17 results on '"Tighe, Jane"'
Search Results
2. Real-world tyrosine kinase inhibitor treatment pathways, monitoring patterns and responses in patients with chronic myeloid leukaemia in the United Kingdom: the UK TARGET CML study.
- Author
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Milojkovic D, Cross NCP, Ali S, Byrne J, Campbell G, Dignan FL, Drummond M, Huntly B, Marshall S, McMullin MF, Neelakantan P, Raghavan M, Sivakumaran M, Tighe J, Wandroo F, Willis F, Glen F, Fildes L, Collington SJ, Ryan J, Clark RE, and Mead AJ
- Subjects
- Adult, Disease Management, Female, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive epidemiology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Male, Middle Aged, Retrospective Studies, Treatment Outcome, United Kingdom epidemiology, Imatinib Mesylate therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Protein Kinase Inhibitors therapeutic use
- Abstract
Management of chronic myeloid leukaemia (CML) has recently undergone dramatic changes, prompting the European LeukemiaNet (ELN) to issue recommendations in 2013; however, it remains unclear whether real-world CML management is consistent with these goals. We report results of UK TARGET CML, a retrospective observational study of 257 patients with chronic-phase CML who had been prescribed a first-line TKI between 2013 and 2017, most of whom received first-line imatinib (n = 203). Although 44% of patients required ≥1 change of TKI, these real-world data revealed that molecular assessments were frequently missed, 23% of patients with ELN-defined treatment failure did not switch TKI, and kinase domain mutation analysis was performed in only 49% of patients who switched TKI for resistance. Major molecular response (MMR; BCR-ABL1
IS ≤0·1%) and deep molecular response (DMR; BCR-ABL1IS ≤0·01%) were observed in 50% and 29%, respectively, of patients treated with first-line imatinib, and 63% and 54%, respectively, receiving a second-generation TKI first line. MMR and DMR were also observed in 77% and 44% of evaluable patients with ≥13 months follow-up, receiving a second-generation TKI second line. We found little evidence that cardiovascular risk factors were considered during TKI management. These findings highlight key areas for improvement in providing optimal care to patients with CML., (© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)- Published
- 2021
- Full Text
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3. Efficacy of daratumumab combination regimen in patients with multiple myeloma: A combined analysis of phase III randomized controlled trials.
- Author
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Htut TW, Thein KZ, Lawrie A, Tighe J, and Preston G
- Abstract
The use of the CD38 monoclonal antibody daratumumab in combination with standard myeloma chemotherapy regimens has been studied extensively in recent years. We undertook an updated meta-analysis of phase III randomized controlled trials (RCT) to determine the efficacy of daratumumab combination regimens. The relative risk for progression was significantly lower in daratumumab-treated cohorts (HR 0.46, 95% CI 0.38-0.55) and this was consistent across newly diagnosed and relapsed cases. No statistically significant improvement was identified in newly diagnosed patients with high-risk cytogenetics and this group remains a therapeutic challenge., Competing Interests: Gavin Preston has received honoraria or meeting sponsorship from Abbvie, Janssen‐Cilag, and Takeda, and has attended meetings sponsored by Celgene, Roche, Bristol‐Myers‐Squibb, Novartis, Gilead, Pfizer, and Napp pharmaceuticals. Jane Tighe has received educational support and travel for meetings from Amgen, Celgene, Sanofi Aventis, Takeda, and Janssen over the years. We had no financial support for this project., (© 2020 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2020
- Full Text
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4. Primary meningococcal arthritis as a presentation of nodal marginal zone lymphoma.
- Author
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Harrop GAJ, Tighe J, and MacKenzie A
- Subjects
- Aged, Humans, Lymphoma, B-Cell, Marginal Zone microbiology, Lymphoma, Follicular microbiology, Male, Arthritis, Infectious microbiology, Lymphoma, B-Cell, Marginal Zone complications, Lymphoma, Follicular complications, Meningococcal Infections microbiology, Neisseria meningitidis
- Abstract
A 68-year-old man presented with a 4-day history of worsening knee and arm pain. On examination, there was erythema and swelling of the left knee and both wrists. Joint aspiration grew Neisseria meningitidis Blood tests showed an unusually high total protein level (100 g/L) and an IgM kappa paraprotein band of 45 g/L on protein electrophoresis. CT showed widespread lymphadenopathy, hepatosplenomegaly and multilevel thoracic vertebral collapse. A bone marrow biopsy revealed a lymphoplasmacytic infiltrate and a lymph node biopsy showed features of nodal marginal zone lymphoma with plasmacytic differentiation., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
- Published
- 2018
- Full Text
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5. Optimizing the management of patients with spinal myeloma disease.
- Author
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Molloy S, Lai M, Pratt G, Ramasamy K, Wilson D, Quraishi N, Auger M, Cumming D, Punekar M, Quinn M, Ademonkun D, Willis F, Tighe J, Cook G, Stirling A, Bishop T, Williams C, Boszczyk B, Reynolds J, Grainger M, Craig N, Hamilton A, Chalmers I, Ahmedzai S, Selvadurai S, Low E, and Kyriakou C
- Subjects
- Female, Humans, Male, Radiography, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Diphosphonates therapeutic use, Magnetic Resonance Imaging, Multiple Myeloma diagnostic imaging, Multiple Myeloma drug therapy, Spinal Neoplasms diagnostic imaging, Spinal Neoplasms drug therapy
- Abstract
Myeloma is one of the most common malignancies that results in osteolytic lesions of the spine. Complications, including pathological fractures of the vertebrae and spinal cord compression, may cause severe pain, deformity and neurological sequelae. They may also have significant consequences for quality of life and prognosis for patients. For patients with known or newly diagnosed myeloma presenting with persistent back or radicular pain/weakness, early diagnosis of spinal myeloma disease is therefore essential to treat and prevent further deterioration. Magnetic resonance imaging is the initial imaging modality of choice for the evaluation of spinal disease. Treatment of the underlying malignancy with systemic chemotherapy together with supportive bisphosphonate treatment reduces further vertebral damage. Additional interventions such as cement augmentation, radiotherapy, or surgery are often necessary to prevent, treat and control spinal complications. However, optimal management is dependent on the individual nature of the spinal involvement and requires careful assessment and appropriate intervention throughout. This article reviews the treatment and management options for spinal myeloma disease and highlights the value of defined pathways to enable the proper management of patients affected by it., (© 2015 John Wiley & Sons Ltd.)
- Published
- 2015
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6. Pulmonary hypertension in POEMS syndrome: resolution following radiotherapy.
- Author
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Brewis MJ, Church AC, Peacock AJ, Thomson S, Tighe J, and Johnson MK
- Abstract
Pulmonary hypertension (PH) is defined by the presence of a mean pulmonary artery pressure (mPAP) ≥25 mmHg. It may be idiopathic or arise as a consequence of a number of diverse conditions. PH has been reported in association with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes), with reversal following systemic treatment with corticosteroids. We report a case of pulmonary hypertension associated with POEMS syndrome treated with radical radiotherapy locally to bone lesions with resolution of systemic disease.
- Published
- 2014
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7. Safety and efficacy of pulsed imatinib with or without G-CSF versus continuous imatinib in chronic phase chronic myeloid leukaemia patients at 5 years follow-up.
- Author
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Gallipoli P, Stobo J, Heaney N, Nicolini FE, Clark R, Wilson G, Tighe J, McLintock L, Hughes T, Michor F, Paul J, Drummond M, and Holyoake TL
- Subjects
- Benzamides adverse effects, Benzamides therapeutic use, Cell Cycle drug effects, Dasatinib, Drug Substitution, Drug Synergism, Follow-Up Studies, Fusion Proteins, bcr-abl blood, Granulocyte Colony-Stimulating Factor adverse effects, Granulocyte Colony-Stimulating Factor therapeutic use, Humans, Imatinib Mesylate, Piperazines adverse effects, Piperazines therapeutic use, Protein Kinase Inhibitors adverse effects, Protein Kinase Inhibitors therapeutic use, Pulse Therapy, Drug, Pyrimidines adverse effects, Pyrimidines therapeutic use, Thiazoles therapeutic use, Treatment Outcome, Benzamides administration & dosage, Granulocyte Colony-Stimulating Factor administration & dosage, Leukemia, Myeloid, Chronic-Phase drug therapy, Piperazines administration & dosage, Protein Kinase Inhibitors administration & dosage, Pyrimidines administration & dosage
- Published
- 2013
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8. Bilateral cerebellopontine angle lesions not always NF2: diagnostic pitfall.
- Author
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Rao A, Lawrie A, Bodkin P, Tighe J, and Kamel M
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- Aged, Ataxia etiology, Combined Modality Therapy, Deafness etiology, Diagnosis, Differential, Fatal Outcome, Humans, Male, Meningeal Neoplasms drug therapy, Meningeal Neoplasms radiotherapy, Multiple Myeloma drug therapy, Multiple Myeloma radiotherapy, Neurofibromatosis 2 diagnosis, Taste Disorders etiology, Tinnitus etiology, Cerebellar Diseases diagnosis, Cerebellopontine Angle, Meningeal Neoplasms diagnosis, Multiple Myeloma diagnosis
- Abstract
Bilateral internal auditory canal (IAC) tumours are almost exclusively associated with bilateral vestibular schwannomas, and there is very little, if anything, that can mimic this appearance. We present a very rare case of a 75-year-old gentleman who initially presented with bilateral IAC tumours and later diagnosed as an isolated primary CNS myeloma without systemic involvement. This is a very rare presentation and has important diagnostic and therapeutic implications. He was treated with a combination of lenalidomide and dexamethasone. The treatment was well tolerated but with limited response. Although rare, metastasis should be considered as a differential diagnosis of IAC lesions.
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- 2012
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9. Re-transplantation after bortezomib-based therapy.
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Morris C, Cook G, Streetly M, Kettle P, Drake M, Quinn M, Cavet J, Tighe J, Kazmi M, Ashcroft J, Cook M, Snowden J, Olujohungbe A, Marshall S, Conn J, Oakervee H, Popat R, and Cavenagh J
- Subjects
- Bortezomib, Humans, Retrospective Studies, Antineoplastic Agents administration & dosage, Boronic Acids administration & dosage, Hematopoietic Stem Cell Transplantation, Multiple Myeloma therapy, Pyrazines administration & dosage
- Published
- 2011
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10. The standard error of measurement is a more appropriate measure of quality for postgraduate medical assessments than is reliability: an analysis of MRCP(UK) examinations.
- Author
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Tighe J, McManus IC, Dewhurst NG, Chis L, and Mucklow J
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- Educational Measurement statistics & numerical data, Humans, Models, Statistical, Monte Carlo Method, Reproducibility of Results, Education, Medical, Graduate, Educational Measurement standards
- Abstract
Background: Cronbach's alpha is widely used as the preferred index of reliability for medical postgraduate examinations. A value of 0.8-0.9 is seen by providers and regulators alike as an adequate demonstration of acceptable reliability for any assessment. Of the other statistical parameters, Standard Error of Measurement (SEM) is mainly seen as useful only in determining the accuracy of a pass mark. However the alpha coefficient depends both on SEM and on the ability range (standard deviation, SD) of candidates taking an exam. This study investigated the extent to which the necessarily narrower ability range in candidates taking the second of the three part MRCP(UK) diploma examinations, biases assessment of reliability and SEM., Methods: a) The interrelationships of standard deviation (SD), SEM and reliability were investigated in a Monte Carlo simulation of 10,000 candidates taking a postgraduate examination. b) Reliability and SEM were studied in the MRCP(UK) Part 1 and Part 2 Written Examinations from 2002 to 2008. c) Reliability and SEM were studied in eight Specialty Certificate Examinations introduced in 2008-9., Results: The Monte Carlo simulation showed, as expected, that restricting the range of an assessment only to those who had already passed it, dramatically reduced the reliability but did not affect the SEM of a simulated assessment. The analysis of the MRCP(UK) Part 1 and Part 2 written examinations showed that the MRCP(UK) Part 2 written examination had a lower reliability than the Part 1 examination, but, despite that lower reliability, the Part 2 examination also had a smaller SEM (indicating a more accurate assessment). The Specialty Certificate Examinations had small Ns, and as a result, wide variability in their reliabilities, but SEMs were comparable with MRCP(UK) Part 2., Conclusions: An emphasis upon assessing the quality of assessments primarily in terms of reliability alone can produce a paradoxical and distorted picture, particularly in the situation where a narrower range of candidate ability is an inevitable consequence of being able to take a second part examination only after passing the first part examination. Reliability also shows problems when numbers of candidates in examinations are low and sampling error affects the range of candidate ability. SEM is not subject to such problems; it is therefore a better measure of the quality of an assessment and is recommended for routine use.
- Published
- 2010
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11. The relationships between Epstein-Barr virus latent membrane protein 1 and regulatory T cells in Hodgkin's lymphoma.
- Author
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Marshall NA, Culligan DJ, Tighe J, Johnston PW, Barker RN, and Vickers MA
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- Adult, Cell Proliferation, Cytokines metabolism, Female, Herpesvirus 4, Human isolation & purification, Hodgkin Disease immunology, Hodgkin Disease therapy, Hodgkin Disease virology, Humans, Male, Middle Aged, T-Lymphocytes, Regulatory metabolism, Hodgkin Disease physiopathology, T-Lymphocytes, Regulatory immunology, Viral Matrix Proteins physiology
- Abstract
Objective: Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is expressed by the malignant cells of about 30% of cases of Hodgkin's lymphoma (HL) and is therefore a potential target for immune attack. Given the predominantly immunosuppressive nature of HL infiltrating lymphocytes (HLILs) and the ability of LMP1 to stimulate regulatory T (Treg) responses in healthy donors, we hypothesized that LMP1 was important in the generation of Treg responses in HL., Methods: We compared T helper (Th) 1, Th2, and Treg responses to LMP1 by peripheral blood mononuclear cells (PBMCs) and HLILs from EBV-positive and -negative HL patients. The number of Treg cells in patients' PBMCs and HLILs was determined by flow cytometry ex vivo. Proliferation ((3)H-thymidine incorporation) and cytokine (interleukin [IL]-10, IL-4 and gamma-interferon) secretion by LMP1-stimulated PBMCs and HLILs was also measured., Results: Ex vivo EBV-positive HL patients had increased numbers of IL-10-secreting/cytotoxic T-lymphocyte-associated antigen-4-expressing cells compared with EBV-negative HL patients. PBMC/HLIL responses to LMP1 from most patients were characterized by IL-10 secretion, although isolated HL patients mounted Th1-like responses. Several responses to LMP1 peptides were made by HLILs, which were otherwise unresponsive to control stimuli., Conclusions: These results suggest that LMP1 epitopes can induce HLIL Treg cells. However, there was no clear evidence of a greater bias toward regulation in EBV-positive HL cases over EBV-negative cases, and thus there are likely to be other mechanisms of Treg cell induction in EBV-negative HL patients. Manipulating the balance of T-helper response to LMP1 might be exploited in immunotherapy of these lymphomas.
- Published
- 2007
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12. Guidelines for the use of imaging in the management of myeloma.
- Author
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D'Sa S, Abildgaard N, Tighe J, Shaw P, and Hall-Craggs M
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- Bone and Bones pathology, Fluorodeoxyglucose F18, Humans, Magnetic Resonance Imaging, Positron-Emission Tomography, Radiopharmaceuticals, Technetium Tc 99m Sestamibi, Tomography, X-Ray Computed, Whole-Body Counting, Bone and Bones diagnostic imaging, Multiple Myeloma diagnosis
- Abstract
In 2001, reference to the use of imaging in the British Committee for Standards in Haematology guidelines for the diagnosis and management of myeloma was confined to the standard use of plain X-rays in the diagnostic skeletal survey and emergency use of computed tomography (CT) and magnetic resonance (MR) imaging in the setting of cord compression. Since then, there has been a steady rise in interest in the use of various imaging techniques in the management of myeloma. The purpose of imaging in the management of myeloma includes the assessment of the extent and severity of the disease at presentation, the identification and characterisation of complications, and the assessment of response to therapy. Plain radiography, CT, and MR imaging are generally established examination techniques in myeloma whilst positron emission tomography (PET) and (99)Technetium sestamibi (MIBI) imaging are promising newer scanning techniques under current evaluation. These stand-alone imaging guidelines discuss recommendations for the use of each modality of imaging at diagnosis and in the follow up of patients with myeloma.
- Published
- 2007
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13. Eradication of minimal residual disease in B-cell chronic lymphocytic leukemia after alemtuzumab therapy is associated with prolonged survival.
- Author
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Moreton P, Kennedy B, Lucas G, Leach M, Rassam SM, Haynes A, Tighe J, Oscier D, Fegan C, Rawstron A, and Hillmen P
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- Adult, Aged, Alemtuzumab, Antibodies, Monoclonal, Humanized, Bone Marrow pathology, Disease-Free Survival, Female, Flow Cytometry, Humans, Male, Middle Aged, Antibodies, Monoclonal therapeutic use, Antibodies, Neoplasm therapeutic use, Antineoplastic Agents therapeutic use, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Neoplasm, Residual
- Abstract
Purpose: To test whether eradication of minimal residual disease (MRD) in B-cell chronic lymphocytic leukemia (CLL) by alemtuzumab is associated with a prolongation of treatment-free and overall survival., Patients and Methods: Ninety-one previously treated patients with CLL (74 men and 17 women; median age, 58 years [range, 32 to 75 years]; 44 were refractory to purine analogs) received a median of 9 weeks of alemtuzumab treatment between 1996 and 2003. Regular bone marrow assessments by MRD flow cytometry were performed with the aim of eradicating detectable MRD (< 1 CLL cell in 10(5) normal cells)., Results: Responses according to National Cancer Institute-sponsored working group response criteria were complete remission (CR) in 32 patients (36%), partial remission (PR) in 17 patients (19%), and no response (NR) in 42 patients (46%). Twenty-two (50%) of 44 purine analog-refractory patients responded to alemtuzumab. Detectable CLL was eradicated from the blood and marrow in 18 patients (20%). Median survival was significantly longer in MRD-negative patients compared with those achieving an MRD-positive CR, PR, or NR. Patients achieving an MRD-negative CR had a longer treatment-free survival than patients with MRD-positive CRs, PR, or NR: MRD-negative CRs, not reached; MRD-positive CRs, 20 months; PRs, 13 months; NR, 6 months (P < .0001). Overall survival for the 18 patients with MRD-negative remissions was 84% at 60 months. Eight (47%) of the MRD-negative patients converted to MRD positivity at a median of 28 months., Conclusion: MRD-negative remission in CLL is achievable with alemtuzumab, leading to an improved overall and treatment-free survival.
- Published
- 2005
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14. Outcomes after alemtuzumab-containing reduced-intensity allogeneic transplantation regimen for relapsed and refractory non-Hodgkin lymphoma.
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Morris E, Thomson K, Craddock C, Mahendra P, Milligan D, Cook G, Smith GM, Parker A, Schey S, Chopra R, Hatton C, Tighe J, Hunter A, Peggs K, Linch D, Goldstone A, and Mackinnon S
- Subjects
- Actuarial Analysis, Adult, Aged, Alemtuzumab, Antibodies, Monoclonal, Humanized, Combined Modality Therapy, Female, Graft vs Host Disease epidemiology, Humans, Lymphoma, Non-Hodgkin drug therapy, Lymphoma, Non-Hodgkin mortality, Male, Middle Aged, Recurrence, Survival Analysis, Treatment Outcome, Antibodies, Monoclonal therapeutic use, Antibodies, Neoplasm therapeutic use, Antineoplastic Agents therapeutic use, Bone Marrow Transplantation, Lymphoma, Non-Hodgkin therapy, Stem Cell Transplantation
- Abstract
We report the outcomes after reduced-intensity conditioning allogeneic stem cell transplantation (RIT) for non-Hodgkin lymphoma (NHL) in 88 patients (low-grade NHL [LG-NHL], n = 41; high-grade NHL [HG-NHL], n = 37; mantle cell lymphoma [MCL], n = 10). Thirty-seven patients had previously received autografts, and 21 were in complete remission (CR) at transplantation. Conditioning therapy consisted of alemtuzumab, fludarabine, and melphalan. Sixty-five patients received peripheral blood stem cells (PBSCs) from HLA-identical siblings, and 23 received bone marrow (BM) from matched unrelated donors. Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporin A. Grade III-IV acute GVHD developed in 4 patients, and chronic GVHD developed in 6 patients. With a median follow-up of 36 months (range, 18-60 months), the actuarial overall survival (OS) rates at 3 years were 34% for HG-NHL, 60% for MCL, and 73% for LG-NHL (P < .001). The 100-day and 3-year transplant-related mortality (TRM) rates for patients with LG-NHL were 2% and 11%, respectively, and were better (P = .01) than they were for patients with HG-NHL (27% and 38%, respectively). The actuarial current progression-free survival (PFS) rate at 3 years, including the rate for patients who achieved remission after donor lymphocyte infusion (DLI) for progression, was 65% for LG-NHL, 50% for MCL, and 34% for HG-NHL (P = .002). Twenty-one patients underwent DLI for matched related donor (MD)-persistent disease or relapse, and 15 underwent DLI for mixed hematopoietic chimerism. Patients who experienced relapses of LG-NHL and chronic lymphocytic leukemia (CLL) achieved excellent PFS with extremely low TRM and GVHD, even when matched related donors were unavailable.
- Published
- 2004
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15. A pilot study of CODOX-M/IVAC in primary refractory or relapsed high-grade non-Hodgkin's lymphoma. A Scotland and Newcastle Lymphoma Group Study.
- Author
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Davidson KL, Devaney MB, Tighe JE, Rogers SY, Dunlop DJ, Mackie MJ, Thomas RV, and Johnson PR
- Subjects
- Adult, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Combined Modality Therapy, Cyclophosphamide administration & dosage, Cyclophosphamide adverse effects, Cytarabine administration & dosage, Cytarabine adverse effects, Disease Progression, Doxorubicin administration & dosage, Doxorubicin adverse effects, Drug Administration Schedule, Etoposide administration & dosage, Etoposide adverse effects, Female, Granulocyte Colony-Stimulating Factor therapeutic use, Hematopoietic Stem Cell Mobilization, Humans, Ifosfamide administration & dosage, Ifosfamide adverse effects, Injections, Spinal, Lenograstim, Leucovorin administration & dosage, Lymphoma, Non-Hodgkin mortality, Lymphoma, Non-Hodgkin therapy, Male, Mesna administration & dosage, Methotrexate administration & dosage, Methotrexate adverse effects, Middle Aged, Pilot Projects, Prognosis, Recombinant Proteins therapeutic use, Sepsis mortality, Treatment Outcome, Vincristine administration & dosage, Vincristine adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lymphoma, Non-Hodgkin drug therapy, Peripheral Blood Stem Cell Transplantation, Salvage Therapy
- Abstract
Background and Objectives: The prognosis in patients with primary refractory or relapsed high grade non-Hodgkin's lymphoma (NHL) is very poor--the 5-year survival being generally reported at 10%., Design and Methods: Multiple salvage regimens have been investigated and, while response rates of 50-80% have been noted in selected patients, the long-term prognosis remains poor. Following the encouraging results in high risk Burkitt's and Burkitt-like lymphoma using the CODOX-M and IVAC protocols, we performed a pilot study using a similar regimen in patients with primary refractory or relapsed high grade NHL., Results: The regimens were modified by a reduction in the intensity of intrathecal therapy. It was planned to mobilize peripheral blood stem cells following the IVAC cycle for use in subsequent autologous peripheral blood stem cell transplantation in chemosensitive patients. The initial plan was to recruit 50 patients, but the study was closed after 8 due to excessive toxicity., Interpretation and Conclusions: We conclude that the CODOX-M/IVAC regimen is too toxic for this group of patients and does not result in better response rates than those to currently available salvage regimens.
- Published
- 2003
16. Detection of cryptic MLL insertions using a commercial dual-color fluorescence in situ hybridization probe.
- Author
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Dyson MJ, Talley PJ, Reilly JT, Stevenson D, Parsons E, and Tighe J
- Subjects
- Adult, Aged, Bone Marrow Cells pathology, Chromosome Mapping, Female, Gene Rearrangement, Histone-Lysine N-Methyltransferase, Humans, In Situ Hybridization, Fluorescence, Karyotyping, Leukemia, Myeloid, Acute pathology, Male, Middle Aged, Myeloid-Lymphoid Leukemia Protein, Telomere genetics, Chromosomes, Human, Pair 11 genetics, DNA Transposable Elements genetics, DNA-Binding Proteins genetics, Leukemia, Myeloid, Acute genetics, Proto-Oncogenes, Transcription Factors
- Abstract
Involvement of the MLL gene located at chromosome region 11q23 is a frequent occurrence in both acute myelocytic leukemia and acute lymphoblastic leukemia. More than 30 loci have now been associated with MLL, usually by reciprocal translocation. Deletions, insertions, and more complex rearrangements of MLL are rarely seen. We present three cases of AML M5 showing no cytogenetic evidence of 11q23 rearrangement, in which a commercial MLL dual-color fluorescence in situ hybridization probe revealed a nonstandard abnormal signal pattern, suggesting cryptic insertion of the MLL gene into its partner gene site.
- Published
- 2003
- Full Text
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17. Leukemic and non-leukemic lymphocytes from patients with Li Fraumeni syndrome demonstrate loss of p53 function, Bcl-2 family dysregulation and intrinsic resistance to conventional chemotherapeutic drugs but not flavopiridol.
- Author
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Pepper C, Thomas A, Hoy T, Tighe J, Culligan D, Fegan C, and Bentley P
- Subjects
- Adolescent, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Apoptosis genetics, B-Lymphocytes drug effects, Cell Cycle drug effects, Cell Cycle genetics, Cell Transformation, Neoplastic drug effects, Cell Transformation, Neoplastic genetics, Cell Transformation, Neoplastic metabolism, Cyclin-Dependent Kinase Inhibitor p21, Cyclins metabolism, Female, Flavonoids pharmacology, Flavonoids therapeutic use, Humans, Leukemia drug therapy, Leukemia genetics, Li-Fraumeni Syndrome drug therapy, Li-Fraumeni Syndrome genetics, Middle Aged, Mutation genetics, Piperidines pharmacology, Piperidines therapeutic use, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins c-bcl-2 genetics, T-Lymphocytes drug effects, T-Lymphocytes metabolism, Tumor Cells, Cultured, Tumor Suppressor Protein p53 genetics, bcl-2-Associated X Protein, Apoptosis drug effects, B-Lymphocytes metabolism, Drug Resistance, Neoplasm genetics, Leukemia metabolism, Li-Fraumeni Syndrome metabolism, Proto-Oncogene Proteins c-bcl-2 metabolism, Tumor Suppressor Protein p53 deficiency
- Abstract
Li Fraumeni syndrome (LFS) is characterised by a predisposition to the early onset of certain tumors and is associated with germline mutation of the anti-oncogene p53. In this study we analysed the in vitro responses of lymphocytes from two LFS patients to chemotherapeutic drugs in terms of apoptosis induction and the expression of key intracellular proteins that regulate this process. One of the LFS patients also suffered from B-cell chronic lymphocytic leukemia (B-CLL) and hence presented with a light-chain restricted B-cell lymphocytosis while the other patient had entirely normal blood counts. The B-lymphocytes from both LFS patients showed a marked degree of resistance to chlorambucil and fludarabine when compared to age-matched controls but were remarkably sensitive to the novel flavone, flavopiridol. Loss of function of p53 was demonstrated by a failure to induce Bax and p21 protein expression. In addition, altered basal expression patterns of Bcl-2 and Bax, two key regulators of apoptosis, were found in the LFS lymphocytes when compared with controls. These results suggest that LFS lymphocytes carrying a p53 mutation show intrinsic resistance to conventional chemotherapeutic drugs and this is associated with dysregulation of Bcl-2 family proteins. Furthermore, The innate resistance profile was similar in leukemic and non-leukemic lymphocytes and was therefore independent of genetic changes acquired during malignant transformation. Novel agents that induce p53-independent cell killing may be useful not only in the treatment of LFS-associated tumors but also drug resistant tumors in general where p53 and/or Bcl-2 family dysregulation is a feature.
- Published
- 2003
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