessive nonrelapse mortality (NRM). Along with decreasing NRM figures, popularity of alloSCT may increase in the near future, possibly with the expense of ASCT. Prospective, randomized studies are needed to evaluate feasibility and efficacy of alloSCT in several clinical settings, as most published evidence is based on retrospective registry data or single-center experiences.
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Affiliation(s)
- Esa Jantunen
- Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
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10
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Burra P, Bizzaro D, Ciccocioppo R, Marra F, Piscaglia AC, Porretti L, Gasbarrini A, Russo FP. Therapeutic application of stem cells in gastroenterology: An up-date. World J Gastroenterol 2011; 17:3870-80. [PMID: 22025875 PMCID: PMC3198016 DOI: 10.3748/wjg.v17.i34.3870] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2010] [Revised: 03/07/2011] [Accepted: 03/14/2011] [Indexed: 02/06/2023] Open
Abstract
Adult stem cells represent the self-renewing progenitors of numerous body tissues, and they are currently classified according to their origin and differentiation ability. In recent years, the research on stem cells has expanded enormously and holds therapeutic promises for many patients suffering from currently disabling diseases. This paper focuses on the possible use of stem cells in the two main clinical settings in gastroenterology, i.e., hepatic and intestinal diseases, which have a strong impact on public health worldwide. Despite encouraging results obtained in both regenerative medicine and immune-mediated conditions, further studies are needed to fully understand the biology of stem cells and carefully assess their putative oncogenic properties. Moreover, the research on stem cells arouses fervent ethical, social and political debate. The Italian Society of Gastroenterology sponsored a workshop on stem cells held in Verona during the XVI Congress of the Federation of Italian Societies of Digestive Diseases (March 6-9, 2010). Here, we report on the issues discussed, including liver and intestinal diseases that may benefit from stem cell therapy, the biology of hepatic and intestinal tissue repair, and stem cell usage in clinical trials.
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Chandesris MO, Malamut G, Verkarre V, Meresse B, Macintyre E, Delarue R, Rubio MT, Suarez F, Deau-Fischer B, Cerf-Bensussan N, Brousse N, Cellier C, Hermine O. Enteropathy-associated T-cell lymphoma: a review on clinical presentation, diagnosis, therapeutic strategies and perspectives. ACTA ACUST UNITED AC 2010; 34:590-605. [PMID: 21050687 DOI: 10.1016/j.gcb.2010.09.008] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Enteropathy-associated T-cell lymphoma (EATL) is a rare complication of celiac disease (<1% of lymphomas) and has a poor prognosis. METHODS International literature review with PubMed search (up to January 2009) of pathophysiological, clinical and therapeutic data. RESULTS EATL is found in patients with a mean age of 59 years, often with a complication that signals its diagnosis. Refractory celiac disease (RCD), equivalent to low-grade intraepithelial T-cell lymphoma, could be an intermediary between celiac disease and high-grade invasive T-cell lymphoma. The median survival is 7 months, with no significant difference between stages; the cumulative 5-year survival is less than 20%. The poor prognosis is determined by disease that has often spread before it is diagnosed (50%), multifocal involvement of the small bowel (50%), poor general health status and undernutrition, and recurrence of complications (infections, perforations, gastrointestinal haemorrhages, occlusions), thus delaying the chemotherapy and contributing to frequent chemotherapy resistance. There is currently no effective and consensual treatment: preventive surgery for complications is controversial, and the results of chemotherapy are disappointing. The classic CHOP protocol (combination of doxorubicin-cyclophosphamide-vincristine-prednisone) does not have satisfactory results and survival remains poor, especially in patients with underlying RCD. High-dose chemotherapy with autotransplantion seems to only improve the prognosis in localised forms. Allogeneic bone marrow transplantation was not evaluated. In all, 1/3 of patients, being unfit for treatment, die before 3 months and half of treated patients stop chemotherapy prematurely due to inefficacy, intolerance and/or complications. CONCLUSION Improvement of the prognosis requires collaboration in order to compose a national cohort, to evaluate new diagnostic and therapeutic strategies and to define prognostic factors.
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Affiliation(s)
- M-O Chandesris
- Service d'hématologie adulte, hôpital Necker-Enfants-Malades, Assistance publique-Hôpitaux de Paris, université Paris V-René-Descartes, 149, rue de Sèvres, 75743 Paris cedex 15, France
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Evaluation of enteropathy-associated T-cell lymphoma comparing standard therapies with a novel regimen including autologous stem cell transplantation. Blood 2010; 115:3664-70. [DOI: 10.1182/blood-2009-07-231324] [Citation(s) in RCA: 159] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Abstract
Enteropathy associated T-cell lymphoma (EATL) is a rare type of peripheral T-cell lymphoma. At present, there are no standardized diagnostic or treatment protocols for EATL. We describe EATL in a population-based setting and evaluate a new treatment with aggressive chemotherapy and autologous stem cell transplantation (ASCT). From 1979 onward the Scotland and Newcastle Lymphoma Group prospectively collected data on all patients newly diagnosed with lymphoma in the Northern Region of England and Scotland. Between 1994 and 1998, records of all patients diagnosed with EATL were reviewed, and 54 patients had features of EATL. Overall incidence was 0.14/100 000 per year. Treatment was systemic chemotherapy (mostly anthracycline-based chemotherapy) with or without surgery in 35 patients and surgery alone in 19 patients. Median progression-free survival (PFS) was 3.4 months and overall survival (OS) was 7.1 months. The novel regimen IVE/MTX (ifosfamide, vincristine, etoposide/methotrexate)–ASCT was piloted from 1998 for patients eligible for intensive treatment, and 26 patients were included. Five-years PFS and OS were 52% and 60%, respectively, and were significantly improved compared with the historical group treated with anthracycline-based chemotherapy (P = .01 and P = .003, respectively). EATL is a rare lymphoma with an unfavorable prognosis when treated with conventional therapies. The IVE/MTX-ASCT regimen is feasible with acceptable toxicity and significantly improved outcome.
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Friedrich C, Schrum J, Chott A, Janka-Schaub G, Kabisch H. Ongoing remission after intensive ALL-type chemotherapy in pediatric intestinal T-cell lymphoma. Pediatr Blood Cancer 2010; 54:610-2. [PMID: 20049930 DOI: 10.1002/pbc.22330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
A rare case of primary intestinal T-cell lymphoma (ITL) of an 8-year-old boy is reported. Medium- to large-sized tumor cells were betaF1+, CD3+, CD8+. TIA-1+, but CD4-, CD5-, CD30-, CD56-, CD20-, CD79a-, TdT-, consistent with an intraepithelial lymphocyte (IEL) origin. They showed monoclonal rearrangement of the T-cell receptor gamma-chain and no evidence of EBV infection. No clinical, histologic, laboratory, or genetic evidence of celiac disease was detected. In adults, ITL is often associated with enteropathy and has a very poor outcome. Our patient remains in first remission 30 months after finishing the acute lymphoblastic leukemia protocol COALL-07-03 high risk standard.
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Affiliation(s)
- Carsten Friedrich
- Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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van de Water JMW, Cillessen SAGM, Visser OJ, Verbeek WHM, Meijer CJLM, Mulder CJJ. Enteropathy associated T-cell lymphoma and its precursor lesions. Best Pract Res Clin Gastroenterol 2010; 24:43-56. [PMID: 20206108 DOI: 10.1016/j.bpg.2009.11.002] [Citation(s) in RCA: 78] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2009] [Accepted: 11/16/2009] [Indexed: 01/31/2023]
Abstract
Enteropathy Associated T-cell Lymphoma (EATL) is an intestinal tumour of intra-epithelial lymphocytes. Based on morphology, immunohistochemistry and genetic profile EATL can be divided into two groups. EATL type I is a large cell lymphoma which is highly associated with Coeliac Disease (CD) and mostly presents with malabsorption, weight loss and CD-related symptoms. EATL type II consists of small to medium-sized cells and presents often with obstruction or perforation of the small bowel. This type of EATL has no known association with CD. When EATL has been diagnosed a thorough diagnostic work-up is needed. This work-up preferably includes video capsule enteroscopy (VCE), double-balloon enteroscopy (DBE), computed tomography (CT) combined with 18F-fluorodeoxyglucose positron emission tomography scan (18F-FDG-PET scan) if possible and magnetic resonance enteroclysis (MRE). Nowadays, most EATL patients are treated with chemotherapy mostly preceded by resection of the tumour and followed by stem cell transplantation. Despite these therapies outcome of EATL remains very poor with a 5-year survival of 8-20%. In order to improve survival prospective multicentre trials, studying new therapies are needed. The combination of chemotherapy, monoclonal antibodies and/or apoptosis inducing small molecules might be a potential treatment for EATL in the (nearby) future.
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Affiliation(s)
- Jolanda M W van de Water
- Department of Gastroenterology and Hepatology, VU University Medical Centre, Amsterdam, The Netherlands.
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Ikebe T, Miyazaki Y, Abe Y, Urakami K, Ohtsuka E, Saburi Y, Saburi M, Ando T, Kohno K, Ogata M, Kadota J. Successful treatment of refractory enteropathy-associated T-cell lymphoma using high-dose chemotherapy and autologous stem cell transplantation. Intern Med 2010; 49:2157-61. [PMID: 20930447 DOI: 10.2169/internalmedicine.49.3409] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
A 65-year-old woman presented with a 6-month history of abdominal pain and watery diarrhea. Type II enteropathy-associated T-cell lymphoma (EATL) was diagnosed based on the clinical presentation and pathological examination of the tumor. The patient received combination chemotherapy but did not achieve remission. Subsequently, high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) were performed. After these therapies, she achieved complete remission, which has been sustained for 18 months. Although the role of HDT-ASCT for EATL is still controversial, the clinical course of this patient suggests that ASCT can improve the prognosis in some patients with EATL.
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Affiliation(s)
- Taichi Ikebe
- Department of Hematology, Oita University Faculty of Medicine, Yufu.
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d’Amore F, Jantunen E, Relander T. Hemopoietic stem cell transplantation in T-cell malignancies: Who, when, and how? Curr Hematol Malig Rep 2009; 4:236-44. [DOI: 10.1007/s11899-009-0031-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Du Z, Chen J, Zhou X, Zhang T, Chen B, Tang F. Composite lymphoma with relapse of enteropathy-type T-cell lymphoma. Leuk Lymphoma 2009; 50:749-56. [DOI: 10.1080/10428190902795519] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Abstract
Coeliac disease is a chronic inflammatory disorder of the small bowel induced in genetically susceptible people by the irritant gluten and possibly other environmental cofactors. The disorder is characterised by a diverse clinical heterogeneity that ranges from asymptomatic to severely symptomatic, and it manifests with frank malabsorption, an increased morbidity attributable to the frequent association with autoimmune disorders and increased mortality resulting from the emergence of T-cell clonal proliferations that predispose the patient to enteropathy-type T-cell lymphoma. Our understanding of the molecular basis for this disorder has improved and enabled the identification of targets for new therapies, although a strict gluten-free diet remains the mainstay of safe and effective treatment. In this Seminar we critically reassess the clinical and diagnostic aspects of this disease and new perspectives in its pathogenesis and treatment.
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Affiliation(s)
- Antonio Di Sabatino
- First Department of Medicine, Centro per lo Studio e la Cura della Malattia Celiaca, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
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Babel N, Paragi P, Chamberlain RS. Management of Enteropathy-Associated T-Cell Lymphoma: An Algorithmic Approach. Case Rep Oncol 2009; 2:36-43. [PMID: 20740143 PMCID: PMC2918827 DOI: 10.1159/000205183] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Perforation of the small intestine is the most lethal complication following induction chemotherapy for enteropathy-associated T-cell lymphoma (EATL). We report a case of EATL with a near perforated jejunal ulcer, and suggest a novel approach towards its management. Surgical resection followed by aggressive chemotherapy should limit chemotherapy-associated gastrointestinal toxicity, thus allowing patients to receive adequate dose and duration of chemotherapy. The presented case highlights potential benefits of surgical intervention prior to chemotherapy for EATL.
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Affiliation(s)
- Nitin Babel
- Department of Surgery, Saint Barnabas Medical Center, Livingston, N.J., USA
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Hagymási K, Molnár B, és Tulassay Z. [Stem cell transplantation in the treatment of gastrointestinal diseases]. Orv Hetil 2008; 149:1449-1455. [PMID: 18632505 DOI: 10.1556/oh.2008.28400] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/13/2023]
Abstract
The stem cells with self-renewal ability are capable to form one or more cell types. They will be in the target of cell and gene therapy because of their multipotency and easy retrieval. Application of adult mesenchymal, neuronal, epidermal and haematopoietic stem cell can be favourable in the treatment of cardiac (myocardial infarction), bone (osteoarthritis), neurological (Parkinson's, Alzheimer's) and hematological (hemophilia, thrombocytopenia) disorders. Authors summarize the knowledge in connection with their application in the therapy of gastrointestinal diseases. Haematopoietic stem cell transplantation has been successful for the treatment of refractory Crohn's disease, as well as in selected group of celiac patients. Mesenchymal stem cell transplantation has been proved beneficial in the prevention of liver fibrotic process. It will gain more grounds in the treatment of autoimmune liver diseases: autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis in the future. Well-designed, multicentric, prospective studies are needed to confirm the results of case reports and clinical studies with small group of patients.
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Affiliation(s)
- Krisztina Hagymási
- Semmelweis Egyetem, Altalános Orvostudományi Kar II. Belgyógyászati Klinika Budapest.
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Al-Toma A, Mulder CJJ. Review article: Stem cell transplantation for the treatment of gastrointestinal diseases--current applications and future perspectives. Aliment Pharmacol Ther 2007; 26 Suppl 2:77-89. [PMID: 18081652 DOI: 10.1111/j.1365-2036.2007.03478.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Haematopoietic stem cell transplantation (HSCT) can be used to cure or ameliorate a variety of non-malignant diseases. These range from inherent defects of haematopoiesis, through metabolic diseases, to severe autoimmune diseases. The rationale for this strategy is based on the concept of immunoablation using high-dose chemotherapy, with subsequent regeneration of naïve T-lymphocytes derived from reinfused haematopoietic progenitor cells. Possibly the use of SCT allows the administration of high-dose chemotherapy resulting in a prompt remission in these therapy-refractory patients. AIM This review highlights the major scientific developments and defines the areas of successful use of HSCT in gastrointestinal disorders and gives a perspective on possible future applications. METHODS A search in the Medline has been conducted and all relevant published data were analysed. RESULTS HSCT has been proved successful in treating refractory Crohn's disease. A selected group of refractory coeliac patients having a high risk of developing enteropathy associated T-cell lymphoma has been recently treated with promising results. In cryptogenic cirrhosis, basic research and unpublished data concerning mesenchymal SCT are encouraging. CONCLUSION In refractory autoimmune gastrointestinal diseases, it seems that high-dose chemotherapy followed by HSCT is feasible and safe and might result in long-term improvement of disease activity.
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Affiliation(s)
- A Al-Toma
- Department of Gastroenterology and Hepatology, VU University Medical Centre, Amsterdam, The Netherlands
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Al-Toma A, Verbeek WHM, Visser OJ, Kuijpers KC, Oudejans JJ, Kluin-Nelemans HC, Mulder CJJ, Huijgens PC. Disappointing outcome of autologous stem cell transplantation for enteropathy-associated T-cell lymphoma. Dig Liver Dis 2007; 39:634-41. [PMID: 17531561 DOI: 10.1016/j.dld.2007.03.009] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2007] [Revised: 03/05/2007] [Accepted: 03/27/2007] [Indexed: 12/11/2022]
Abstract
BACKGROUND Despite treatment, enteropathy-associated T-cell lymphoma has a very poor outcome. Chemotherapy can be complicated by small bowel perforation, gastrointestinal bleeding and development of enterocolic fistulae. Here we report on the feasibility, safety and efficacy of high-dose chemotherapy followed by autologous stem cell transplantation in patients with enteropathy-associated T-cell lymphoma (three upfront and one at relapse), with or without prior partial small bowel resection. METHODS Four patients [two males, two females, mean age 65 years (range 60-69 years)] received high-dose chemotherapy followed by autologous stem cell transplantation. Partial small bowel resection has been performed in three patients. RESULTS All four patients completed the mobilization and leucopheresis procedures successfully and subsequently received conditioning chemotherapy and transplantation. Engraftment occurred in all patients. No major non-haematological toxicity or transplantation-related mortality was observed. One patient has ongoing complete remission 32 months after transplantation. Three patients died from relapse within few months after autologous stem cell transplantation. CONCLUSIONS Autologous stem cell transplantation seems unsatisfactory for patients with enteropathy-associated T-cell lymphoma. More intensive conditioning and aggressive chemotherapy with/or without targeted immunotherapy as well as allogenous stem cell transplantation needs to be explored.
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Affiliation(s)
- A Al-Toma
- Department of Gastroenterology, VU University Medical Centre, Amsterdam, The Netherlands
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Ciccocioppo R, Perfetti V, Corazza GR. Treating ETTCL: A matter of early diagnosis and chemotherapy strategies. Dig Liver Dis 2007; 39:642-5. [PMID: 17531553 DOI: 10.1016/j.dld.2007.04.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/20/2007] [Indexed: 02/07/2023]
Affiliation(s)
- R Ciccocioppo
- First Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Italy
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Bishton MJ, Haynes AP. Combination chemotherapy followed by autologous stem cell transplant for enteropathy-associated T cell lymphoma. Br J Haematol 2007; 136:111-3. [PMID: 17116129 DOI: 10.1111/j.1365-2141.2006.06371.x] [Citation(s) in RCA: 69] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Enteropathy-associated T cell lymphoma (EATL) is a rare entity associated with coeliac disease, with a poor prognosis due to perforation and gastro-intestinal bleeding during treatment, and a high relapse risk. Six patients were treated with two cycles of IVE (ifosphamide, etoposide, epirubicin), followed by two cycles of high-dose methotrexate (3 g/m(2)) with folinic acid rescue and a BEAM (carmustine, etoposide, cytarabine, melphalan) autograft. Enteral feeding was given throughout treatment. Four patients remain alive in complete remission at 1.83-4.32 years; two have relapsed. Given the historically poor outcome in these patients, this regimen appears very promising in the treatment of EATL.
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Affiliation(s)
- Mark J Bishton
- Department of Haematology, Nottingham City Hospital, Nottingham, UK
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Hönemann D, Prince HM, Hicks RJ, Seymour JF. Enteropathy-associated T-cell lymphoma without a prior diagnosis of coeliac disease: diagnostic dilemmas and management options. Ann Hematol 2004; 84:118-21. [PMID: 15452669 DOI: 10.1007/s00277-004-0953-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2004] [Accepted: 08/30/2004] [Indexed: 01/01/2023]
Abstract
Enteropathy-associated T-cell lymphoma (EATL) ultimately develops in 7-10% of patients with long-standing coeliac disease. In patients without a prior diagnosis of coeliac disease this is a very rare disorder, and the diagnosis in such cases is often difficult and delayed due to the non-specific nature of the symptoms and a very low index of clinical suspicion. Standard anti-lymphoma therapies have minimal utility in patients with EATL, and their prognosis is poor. An added difficulty is the high risk of intestinal perforation especially with the commencement of treatment due to the multifocal nature of bowel disease and poor underlying nutrition and tissue integrity. To illustrate these problems and provide an example of how these issues may be addressed, we report the case of a patient with EATL who was completely asymptomatic from unsuspected underlying coeliac disease and presented initially with back pain followed by bowel obstruction. He was treated with gut rest with total parenteral nutrition before commencing an intensive chemotherapy regimen [hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone)] and is currently well in ongoing complete remission 34 months later.
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