293 results on '"T. A. Lister"'
Search Results
2. Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification
- Author
-
T. Andrew Lister, Lawrence H. Schwartz, Sally F. Barrington, Bruce D. Cheson, Franco Cavalli, Richard I. Fisher, and Emanuele Zucca
- Subjects
Cancer Research ,medicine.medical_specialty ,International Cooperation ,Fluorodeoxyglucose F18 ,Predictive Value of Tests ,hemic and lymphatic diseases ,Refractory Hodgkin Lymphoma ,medicine ,Humans ,Refractory Diffuse Large B-Cell Lymphoma ,Medical physics ,Neoplasm Staging ,Fluorodeoxyglucose ,medicine.diagnostic_test ,business.industry ,Lymphoma, Non-Hodgkin ,Liver Neoplasms ,Cancer ,Prognosis ,medicine.disease ,Hodgkin Disease ,Lymphoma ,Clinical trial ,Treatment Outcome ,Oncology ,Positron emission tomography ,Positron-Emission Tomography ,Radiology ,Primary mediastinal B-cell lymphoma ,Radiopharmaceuticals ,Bone Marrow Neoplasms ,Tomography, X-Ray Computed ,business ,medicine.drug - Abstract
The purpose of this work was to modernize recommendations for evaluation, staging, and response assessment of patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). A workshop was held at the 11th International Conference on Malignant Lymphoma in Lugano, Switzerland, in June 2011, that included leading hematologists, oncologists, radiation oncologists, pathologists, radiologists, and nuclear medicine physicians, representing major international lymphoma clinical trials groups and cancer centers. Clinical and imaging subcommittees presented their conclusions at a subsequent workshop at the 12th International Conference on Malignant Lymphoma, leading to revised criteria for staging and of the International Working Group Guidelines of 2007 for response. As a result, fluorodeoxyglucose (FDG) positron emission tomography (PET)–computed tomography (CT) was formally incorporated into standard staging for FDG-avid lymphomas. A modification of the Ann Arbor descriptive terminology will be used for anatomic distribution of disease extent, but the suffixes A or B for symptoms will only be included for HL. A bone marrow biopsy is no longer indicated for the routine staging of HL and most diffuse large B-cell lymphomas. However, regardless of stage, general practice is to treat patients based on limited (stages I and II, nonbulky) or advanced (stage III or IV) disease, with stage II bulky disease considered as limited or advanced disease based on histology and a number of prognostic factors. PET-CT will be used to assess response in FDG-avid histologies using the 5-point scale. The product of the perpendicular diameters of a single node can be used to identify progressive disease. Routine surveillance scans are discouraged. These recommendations should improve evaluation of patients with lymphoma and enhance the ability to compare outcomes of clinical trials.
- Published
- 2014
- Full Text
- View/download PDF
3. EZH2 mutations are frequent and represent an early event in follicular lymphoma
- Author
-
Andreas Rosenwald, Erlend B. Smeland, T. Andrew Lister, Sameena Iqbal, Vera Grossmann, John G. Gribben, Alexander Kohlmann, George E. Wright, Lisa M. Rimsza, Claude Chelala, Nikolay Popov, German Ott, Robert Kerrin Hills, Randy D. Gascoyne, Andrew Clear, King Tan, Abigail M. Lee, Hajnalka Rajnai, Olivier Elemento, Wing C. Chan, Louis M. Staudt, Shamzah Araf, Ciaran O'Riain, Jessica Okosun, Rita M. Braziel, Janet Matthews, Torsten Haferlach, Jun Wang, Jacek Marzec, Elias Campo, András Matolcsy, Jude Fitzgibbon, Silvia Montoto, and Csaba Bödör
- Subjects
endocrine system ,Time Factors ,Methyltransferase ,medicine.medical_treatment ,DNA Mutational Analysis ,Immunology ,Follicular lymphoma ,Kaplan-Meier Estimate ,macromolecular substances ,Biology ,medicine.disease_cause ,Biochemistry ,Targeted therapy ,Cohort Studies ,Gene Frequency ,hemic and lymphatic diseases ,Biomarkers, Tumor ,medicine ,Humans ,Enhancer of Zeste Homolog 2 Protein ,Lymphoma, Follicular ,Allele frequency ,Mutation ,Lymphoid Neoplasia ,MEF2 Transcription Factors ,Gene Expression Profiling ,EZH2 ,Polycomb Repressive Complex 2 ,Germinal center ,Cell Biology ,Hematology ,medicine.disease ,CREB-Binding Protein ,Lymphoma ,Disease Progression ,Cancer research ,Receptors, Tumor Necrosis Factor, Member 14 - Abstract
Gain of function mutations in the H3K27 methyltransferase EZH2 represent a promising therapeutic target in germinal center lymphomas. In this study, we assessed the frequency and distribution of EZH2 mutations in a large cohort of patients with follicular lymphoma (FL) (n = 366) and performed a longitudinal analysis of mutation during the disease progression from FL to transformed FL (tFL) (n = 33). Mutations were detected at 3 recurrent mutation hot spots (Y646, A682, and A692) in 27% of FL cases with variant allele frequencies (VAF) ranging from 2% to 61%. By comparing VAF of EZH2 with other mutation targets (CREBBP, MLL2, TNFRSF14, and MEF2B), we were able to distinguish patients harboring clonal EZH2 mutation from rarer cases with subclonal mutations. Overall, the high incidence of EZH2 mutations in FL and their stability during disease progression makes FL an appropriate disease to evaluate EZH2 targeted therapy.
- Published
- 2013
- Full Text
- View/download PDF
4. Breast cancer risk following Hodgkin lymphoma radiotherapy in relation to menstrual and reproductive factors
- Author
-
Isabel Syndikus, Andrea M. Stevens, T. A. Lister, H Lucraft, David Cunningham, John Radford, Dianne Gilson, Alan Horwich, Rosie Cooke, Michael Jones, S J Harris, S Falk, Peter Hoskin, Timothy M Illidge, Barry W. Hancock, David C. Linch, M. V. Williams, and Anthony J. Swerdlow
- Subjects
Adult ,Cancer Research ,medicine.medical_specialty ,Neoplasms, Radiation-Induced ,Epidemiology ,supradiaphragmatic radiotherapy ,Breast Neoplasms ,Cohort Studies ,03 medical and health sciences ,breast cancer ,0302 clinical medicine ,Breast cancer ,Pregnancy ,medicine ,Humans ,030212 general & internal medicine ,Reproductive History ,Menarche ,Gynecology ,Wales ,Obstetrics ,business.industry ,Age Factors ,Case-control study ,Odds ratio ,Middle Aged ,medicine.disease ,Hodgkin Disease ,3. Good health ,Menopause ,England ,Oncology ,Case-Control Studies ,030220 oncology & carcinogenesis ,Cohort ,Female ,business ,Hodgkin lymphoma ,Cohort study - Abstract
Background: Women treated with supradiaphragmatic radiotherapy (sRT) for Hodgkin lymphoma (HL) at young ages have a substantially increased breast cancer risk. Little is known about how menarcheal and reproductive factors modify this risk. Methods: We examined the effects of menarcheal age, pregnancy, and menopausal age on breast cancer risk following sRT in case–control data from questionnaires completed by 2497 women from a cohort of 5002 treated with sRT for HL at ages
- Published
- 2013
- Full Text
- View/download PDF
5. Breast Cancer Risk After Supradiaphragmatic Radiotherapy for Hodgkin's Lymphoma in England and Wales: A National Cohort Study
- Author
-
Isabel Syndikus, Barry W. Hancock, John Radford, H Lucraft, Andrew Bates, David Cunningham, Andrea M. Stevens, M. V. Williams, Alan Horwich, Dianne Gilson, Peter Hoskin, T. Andrew Lister, Anthony J. Swerdlow, Rosie Cooke, Stephen Falk, David C. Linch, and Sarah J. Harris
- Subjects
Adult ,Risk ,Cancer Research ,medicine.medical_specialty ,Neoplasms, Radiation-Induced ,Adolescent ,medicine.medical_treatment ,Diaphragm ,Breast Neoplasms ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,medicine ,Humans ,030304 developmental biology ,Gynecology ,0303 health sciences ,Wales ,business.industry ,Age Factors ,Absolute risk reduction ,Radiotherapy Dosage ,Ductal carcinoma ,Hodgkin's lymphoma ,medicine.disease ,Hodgkin Disease ,3. Good health ,Radiation therapy ,Standardized mortality ratio ,England ,Oncology ,030220 oncology & carcinogenesis ,Cohort ,business ,Cohort study - Abstract
Purpose To investigate breast cancer risk after supradiaphragmatic radiotherapy administered to young women with Hodgkin's lymphoma (HL) in a much larger cohort than previously to provide data for patient follow-up and screening individualized according to treatment type, age, and time point during follow-up. Patients and Methods Breast cancer risk was assessed in 5,002 women in England and Wales treated for HL with supradiaphragmatic radiotherapy at age < 36 years from 1956 to 2003, who underwent follow-up with 97% completeness until December 31, 2008. Results Breast cancer or ductal carcinoma in situ developed in 373 patients, with a standardized incidence ratio (SIR) of 5.0 (95% CI, 4.5 to 5.5). SIRs were greatest for those treated at age 14 years (47.2; 95% CI, 28.0 to 79.8) and continued to remain high for at least 40 years. The maximum absolute excess risk was at attained ages 50 to 59 years. Alkylating chemotherapy or pelvic radiotherapy diminished the risk, but only for women treated at age ≥ 20 years, not for those treated when younger. Cumulative risks were tabulated in detail; for 40-year follow-up, the risk for patients receiving ≥ 40 Gy mantle radiotherapy at young ages was 48%. Conclusion This article provides individualized risk estimates based on large numbers for patients with HL undergoing follow-up after radiotherapy at young ages. Follow-up of such women needs to continue for 40 years or longer and may require more-intensive screening regimens than those in national general population programs. Special consideration is needed of potential measures to reduce breast cancer risk for girls treated with supradiaphragmatic radiotherapy at pubertal ages.
- Published
- 2012
- Full Text
- View/download PDF
6. T-cell replete fludarabine/cyclophosphamide reduced intensity allogeneic stem cell transplantation for lymphoid malignancies
- Author
-
T. Andrew Lister, Heather Oakervee, Samir G. Agrawal, Jamie Cavenagh, Denise Syndercombe-Court, Finlay MacDougall, David Taussig, Rebecca Auer, John G. Gribben, and Jeff K. Davies
- Subjects
Adult ,Oncology ,medicine.medical_specialty ,Transplantation Conditioning ,Cyclophosphamide ,T-Lymphocytes ,Follicular lymphoma ,Graft vs Host Disease ,Autologous stem-cell transplantation ,Recurrence ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Multiple myeloma ,Aged ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,medicine.disease ,Survival Analysis ,Lymphoproliferative Disorders ,Fludarabine ,Surgery ,Transplantation ,Regimen ,Hematologic Neoplasms ,business ,Vidarabine ,medicine.drug - Abstract
The relative merits of reduced-intensity allogeneic stem cell transplantation (RISCT) for high-risk indolent lymphoid malignancies are emerging, although the preferred conditioning regimen to manage the risks of graft-versus-host disease (GVHD) is not clearly defined. Here we report the outcome of 73 patients with lymphoid malignancies who received RISCT with a fludarabine/cyclophosphosphamide conditioning regimen and a median follow-up of 3 years. Median age was 54 years. Forty-eight per cent of patients had previously undergone autologous stem cell transplantation with a median of three prior therapies. Non-relapse mortality at 3 years was 19% but only 5% for patients with multiple myeloma (MM). Three-year overall survival and current progression-free survival was 67% and 63% respectively. Grade 2-4 acute GVHD occurred in 14% of patients while 49% had chronic GVHD requiring systemic immunosuppression. The preparatory regimen in this study has the advantage of reduced acute GVHD and low mortality, notably in patients with MM. In addition, this strategy provides long-term disease control in a significant proportion of patients with particular benefit in those with high-risk follicular lymphoma.
- Published
- 2012
- Full Text
- View/download PDF
7. SNP rs6457327 in the HLA region on chromosome 6p is predictive of the transformation of follicular lymphoma
- Author
-
Sameena Iqbal, Lucia Conde, David Wrench, Csaba Bödör, T. Andrew Lister, Jean-Baptiste Cazier, Janet Matthews, Christine F. Skibola, Maria Calaminici, John G. Gribben, Emanuela Carlotti, Jude Fitzgibbon, Silvia Montoto, and Pamela Leighton
- Subjects
medicine.medical_specialty ,Time Factors ,Immunology ,Follicular lymphoma ,Single-nucleotide polymorphism ,Human leukocyte antigen ,Biology ,Polymorphism, Single Nucleotide ,Biochemistry ,Germline ,International Prognostic Index ,HLA Antigens ,Risk Factors ,Internal medicine ,medicine ,Humans ,SNP ,Lymphoma, Follicular ,Lymphoid Neoplasia ,Hematology ,Cancer ,Cell Biology ,Middle Aged ,medicine.disease ,United Kingdom ,Cell Transformation, Neoplastic ,Chromosomes, Human, Pair 6 - Abstract
Inherited risk determinants for follicular lymphoma (FL) have recently been described in the immune gene-rich human leukocyte antigen region on chromosome 6p. The known importance of host immune response to FL survival led us to evaluate these germline factors in FL outcome. We confirm the association of single nucleotide polymorphisms rs10484561 (P = 3.5 × 10−9) and rs6457327 (P = .008) with risk of FL and demonstrate that rs6457327 predicts both time to (P = .02) and risk of (P < .01) FL transformation independently of clinical variables, including the Follicular Lymphoma International Prognostic Index.
- Published
- 2011
- Full Text
- View/download PDF
8. Increased angiogenic sprouting in poor prognosis FL is associated with elevated numbers of CD163+ macrophages within the immediate sprouting microenvironment
- Author
-
Kelly J. Morris, Alan G. Ramsay, Andrew Clear, Maria Calaminici, Finlay MacDougall, Abigail M. Lee, Gavin Kelly, T. Andrew Lister, John G. Gribben, and Simon Hallam
- Subjects
Pathology ,medicine.medical_specialty ,Angiogenesis ,Biopsy ,Immunology ,Follicular lymphoma ,Antigens, Differentiation, Myelomonocytic ,Receptors, Cell Surface ,Biology ,Biochemistry ,Neovascularization ,Antigens, CD ,Biomarkers, Tumor ,medicine ,Humans ,Lymphoma, Follicular ,Lymphoid Neoplasia ,Tissue microarray ,Neovascularization, Pathologic ,medicine.diagnostic_test ,Macrophages ,Cell Biology ,Hematology ,Prognosis ,medicine.disease ,Lymphoma ,Platelet Endothelial Cell Adhesion Molecule-1 ,cardiovascular system ,medicine.symptom ,CD163 ,Sprouting - Abstract
Follicular lymphoma has considerable clinical heterogeneity, and there is a need for easily quantifiable prognostic biomarkers. Microvessel density has been shown to be a useful prognostic factor based on numerical assessment of vessel numbers within histologic sections in some studies, but assessment of tumor neovascularization through angiogenic sprouting may be more relevant. We therefore examined the smallest vessels, single-staining structures measuring less than 30 μm2 in area, seen within histologic sections, and confirmed that they were neovascular angiogenic sprouts using extended focal imaging. Tissue microarrays composing diagnostic biopsies from patients at the extremes of survival of follicular lymphoma were analyzed with respect to numbers of these sprouts. This analysis revealed higher angiogenic activity in the poor prognostic group and demonstrated an association between increased sprouting and elevated numbers of infiltrating CD163+ macrophages within the immediate microenvironment surrounding the neovascular sprout.
- Published
- 2010
- Full Text
- View/download PDF
9. Leukemia-initiating cells from some acute myeloid leukemia patients with mutated nucleophosmin reside in the CD34− fraction
- Author
-
Emmanuel Griessinger, John G. Gribben, Dominique Bonnet, Tina Luke, Debra M. Lillington, T. Andrew Lister, Jamie Cavenagh, Kirsty Sharrock, Jacques Vargaftig, Samir G. Agrawal, Farideh Miraki-Moud, Heather Oakervee, and David Taussig
- Subjects
medicine.medical_specialty ,Myeloid ,Immunology ,CD34 ,Antigens, CD34 ,Cell Separation ,Mice, SCID ,Biology ,Immunotherapy, Adoptive ,Biochemistry ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Mice, Inbred NOD ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Animals ,Humans ,030304 developmental biology ,Erythroid Precursor Cells ,Mice, Knockout ,0303 health sciences ,Nucleophosmin ,Myeloid Neoplasia ,Hematology ,Nuclear Proteins ,Myeloid leukemia ,Cell Biology ,medicine.disease ,ADP-ribosyl Cyclase 1 ,Xenograft Model Antitumor Assays ,3. Good health ,Leukemia, Myeloid, Acute ,Haematopoiesis ,Leukemia ,Phenotype ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Neoplastic Stem Cells ,Cancer research ,Mutant Proteins - Abstract
Leukemia-initiating cells (LICs) in acute myeloid leukemia (AML) are believed to be restricted to the CD34+ fraction. However, one of the most frequently mutated genes in AML is nucleophosmin (NPM), and this is associated with low CD34 expression. We, therefore, investigated whether NPM-mutated AMLs have LICs restricted to the CD34+ fraction. We transplanted sorted fractions of primary NPM-mutated AML into immunodeficient mice to establish which fractions initiate leukemia. Approximately one-half of cases had LICs exclusively within the CD34− fraction, whereas the CD34+ fraction contained normal multilineage hematopoietic repopulating cells. Most of the remaining cases had LICs in both CD34+ and CD34− fractions. When samples were sorted based on CD34 and CD38 expression, multiple fractions initiated leukemia in primary and secondary recipients. The data indicate that the phenotype of LICs is more heterogeneous than previously realized and can vary even within a single sample. This feature of LICs may make them particularly difficult to eradicate using therapies targeted against surface antigens.
- Published
- 2010
- Full Text
- View/download PDF
10. Negative immunomagnetic selection of T cells from peripheral blood of presentation AML specimens
- Author
-
John G. Gribben, Rifca Le Dieu, David Taussig, and T. Andrew Lister
- Subjects
CD36 Antigens ,CD4-Positive T-Lymphocytes ,Myeloid ,T cell ,Sialic Acid Binding Ig-like Lectin 3 ,Immunology ,Interleukin-3 Receptor alpha Subunit ,CD34 ,Antigens, Differentiation, Myelomonocytic ,Antigens, CD34 ,CD8-Positive T-Lymphocytes ,Biology ,Antibodies ,Immune system ,Antigen ,Antigens, CD ,medicine ,Humans ,Immunology and Allergy ,Cytotoxic T cell ,Granulocyte Precursor Cells ,Immunomagnetic Separation ,Flow Cytometry ,medicine.disease ,CD11c Antigen ,Leukemia, Myeloid, Acute ,Leukemia ,medicine.anatomical_structure ,T cell selection - Abstract
To date, studies on T cells in acute myeloid leukemia (AML) have been limited to flow cytometric analysis of whole peripheral blood mononuclear cell (PBMC) specimens or functional work looking at the impact of AML myeloblasts on normal or remission T cells. This lack of information on T cells at the time of presentation with disease is due in part to the difficulty in isolating sufficiently pure T cells from these specimens for further study. Negative immunomagnetic selection has been the method of choice for isolating immune cells for functional studies due to concerns that binding antibodies to the cell surface may induce cellular activation, block ligand-receptor interactions or result in immune clearance. In order specifically to study T cells in presentation AML specimens, we set out to develop a method of isolating highly pure CD4 and CD8 T cells by negative selection from the peripheral blood (PB) of newly diagnosed AML patients. This technique, unlike T cell selection from PB from normal individuals or from patients with chronic lymphocytic leukaemia, was extremely problematic due to properties of the leukaemic myeloblasts. A successful method was eventually optimized requiring the use of a custom antibody cocktail consisting of CD33, CD34, CD123, CD11c and CD36, to deplete myeloblasts.
- Published
- 2009
- Full Text
- View/download PDF
11. Array-based DNA methylation profiling in follicular lymphoma
- Author
-
Louis M. Staudt, Ciaran O'Riain, Andreas Rosenwald, C. Fleischmann, Elias Campo, J. Yeboah-Afari, G. W. Wright, Erlend B. Smeland, Karin E. Summers, W. C. Chan, Tim Crook, T. A. Lister, Rita M. Braziel, Derville O’Shea, S. Reimer, R. Le Dieu, Lisa M. Rimsza, Nathalie A. Johnson, Leena Bhaw-Rosun, German Ott, Randy D. Gascoyne, Charles A. Mein, G. Kelly, Paul Smith, Youwen Yang, Jude Fitzgibbon, and John G. Gribben
- Subjects
Adult ,Cancer Research ,Adolescent ,Follicular lymphoma ,Biology ,Methylation ,Article ,Epigenesis, Genetic ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,follicular lymphoma ,Gene expression ,medicine ,Humans ,Child ,Lymphoma, Follicular ,Aged ,Oligonucleotide Array Sequence Analysis ,030304 developmental biology ,Aged, 80 and over ,Regulation of gene expression ,0303 health sciences ,Gene Expression Profiling ,transformation ,Hematology ,DNA Methylation ,Middle Aged ,medicine.disease ,3. Good health ,Gene Expression Regulation, Neoplastic ,Gene expression profiling ,Haematopoiesis ,Oncology ,CpG site ,Child, Preschool ,030220 oncology & carcinogenesis ,DNA methylation ,gene expression ,Cancer research ,CpG Islands ,Lymph Nodes ,polycomb - Abstract
Quantitative methylation profiling was performed using the Illumina GoldenGate Assay in untreated Follicular Lymphoma (FL) (164), paired pre- and post-transformation FL (20), benign haematopoietic (24) samples and purified B & T cells from two FL cases. Methylation values allowed separation of untreated FL samples from controls with one exception based primarily on tumour-specific gains of methylation typically occurring within CpG islands. Genes which are targets for epigenetic repression in stem cells by Polycomb Repressor Complex 2 were significantly overrepresented among hypermethylated genes. Methylation profiles were conserved in sequential FL and t-FL biopsies suggesting that widespread methylation represents an early event in lymphomagenesis and may not contribute substantially to transformation. Significant (p
- Published
- 2009
- Full Text
- View/download PDF
12. BCL2 protein expression in follicular lymphomas with t(14;18) chromosomal translocations
- Author
-
Teresa Marafioti, David Y. Mason, Margaret Jones, Lisa J. Campbell, Andrew Clear, Jacqueline Cordell, Abigail M. Lee, T. Andrew Lister, Noraidah Masir, and Lindsey K. Goff
- Subjects
DNA Mutational Analysis ,Follicular lymphoma ,Somatic hypermutation ,Biology ,Immunofluorescence ,medicine.disease_cause ,Translocation, Genetic ,Epitope ,immune system diseases ,hemic and lymphatic diseases ,Biomarkers, Tumor ,medicine ,Humans ,Lymphoma, Follicular ,neoplasms ,In Situ Hybridization, Fluorescence ,Cell Proliferation ,Chromosomes, Human, Pair 14 ,Mutation ,medicine.diagnostic_test ,Hematology ,medicine.disease ,Immunohistochemistry ,Molecular biology ,Genes, bcl-2 ,Lymphoma ,Ki-67 Antigen ,Proto-Oncogene Proteins c-bcl-2 ,biology.protein ,biological phenomena, cell phenomena, and immunity ,Antibody ,Chromosomes, Human, Pair 18 ,Immunostaining - Abstract
The t(14;18)(q32;q21) chromosomal translocation induces BCL2 protein overexpression in most follicular lymphomas. However the expression of BCL2 is not always homogeneous and may demonstrate a variable degree of heterogeneity. This study analysed BCL2 protein expression pattern in 33 cases of t(14;18)-positive follicular lymphomas using antibodies against two different epitopes (i.e. the widely used antibody BCL2/124 and an alternative antibody E17). 16/33 (49%) cases demonstrated strong BCL2 expression. In 10/33 (30%) cases, BCL2 expression was heterogeneous and in some of these, its loss appeared to be correlated with cell proliferation, as indicated by Ki67 expression. Double immunofluorescence labelling confirmed an inverse BCL2/Ki67 relationship, where in 24/28 (86%) cases cellular expression of BCL2 and Ki67 was mutually exclusive. In addition, seven BCL2 'pseudo-negative' cases were identified in which immunostaining was negative with antibody BCL2/124, but positive with antibody E17. Genomic DNA sequencing of these 'pseudo-negative' cases demonstrated eleven mutations in four cases and nine of these were missense mutations. It can be concluded that in follicular lymphomas, despite carrying the t(14;18) translocations, BCL2 protein expression may be heterogeneous and loss of BCL2 could be related to cell proliferation. Secondly, mutations in translocated BCL2 genes appear to be common and may cause BCL2 pseudo-negative immunostaining.
- Published
- 2009
- Full Text
- View/download PDF
13. Mutation of the Wilms’ Tumor 1 Gene Is a Poor Prognostic Factor Associated With Chemotherapy Resistance in Normal Karyotype Acute Myeloid Leukemia: The United Kingdom Medical Research Council Adult Leukaemia Working Party
- Author
-
David C. Linch, Claire Green, Alan Kenneth Burnett, Jane Stevens, T. Andrew Lister, Hilmar Quentmeier, Rosemary E. Gale, Hans G. Drexler, Robert Kerrin Hills, Christopher Allen, Ioannis Kakkas, Jude Fitzgibbon, Priya Virappane, Karin E. Summers, and Dominique Bonnet
- Subjects
Cancer Research ,medicine.medical_specialty ,Myeloid ,business.industry ,Myeloid leukemia ,Induction chemotherapy ,Wilms' tumor ,Gene mutation ,medicine.disease ,Minimal residual disease ,Gastroenterology ,Leukemia ,medicine.anatomical_structure ,Oncology ,Internal medicine ,Immunology ,Medicine ,Cumulative incidence ,business - Abstract
Purpose To determine the clinical relevance of Wilms’ tumor 1 (WT1) gene mutations in acute myeloid leukemia (AML) with normal karyotype (NK). Patients and Methods Exons 7 and 9 of WT1 were screened in samples from 470 young adult NK AMLs using a combination of direct sequencing and high-resolution capillary electrophoresis. Results Overall, 51 mutations were detected in 47 cases (10%): 46 frameshift mutations with insertion/deletion of one to 28 base pairs in exon 7 (n = 45) or exon 9 (n = 1), with a median mutant level of 45% (range, 8% to 86%), and five substitutions in exon 9: D396N (n = 3), H397Y (n = 1) and H397Q (n = 1). Patients with WT1 mutations had an inferior response to induction chemotherapy compared with wild-type cases (complete remission rate, 79% v 90%, odds ratio [OR] = 3.02; 95% CI, 1.17 to 7.82; P = .02), a higher rate of resistant disease (15% v 4%; OR = 9.33; 95% CI, 2.38 to 36.6; P = .001), an increased cumulative incidence of relapse (67% v 43%, hazard ratio [HR] = 3.02; 95% CI, 1.69 to 5.38; P = .0008), with a reduction in both relapse-free survival (22% v 44%; HR = 2.16; 95% CI, 1.32 to 3.55; P = .005) and overall survival (26% v 47%; HR = 1.91; 95% CI, 1.23 to 2.95; P = .007) at 5 years. In multivariate analysis, which included FLT3 internal tandem duplication and NPM1 mutation status, the presence of a WT1 mutation remained an independent adverse prognostic factor. Conclusion WT1 mutations are a negative prognostic indicator in NK AML and may be suitable for the development of targeted therapy.
- Published
- 2008
- Full Text
- View/download PDF
14. Long-term follow-up of high-dose treatment with autologous haematopoietic progenitor cell support in 693 patients with follicular lymphoma: an EBMT registry study
- Author
-
Shimon Slavin, Christian Gisselbrecht, G. Taghipour, L. Fouillard, Anna Sureda, N. Schmitz, H. Tilly, Silvia Montoto, Carmen Canals, Christophe Fruchart, T. A. Lister, Ama Z. S. Rohatiner, Augustin Ferrant, Veronique Leblond, Corinne Haioun, Eulogio Conde, Noel-Jean Milpied, and Anthony H. Goldstone
- Subjects
Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Follicular lymphoma ,Bone Marrow Cells ,Transplantation, Autologous ,Disease-Free Survival ,Internal medicine ,medicine ,Humans ,Registries ,Progenitor cell ,Lymphoma, Follicular ,Bone Marrow Transplantation ,Hematology ,business.industry ,Stem Cells ,Remission Induction ,Secondary Myelodysplastic Syndrome ,Middle Aged ,Hematopoietic Stem Cells ,medicine.disease ,Surgery ,Lymphoma ,Regimen ,Haematopoiesis ,Leukemia ,Treatment Outcome ,Female ,business - Abstract
To evaluate the outcome of a large series of patients who received high-dose treatment (HDT) for follicular lymphoma (FL), 693 patients undergoing HDT (total-body irradiation (TBI)-containing regimen: 58%; autologous bone marrow (BM)/peripheral blood progenitor cells (PBPCs): 378/285 patients) were included in the study. A total of 375 patients (54%) developed recurrent lymphoma, 10-year progression-free survival (PFS) being 31%. On multivariate analysis, younger age (P=0.003) and HDT in first complete remission (CR1) (P
- Published
- 2007
- Full Text
- View/download PDF
15. Myeloablative Therapy With Autologous Bone Marrow Transplantation for Follicular Lymphoma at the Time of Second or Subsequent Remission: Long-Term Follow-Up
- Author
-
Arnold S. Freedman, John Apostolidis, Janet Matthews, Peter Mauch, Ama Z. S. Rohatiner, Donna Neuberg, Andrew Davies, Lee M. Nadler, John G. Gribben, and T. Andrew Lister
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Cyclophosphamide ,Follicular lymphoma ,Transplantation, Autologous ,Recurrence ,Humans ,Medicine ,Lymphoma, Follicular ,Survival rate ,Bone Marrow Transplantation ,Retrospective Studies ,business.industry ,Remission Induction ,Cancer ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Lymphoma ,Surgery ,Survival Rate ,Transplantation ,Treatment Outcome ,medicine.anatomical_structure ,Oncology ,Disease Progression ,Female ,Bone marrow ,business ,Whole-Body Irradiation ,medicine.drug - Abstract
Purpose The aim of this retrospective analysis was to determine the outcome of patients with follicular lymphoma who received myeloablative therapy supported by autologous bone marrow transplantation as consolidation of second or subsequent remission, with a minimum follow-up of 12 years. Patients and Methods One hundred twenty-one adults received cyclophosphamide (CY) and total-body irradiation (TBI) supported by autologous bone marrow transplantation, with the marrow mononuclear cell fraction having been treated with monoclonal antibodies and complement. Data from St Bartholomew's Hospital and Dana-Farber Cancer Institute were combined for the purpose of this analysis because the patients were treated in an identical manner. Results Fifty-seven patients are alive, 41 without progression between 9 and 19 years; 64 patients have died, 20 without progression. With a median follow-up of 13.5 years, 60 patients have developed recurrent lymphoma. There is an apparent plateau on the remission duration curve at 48% at 12 years. Survival of patients treated in second remission was significantly longer than the survival of patients treated later in the course of the illness. Both remission duration and overall survival were also significantly longer for patients treated in second remission compared with an age-matched, remission-matched group of patients treated at St Bartholomew's Hospital before the introduction of this treatment. However, use of CY+TBI was associated with a significant risk of secondary myelodysplasia and secondary acute myeloblastic leukemia, resulting in 15 patient deaths. Conclusion These mature data confirm that prolonged freedom from recurrence may be achieved with myeloablative therapy and that a plateau on the curve seems to emerge with long follow-up.
- Published
- 2007
- Full Text
- View/download PDF
16. Recurrent mTORC1-activating RRAGC mutations in follicular lymphoma
- Author
-
Csaba Bödör, Leire Escudero-Ibarz, Andrew Davies, Rachel L. Wolfson, Hilmar Quentmeier, Reiner Siebert, Ahad F. Al Seraihi, Sameena Iqbal, Claude Chelala, Julia Richter, Janet Matthews, Ming-Qing Du, Jessica Okosun, Lucy Wilkins, Andrew Jack, Stephan H. Bernhart, Sharon Barrans, Silvia Montoto, Peter Johnson, Shamzah Araf, T. Andrew Lister, Alejo Efeyan, David M. Sabatini, Jonathan C. Strefford, Maria Calaminici, Andrew Clear, Rebecca Auer, Graham Packham, John G. Gribben, José Afonso Guerra-Assunção, Christopher Mansbridge, Roberto Zoncu, Jude Fitzgibbon, Jun Wang, Brian M. Castellano, Massachusetts Institute of Technology. Department of Biology, Whitehead Institute for Biomedical Research, Koch Institute for Integrative Cancer Research at MIT, Sabatini, David, Wolfson, Rachel Laura, and Efeyan, Alejo
- Subjects
0301 basic medicine ,Molecular Sequence Data ,Follicular lymphoma ,Mechanistic Target of Rapamycin Complex 1 ,Gene mutation ,Biology ,medicine.disease_cause ,Article ,03 medical and health sciences ,Genetics ,medicine ,Animals ,Humans ,Amino Acid Sequence ,B-cell lymphoma ,Lymphoma, Follicular ,Exome ,Monomeric GTP-Binding Proteins ,Mutation ,Sequence Homology, Amino Acid ,TOR Serine-Threonine Kinases ,medicine.disease ,Lymphoma ,030104 developmental biology ,Multiprotein Complexes ,Cancer research ,Clone (B-cell biology) ,Diffuse large B-cell lymphoma - Abstract
Follicular lymphoma is an incurable B cell malignancy characterized by the t(14;18) translocation and mutations affecting the epigenome. Although frequent gene mutations in key signaling pathways, including JAK-STAT, NOTCH and NF-κB, have also been defined, the spectrum of these mutations typically overlaps with that in the closely related diffuse large B cell lymphoma (DLBCL). Using a combination of discovery exome and extended targeted sequencing, we identified recurrent somatic mutations in RRAGC uniquely enriched in patients with follicular lymphoma (17%). More than half of the mutations preferentially co-occurred with mutations in ATP6V1B2 and ATP6AP1, which encode components of the vacuolar H+-ATP ATPase (V-ATPase) known to be necessary for amino acid−induced activation of mTORC1. The RagC variants increased raptor binding while rendering mTORC1 signaling resistant to amino acid deprivation. The activating nature of the RRAGC mutations, their existence in the dominant clone and their stability during disease progression support their potential as an excellent candidate for therapeutic targeting., Experimental Cancer Medicine Centres
- Published
- 2015
17. Immunotherapy for Acute Myelogenous Leukemia
- Author
-
G H Fairley, T. A. Lister, T McElwain, P. Alexander, D Crowther, and R L Powles
- Subjects
medicine.medical_specialty ,Chemotherapy ,Myeloid ,business.industry ,medicine.medical_treatment ,Induction chemotherapy ,Spontaneous remission ,Immunotherapy ,medicine.disease ,Surgery ,Myelogenous ,Leukemia ,medicine.anatomical_structure ,medicine ,business ,BCG vaccine - Abstract
One hundred and seven untreated patients with acute myelogenous leukemia (AML) were admitted to St. Bartholomew's Hospital between the 10th October 1970 and the 31st January 1973. Before receiving drugs to induce remission they were allocated alternatively into 2 groups to decide their remission treatment, a group to receive chemotherapy alone and a group to receive the same chemotherapy with immunotherapy. The patients were then given induction chemotherapy and 45 of them attained complete remission. All patients in remission then received chemotherapy consisting of 5 days treatment every 28 days. Patients receiving immunotherapy were also given multiple weekly intradermal injections of irradiated stored AML cells and Glaxo BCG using a Heaf gun. There were 19 patients in the group which received only chemotherapy during remission; 7 of these patients remain alive (median survival after attaining remission--303 days) and only 5 are still in their first remission (median remission length 188 days). Twenty three patients were allocated to receive immunotherapy during remission in addition to chemotherapy and 16 remain alive (median 545 days) and 8 are in their first remission (median 312 days). The difference in survival of the 2 groups is significant with a sigma value of 0.003.
- Published
- 2015
- Full Text
- View/download PDF
18. Neurotoxicity of High-Dose Cytosine Arabinoside
- Author
-
T. A. Lister, H. S. Dhaliwal, M. A. Richards, A. Z. S. Rohatiner, B. F. Smith, J. H. Waxman, Trivadi S. Ganesan, M. L. Slevin, and M. J. Barnett
- Subjects
business.industry ,Neuro oncology ,MEDLINE ,Neurotoxicity ,Pharmacology ,medicine.disease ,Clinical trial ,chemistry.chemical_compound ,chemistry ,Toxicity ,Cytarabine ,Medicine ,business ,Cytosine ,medicine.drug - Published
- 2015
- Full Text
- View/download PDF
19. Life expectancy of young adults with follicular lymphoma
- Author
-
Gianluca Gaidano, Annarita Conconi, Silvia Montoto, John G. Gribben, Armando López-Guillermo, Emanuele Zucca, Paola M.V. Rancoita, Michele Ghielmini, Chiara Lobetti-Bodoni, Emili Montserrat, Janet Matthews, Francesco Bertoni, Rita Coutinho, Alden A. Moccia, F. Cavalli, Silvia Franceschetti, T. A. Lister, Conconi, A, Lobetti Bodoni, C, Montoto, S, Lopez Guillermo, A, Coutinho, R, Matthews, J, Franceschetti, S, Bertoni, F, Moccia, A, Rancoita, PAOLA MARIA VITTORIA, Gribben, J, Cavalli, F, Gaidano, G, Lister, A, Montserrat, E, Ghielmini, M, and Zucca, E.
- Subjects
medicine.medical_specialty ,Multivariate analysis ,business.industry ,Follicular lymphoma ,Retrospective cohort study ,Hematology ,medicine.disease ,Surgery ,International Prognostic Index ,Oncology ,Internal medicine ,Statistical significance ,Medicine ,Rituximab ,Progression-free survival ,Young adult ,business ,medicine.drug ,follicular lymphoma, age, life expectancy, young adults, prognosis, survival - Abstract
Background: This study was aimed at investigating the clinical features and outcomes of follicular lymphoma ( FL) patients younger than 40 years, which have not been extensively investigated yet. Patients and methods: One hundred and fifty- five patients younger than 40 years were retrospectively studied from a series of 1002 FL patients diagnosed in four different European Oncology Centres ( Barcelona, Spain; Bellinzona, Switzerland; London, UK; Novara, Italy) from 1985 to 2010. Results: Patients younger than 40 had a lower incidence of elevated LDH, high beta2- microglobulin, and a high- risk Follicular Lymphoma International Prognostic Index ( FLIPI) score, whereas bone marrow involvement and bulky and disseminated lymphadenopathy were more frequent. At a median follow- up of 10 years, younger patients, in comparison with those older than 40, had significantly better overall ( OS), cause- specific survival ( CSS), and progression- free survival ( PFS), with 10- year OS rate of 81% versus 51% ( P < 0.0001), 10- year CSS rate of 82% versus 60% ( P < 0.0001), and 10- year PFS of 39% versus 24% ( P = 0.0098). However, there were no significant CSS and PFS differences in comparison with the patients aged 40- 60. In multivariate analysis, having the lymphoma diagnosed in the last two decades and a favourable FLIPI score were associated with a significantly longer PFS and CSS in younger patients, whereas only FLIPI retained statistical significance for OS. Conclusions: In our series, FL patients younger than 40 have a median OS of 24 years and their outcome seems to be improving over time. However, they still have a significantly shorter life expectancy than that of an age- matched general healthy population.
- Published
- 2015
20. Number of CD4+ Cells and Location of Forkhead Box Protein P3–Positive Cells in Diagnostic Follicular Lymphoma Tissue Microarrays Correlates With Outcome
- Author
-
T. Andrew Lister, Andrew Norton, Abigail M. Lee, Maria Calaminici, Finlay MacDougall, John G. Gribben, Andrew Clear, Janet Matthews, Suzanne Jordan, Lindsey K. Goff, and Andrew Davies
- Subjects
CD4-Positive T-Lymphocytes ,Cancer Research ,Pathology ,medicine.medical_specialty ,Tissue microarray ,business.industry ,Protein Array Analysis ,Follicular lymphoma ,FOXP3 ,Forkhead Transcription Factors ,medicine.disease ,Stem cell marker ,Immunohistochemistry ,Survival Analysis ,Follicular cell ,Lymphoma ,medicine.anatomical_structure ,Oncology ,medicine ,Humans ,IL-2 receptor ,business ,Lymphoma, Follicular ,Lymph node - Abstract
Purpose To examine the immune microenvironment in diagnostic follicular lymphoma (FL) biopsies and evaluate its prognostic significance. Patients and Methods Immunohistochemistry was used to study numbers and location of cells staining positive for immune cell markers CD4, CD7, CD8, CD25, CD68, forkhead box protein P3 (FOXP3), T-cell intracellular antigen-1, and Granzyme B in tissue microarrays of paraffin-embedded, diagnostic lymph node biopsies taken from 59 FL patients who lived less than 5 years (short-survival group; n = 34) and more than 15 years (long-survival group; n = 25). Results CD4 and FOXP3 expression were significantly different between the two groups. Samples from the long-survival group were more likely than those from the short-survival group to have CD4+ staining cells and to have FOXP3-positive cells in a perifollicular location. Conclusion This study has identified differences in immune cell composition of the diagnostic FL lymph node immune microenvironment and these have the potential for use as prognostic biomarkers in a routine histopathology setting.
- Published
- 2006
- Full Text
- View/download PDF
21. Recombinant human granulocyte macrophage colony stimulating factor following alternating non cross resistant chemotherapy in hodgkin's disease
- Author
-
J. A. L. Amess, M. A. Horton, T. A. Lister, E. Dorey, Peter F. M. Wrigley, A. M. Oza, A. Z. S. Rohatiner, M. Leahy, and C. L. Davis
- Subjects
Adult ,Male ,Cancer Research ,Vincristine ,medicine.medical_specialty ,Leukocytosis ,medicine.medical_treatment ,Procarbazine ,Gastroenterology ,Drug Administration Schedule ,Immunophenotyping ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Infusions, Intravenous ,Etoposide ,Chemotherapy ,Chlorambucil ,business.industry ,Remission Induction ,Granulocyte-Macrophage Colony-Stimulating Factor ,Hematology ,General Medicine ,Middle Aged ,medicine.disease ,Hodgkin Disease ,Recombinant Proteins ,Vinblastine ,Endocrinology ,Oncology ,Prednisolone ,Female ,business ,Progressive disease ,medicine.drug - Abstract
Fourteen patients with Hodgkin's disease (two previously untreated, 12 following relapse or with refractory disease) were treated with a combination chemotherapy regimen comprising chlorambucil, vinblastine, procarbazine, prednisolone, etoposide, vincristine and adriamycin administered on days 1-8. Recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) (mammalian glycosylated, Sandoz/Schering-Plough) was administered after alternate cycles of chemotherapy from day 10 for 7 days by continuous intravenous (i.v.) infusion in 12 patients in a dose finding study (dose: 2 micrograms/kg/day in four patients, 4 micrograms/kg/day in four patients and 8 micrograms/kg/day in four patients) and by daily subcutaneous (s/c) injections in two patients (8 micrograms/kg/day). There was a rapid peripheral leucocytosis following the rhGM-CSF, reaching a peak at 1-2 days in 12/14 patients. The initial leucocytosis was composed of neutrophils followed by a rise in immature myeloid cells. There was no difference observed in the duration or depth of the nadir following chemotherapy or in the rate of recovery of peripheral white cell counts between cycles with and without rhGM-CSF in patients treated with 2 and 4 micrograms/kg/day. At the dose of 8 micrograms/kg/day, 3/6 patients had a shorter nadir duration in the cycle with rhGM-CSF, compared with cycle without rhGM-CSF. There was no difference in frequency of infection in cycles with and without rhGM-CSF. Following chemotherapy, six patients achieved clinical remission, six partial remission and two had progressive disease.
- Published
- 2006
- Full Text
- View/download PDF
22. Bortezomib Therapy in Patients With Relapsed or Refractory Lymphoma: Potential Correlation of In Vitro Sensitivity and Tumor Necrosis Factor Alpha Response With Clinical Activity
- Author
-
Susan Hoare, John Radford, Elizabeth Trehu, Sandra J. Strauss, Simon P. Joel, Lynda Millard, Peter Johnson, Frances R. Balkwill, Sarah Vinnecombe, T. Andrew Lister, Ama Z. S. Rohatiner, David P. Schenkein, Anthony Boral, and Lenushka Maharaj
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Pathology ,Lymphoma ,Cell Survival ,medicine.medical_treatment ,Follicular lymphoma ,Antineoplastic Agents ,Gastroenterology ,Lymphoplasmacytic Lymphoma ,Bortezomib ,Recurrence ,Cell Line, Tumor ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Aged ,Tumor Necrosis Factor-alpha ,business.industry ,Middle Aged ,medicine.disease ,Boronic Acids ,Leukemia ,Peripheral neuropathy ,Cytokine ,Oncology ,Doxorubicin ,Pyrazines ,Cytokines ,Female ,Mantle cell lymphoma ,business ,medicine.drug - Abstract
Purpose To determine the efficacy of bortezomib in patients with lymphoid malignancy, correlating clinical response with effect on plasma cytokines and in vitro activity in primary cultures. Patients and Methods Patients received bortezomib (1.3 mg/m2) on days 1, 4, 8, and 11 of a 3-week cycle. Plasma tumor necrosis factor alpha (TNF-α) and interleukin-6 were measured before each treatment, and bortezomib activity was examined in patient samples grown in primary culture. Results Fifty-one patients received a total of 193 cycles of treatment. Twenty-four patients had mantle cell lymphoma (MCL), 13 had follicular lymphoma (FL), six had lymphoplasmacytic lymphoma, six had Hodgkin's disease (HD), and one each had diffuse large B-cell lymphoma and adult T-cell leukemia/lymphoma. Patients were heavily pretreated with a median of four previous therapies. Significant grade 3 to 4 toxicities were thrombocytopenia (n = 22), fatigue (n = 10), and peripheral neuropathy (n = 3). Seven patients with MCL responded to treatment (one complete response, six partial responses [PRs]; overall response rate, 29%). Two patients with FL achieved a late PR 3 months after discontinuing therapy. Two patients with Waldenström's macroglobulinemia and one patient with HD achieved a PR. MCL primary cultures demonstrated greater sensitivity to bortezomib than FL (median 50% effective concentration for viability, 209 nmol/L v 1,311 nmol/L, respectively; P = .07), which correlated with clinical response. A median reduction in plasma TNF-α of 98% was observed in six patients with MCL who responded to bortezomib compared with a reduction of 38% in six nonresponders (P = .07). Conclusion Bortezomib demonstrates encouraging efficacy in MCL in heavily pretreated individuals. Response was associated with a reduction in plasma TNF-α and in vitro sensitivity in a small number of patients.
- Published
- 2006
- Full Text
- View/download PDF
23. AML engraftment in the NOD/SCID assay reflects the outcome of AML: implications for our understanding of the heterogeneity of AML
- Author
-
Ama Z. S. Rohatiner, Claude Preudhomme, Daniel J. Pearce, Kazem Zibara, Dominique Bonnet, Bryan D. Young, David Taussig, Lan-Lan Smith, Christopher M. Ridler, and T. Andrew Lister
- Subjects
Myeloid ,Immunology ,Mice, SCID ,Nod ,Biochemistry ,Mice ,Mice, Inbred NOD ,Predictive Value of Tests ,Gene Duplication ,hemic and lymphatic diseases ,medicine ,Animals ,Humans ,neoplasms ,Severe combined immunodeficiency ,Neoplasia ,business.industry ,Graft Survival ,Age Factors ,Nuclear Proteins ,Myeloid leukemia ,Cell Biology ,Hematology ,Prognosis ,medicine.disease ,Leukemia, Myeloid, Acute ,Leukemia ,medicine.anatomical_structure ,fms-Like Tyrosine Kinase 3 ,Fms-Like Tyrosine Kinase 3 ,Neoplastic Stem Cells ,Biological Assay ,Stem cell ,business ,Nucleophosmin ,Neoplasm Transplantation ,Stem Cell Transplantation ,Homing (hematopoietic) - Abstract
The nonobese diabetic/severe combined immunodeficient (NOD/SCID) assay is the current model for assessment of human normal and leukemic stem cells. We explored why 51% of 59 acute myeloid leukemia (AML) patients were unable to initiate leukemia in NOD/SCID mice. Increasing the cell dose, using more permissive recipients, and alternative tissue sources did not cause AML engraftment in most previously nonengrafting AML samples. Homing of AML cells to the marrow was the same between engrafters and nonengrafters. FLT3 internal tandem duplication (ITD) and nucleophosmin mutations occurred at a similar frequency in engrafters and nonengrafters. The only variable that was related to engraftment ability was the karyotypically defined risk stratification of individual AML cases. Of interest, follow-up of younger patients with intermediate-risk AML revealed a significant difference in overall survival between NOD/SCID engrafting and nonengrafting AMLs. Hence, the ability of AML to engraft in the NOD/SCID assay seems to be an inherent property of AML cells, independent of homing, conditioning, or cell frequency/source, which is directly related to prognosis. Our results suggest an important difference between leukemic initiating cells between engrafting and nonengrafting AML cases that correlates with treatment response.
- Published
- 2006
- Full Text
- View/download PDF
24. Secondary Central Nervous System Lymphoma: Risk Factors and Prophylaxis
- Author
-
T. Andrew Lister and Silvia Montoto
- Subjects
Oncology ,medicine.medical_specialty ,Pathology ,medicine.drug_class ,Antibiotics ,Central nervous system ,Central Nervous System Neoplasms ,International Prognostic Index ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,Epidemiology ,medicine ,Humans ,Risk factor ,Antibiotics, Antineoplastic ,Hematology ,business.industry ,Lymphoma, Non-Hodgkin ,medicine.disease ,Lymphoma ,medicine.anatomical_structure ,Mantle cell lymphoma ,Neoplasm Recurrence, Local ,business - Abstract
Patients diagnosed with diffuse large-cell lymphoma, peripheral T-cell non-Hodgkin's lymphoma or mantle cell lymphoma (either with a high serum lactate dehydrogenase level), more than one extranodal site, or who are a high risk according to the international Prognostic Index, should receive central nervous system prophylaxis either with intrathecal or high-dose systemic chemotherapy. The appropriateness of the same prophylaxis at relapse needs to be addressed in further studies.
- Published
- 2005
- Full Text
- View/download PDF
25. The clinical course of follicular lymphoma
- Author
-
T. Andrew Lister and Ama Z. S. Rohatiner
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Lymphoma, Non-Hodgkin ,Clinical Biochemistry ,Clinical course ,Follicular lymphoma ,Disease ,Prognosis ,medicine.disease ,Lymphoma ,Natural history ,Cell Transformation, Neoplastic ,medicine.anatomical_structure ,Treatment modality ,Internal medicine ,Immunology ,Disease Progression ,medicine ,Humans ,Survival advantage ,business ,Lymphoma, Follicular ,B cell - Abstract
Follicular lymphoma serves as a paradigm for the other subtypes of non-Hodgkin's lymphoma previously collectively known as 'indolent' or 'low-grade'. As such, its clinical course (that is, the natural history as influenced by conventional therapy) can act as a useful baseline against which the efficacy of new approaches may be assessed. The illness is characterised by repeated responsiveness to treatment but typically this is transient and incomplete. Death occurs at a median of 9-10 years after diagnosis, generally as a consequence of resistant disease, transformation to diffuse large B cell pathology or as a result of side effects of therapy. It has been demonstrated that there is no survival advantage associated with starting treatment prior to there being a clinical need to do so. It is hoped that the advent of new treatment modalities will alter the inexorable pattern of recurrence.
- Published
- 2005
- Full Text
- View/download PDF
26. Tositumomab and Iodine I 131 Tositumomab for Recurrent Indolent and Transformed B-Cell Non-Hodgkin’s Lymphoma
- Author
-
Ivana N. Micallef, J.A. Lawrance, Maggie A Harris, H. Jan, T. A. Lister, S.J. Mather, Keith E. Britton, J. A. L. Amess, S Owens, John Radford, D.P. Deakin, Simon J Howell, B.M. Carrington, A. Z. S. Rohatiner, Andrew Davies, S. Kroll, J Clayton, R. Foley, Andrew J. Norton, and Sarah Vinnicombe
- Subjects
Adult ,Cancer Research ,medicine.medical_specialty ,Immunoconjugates ,Lymphoma, B-Cell ,medicine.medical_treatment ,Phases of clinical research ,Antineoplastic Agents ,Iodine I 131 Tositumomab ,Gastroenterology ,Tositumomab ,Iodine Radioisotopes ,Internal medicine ,medicine ,Humans ,Survival rate ,B cell ,Aged ,business.industry ,Antibodies, Monoclonal ,Middle Aged ,Radioimmunotherapy ,Antigens, CD20 ,medicine.disease ,Lymphoma ,Non-Hodgkin's lymphoma ,Survival Rate ,medicine.anatomical_structure ,Oncology ,Neoplasm Recurrence, Local ,business ,Nuclear medicine ,medicine.drug - Abstract
PurposeAn open-label phase II study was conducted at two centers to establish the efficacy and safety of tositumomab and iodine I 131 tositumomab at first or second recurrence of indolent or transformed indolent B-cell lymphoma.Patients and MethodsA single dosimetric dose was followed at 7 to 14 days by the patient-specific administered radioactivity required to deliver a total body dose of 0.75 Gy (reduced to 0.65 Gy for patients with platelets counts of 100 to 149 × 109/L). Forty of 41 patients received both infusions.ResultsThirty-one of 41 patients (76%) responded, with 20 patients (49%) achieving either a complete (CR) or unconfirmed complete remission [CR(u)] and 11 patients (27%) achieving a partial remission. Response rates were similar in both indolent (76%) and transformed disease (71%). The overall median duration of remission was 1.3 years. The median duration of remission has not yet been reached for those patients who achieved a CR or CR(u). Eleven patients continue in CR or CR(u) between 2.6+ and 5.2+ years after therapy. Therapy was well tolerated; hematologic toxicity was the principal adverse event. Grade 3 or 4 anemia, neutropenia, and thrombocytopenia were observed in 5%, 45%, and 32% of patients, respectively. Secondary myelodysplasia has occurred in one patient. Four patients developed human antimouse antibodies after therapy. Five of 38 assessable patients have developed an elevated thyroid-stimulating hormone; treatment with thyroxine has been initiated in one patient.ConclusionHigh overall and CR rates were observed after a single dose of tositumomab and iodine I 131 tositumomab in this patient group. Toxicity was modest and easily managed.
- Published
- 2004
- Full Text
- View/download PDF
27. Genome-wide analysis of acute myeloid leukemia with normal karyotype reveals a unique pattern of homeobox gene expression distinct from those with translocation-mediated fusion events
- Author
-
J. A. L. Amess, Tracy Chaplin, Debra M. Lillington, Bryan D. Young, Silvana Debernardi, T. Andrew Lister, Ama Z. S. Rohatiner, and Simon Tomlinson
- Subjects
Adult ,Male ,Cancer Research ,Myeloid ,Oncogene Proteins, Fusion ,Chromosomal translocation ,Biology ,Leukemia, Myelomonocytic, Acute ,Translocation, Genetic ,Leukemia, Promyelocytic, Acute ,Bone Marrow ,hemic and lymphatic diseases ,Genetics ,medicine ,Cluster Analysis ,Humans ,RNA, Neoplasm ,Child ,Aged ,Oligonucleotide Array Sequence Analysis ,Regulation of gene expression ,Genome, Human ,Gene Expression Profiling ,Genes, Homeobox ,Myeloid leukemia ,Karyotype ,Middle Aged ,medicine.disease ,Molecular biology ,Gene Expression Regulation, Neoplastic ,Leukemia, Myeloid, Acute ,homeobox A9 ,Leukemia ,medicine.anatomical_structure ,Leukemia, Myeloid ,Karyotyping ,Cytogenetic Analysis ,Leukocytes, Mononuclear ,Homeobox ,Female ,Genes, Neoplasm - Abstract
Gene expression profiles were determined from presentation peripheral blood and bone marrow samples of 28 patients with acute myeloid leukemia (AML). Hierarchical clustering sorted the profiles into separate groups, each representing one of the major cytogenetic classes in AML [i.e., t(8;21), t(15;17), inv(16), 11q23, and normal karyotype]. Statistical group comparison identified genes whose expression was strongly correlated with these chromosomal classes. Moreover, the normal karyotype AMLs were characterized by distinctive up-regulation of certain members of the class I homeobox A and B gene families, implying a common underlying genetic lesion. These data reveal novel diagnostic and therapeutic targets and demonstrate the potential of microarray-based dissection of AML.
- Published
- 2003
- Full Text
- View/download PDF
28. Mutations ofCEBPA in acute myeloid leukemia FAB types M1 and M2
- Author
-
Amanda Dixon-McIver, Matthew L. Smith, T. Andrew Lister, Ama Z. S. Rohatiner, J. A. L. Amess, Michael J. Neat, Maxine Cambal-Parrales, Jennifer Snaddon, Rachael Arch, and Jude Fitzgibbon
- Subjects
Adult ,Male ,Biallelic Mutation ,Cancer Research ,Adolescent ,DNA Mutational Analysis ,Molecular Sequence Data ,Population ,Locus (genetics) ,Biology ,Gene mutation ,Risk Factors ,CEBPA ,CCAAT-Enhancer-Binding Protein-alpha ,Genetics ,medicine ,Humans ,Amino Acid Sequence ,education ,Aged ,Aged, 80 and over ,Leucine Zippers ,education.field_of_study ,medicine.diagnostic_test ,Myeloid leukemia ,DNA, Neoplasm ,Middle Aged ,medicine.disease ,Molecular biology ,Leukemia, Myeloid, Acute ,Leukemia ,Mutation ,Female ,Fluorescence in situ hybridization - Abstract
CEBPA encodes the transcription factor C/EBPα and is specifically up-regulated during granulocytic differentiation. The gene is mutated in approximately 20% of patients with acute myeloid leukemia (AML) FAB type M2 and occurs in the absence of the t(8;21). In much the same way as specific translocations are associated with a particular AML FAB type, the identification of non-random associations of gene mutation with karyotype or FAB type may be helpful in elucidating the molecular basis of certain forms of leukemia. To confirm these initial findings, 99 patients with AML FAB type M1 or M2 were screened for CEBPA mutations by use of a PCR–single-strand conformational polymorphism and sequencing approach. Nine CEBPA mutations were identified in eight patients. The mutations were clustered toward the COOH terminal of the protein and occurred exclusively in the intermediate cytogenetic risk group (8/64, 12.5%). Two patients with biallelic mutation, one homozygous for 1137Ins (57 bp) and another with two CEBPA mutations, 1096Ins (27 bp) and 363Ins (GGCC), were observed. There was no evidence for deletion of this region in the other six mutated samples analyzed by fluorescence in situ hybridization with a BAC clone spanning the CEBPA locus. CEBPA mutation status was not demonstrated to be of prognostic importance in this patient group, although this may reflect the selection and size of the AML population studied. In conclusion, mutation of CEBPA is a recurrent finding in AML and appears specific to the intermediate cytogenetic risk group patients. © 2003 Wiley-Liss, Inc.
- Published
- 2003
- Full Text
- View/download PDF
29. The relative role of peripheral blood and bone marrow for monitoring molecular evidence of disease in follicular lymphoma by quantitative real-time polymerase chain reaction
- Author
-
Andrew Davies, Victoria Cornelius, J. A. L. Amess, Jude Fitzgibbon, Lindsey K. Goff, Michael Jenner, Janet Matthews, Andrew J. Norton, T. Andrew Lister, Karin E. Summers, and Ama Z. S. Rohatiner
- Subjects
Pathology ,medicine.medical_specialty ,Neoplasm, Residual ,Follicular lymphoma ,Biology ,Polymerase Chain Reaction ,law.invention ,Bone Marrow ,law ,medicine ,Humans ,Neoplasm ,Lymphoma, Follicular ,Polymerase chain reaction ,Chromosomes, Human, Pair 14 ,Gene Rearrangement ,Chromosome Breakage ,Hematology ,Gene rearrangement ,medicine.disease ,Molecular biology ,Lymphoma ,Blood ,Real-time polymerase chain reaction ,medicine.anatomical_structure ,Bone marrow ,Chromosome breakage ,Chromosomes, Human, Pair 18 - Abstract
Peripheral blood (PB) and bone marrow (BM) are used interchangeably for t(14;18) (IgH/BCL-2) molecular monitoring in follicular lymphoma (FL) and detection of rearrangement after treatment has been correlated to increased risk of relapse. To determine the relative value of each tissue, MBR t(14;18) was quantified by real-time polymerase chain reaction in 52 simultaneous paired PB and BM samples from 38 FL patients. In total, 79% of sample pairs taken in remission (n = 19) or when no morphological disease was evident in the BM (n = 29) had t(14;18) copy number within one log difference and the median difference was small. These findings suggest that, in remission, PB may be adequately monitored. In general, however, higher copy number was detected in BM than in the corresponding PB sample.
- Published
- 2002
- Full Text
- View/download PDF
30. JH probe real-time quantitative polymerase chain reaction assay for Bcl-2/IgH rearrangements
- Author
-
Karin E. Summers, J. A. L. Amess, Lindsey K. Goff, Bryan D. Young, Michael Jenner, Andrew Norton, Jude Fitzgibbon, Rachael Arch, and T. Andrew Lister
- Subjects
Inverse polymerase chain reaction ,Breakpoint ,Follicular lymphoma ,Molecular evidence ,Hematology ,Biology ,medicine.disease ,Molecular biology ,Germline ,chemistry.chemical_compound ,Real-time polymerase chain reaction ,chemistry ,TaqMan ,medicine ,DNA - Abstract
Summary. Follicular lymphoma (FL) characteristically bears the t(14;18)(q32;q21). However, only ∼75% of the consequent Bcl-2 breakpoints lie within the major breakpoint region (MBR) or the minor cluster region (mcr). While these can be quantified by cluster region-specific real-time quantitative polymerase chain reaction (RQ-PCR), a significant proportion of cases are left requiring a customized approach. Therefore, an RQ-PCR assay for the quantification of Bcl-2/IgH breakpoints has been developed that uses germline JH TaqMan probes and germline JH primers in combination with customized forward primers. Validation of this approach by comparison with an established MBR RQ-PCR showed both techniques to be concordant across a wide range of copy numbers with a sensitivity of five copies per 105 cells. In addition, to generate standard curves equating to diverse Bcl-2/IgH rearrangements, a strategy for using placental DNA as a surrogate standard was devised. The performance of the assay in detecting molecular evidence of disease in sequential biopsies from five patients (three with atypical Bcl-2/IgH breakpoints identified by long-range or inverse PCR, one MBR+ and one mcr+) was tested. This alternative approach represents a sensitive and specific means of quantifying common and atypical Bcl-2/IgH rearrangements and maximizes the number of patients with FL suitable for molecular monitoring.
- Published
- 2002
- Full Text
- View/download PDF
31. Genetic susceptibility to Hodgkin's disease and secondary neoplasias: FISH analysis reveals patients at high risk of developing secondary neoplasia
- Author
-
Ivana N. Micallef, T. A. Lister, Janet Matthews, E. Carpenter, J. A. L. Amess, Bryan D. Young, N.J. Foot, A. Z. S. Rohatiner, M. J. Neat, and Debra M. Lillington
- Subjects
Oncology ,medicine.medical_specialty ,Pathology ,Cyclophosphamide ,medicine.medical_treatment ,Transplantation, Autologous ,Risk Factors ,Internal medicine ,medicine ,Genetic predisposition ,Humans ,Genetic Predisposition to Disease ,Risk factor ,Antineoplastic Agents, Alkylating ,In Situ Hybridization, Fluorescence ,Retrospective Studies ,Chemotherapy ,business.industry ,Hematopoietic Stem Cell Transplantation ,Neoplasms, Second Primary ,Retrospective cohort study ,Hematology ,Total body irradiation ,medicine.disease ,Combined Modality Therapy ,Hodgkin Disease ,Lymphoma ,Survival Rate ,Leukemia ,Leukemia, Myeloid ,Acute Disease ,business ,Whole-Body Irradiation ,medicine.drug - Abstract
Background: Cytotoxic drugs administered before high-dose therapy (HDT) represent a significant factor in the development of leukemic complications in patients with lymphoid malignancies. This retrospective study was used to detect evidence of abnormal therapy-related myelodysplasia/secondary acute myeloid leukaemia (tMDS/sAML) clones before HDT in a subset of patients who subsequently developed secondary neoplasia. Patients and methods: 230 patients with non-Hodgkin's lymphoma (NHL) underwent HDT comprising cyclophosphamide and total body irradiation (TBI) with autologous hematopoietic progenitorcell support. Thirty-three patients have developed tMDS/sAML and 20 of these were screened for the presence of emerging therapy-related abnormalities before HDT. A further 24 patients without evidence of secondary neoplasia were screened using fluorescence in situ hybridisation (FISH). Results: Significant levels of abnormal cells were identified in 20/20 patients screened who have developed secondary neoplasia compared with only three of 24 patients in the HDT control group who have not. The latter three patients have since died. Conclusions: The triple FISH assay was developed to detect loss of chromosomal material from 5q3 1, 7q22 and 13q14. It can potentially identify those patients at risk of alkylating agent-induced leukaemia before they proceed to HDT. Used in a prospective manner, the triple FISH assay could permit more informed clinical management.
- Published
- 2002
- Full Text
- View/download PDF
32. Frequency of leukemic initiating cells does not depend on the xenotransplantation model used
- Author
-
Dominique Bonnet, Emmanuel Griessinger, Jacques Vargaftig, David Taussig, Heather Oakervee, T. A. Lister, James D. Cavenagh, Fernando Anjos-Afonso, and John G. Gribben
- Subjects
Cancer Research ,Neoplasm Transplantation ,Myeloid ,Xenotransplantation ,medicine.medical_treatment ,Transplantation, Heterologous ,Heterologous ,CD47 Antigen ,Biology ,Article ,Mice ,Mice, Inbred NOD ,medicine ,Animals ,Humans ,Receptors, Interleukin-2 ,Hematology ,medicine.disease ,Transplantation ,Disease Models, Animal ,Leukemia, Myeloid, Acute ,Leukemia ,medicine.anatomical_structure ,Oncology ,Immunology ,Neoplastic Stem Cells - Abstract
Frequency of leukemic initiating cells does not depend on the xenotransplantation model used
- Published
- 2011
- Full Text
- View/download PDF
33. Treatment of Hodgkin lymphoma: a 50-year perspective
- Author
-
George P. Canellos, Jonathan W. Friedberg, Vincent T. DeVita, T. Andrew Lister, and Saul A. Rosenberg
- Subjects
Cancer Research ,Disease free survival ,Treatment outcome ,Vinblastine ,Disease-Free Survival ,Bleomycin ,X ray computed ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Biomarkers, Tumor ,Humans ,Mechlorethamine ,Cyclophosphamide ,Etoposide ,Neoplasm Staging ,Clinical Trials as Topic ,business.industry ,Medical school ,Cancer ,History, 20th Century ,Stanford Cancer Institute ,medicine.disease ,Hodgkin Disease ,Dacarbazine ,Europe ,Survival Rate ,Treatment Outcome ,Oncology ,Doxorubicin ,Vincristine ,Positron-Emission Tomography ,Procarbazine ,Hodgkin lymphoma ,Prednisone ,Neoplasm staging ,business ,Tomography, X-Ray Computed ,Classics - Abstract
George P. Canellos, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA Saul A. Rosenberg, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA Jonathan W. Friedberg, James P. Wilmont Cancer Center, University of Rochester, Rochester, NY T. Andrew Lister, Barts Cancer Institute, University of London, London, United Kingdom Vincent T. DeVita, Yale Cancer Center, Yale University School of Medicine, New Haven, CT
- Published
- 2014
34. Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma
- Author
-
Sameena Iqbal, Derville O’Shea, Cheng Yuan Yang, Elia Stupka, Jun Wang, Jude Fitzgibbon, Andrew Davies, Jacek Marzec, Richard J. Byers, Charles A. Mein, András Matolcsy, David Wrench, Sören Boller, Monika Bozek, Andrew Norton, T. Andrew Lister, Maria Calaminici, John G. Gribben, Georg Lenz, Silvia Montoto, Rudolf Grosschedl, Kiran Tawana, Csaba Bödör, Yuhong Fan, Claude Chelala, Janet Matthews, Nikolay Popov, Davide Cittaro, Ciaran O'Riain, Jessica Okosun, Shamzah Araf, Emanuela Carlotti, Chenyi Pan, and Charles H. Lawrie
- Subjects
Molecular Sequence Data ,Follicular lymphoma ,Genomics ,Biology ,Polymorphism, Single Nucleotide ,Deep sequencing ,Article ,Cohort Studies ,Histones ,Genetics ,medicine ,Cluster Analysis ,Humans ,Enhancer of Zeste Homolog 2 Protein ,Exome ,B-cell lymphoma ,Gene ,Lymphoma, Follicular ,B cell ,Phylogeny ,Tumor Necrosis Factor alpha-Induced Protein 3 ,Base Sequence ,EZH2 ,Intracellular Signaling Peptides and Proteins ,Polycomb Repressive Complex 2 ,High-Throughput Nucleotide Sequencing ,Nuclear Proteins ,Molecular Sequence Annotation ,Sequence Analysis, DNA ,medicine.disease ,CREB-Binding Protein ,Neoplasm Proteins ,DNA-Binding Proteins ,medicine.anatomical_structure ,Cell Transformation, Neoplastic ,Mutagenesis ,Mutation ,Myeloid Differentiation Factor 88 ,Disease Progression ,Trans-Activators - Abstract
Follicular lymphoma is an incurable malignancy, with transformation to an aggressive subtype representing a critical event during disease progression. Here we performed whole-genome or whole-exome sequencing on 10 follicular lymphoma-transformed follicular lymphoma pairs followed by deep sequencing of 28 genes in an extension cohort, and we report the key events and evolutionary processes governing tumor initiation and transformation. Tumor evolution occurred through either a 'rich' or 'sparse' ancestral common progenitor clone (CPC). We identified recurrent mutations in linker histone, JAK-STAT signaling, NF-κB signaling and B cell developmental genes. Longitudinal analyses identified early driver mutations in chromatin regulator genes (CREBBP, EZH2 and KMT2D (MLL2)), whereas mutations in EBF1 and regulators of NF-κB signaling (MYD88 and TNFAIP3) were gained at transformation. Collectively, this study provides new insights into the genetic basis of follicular lymphoma and the clonal dynamics of transformation and suggests that personalizing therapies to target key genetic alterations in the CPC represents an attractive therapeutic strategy.
- Published
- 2014
35. Pivotal Study of Iodine I 131 Tositumomab for Chemotherapy-Refractory Low-Grade or Transformed Low-Grade B-Cell Non-Hodgkin’s Lymphomas
- Author
-
R. J. Stagg, Oliver W. Press, Mansoor N. Saleh, Susan J. Knox, J. M. Vose, Mark S. Kaminski, Andrew D. Zelenetz, L. Fehrenbacher, George F. Tidmarsh, John P. Leonard, Stewart Kroll, Richard L. Wahl, and T. A. Lister
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Lymphoma, B-Cell ,medicine.medical_treatment ,Ibritumomab tiuxetan ,Iodine I 131 Tositumomab ,Gastroenterology ,Tositumomab ,Iodine Radioisotopes ,Refractory ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Aged ,Chemotherapy ,business.industry ,Lymphoma, Non-Hodgkin ,Antibodies, Monoclonal ,Middle Aged ,medicine.disease ,Lymphoma ,Clinical trial ,Radiation therapy ,Oncology ,Drug Resistance, Neoplasm ,Female ,business ,Nuclear medicine ,medicine.drug - Abstract
PURPOSE: To evaluate the efficacy and safety of tositumomab and iodine I 131 tositumomab (Bexxar; Corixa Corp, Seattle, WA, and GlaxoSmithKline, Philadelphia, PA) in patients with chemotherapy-refractory low-grade or transformed low-grade non-Hodgkin’s lymphoma (NHL) and to compare its efficacy to the patients’ last qualifying chemotherapy (LQC) regimens. PATIENTS AND METHODS: Sixty patients who had been treated with at least two protocol-specified qualifying chemotherapy regimens and had not responded or progressed within 6 months after their LQC were treated with a single course of iodine I 131 tositumomab. RESULTS: Patients had received a median of four prior chemotherapy regimens. A partial or complete response (CR) was observed in 39 patients (65%) after iodine I 131 tositumomab, compared with 17 patients (28%) after their LQC (P < .001). The median duration of response (MDR) was 6.5 months after iodine I 131 tositumomab, compared with 3.4 months after the LQC (P < .001). Two patients (3%) had a CR after their LQC, compared with 12 (20%) after iodine I 131 tositumomab (P < .001). The MDR for CR was 6.1 months after the LQC and had not been reached with follow-up of more than 47 months after iodine I 131 tositumomab. An independent review panel verified that 32 (74%) of the 43 patients with nonequivalent durations of response (> 30 days difference) had a longer duration of response after iodine I 131 tositumomab (P < .001). Only one patient was hospitalized for neutropenic fever. Five patients (8%) developed human antimurine antibodies, and one (2%) developed an elevated TSH level after treatment. Myelodysplasia was diagnosed in four patients in follow-up. CONCLUSION: A single course of iodine I 131 tositumomab was significantly more efficacious than the LQC received by extensively pretreated patients with chemotherapy-refractory, low-grade, or transformed low-grade NHL and had an acceptable safety profile.
- Published
- 2001
- Full Text
- View/download PDF
36. A randomized controlled trial to evaluate the role of interferon as initial and maintenance therapy in patients with follicular lymphoma
- Author
-
A. Z. S. Rohatiner, Helena M. Earl, Owen Price, John Radford, Angelia R. Wilson, T. A. Lister, David P Deakin, and Sharon Love
- Subjects
Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Maintenance ,medicine.medical_treatment ,Follicular lymphoma ,initial therapy ,Antineoplastic Agents ,Disease-Free Survival ,Drug Administration Schedule ,maintenance ,law.invention ,follicular lymphoma ,Randomized controlled trial ,Maintenance therapy ,law ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Lymphoma, Follicular ,Survival rate ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,Cancer staging ,Aged, 80 and over ,Chemotherapy ,Chlorambucil ,business.industry ,Remission Induction ,Regular Article ,interferon ,Middle Aged ,medicine.disease ,Lymphoma ,Survival Rate ,Immunology ,Interferon ,Female ,Interferons ,Initial therapy ,business ,medicine.drug - Abstract
The purpose of this study was to evaluate the role of interferon as initial and maintenance therapy in patients with newly diagnosed follicular lymphoma. Between 1984 and 1994, 204 patients with newly diagnosed Stage III or Stage IV follicular lymphoma were randomized to receive either, Chlorambucil (CB): 10 mg daily for 6 weeks, followed by a 2-week interval, with 3 subsequent 2-week treatment periods at the same dose, separated by 2-week intervals, or, CB given concurrently with interferon (IFN). IFN was given at a dose of 3 × 106units thrice weekly, subcutaneously, throughout the 18-week treatment period. Responding patients were subsequently randomized to receive maintenance IFN at the dose and schedule described above, or to expectant management. The overall response rate was 161/204 (78%), complete remission being achieved in 24% of patients. Neither the addition of IFN to the initial treatment, nor the use of maintenance IFN influenced response rate, remission duration or survival. This study was undertaken to determine whether IFN, given in combination with, and then subsequent to, CB would alter the clinical course of patients with follicular lymphoma. Disappointingly, this objective was not achieved, no advantage having been demonstrated for the addition of IFN. © 2001 Cancer Research Campaign http://www.bjcancer.com
- Published
- 2001
- Full Text
- View/download PDF
37. Detection of Chromosome Abnormalities Pre–High-Dose Treatment in Patients Developing Therapy-Related Myelodysplasia and Secondary Acute Myelogenous Leukemia After Treatment for Non-Hodgkin’s Lymphoma
- Author
-
Emily Carpenter, J. A. L. Amess, Ivana N.M. Micallef, Janet Matthews, Debra M. Lillington, Bryan D. Young, Ama Z. S. Rohatiner, Michael J. Neat, Nicola Foot, and T. Andrew Lister
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Pathology ,Cyclophosphamide ,medicine.medical_treatment ,chemistry.chemical_compound ,Internal medicine ,medicine ,Humans ,In Situ Hybridization, Fluorescence ,Chromosome Aberrations ,Chemotherapy ,business.industry ,Lymphoma, Non-Hodgkin ,Cytogenetics ,Neoplasms, Second Primary ,medicine.disease ,Nitrogen mustard ,Non-Hodgkin's lymphoma ,Lymphoma ,Radiation therapy ,Leukemia, Myeloid, Acute ,chemistry ,Myelodysplastic Syndromes ,business ,Complication ,medicine.drug - Abstract
PURPOSE: To assess whether pre–high-dose therapy (HDT)–related factors play a critical role in the development of therapy-related myelodysplasia (tMDS) or secondary acute myelogenous leukemia (sAML). PATIENTS AND METHODS: Twenty-nine of 230 patients with a primary diagnosis of non-Hodgkin’s lymphoma (NHL) developed tMDS/sAML after HDT comprising cyclophosphamide and total-body irradiation (TBI) supported by autologous hematopoietic progenitor cells. G-banding and fluorescence in-situ hybridization (FISH) were used to detect clonal cytogenetic abnormalities. RESULTS: The majority of patients showed complex karyotypes at diagnosis of tMDS/sAML containing, in particular, complete or partial loss of chromosomes 5 and/or 7. Using single locus–specific FISH probes, significant levels of clonally abnormal cells were found before HDT in 20 of 20 tMDS/sAML patients screened, compared with three of 24 patients screened who currently have not developed tMDS/sAML, at a median follow-up of 5.9 years after HDT. CONCLUSION: Prior cytotoxic therapy may play an important etiologic role and may predispose to the development of tMDS/sAML. Using a triple FISH assay designed to detect loss of chromosomal material from 5q31, 7q22, or 13q14, significant levels of abnormal cells can be detected before HDT and may predict which patients are at increased risk of developing secondary disease. Further prospective evaluation of this FISH assay is warranted to determine its predictive power in this setting.
- Published
- 2001
- Full Text
- View/download PDF
38. High-Dose Therapy and Autologous Stem-Cell Support for Chemosensitive Transformed Low-Grade Follicular Non-Hodgkin’s Lymphoma: A Case-Matched Study From the European Bone Marrow Transplant Registry
- Author
-
Catherine D. Williams, C. N. Harrison, A. K. Blystad, G. Taghipour, Andrew J. Norton, A. H. Goldstone, B. Coiffier, N. Schmitz, and T. A. Lister
- Subjects
Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Bone marrow transplant ,medicine.medical_treatment ,Disease-Free Survival ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Follicular phase ,medicine ,Humans ,Lymphoma, Follicular ,Bone Marrow Transplantation ,Chemotherapy ,Dose-Response Relationship, Drug ,business.industry ,Lymphoma, Non-Hodgkin ,Mortality rate ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Lymphoma ,Surgery ,Survival Rate ,Cell Transformation, Neoplastic ,High dose therapy ,medicine.anatomical_structure ,Case-Control Studies ,Disease Progression ,Female ,Bone marrow ,Stem cell ,business ,Follow-Up Studies - Abstract
PURPOSE: To assess the outcome of high-dose therapy with autologous stem-cell support in patients with histologic transformation of low-grade follicular non-Hodgkin’s lymphoma (NHL) and identify significant prognostic factors, as well as to compare survival of these patients with that of patients with matched low-grade and de novo high- or intermediate-grade NHL undergoing the same procedure. PATIENTS AND METHODS: Fifty patients with transformed low-grade NHL have been reported to the European Bone Marrow Transplant registry. Outcome from high-dose therapy and significant prognostic factors were analyzed. Their survival was also compared with that of 200 patients with matched low-grade NHL and 200 patients with matched de novo high- or intermediate-grade NHL by a case-matched analysis. RESULTS: The procedure-related death rate among the 50 transformed NHL patients was 18%. Overall survival (OS) and progression-free survival (PFS) rates were 51% and 30% at 5 years, respectively. Median PFS time was 13 months. Raised lactate dehydrogenase levels at transformation (P = .0031) was identified as the only adverse significant predictor of PFS on multivariate analysis. A subgroup of patients with residual chemosensitive disease who attained complete remission after high-dose therapy had the best outcome, with an OS at 5 years of 69%. A comparison with matched patients with low-grade disease and with de novo high- or intermediate-grade lymphoma showed no significant difference in OS (P = .939 and P = .438, respectively). CONCLUSION: Patients with chemosensitive transformed lymphoma should be seriously considered for high-dose therapy and autologous stem-cell support.
- Published
- 2001
- Full Text
- View/download PDF
39. Localisation of a novel region of recurrent amplification in follicular lymphoma to an ?6.8 Mb region of 13q32-33
- Author
-
Deborah Burford, T. Andrew Lister, Andrew J. Norton, Jude Fitzgibbon, Michael Jenner, Kevin Ashcroft, Nicola Foot, Andy Dunham, Michael J. Neat, and Lindsey K. Goff
- Subjects
Cancer Research ,Oncogene ,Follicular lymphoma ,Biology ,Malignancy ,medicine.disease ,Molecular biology ,Lymphoma ,chemistry.chemical_compound ,chemistry ,Follicular phase ,Genetics ,medicine ,Metaphase ,DNA ,Chromosome 13 - Abstract
Follicular lymphoma (FL) is characterised by the presence of the t(14;18)(q32;q21) and represents ∼25% of new cases of non-Hodgkin's lymphoma. While the t(14;18) is a well-documented rearrangement, the role of secondary cytogenetic abnormalities in the development and progression of these tumours remains unclear. Comparative genomic hybridisation was used to characterise changes in DNA copy number in tumour DNA from patients with this malignancy. The mean numbers of deletion and amplification events found in each of the 45 samples studied were 1.8 and 2.3, respectively. Regions of recurrent (>10% tumour samples) gain involved chromosomes 2p13-16 (16%), 7 (20%), 12 (16%), 13q21-33 (18%), 18 (27%), and X (36%) and frequent losses localised to 6q (29%) and 17p (20%). Amplification of chromosome 13 represents a novel finding in FL. The minimal amplified region was refined to a 6.8-Mb interval of 13q32-33 between the BAC clones 88K16 and 44H20 by fluorescence in situ hybridisation studies using metaphase chromosomes derived from tumour material. There are a number of reports in the literature suggesting that amplification of chromosome 13 also occurs in other human cancers. The location of the putative oncogene on 13q described here in follicular and transformed lymphoma may also be important in the evolution of many other malignancies. © 2001 Wiley-Liss, Inc.
- Published
- 2001
- Full Text
- View/download PDF
40. The use of real-time quantitative polymerase chain reaction and comparative genomic hybridization to identify amplification of the REL gene in follicular lymphoma
- Author
-
Charles Crawley, Emma Jones, Michael J. Neat, Lindsey K. Goff, T. Andrew Lister, R. K. Gupta, and Louise Jones
- Subjects
Real-time polymerase chain reaction ,Follicular lymphoma ,medicine ,Hematology ,Biology ,medicine.disease ,Molecular biology ,Gene ,Comparative genomic hybridization - Published
- 2000
- Full Text
- View/download PDF
41. The use of real-time quantitative polymerase chain reaction and comparative genomic hybridization to identify amplification of the REL gene in follicular lymphoma
- Author
-
Louise Jones, R. K. Gupta, Michael J. Neat, Lindsey K. Goff, Emma Jones, T. Andrew Lister, and Charles Crawley
- Subjects
Gene Amplification ,NF-kappa B ,Transcription Factor RelA ,Large-cell lymphoma ,Follicular lymphoma ,Locus (genetics) ,Hematology ,Biology ,medicine.disease ,Polymerase Chain Reaction ,Gene dosage ,Molecular biology ,law.invention ,Real-time polymerase chain reaction ,law ,Gene duplication ,Image Processing, Computer-Assisted ,medicine ,Cancer research ,Humans ,Lymphoma, Follicular ,In Situ Hybridization ,Polymerase chain reaction ,DNA Primers ,Comparative genomic hybridization - Abstract
Using comparative genomic hybridization (CGH), aberrations in DNA copy number were studied before and after transformation of follicular lymphoma to diffuse large B-cell lymphoma in six patients (15 lymph node biopsies in total). The most common and also the most discrete and intense amplification occurring in four out of 15 biopsies from three different patients was of 2p13-16. Using real-time quantitative polymerase chain reaction (RQ-PCR), REL amplification was found to be implicated at this locus. This technique also identified amplified REL in a further two biopsies, presumably below the detection level of CGH. REL amplification was quantified by comparing it, in most cases, with three endogenous reference genes, albumin, beta2-microglobulin and CD8alpha, that lie close to REL on 2p. There was no correlation apparent between 2p13-16 amplification or REL amplification and transformation. This study shows the usefulness of coupling CGH, for detecting recurring abnormalities, with the real-time PCR technique for rapid gene dosage quantification and confirms that the REL gene is a potential candidate in the pathogenesis of a particular subset of follicular lymphomas.
- Published
- 2000
- Full Text
- View/download PDF
42. A UK multicentre phase II study of rituximab (chimaeric anti-CD20 monoclonal antibody) in patients with follicular lymphoma, with PCR monitoring of molecular response
- Author
-
R. Pettengell, Anthony H. Goldstone, R K Gupta, J. Hughes, K. E. Summers, Barry W. Hancock, R. A. Popescu, T. A. Lister, Ama Z. S. Rohatiner, David Cunningham, Peter Johnson, J.W. Sweetenham, James M. Foran, and E M Bessell
- Subjects
CD20 ,medicine.medical_specialty ,biology ,Follicular lymphoma ,Phases of clinical research ,Hematology ,Gene rearrangement ,medicine.disease ,Gastroenterology ,Lymphoma ,medicine.anatomical_structure ,Internal medicine ,Immunology ,Monoclonal ,biology.protein ,medicine ,Rituximab ,Bone marrow ,medicine.drug - Abstract
Follicular lymphoma (FL) cells express CD20 and are associated in most cases with the t(14;18) chromosomal translocation. A multicentre study was undertaken between January 1997 and January 1998 to assess the complete response rate (CR) and overall response rate (RR) to rituximab, a chimaeric anti-CD20 monoclonal antibody. Seventy patients with previously treated FL received rituximab (375 mg/m2/week x4, by intravenous infusion). Restaging studies were performed 1 and 2 months after therapy. Molecular monitoring for the presence of cells harbouring the Bcl-2/JH gene rearrangement in the peripheral blood (PB) and bone marrow (BM) was performed before and after treatment using a two-step semi-nested polymerase chain reaction (PCR) assay. The overall RR was 32/70 (46%), being highest in patients who had received only one previous treatment (12/15, 80%). However, only two patients achieved a CR. The median duration of response was 11 months. Thirteen of 21 evaluable 'PCR-positive' patients (62%) became 'PCR-negative' in PB and/or BM samples 1 month after rituximab, although this did not correlate with clinical response. Treatment was generally well tolerated, although one patient developed Stevens-Johnson syndrome. Rituximab was shown to be active in FL, and in some cases PB and/or BM became PCR negative. Studies in combination with cytotoxic chemotherapy to increase the CR rate are warranted.
- Published
- 2000
- Full Text
- View/download PDF
43. The World Health Organization classification of neoplastic diseases of the haematopoietic and lymphoid tissues: report of the Clinical Advisory Committee Meeting, Airlie House, Virginia, November 1997
- Author
-
Jacques Diebold, Elaine S. Jaffe, James W. Vardiman, Nancy L. Harris, Clara D. Bloomfield, Hans Konrad Müller-Hermelink, T. A. Lister, and G. Flandrin
- Subjects
medicine.medical_specialty ,Pathology ,Histology ,Myeloid ,business.industry ,Advisory committee ,Gold standard ,MEDLINE ,General Medicine ,Disease ,medicine.disease ,Pathology and Forensic Medicine ,Lymphoma ,medicine.anatomical_structure ,International Prognostic Index ,Family medicine ,medicine ,business ,Hematopathology - Abstract
Introduction Since 1995, the European Association of Pathologists (EAHP) and the Society for Hematopathology (SH) have been developing a new World Health Organization (WHO) classification of haematological malignancies. The classification includes lymphoid, myeloid, histiocytic and mast cell neoplasms. Design The WHO project involves 10 committees of pathologists, who have developed lists and definitions of disease entities. A Clinical Advisory Committee (CAC) of international haematologists and oncologists was formed to ensure that the classification will be useful to clinicians. A meeting was held in November 1997 to discuss clinical issues related to the classification. Results The WHO has adopted the ‘Revised European–American Classification of Lymphoid Neoplasms’ (REAL), published in 1994 by the International Lymphoma Study Group (ILSG), as the classification of lymphoid neoplasms. This approach to classification is based on the principle that a classification is a list of ‘real’ disease entities, which are defined by a combination of morphology, immunophenotype, genetic features and clinical features. The relative importance of each of these features varies among diseases, and there is no one ‘gold standard’. The WHO classification has applied the principles of the REAL classification to myeloid and histiocytic neoplasms. The classification of myeloid neoplasms recognizes distinct entities defined by a combination of morphology and cytogenetic abnormalities. The CAC meeting, which was organized around a series of clinical questions, was able to reach a consensus on most of the questions posed. The questions and the consensus are discussed in detail below. Among other things, the CAC concluded that clinical groupings of lymphoid neoplasms was neither necessary nor desirable. Patient treatment is determined by the specific type of lymphoma, with the addition of grade within the tumour type, if applicable, and clinical prognostic factors such as the international prognostic index (IPI). Conclusion The experience of developing the WHO classification has produced a new and exciting degree of cooperation and communication between oncologists and pathologists from around the world, which should facilitate progress in the understanding and treatment of haematological malignancies.
- Published
- 2000
- Full Text
- View/download PDF
44. The World Health Organization Classification of Neoplasms of the Hematopoietic and Lymphoid Tissues: Report of the Clinical Advisory Committee Meeting – Airlie House, Virginia, November, 1997
- Author
-
T. A. Lister, Nancy L. Harris, Elaine S. Jaffe, G. Flandrin, Clara D. Bloomfield, Hans Konrad Müller-Hermelink, Jacques Diebold, and James W. Vardiman
- Subjects
Pathology ,medicine.medical_specialty ,Myeloid ,business.industry ,Advisory committee ,Gold standard ,MEDLINE ,Hematology ,Disease ,medicine.disease ,Lymphoma ,medicine.anatomical_structure ,International Prognostic Index ,Family medicine ,medicine ,business ,Hematopathology - Abstract
Introduction Since 1995, the European Association of Pathologists and the Society for Hematopathology have been developing a new World Health Organization (WHO) classification of hematologic malignancies. The classification includes lymphoid, myeloid, histiocytic, and mast cell neoplasms. Materials and methods The WHO project involves ten committees of pathologists, who have developed lists and definitions of disease entities. A Clinical Advisory Committee (CAC) of international hematologists and oncologists was formed to ensure that the classification will be useful to clinicians. A meeting was held in November 1997 to discuss clinical issues related to the classification. Results WHO has adopted the 'Revised European-American Classification of Lymphoid Neoplasms' (REAL), published in 1994 by the International Lymphoma Study Group (ILSG), as the classification of lymphoid neoplasms. This approach to classification is based on the principle that a classification is a list of 'real' disease entities, which are defined by a combination of morphology, immunophenotype, genetic features, and clinical features. The relative importance of each of these features varies among diseases, and there is no one 'gold standard'. The WHO classification has applied the principles of the REAL classification to myeloid and histiocytic neoplasms. The classification of myeloid neoplasms recognizes distinct entities defined by a combination of morphology and cytogenetic abnormalities. The CAC meeting, which was organized around a series of clinical questions, was able to reach a consensus on most of the questions posed. The questions and the consensus are discussed in detail below. Among other things, the CAC concluded that clinical groupings of lymphoid neoplasms were neither necessary nor desirable. Patient treatment is determined by the specific type of lymphoma, with the addition of grade within the tumor type, if applicable, and clinical prognostic factors such as the international prognostic index (IPI). Conclusion The experience of developing the WHO classification has produced a new and exciting degree of cooperation and communication between oncologists and pathologists from around the world, which should facilitate progress in the understanding and treatment of hematologic malignancies.
- Published
- 2000
- Full Text
- View/download PDF
45. Factors which predict unsuccessful mobilisation of peripheral blood progenitor cells following G-CSF alone in patients with non-Hodgkin's lymphoma
- Author
-
C Wiggins, R K Gupta, M Leonhardt, E Okukenu, C R Crawley, T. A. Lister, Ama Z. S. Rohatiner, Janet Matthews, James D. Cavenagh, James M. Foran, I.N. Micallef, Mike Bradburn, Ashiq Salam, and John Apostolidis
- Subjects
Adult ,Male ,Antimetabolites, Antineoplastic ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Gastroenterology ,Bone Marrow ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Granulocyte Colony-Stimulating Factor ,Humans ,Medicine ,Leukapheresis ,Progenitor cell ,Hematology ,business.industry ,Lymphoma, Non-Hodgkin ,Remission Induction ,Lymphoblastic lymphoma ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Hematopoietic Stem Cell Mobilization ,Non-Hodgkin's lymphoma ,Lymphoma ,Surgery ,Fludarabine ,medicine.anatomical_structure ,Female ,Bone marrow ,business ,Vidarabine ,medicine.drug - Abstract
Introduction: High-dose therapy with haematopoietic progenitor cell support has increasingly been utilised for patients with haematological malignancies. Peripheral blood is the stem cell source of choice, however, various mobilisation strategies are used by diAerent centres. Patients and methods: Over a 2-year period, 52 patients with non-Hodgkin’s lymphoma (median age 47 years, range 16‐64 years) underwent peripheral blood progenitor cell mobilisation using G-CSF alone (16 mg/kg/day). The harvest was considered successful if 51610 6 CD34 + cells/kg were collected by leukapheresis. The histological subtypes of nonHodgkin’s lymphoma comprised: follicular (24 patients), diAuse large B-cell (14 patients), lymphoplasmacytoid (four patients), mantle cell (three patients), lymphoblastic lymphoma (one patient) and small lymphocytic lymphoma/chronic lymphocytic leukaemia (six patients). The median interval from diagnosis of non-Hodgkin’s lymphoma to mobilisation was 27 months (range 2 months to 17 years). The median number of prior treatment episodes was 2 (range 1‐5); 26 patients had received fludarabine alone or in combination. At the time of peripheral blood progenitor cell mobilisation, 20 patients were in 1st remission and 32 were in 52nd remission; 30 patients were in partial remission and 22 were in complete remission; the bone marrow was involved in nine patients. Results: Peripheral blood progenitor cell mobilisation/harvest was unsuccessful in 19 out of 52 (37%) patients (mobilisation: 18, harvest: 1). The factors associated with unsuccessful mobilisation or harvest were: prior fludarabine therapy (P=0.002), bone marrow involvement at diagnosis (P=0.002), bone marrow involvement anytime prior to mobilisation (P=0.02), histological diagnosis of follicular, mantle cell, or lymphoplasmacytoid lymphoma, or small lymphocytic lymphoma/chronic lymphocytic leukaemia (P=0.03) and female gender (P=0.04). Conclusion: Although peripheral blood progenitor cells can be successfully mobilised and harvested from the majority of patients with non-Hodgkin’s lymphoma after treatment with G-CSF alone, the latter is unsuccessful in approximately one-third of patients. These factors should be taken into account when patients are being considered for high-dose treatment. The Hematology Journal (2000) 1, 367‐373
- Published
- 2000
- Full Text
- View/download PDF
46. The World Health Organization Classification of Neoplastic Diseases of the Hematopoietic and Lymphoid Tissues
- Author
-
Hans Konrad Müller-Hermelink, Clara D. Bloomfield, Elaine S. Jaffe, G. Flandrin, Jacques Diebold, James W. Vardiman, T. A. Lister, and Nancy L. Harris
- Subjects
medicine.medical_specialty ,Pathology ,Myeloid ,business.industry ,Advisory committee ,MEDLINE ,Hematology ,Disease ,medicine.disease ,World health ,Lymphoma ,medicine.anatomical_structure ,International Prognostic Index ,Oncology ,Family medicine ,Medicine ,business ,Hematopathology - Abstract
Summary Introduction Since 1995, the European Association of Pathologists (EAHP) and the Society for Hematopathology (SH) have been developing a new World Health Organization (WHO) Classification of hematologic malignancies. The classification includes lymphoid, myeloid, histiocytic, and mast cell neoplasms. Design The WHO project involves 10 committees of pathologists, who have developed lists and definitions of disease entities. A Clinical Advisory Committee (CAC) ) of international hematologists and oncologists was formed to ensure that the classification will be useful to clinicians. A meeting was held in November, 1997, to discuss clinical issues related to the classification. Results The WHO has adopted the ‘Revised European–American Classification of Lymphoid Neoplasms’ (R.E.A.L.), published in 1994 by the International Lymphoma Study Group (ILSG), as the classification of lymphoid neoplasms. This approach to classification is based on the principle that a classification is a list of ‘real’ disease entities, which are defined by a combination of morphology, immunophenotype, genetic features, and clinical features. The relative importance of each of these features varies among diseases, and there is no one ‘gold standard’. The WHO Classification has applied the principles of the R.E.A.L. Classification to myeloid and histiocytic neoplasms. The classification of myeloid neoplasms recognizes distinct entities defined by a combination of morphology and cytogenetic abnormalities. The CAC meeting, which was organized around a series of clinical questions, was able to reach a consensus on most of the questions posed. The questions and the consensus are discussed in detail below. Among other things, the CAC concluded that clinical groupings of lymphoid neoplasms were neither necessary nor desirable. Patient treatment is determined by the specific type of lymphoma, with the addition of grade within the tumor type, if applicable, and clinical prognostic factors such as the international prognostic index (IPI). Conclusion The experience of developing the WHO Classification has produced a new and exciting degree of cooperation and communication between oncologists and pathologists from around the world, which should facilitate progress in the understanding and treatment of hematologic malignancies.
- Published
- 1999
- Full Text
- View/download PDF
47. World Health Organization Classification of Neoplastic Diseases of the Hematopoietic and Lymphoid Tissues: Report of the Clinical Advisory Committee Meeting—Airlie House, Virginia, November 1997
- Author
-
Jacques Diebold, James W. Vardiman, Clara D. Bloomfield, Elaine S. Jaffe, G. Flandrin, T. Andrew Lister, Nancy L. Harris, and H. Konrad Muller-Hermelink
- Subjects
Cancer Research ,medicine.medical_specialty ,Pathology ,Myeloid ,business.industry ,Advisory committee ,MEDLINE ,Disease ,medicine.disease ,World health ,Lymphoma ,medicine.anatomical_structure ,Oncology ,Family medicine ,medicine ,Hematopathology ,business ,French–American–British classification - Abstract
PURPOSE: The European Association of Hematopathologists and the Society for Hematopathology have developed a new World Health Organization (WHO) classification of hematologic malignancies, including lymphoid, myeloid, histiocytic, and mast cell neoplasms. DESIGN: Ten committees of pathologists developed lists and definitions of disease entities. A clinical advisory committee (CAC) of international hematologists and oncologists was formed to ensure that the classification would be useful to clinicians. The CAC met in November 1997 to discuss clinical issues related to the classification. RESULTS: The WHO uses the Revised European-American Lymphoma (REAL) classification, published in 1994 by the International Lymphoma Study Group, to categorize lymphoid neoplasms. The REAL classification is based on the principle that a classification is a list of “real” disease entities, which are defined by a combination of morphology, immunophenotype, genetic features, and clinical features. The relative importance of each of these features varies among diseases, and there is no one gold standard. The WHO classification applies the principles of the REAL classification to myeloid and histiocytic neoplasms. The classification of myeloid neoplasms recognizes distinct entities defined by a combination of morphology and cytogenetic abnormalities. At the CAC meeting, which was organized around a series of clinical questions, participants reached a consensus on most of the questions posed. They concluded that clinical groupings of lymphoid neoplasms were neither necessary nor desirable. Patient treatment is determined by the specific type of lymphoma, with the addition of grade within the tumor type, if applicable, and clinical prognostic factors, such as the International Prognostic Index. CONCLUSION: The WHO classification has produced a new and exciting degree of cooperation and communication between oncologists and pathologists from around the world, which should facilitate progress in the understanding and treatment of hematologic malignancies.
- Published
- 1999
- Full Text
- View/download PDF
48. Tumour necrosis factor polymorphisms and susceptibility to follicular lymphoma
- Author
-
Janet Matthews, Jude Fitzgibbon, T. A. Lister, D Grenzelias, and R. K. Gupta
- Subjects
biology ,business.industry ,medicine.medical_treatment ,Haplotype ,Follicular lymphoma ,Chromosomal translocation ,Hematology ,medicine.disease ,Major histocompatibility complex ,Lymphoma ,Cytokine ,Immunology ,Cancer research ,biology.protein ,Medicine ,Allele ,business ,Allele frequency - Abstract
Follicular lymphoma is characterized in 85% of patients by the presence of a t(14;18) chromosomal translocation that results in overproduction of BCL2. In this study the distribution of high and low expressing TNF alleles at the TNF (-308) and LTalpha (+252) polymorphic sites in 121 patients with follicular lymphoma and 88 control individuals has been analysed. A reduction in high expressing haplotypes in patients compared to normal controls was found (P = 0.055), with no significant difference observed in response rate or overall survival between patients with high or low expressing haplotypes. These results suggest that the TNF locus, or an adjacent locus within the MHC region, is an important genetic risk factor in this disease.
- Published
- 1999
- Full Text
- View/download PDF
49. CT appearances of mucosa-associated lymphoid tissue (MALT) lymphoma
- Author
-
Rodney H. Reznek, A. Z. S. Rohatiner, P. Kessar, T. A. Lister, and Andrew J. Norton
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pathology ,Biopsy ,medicine.medical_treatment ,Diagnosis, Differential ,Stomach Neoplasms ,immune system diseases ,hemic and lymphatic diseases ,Butylscopolammonium Bromide ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Aged ,medicine.diagnostic_test ,business.industry ,Stomach ,Parasympatholytics ,MALT lymphoma ,Lymphoma, B-Cell, Marginal Zone ,General Medicine ,Middle Aged ,medicine.disease ,Lymphoma ,medicine.anatomical_structure ,Lymphatic system ,Injections, Intravenous ,Female ,Gastrectomy ,Lymph ,Radiology ,Tomography, X-Ray Computed ,business ,Mucosa-associated lymphoid tissue - Abstract
Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade lymphoma that differs from high-grade non-Hodgkin lymphoma both clinically and histologically. The CT appearances of MALT lymphoma are described. Of 40 patients referred with biopsy-proven MALT lymphoma, only seven had not had gastrectomy or chemotherapy prior to CT examination. The CT scans of these seven cases were analysed for the degree and extent of gastric wall thickening, enlargement of abdominal and extra-abdominal lymph nodes, and presence of extra-nodal disease. In all patients the stomach was distended with oral contrast medium and scans performed at narrow collimation, after intravenous administration of 20 mg hyoscine butylbromide. In six patients focal thickening of the gastric wall was 1 cm or less. One patient had thickening of over 4 cm. There was no enlargement of abdominal or extra-abdominal lymph nodes or extension to adjacent organs. Thus on CT, at presentation, MALT lymphoma results in minimal gastric wall thickening, unlike high-grade non-Hodgkin lymphoma, which typically causes bulky gastric disease, nodal enlargement and extension into adjacent organs. CT is therefore of limited value in monitoring response to treatment. With disease greater than minimal thickening, transformation to a higher grade should be considered.
- Published
- 1999
- Full Text
- View/download PDF
50. A Prognostic Score for Advanced Hodgkin's Disease
- Author
-
Dirk Hasenclever, Volker Diehl, James O. Armitage, David Assouline, Magnus Björkholm, Ercole Brusamolino, George P. Canellos, Patrice Carde, Derek Crowther, David Cunningham, Houchingue Eghbali, Christophe Ferm, Richard I. Fisher, John H. Glick, Bengt Glimelius, Paolo G. Gobbi, Harald Holte, Sandra J. Horning, T. Andrew Lister, Dan L. Longo, Franco Mandelli, Aaron Polliack, Stephen J. Proctor, Lena Specht, John W. Sweetenham, and Gillian Vaughan Hudson
- Subjects
BEACOPP ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Standard treatment ,Combination chemotherapy ,General Medicine ,Hodgkin's lymphoma ,medicine.disease ,Surgery ,Stanford V ,ABVD ,Internal medicine ,medicine ,Refractory Hodgkin Lymphoma ,business ,Survival rate ,medicine.drug - Abstract
Background Two thirds of patients with advanced Hodgkin's disease are cured with current approaches to treatment. Prediction of the outcome is important to avoid overtreating some patients and to identify others in whom standard treatment is likely to fail. Methods Data were collected from 25 centers and study groups on a total of 5141 patients treated with combination chemotherapy for advanced Hodgkin's disease, with or without radiotherapy. The data included the outcome and 19 demographic and clinical characteristics at diagnosis. The end point was freedom from progression of disease. Complete data were available for 1618 patients; the final Cox model was fitted to these data. Data from an additional 2643 patients were used for partial validation. Results The prognostic score was defined as the number of adverse prognostic factors present at diagnosis. Seven factors had similar independent prognostic effects: a serum albumin level of less than 4 g per deciliter, a hemoglobin level of less than 10.5 g pe...
- Published
- 1998
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.