Andrew Lister

University of Leicester, Leiscester, England, United Kingdom

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Publications (33)

  • [Show abstract] [Hide abstract] ABSTRACT: Background: This study was aimed at investigating the clinical features and outcome 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, United Kingdom; Novara, Italy) from 1985 to 2010. Results: Patients younger than 40 had a lower incidence of elevated LDH, high beta2-microglobulin and high risk Follicular Lymphoma International Prognostic Index (FLIPI) score, whereas bone marrow involvement, 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% vs 51% (P<0.0001), 10-year CSS rate of 82% vs 60%, (P<0.0001) and 10-year PFS of 39% vs 24% (P=0.0098). However, there were no significant CSS and PFS differences in comparison with the patients aged 40 to 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, while 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.
    Article · Sep 2015 · Annals of Oncology
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    [Show abstract] [Hide abstract] ABSTRACT: It is unclear whether patients with early-stage Hodgkin's lymphoma and negative findings on positron-emission tomography (PET) after three cycles of chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) require radiotherapy. Patients with newly diagnosed stage IA or stage IIA Hodgkin's lymphoma received three cycles of ABVD and then underwent PET scanning. Patients with negative PET findings were randomly assigned to receive involved-field radiotherapy or no further treatment; patients with positive PET findings received a fourth cycle of ABVD and radiotherapy. This trial assessing the noninferiority of no further treatment was designed to exclude a difference in the 3-year progression-free survival rate of 7 or more percentage points from the assumed 95% progression-free survival rate in the radiotherapy group. A total of 602 patients (53.3% male; median age, 34 years) were recruited, and 571 patients underwent PET scanning. The PET findings were negative in 426 of these patients (74.6%), 420 of whom were randomly assigned to a study group (209 to the radiotherapy group and 211 to no further therapy). At a median of 60 months of follow-up, there had been 8 instances of disease progression in the radiotherapy group, and 8 patients had died (3 with disease progression, 1 of whom died from Hodgkin's lymphoma); there had been 20 instances of disease progression in the group with no further therapy, and 4 patients had died (2 with disease progression and none from Hodgkin's lymphoma). In the radiotherapy group, 5 of the deaths occurred in patients who received no radiotherapy. The 3-year progression-free survival rate was 94.6% (95% confidence interval [CI], 91.5 to 97.7) in the radiotherapy group and 90.8% (95% CI, 86.9 to 94.8) in the group that received no further therapy, with an absolute risk difference of -3.8 percentage points (95% CI, -8.8 to 1.3). The results of this study did not show the noninferiority of the strategy of no further treatment after chemotherapy with regard to progression-free survival. Nevertheless, patients in this study with early-stage Hodgkin's lymphoma and negative PET findings after three cycles of ABVD had a very good prognosis either with or without consolidation radiotherapy. (Funded by Leukaemia and Lymphoma Research and others; RAPID number, NCT00943423.).
    Full-text Article · Apr 2015 · New England Journal of Medicine
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    [Show abstract] [Hide abstract] ABSTRACT: Background: Modern treatment of Hodgkin's lymphoma (HL) has transformed its prognosis but causes late effects, including premature menopause. Cohort studies of premature menopause risks after treatment have been relatively small, and knowledge about these risks is limited. Methods: Nonsurgical menopause risk was analyzed in 2127 women treated for HL in England and Wales at ages younger than 36 years from 1960 through 2004 and followed to 2003 through 2012. Risks were estimated using Cox regression, modified Poisson regression, and competing risks. All statistical tests were two-sided. Results: During follow-up, 605 patients underwent nonsurgical menopause before age 40 years. Risk of premature menopause increased more than 20-fold after ovarian radiotherapy, alkylating chemotherapy other than dacarbazine, or BEAM (bis-chloroethylnitrosourea [BCNU], etoposide, cytarabine, melphalan) chemotherapy for stem cell transplantation, but was not statistically significantly raised after adriamycin, bleomycin, vinblastine, dacarbazine (ABVD). Menopause generally occurred sooner after ovarian radiotherapy (62.5% within five years of ≥5 Gy treatment) and BEAM (50.9% within five years) than after alkylating chemotherapy (24.2% within five years of ≥6 cycles), and after treatment at older than at younger ages. Cumulative risk of menopause by age 40 years was 81.3% after greater than or equal to 5Gy ovarian radiotherapy, 75.3% after BEAM, 49.1% after greater than or equal to 6 cycles alkylating chemotherapy, 1.4% after ABVD, and 3.0% after solely supradiaphragmatic radiotherapy. Tables of individualized risk information for patients by future period, treatment type, dose and age are provided. Conclusions: Patients treated with HL need to plan intended pregnancies using personalized information on their risk of menopause by different future time points.
    Full-text Article · Aug 2014 · JNCI Journal of the National Cancer Institute
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    Ama Z. S. Rohatiner · Matthew L. Smith · Orietta Spinelli · [...] · Andrew Lister
    Full-text Article · Jul 2014 · British Journal of Haematology
  • [Show abstract] [Hide abstract] ABSTRACT: To assess the impact of cancer (IOC) on subsequent quality of life (QOL), 718 long-term haematological cancer survivors completed validated psychosocial, functional and QOL scales, including IOC. Fifteen percent reported significant psychological distress, 18% high levels of fatigue and 10% moderate to severe functional impairment. These groups of participants also showed poorer QOL. There were no significant differences in psychological distress (P = 0·76), fatigue (P = 0·23) or functional impairment (P = 0·74) across different cancer subtypes. Two separate hierarchical regression analyses examined the combined association of disease-type, psychosocial and other factors on negative and positive IOC scores respectively. Higher negative IOC scores were significantly associated (P ≤ 0·001) with medical comorbidity, psychological distress, lower social support, high fatigue levels and functional impairment. Paediatric patients (diagnosed at <17 years) were significantly more negative than adult patients (P = 0·001); greater years since diagnosis was significantly (P < 0·001) associated with less negative IOC. Higher positive IOC was associated with acute leukaemia (P = 0·01); lower positive IOC with paediatric patients (P < 0·001), white ethnicity (P < 0·001), higher education (P = 0·003), no partner (P = 0·01) and lower social support (P = 0·01). Screening for medical comorbidity, psychological distress and fatigue identifies those needing most support and should allow earlier interventions to address negative and positive IOC to improve the well-being of cancer survivors.
    Article · Dec 2013 · British Journal of Haematology
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    [Show abstract] [Hide abstract] ABSTRACT: Background: Myelotoxicity during initial cycles of chemotherapy for Hodgkin lymphoma is associated with better outcome, supporting the concept of individualised dosing based on pharmacodynamic end points to optimise results. This study was performed to identify the maximum tolerated dose (MTD) of doxorubicin within cycles 1–3 ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). Circulating biomarkers of response (nucleosomal DNA, nDNA) and epithelial toxicity (Cytokeratin 18, CK18) were also measured. Methods: Dose escalation of doxorubicin in cycles 1–3 ABVD supported by pegfilgrastim was performed on a six-patient cohort basis (35, 45 and 55 mg m–2) with doxorubicin reduced to 25 mg m–2 or omitted in cycles 4–6 to maintain cumulative exposure of 103–130% standard ABVD. BVD was given at standard doses throughout. Six additional subjects were recruited at the MTD. Results: Twenty-four subjects were recruited. Dose-limiting toxicities (DLTs) of grade 3 neuropathy, pneumonitis, palmar-plantar erythema and neutropenic infection were observed at 55 mg m–2, so 45 mg m–2 was declared the MTD. In patients who subsequently experienced DLT at any time, large increases in CK18 were seen on day 3 of cycle 1 ABVD. Conclusion: Escalated ABVD incorporating doxorubicin at 45 mg m–2 in cycles 1–3 can be delivered safely with pegfilgrastim support. Circulating cell death biomarkers may assist in the development of future individualised dosing strategies.
    Full-text Article · Oct 2013 · British Journal of Cancer
  • [Show abstract] [Hide abstract] ABSTRACT: We have previously reported presentation serum selenium level to be predictive of outcome in diffuse large B-cell lymphoma. This has now been studied in a further 430 patients, 163 with acute myeloid leukaemia (AML), 156 with Hodgkin Lymphoma (HL), and 111 with Follicular Lymphoma (FL). Serum selenium was below the UK normal reference range in 45% of patients, and correlated with serum albumin (r=0·24-0·46, P<0·001-0·003) in all tumour types. Independent predictors of presentation selenium were; French-American-British subtype and albumin (P<0·001 for both) in AML, haemoglobin (P=0·002) and B-symptoms (P=0·01) in HL, and albumin (P<0·001) in FL. In AML and HL, response to first line therapy was lower in patients with low serum selenium, but selenium was no longer predictive of response when other variables were entered into a multivariate model. Low selenium was also associated with a worse overall survival in FL [Hazard Ratio (HR) 2·3, 95% confidence interval (CI) 1·4, 4·0] and a trend to a worse overall survival in AML (HR 1·43, 95% CI 0·96, 2·13) by univariate Cox regression analysis, but not by multivariate analysis. In conclusion, low serum selenium is associated with a worse outcome in patients with haematological malignancies, but is not independently predictive, suggesting that it reflects other factors.
    Article · Aug 2011 · British Journal of Haematology
  • [Show abstract] [Hide abstract] ABSTRACT: Intensification of chemotherapy in adults with acute lymphoblastic leukemia (ALL) has improved outcome. The aim of this analysis was to evaluate outcome of patients treated with an intensive regimen based on that used in the German national trials, but adapted in order to enable treatment to be given mainly on an out-patient basis, once complete remission (CR) had been achieved. Between 2000 and 2007, 53 patients with Philadelphia chromosome-negative ALL (40 with B-ALL and 13, T-ALL) received treatment. CR was achieved in 47/53 (89%), with no significant difference in CR rate between B- and T-ALL. At a median follow-up of 6.3 years, 25 patients are alive, 23 (43%) in 1st CR, and 20 have relapsed. No patient died in CR due to treatment-related toxicity. At 5 years, overall survival was 50%, and disease-free survival, 53%. Thirty four of the 47 patients in whom CR was achieved completed therapy and are evaluable for duration of hospital stay and number of Day Unit attendances. The median time in hospital during the year of treatment was 10 weeks (range, 6-44) with no significant difference between patients ≤ vs. >30 years old. It was possible to administer this intensive protocol largely on an out-patient basis without compromising patient safety.
    Article · Jun 2011 · Annals of Hematology
  • [Show abstract] [Hide abstract] ABSTRACT: The Lunenburg Lymphoma Biomarker Consortium (LLBC) evaluated the prognostic value of IHC biomarkers in a large series of patients with diffuse large B-cell lymphoma (DLBCL). Clinical data and tumor samples were retrieved from 12 studies from Europe and North America, with patients treated before or after the rituximab era. Using tissue microarrays from 1514 patients, IHC for BCL2, BCL6, CD5, CD10, MUM1, Ki67, and HLA-DR was performed and scored according to previously validated protocols. Optimal cut points predicting overall survival of patients treated in the rituximab era could only be determined for CD5 (P = .003) and Ki67 (P = .02), whereas such cut points for BCL2, BCL6, HLA-DR, and MUM1 could only be defined in patients not receiving rituximab. A prognostic model for patients treated in the rituximab era identified 4 risk groups using BCL2, Ki67, and International Prognostic Index (IPI) with improved discrimination of low-risk patients. Newly recognized correlations between specific biomarkers and IPI highlight the importance of carefully controlling for clinical and biologic factors in prognostic models. These data demonstrate that the IPI remains the best available index in patients with DLBCL treated with rituximab and chemotherapy.
    Article · May 2011 · Blood
  • R. Johnson · P. Greaves · M. Powell · [...] · A. Lister
    Conference Paper · Apr 2011
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    [Show abstract] [Hide abstract] ABSTRACT: Leukemia is one of the leading journals in hematology and oncology. It is published monthly and covers all aspects of the research and treatment of leukemia and allied diseases. Studies of normal hemopoiesis are covered because of their comparative relevance.
    Full-text Article · Jan 2011 · Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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    [Show abstract] [Hide abstract] ABSTRACT: Patients with follicular lymphoma can have long survival times, but disease progression typically occurs 3-5 years after initial treatment. We assessed the potential benefit of 2 years of rituximab maintenance after first-line treatment in patients with follicular lymphoma receiving a rituximab plus chemotherapy regimen. Methods The randomised, open-label PRIMA study was undertaken in 223 centres in 25 countries. 1217 patients with previously untreated follicular lymphoma needing systemic therapy received one of three non-randomised immunochemotherapy induction regimens used in routine practice. 1019 patients achieving a complete or partial response were then randomly assigned to receive 2 years of rituximab maintenance therapy (375 mg/m(2) every 8 weeks) or observation. Treatment was assigned equally by centralised block randomisation, stratified by induction regimen, response, region, and centre. Neither the participants nor those giving the interventions, assessing outcomes, and analysing data were masked to group assignments. The primary endpoint was progression-free survival (PFS). Analysis was by intention to treat. This trial is registered with, number NCT00140582. Findings 505 patients were assigned to rituximab maintenance and 513 to observation (one patient died during randomisation). With a median follow-up of 36 months (IQR 30-42), PFS was 74.9% (95% CI 70.9-78.9) in the rituximab maintenance group (130 patients progressed) and 57.6% (53.2-62.0) in the observation group (218 progressed; hazard ratio [HR] 0.55, 95% CI 0.44-0.68, p
    Full-text Article · Jan 2011 · The Lancet
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    Agathoclis Agathocleous · Ama Z Rohatiner · Simon Rule · [...] · Andrew Lister
    [Show abstract] [Hide abstract] ABSTRACT: The combination of bortezomib and rituximab was evaluated in patients with mantle cell lymphoma (MCL), follicular lymphoma (FL) and Waldenström macroglobulinaemia (WM), in a Phase I and later, a randomized Phase II study. In the randomized study, 42 patients with recurrent/refractory disease received either: bortezomib 1·3 mg/m(2) on days 1, 4, 8 and 11 of a 3-week cycle with rituximab 375 mg/m(2) on day 1 (21 patients) or: bortezomib 1·6 mg/m(2) and rituximab on days 1, 8, 15 and 22 of a 5-week cycle (with rituximab being given only in cycles 1 and 4).Twenty-eight patients were withdrawn (toxicity 16, progression 7, and 'patient choice' 5). The main toxicities were neurological, gastro-intestinal and haematological. The overall response rate was 28/42(67%) and by histology: MCL 11/19, FL 8/15, and WM 9/10. Ten of 28 responding patients remained progression-free at 1-3·5 years. Toxicity and efficacy were equivalent between the two groups. The combination has significant toxicity but is effective, particularly in patients with WM.
    Full-text Article · Nov 2010 · British Journal of Haematology
  • [Show abstract] [Hide abstract] ABSTRACT: Background. Heterozygous mutations in isocitrate dehydrogenase 1 (IDH1) were recently identified in AML using massively parallel DNA sequencing. These mutations occur in ~8% of AMLs and appear to have a higher frequency in normal karyotype patients. The IDH1 gene is a major mutational target in brain cancer, where the mutation leads to a gain-of-function. This results in the production and accumulation of 2-HG from the normal IDH1 metabolic product α-ketoglutarate, produced by the unaffected copy of the protein. Aim. In this study we set out to determine whether elevated 2-HG resulting from IDH1 mutations is also present in acute leukaemia. Methods. R132 mutation screening was performed by PCR-sequencing in 66 AML cell-lines and 48 normal karyotype AMLs. Intracellular 2-HG concentration in primary AML cells was determined using a LC/MS-MS technique. Results. The R132 mutation was not detected in any of the 66 AML cell lines tested, but was present in 4/48 (8.5%) normal karyotype primary cases of AML. Three samples showed a R132H mutation with one sample containing an R132C alteration. Sufficient stored material was available from IDH1 mutated (n=3) and wild-type (n= 25) primary AMLs to determine intracellular 2-HG. Markedly elevated 2-HG was found in all three of the mutated cases (531, 919 and 1765 ng/106 cells). In contrast, in 25 of 25 primary AMLs without the mutation intracellular 2-HG was <17.5 ng/106 cells. In IDH1 W T AML cell lines, exposure to exogenous 2-HG at concentrations of 1-10 μg/mL resulted in intracellular concentrations of 380-670 ng/106 cells. Although the uptake of 2-HG was not linear, the resulting intracellular concentration was similar to that seen in IDH1 MUT cells. Conclusions. Markedly elevated 2-HG levels are found in AML cells heterozygous for mutations in IDH1 and likely lead t o elevated 2-HG in cells of the neighbouring microenvironment. We are currently investigating the mechanisms by which elevated 2-HG may be linked to leukaemogenesis or outcome
    Article · Jun 2010 · Haematologica
  • D. Taussig · F. Miraki-Moud · A. Lister · [...] · J. Gribben
    Conference Paper · Jun 2010
  • [Show abstract] [Hide abstract] ABSTRACT: To investigate the relationship between Bcl-2 protein expression and cell proliferation at single-cell level in B-cell lymphomas using double-labelling techniques. The relationship between Bcl-2 protein expression and cell proliferation was explored in 124 cases of B-cell lymphoma using double immunofluorescence labelling for Bcl-2 and Ki67. In follicular lymphoma, marginal zone lymphoma and a subset of chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL), neoplastic cells tended to lose Bcl-2 when they are in cell cycle. This pattern is usually maintained in both follicular lymphoma and CLL/SLL when they undergo high-grade transformation. In mantle cell lymphoma, diffuse large B-cell lymphoma and a subset of CLL/SLL, the inverse relationship (between Bcl-2 and Ki67) was not observed, i.e. the proliferating cells tended to show co-expression of Bcl-2. In low-grade lymphomas, including those that are transformed, Bcl-2 expression is lost when cell proliferate. However, in more aggressive tumours (i.e. mantle cell and de novo diffuse large B-cell lymphomas) the inverse Bcl-2/Ki67 relationship was not observed. It would be of interest to explore the clinical implications in lymphoma of the presence and absence of the inverse Bcl-2/Ki67 pattern.
    Article · Apr 2010 · Histopathology
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    [Show abstract] [Hide abstract] ABSTRACT: PURPOSE The randomized First-Line Indolent Trial (FIT) was conducted in patients with advanced follicular lymphoma (FL), to evaluate the safety and efficacy of yttrium-90 ((90)Y) ibritumomab tiuxetan given as consolidation of complete or partial remission. This study of minimal residual disease was undertaken in parallel, to determine the rate of conversion from bcl-2 polymerase chain reaction (PCR) -detectable to -undetectable status and the corresponding effect on progression-free survival (PFS). PATIENTS AND METHODS Blood samples from 414 patients ((90)Y-ibritumomab, n = 208; control, n = 206) were evaluated using real-time quantitative polymerase chain reaction (RQ-PCR); 186 were found to have the bcl-2 rearrangement and were thus eligible for inclusion in the RQ-PCR analysis. Results Overall, 90% of treated patients converted from bcl-2 PCR-detectable to -undetectable disease status, compared with 36% in the control group. Treatment significantly prolonged median PFS in patients converting to bcl-2 PCR-undetectable status (40.8 v 24.0 months in the control group; P < .01, hazard ratio [HR], 0.399). In patients who had bcl-2 PCR-detectable disease at random assignment, treatment significantly prolonged median PFS (38.4 v 8.2 months in the control group; P < .01, HR, 0.293). CONCLUSION Eradication of PCR-detectable disease occurred more frequently after treatment with (90)Y-ibritumomab tiuxetan and was associated with prolongation of PFS.
    Full-text Article · Oct 2009 · Journal of Clinical Oncology
  • Article · Sep 2009 · British Journal of Haematology
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    [Show abstract] [Hide abstract] ABSTRACT: Follicular lymphoma (FL) is genetically characterized by the presence of the t(14;18)(q32;q21) chromosomal translocation in approximately 90% of cases. In contrast to FL carrying the t(14;18), their t(14;18)-negative counterparts are less well studied about their immunohistochemical, genetic, molecular, and clinical features. Within a previously published series of 184 FLs grades 1 to 3A with available gene expression data, we identified 17 FLs lacking the t(14;18). Comparative genomic hybridization and high-resolution single nucleotide polymorphism (SNP) array profiling showed that gains/amplifications of the BCL2 gene locus in 18q were restricted to the t(14;18)-positive FL subgroup. A comparison of gene expression profiles showed an enrichment of germinal center B cell-associated signatures in t(14;18)-positive FL, whereas activated B cell-like, NFkappaB, proliferation, and bystander cell signatures were enriched in t(14;18)-negative FL. These findings were confirmed by immunohistochemistry in an independent validation series of 84 FLs, in which 32% of t(14;18)-negative FLs showed weak or absent CD10 expression and 91% an increased Ki67 proliferation rate. Although overall survival did not differ between FL with and without t(14;18), our findings suggest distinct molecular features of t(14;18)-negative FL.
    Full-text Article · Jun 2009 · Blood
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    [Show abstract] [Hide abstract] ABSTRACT: Aurora kinases play a critical role in regulating mitosis and cell division, and their overexpression has been implicated in the survival and proliferation of human cancer. In this study, we report the in vitro and in vivo activities of AZD1152, a compound that has selectivity for aurora B kinase, in acute myeloid leukemia (AML) cell lines, primary AML samples, and cord blood cells. AZD1152 exerted antiproliferative or cytotoxic effects in all cell lines studied, inhibited the phosphorylation of histone H3 (pHis H3) on Ser10 in a dose-dependent manner, and resulted in cells with >4N DNA content. THP-1 cells treated with AZD1152 accumulated in a state of polyploidy and showed a senescent response to the drug, in contrast to the apoptotic response seen in other cell lines. Accordingly, AZD1152 profoundly affected the growth of AML cell lines and primary AML in an in vivo xenotransplantation model. However, concentration-dependent effects on cell growth, apoptosis, and cell cycle progression were also observed when human cord blood and primary lineage-negative stem and progenitor cells were analyzed in vitro and in vivo. These data suggest that the inhibition of aurora B kinase may be a useful therapeutic strategy in the treatment of AML and that further exploration of dosing and treatment schedules is warranted in clinical trials.
    Full-text Article · Apr 2009 · Cancer Research