Publications
212 results found
Little C, Szydlo R, Aw TC, et al., 2020, Effect of direct-acting oral anticoagulants (DOACs) on bleeding and blood product usage in cardiac surgery compared to warfarin and controls, British Journal of Haematology, Vol: 190, Pages: 284-293, ISSN: 0007-1048
In this retrospective, single-centre, observational study, we assessed (i) use of anticoagulant and antiplatelet (AP) therapy, (ii) the duration of direct-acting oral anticoagulant (DOAC) discontinuation, (iii) renal function and (iv) PT and APTT as predictors of bleeding and blood product usage; in adults (>18 years) undergoing major cardiac surgery from 01.01.2015 to 31.12.2018. Comparisons were made between each treatment group (warfarin, DOAC and DOAC + AP) and untreated controls, and between warfarin and DOAC. A total of 2928 patients were included for analysis. Median (range) of DOAC discontinuation prior to surgery was five days (1-22) for DOAC and five days (2-7) for DOAC + AP. There were no differences in bleeding between anticoagulant groups versus control, or DOAC versus warfarin. There were no differences in blood product use between DOAC and warfarin patients. The duration of DOAC discontinuation but not the creatinine clearance influenced bleeding and blood products use. Thrombosis occurred in 0·7% and 3·1% in controls and patients on warfarin respectively (P = 0·099) with none among patients on DOAC or DOAC + AP. The PT/APTT had no predictive value. Median five-day discontinuation of DOAC +/- AP irrespective of renal function prevents an increase in bleeding compared to patients on warfarin or controls with no increase in thrombosis.
Nacheva E, Ahyee T, Addada J, et al., 2020, Absence of damaging effects of stem cell donation in unrelated donors assessed by FISH and gene variance screening, BONE MARROW TRANSPLANTATION, Vol: 55, Pages: 1290-1296, ISSN: 0268-3369
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- Citations: 1
Nteliopoulos G, Bazeos A, Claudiani S, et al., 2019, Somatic variants in epigenetic modifiers can predict failure of response to imatinib but not to second-generation tyrosine kinase inhibitors, Haematologica, Vol: 104, Pages: 2400-2409, ISSN: 0390-6078
There are no validated molecular biomarkers to identify newly-diagnosed individuals with chronic-phase chronic myeloid leukaemia likely to respond poorly to imatinib and who might benefit from first-line treatment with a more potent second-generation tyrosine kinase-inhibitor. Our inability to predict these 'high-risk' individuals reflects the poorly understood heterogeneity of the disease. To investigate the potential of genetic variants in epigenetic modifiers as biomarkers at diagnosis, we used Ion Torrent next-generation sequencing of 71 candidate genes for predicting response to tyrosine kinase-inhibitors and probability of disease progression. 124 subjects with newly-diagnosed chronic-phase chronic myeloid leukaemia began with imatinib (n=62) or second-generation tyrosine kinase-inhibitors (n=62) and were classified as responders or non-responders based on the BCRABL1 transcript levels within the first year and the European LeukemiaNet criteria for failure. Somatic variants affecting 21 genes (e.g. ASXL1, IKZF1, DNMT3A, CREBBP) were detected in 30% of subjects, most of whom were non-responders (41% non-responders, 18% responders to imatinib, 38% non-responders, 25% responders to second-generation tyrosine kinase-inhibitors). The presence of variants predicted the rate of achieving a major molecular response, event-free survival, progression-free survival and chronic-myeloid-leukaemia-related survival in the imatinib but not the second-generation tyrosine kinase-inhibitors cohort. Rare germline variants had no prognostic significance irrespective of treatment while some pre-leukaemia variants suggest a multi-step development of chronic myeloid leukaemia. Our data suggest that identification of somatic variants at diagnosis facilitates stratification into imatinib responders/non-responders, thereby allowing earlier use of second-generation tyrosine kinase-inhibitors, which, in turn, may overcome the negative impact of such variants on disease progression.
Claudiani S, Metelli S, Kamvar R, et al., 2019, Introducing a Predictive Score for Successful Treatment Free Remission in Chronic Myeloid Leukemia (CML), BLOOD, Vol: 134, ISSN: 0006-4971
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- Citations: 4
McLornan D, Szydlo R, Koster L, et al., 2019, Myeloablative and Reduced-Intensity Conditioned Allogeneic Hematopoietic Stem Cell Transplantation in Myelofibrosis: A Retrospective Study by the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation, BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, Vol: 25, Pages: 2167-2171, ISSN: 1083-8791
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- Citations: 49
Claudiani S, Gatenby A, Szydlo R, et al., 2019, MR4 sustained for 12 months is associated with stable deep molecular responses in chronic myeloid leukemia, Haematologica, Vol: 104, Pages: 2206-2214, ISSN: 0390-6078
The majority of patients with newly diagnosed chronic myeloid leukaemia will enjoy a life expectancy equivalent to that of unaffected individuals, but will remain on life-long treatment with a concomitant requirement for on-going hospital interactions for molecular monitoring and drug dispensing. In order to determine more accurately the frequency of monitoring required, we performed a real-life retrospective single-centre cohort study of 450 patients with chronic myeloid leukaemia in at least major molecular remission (MR3) to analyse the risk of loss of MR3 (defined as at least 2 consecutive RT-qPCR results >0.1% IS). Patient who achieved sustained MR4 (sMR4, BCR-ABL1 RT-qPCR <0.01% IS for 12 months) had a probability of loss of MR3 at 1 and 5 years of 0 and 2.6% (95% CI,1.2-5.4) respectively, compared to 4.4% (95% CI, 1.9-9.8) and 25.4% (95% CI, 16.7-36.7) respectively, in those who achieved sustained MR3 (sMR3) but not sMR4 (p <0.001). No patient who improved their response to a deep molecular level (at least MR4) lost MR3 if they were considered compliant, had no history of resistance and remained on standard dose TKI. MR4 maintained for at least 1 year represents a secure response threshold for patients with chronic myeloid leukaemia, after which no MR3 loss occurs if certain conditions are satisfied (standard TKI dose, full compliance and lack of previous TKI resistance). This finding may justify reduction of the frequency of hospital interaction, with an associated positive impact on quality of life, survivorship and economic burden to both patients and healthcare providers.
Hinton R, Levy S, Szydlo R, et al., 2019, A novel Haemato-oncology Frailty (HOF) score tool predicts survival in over 80s with Multiple Myeloma, BRITISH JOURNAL OF HAEMATOLOGY, ISSN: 0007-1048
Innes A, Wooley P, Szydlo R, et al., 2019, Complete remission with incomplete count recovery (CRi) prior to allogeneic HCT for acute myeloid leukaemia is associated with a high non-relapse mortality., Leukemia, Vol: 34, Pages: 667-670, ISSN: 1476-5551
Mayor NP, Hayhurst JD, Turner TR, et al., 2019, A reply to Hurley et al. regarding Recipients Receiving Better HLA-Matched Hematopoietic Cell Transplantation Grafts, Uncovered by a Novel HLA Typing Method, Have Superior Survival: A Retrospective Study., Biol Blood Marrow Transplant, Vol: 25, Pages: e270-e271
Iskander D, Roberts I, Rees C, et al., 2019, Impaired cellular and humoral immunity is a feature of Diamond-Blackfan anaemia; experience of 107 unselected cases in the United Kingdom., British Journal of Haematology, Vol: 186, Pages: 321-326, ISSN: 1365-2141
Diamond-Blackfan anaemia (DBA) is a rare bone marrow failure syndrome characterised by anaemia, congenital anomalies and cancer predisposition. Although infections are the second leading cause of mortality in non-transplanted patients, immune function is largely unexplored. We identified quantitative deficits in serum immunoglobulins and/or circulating T, natural killer and B lymphocytes in 59 of 107 unselected patients (55·1%) attending our centre over a 7-year period. Immune abnormalities were independent of ribosomal protein genotype and arose in both steroid-treated and steroid-untreated patients. In summary, these data highlight the high prevalence and spectrum of infections and immune defects in DBA.
Baccarani M, Castagnetti F, Gugliotta G, et al., 2019, The proportion of different BCR-ABL1 transcript types in chronic myeloid leukemia. An international overview, Leukemia, Vol: 33, Pages: 1173-1183, ISSN: 1476-5551
There are different BCR-ABL1 fusion genes that are translated into proteins that are different from each other, yet all leukemogenic, causing chronic myeloid leukemia (CML) or acute lymphoblastic leukemia. Their frequency has never been systematically investigated. In a series of 45503 newly diagnosed CML patients reported from 45 countries, it was found that the proportion of e13a2 (also known as b2a2) and of e14a2 (also known as b3a2), including the cases co-expressing e14a2 and e13a2, was 37.9% and 62.1%, respectively. The proportion of these two transcripts was correlated with gender, e13a2 being more frequent in males (39.2%) than in females (36.2%), was correlated with age, decreasing from 39.6% in children and adolescents down to 31.6% in patients ≥ 80 years old, and was not constant worldwide. Other, rare transcripts were reported in 666/34561 patients (1.93%). The proportion of rare transcripts was associated with gender (2.27% in females and 1.69% in males) and with age (from 1.79% in children and adolescents up to 3.84% in patients ≥ 80 years old). These data show that the differences in proportion are not by chance. This is important, as the transcript type is a variable that is suspected to be of prognostic importance for response to treatment, outcome of treatment, and rate of treatment-free remission.
Beckerson J, Szydlo RM, Hickson M, et al., 2019, Impact of route and adequacy of nutritional intake on outcomes of allogeneic haematopoietic cell transplantation for haematologic malignancies, Clinical Nutrition, Vol: 38, Pages: 738-744, ISSN: 0261-5614
BACKGROUND: Allogeneic haematopoietic cell transplantation (HCT) is often associated with poor oral intake due to painful mucositis and gastrointestinal sequalae that occur following a preparative regimen of intensive chemotherapy and/or total body radiation. Although attractive to assume that optimal nutrition improves HCT outcomes, there are limited data to support this. It is also unclear whether artificial nutrition support should be provided as enteral tube feeding or parenteral nutrition (PN). METHODS: We analysed day-100 non-relapse mortality (NRM), incidence of acute graft-versus-host disease (GvHD), acute gastrointestinal GvHD, 5-year survival and GvHD-free/relapse-free survival (GRFS) according to both route and adequacy of nutritional intake prior to neutrophil engraftment, together with other known prognostic factors, in a retrospective cohort of 484 patients who underwent allogeneic HCT for haematologic malignancy between 2000 and 2014. RESULTS: Multivariate analyses showed increased NRM with inadequate nutrition (hazard ratio (HR) 4.1; 95% confidence interval (CI) 2.2-7.2) and adequate PN (HR 2.9; 95% CI 1.6-5.4) compared to adequate enteral nutrition (EN) both P < .001. There were increased incidences of gastrointestinal GvHD of any stage and all GvHD ≥ grade 2 in patients who received PN (odds ratio (OR) 2.0; 95% CI 1.2-3.3; P = .006, and OR 1.8; 95% CI 1.1-3.0; P = .018, respectively), compared to adequate EN. Patients who received adequate PN and inadequate nutrition also had reduced probabilities of survival and GRFS at 5 years. CONCLUSION: Adequate EN during the early transplantation course is associated with reduced NRM, improved survival and GRFS at 5 years. Furthermore, adequate EN is associated with lower incidence of overall and gut acute GvHD than PN, perhaps because of its ability to maintain mucosal integrity, modulate the immune response to intensive chemo/radiotherapy and support the gastroi
Galleu A, Milojkovic D, Deplano S, et al., 2019, Mesenchymal stromal cells for acute graft-versus-host disease: response at 1 week predicts probability of survival, British Journal of Haematology, Vol: 185, Pages: 89-92, ISSN: 1365-2141
Mesenchymal stromal cells (MSCs) have been successfully used for the treatment of steroid-resistant graft-versus-host-disease (GvHD). However, the lack of early predictors of clinical responses impacts on the time at which to add further treatment and consequently the design of informative clinical trials. Here, we present the UK experience of one of the largest cohorts of GvHD patients undergoing MSC infusions so far reported. We show that clinical responses assessed as early as 1 week after MSC infusion predict patients' overall survival. In our cohort, cell dose, patients' age and type of organ involvement are crucial factors associated with clinical responses.
Arachchillage DRJ, Alavian S, Griffin J, et al., 2019, Efficacy and safety of prothrombin complex concentrate in patients treated with rivaroxaban or apixaban compared to warfarin presenting with major bleeding, British Journal of Haematology, Vol: 184, Pages: 808-816, ISSN: 1365-2141
This retrospective study investigated the efficacy and safety of prothrombin complex concentrates (PCCs) for management of major bleeding events (MBE) in 344 patients receiving the anticoagulants rivaroxaban, apixaban or warfarin during the period January 2016 to April 2018. Median (range) PCC dose was 2000 units (1000-4500). Intracranial haemorrhage (ICH) was the most common indication (137/344, 39·8%) for PCC use followed by gastrointestinal bleeding (93/344, 27%). ICH patients more frequently received rivaroxaban (62·5%) or apixaban (52·5%) compared to warfarin (34·5%), P = 0·002; and visceral bleeding patients received warfarin more frequently (24·2%) than rivaroxaban (5%) or apixaban (10%), P = 0·003. Median rivaroxaban and apixaban levels were 230 ng/ml (47-759) and 159 ng/ml (45-255). Median International Normalised Ratio pre- and post-PCC in patients on warfarin were 3·4 (1·9-15·4) and 1·2 (1·0-1·9). Blood products use was the same between groups. Thirty-day mortality and re-bleeding rates in patients with ICH were 35% (P = 0·50) and 18% (P = 0·90) with no differences between the groups. Thrombosis occurred in 4·1% patients within 30 days with no difference between groups. Two of 91 (2·2%) patients with ICH only (both on warfarin) had ischaemic strokes within 30 days post-PCC. In conclusion, there was no difference in the safety (thrombosis) or efficacy (30-day mortality, re-bleeding) in use of PCC for MBE in patients on warfarin, rivaroxaban or apixaban.
Mayor NP, Hayhurst JD, Turner TR, et al., 2019, Recipients Receiving Better HLA-Matched Hematopoietic Cell Transplantation Grafts, Uncovered by a Novel HLA Typing Method, Have Superior Survival: A Retrospective Study, BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, Vol: 25, Pages: 443-450, ISSN: 1083-8791
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- Citations: 64
Varghese V, Magnani L, Harada N, et al., 2019, FOXM1 modulates 5-FU resistance in colorectal cancer through regulating TYMS expression, Scientific Reports, Vol: 9, ISSN: 2045-2322
Resistance to 5-Fluoruracil (5-FU) has been linked to elevated expression of the main target, thymidylate synthase (TYMS), which catalyses the de novo pathway for production of deoxythymidine monophosphate. The potent oncogenic forkhead box transcription factor, FOXM1 is is regulated by E2F1 which also controls TYMS. This study reveals a significant role of FOXM1 in 5-FU resistance. Overexpression and knock-down studies of FOXM1 in colon cancer cells suggest the importance of FOXM1 in TYMS regulation. ChIP and global ChIP-seq data also confirms that FOXM1 can also potentially regulate other 5-FU targets, such as TYMS, thymidine kinase 1 (TK-1) and thymidine phosphorylase (TYMP). In human colorectal cancer tissue specimens, a strong correlation of FOXM1 and TYMS staining was observed. Elevated FOXM1 and TYMS expression was also observed in acquired 5-FU resistant colon cancer cells (HCT116 5-FU Res). A synergistic effect was observed following treatment of CRC cells with an inhibitor of FOXM1, thiostrepton, in combination with 5-FU. The combination treatment decreased colony formation and migration, and induced cell cycle arrest, DNA damage, and apoptosis in CRC cell lines. In summary, this research demonstrated that FOXM1 plays a pivotal role in 5-FU resistance at least partially through the regulation of TYMS.
Khoder A, Alsuliman A, Basar R, et al., 2018, Evidence for B cell exhaustion in chronic graft-versus-host disease, Frontiers in Immunology, Vol: 8, ISSN: 1664-3224
Chronic graft-versus-host disease (cGvHD) remains a major complication of allogeneic hematopoietic stem cell transplantation (HSCT). A number of studies support a role for B cells in the pathogenesis of cGvHD. In this study, we report the presence of an expanded population of CD19+CD21− B cells with features of exhaustion in the peripheral blood of patients with cGvHD. CD21− B cells were significantly increased in patients with active cGvHD compared to patients without cGvHD and healthy controls (median 12.2 versus 2.12 versus 3%, respectively; p < 0.01). Compared with naïve (CD27−CD21+) and classical memory (CD27+CD21+) B cells, CD19+CD21− B cells in cGvHD were CD10 negative, CD27 negative and CD20hi, and exhibited features of exhaustion, including increased expression of multiple inhibitory receptors such as FCRL4, CD22, CD85J, and altered expression of chemokine and adhesion molecules such as CD11c, CXCR3, CCR7, and CD62L. Moreover, CD21− B cells in cGvHD patients were functionally exhausted and displayed poor proliferative response and calcium mobilization in response to B-cell receptor triggering and CD40 ligation. Finally, the frequencies of circulating CD21− B cells correlated with cGvHD severity in patients after HSCT. Our study further characterizes B cells in chronic cGVHD and supports the use of CD21−CD27−CD10− B cell frequencies as a biomarker of disease severity.
Palmieri C, Szydlo R, Miller M, et al., 2017, IPET study: an FLT-PET window study to assess the activity of the steroid sulfatase inhibitor irosustat in early breast cancer, Breast Cancer Research and Treatment, Vol: 166, Pages: 527-539, ISSN: 0167-6806
BACKGROUND: Steroid sulfatase (STS) is involved in oestrogen biosynthesis and irosustat is a first generation, irreversible steroid sulfatase inhibitor. A pre-surgical window-of-opportunity study with irosustat was undertaken in estrogen receptor-positive (ER+) breast cancer to assess the effect of irosustat on tumour cell proliferation as measured by 3'-deoxy-3'-[18F] fluorothymidine uptake measured by PET scanning (FLT-PET) and Ki67. METHODS: Postmenopausal women with untreated ER+ early breast cancer were recruited, and imaged with FLT-PET at baseline and after at least 2 weeks treatment with irosustat, 40 mg once daily orally. The primary endpoint was changed in FLT uptake; secondary endpoints included safety and tolerability of irosustat, changes in tumoral Ki67 and steroidogenic enzymes expression and circulating steroid hormone levels. RESULTS: Thirteen women were recruited, and ten started irosustat for 2 weeks, followed by repeat FLT-PET scans in eight. Defining response as decreases of ≥20% in standardized uptake value (SUV) or ≥30% in Ki, 1 (12.5% (95% CI 2-47%, p = 0.001)) and 3 (43% (95% CI 16-75%, p = <0.001) patients, respectively, responded. 6 out of 7 patients had a Ki67 reduction (range = -19.3 to 76.4%), and median percentage difference in Ki67 was 52.3% (p = 0.028). In one patient with a low baseline STS expression, a 19.7% increase in Ki67 was recorded. STS decreases were seen in tumours with high basal STS expression, significant decreases were also noted in aromatase, and 17β-hydroxysteroid dehydrogenase type 1 and 2. Irosustat was generally well tolerated with all adverse event CTCAE Grade ≤2. CONCLUSIONS: Irosustat resulted in a significant reduction in FLT uptake and Ki67, and is well tolerated. These data are the first demonstrating clinical activity of irosustat in early breast cancer. Baseline expression of STS may be a biomarker of sensitivity to irosustat.
Nikolajeva O, Rocha V, Danby R, et al., 2017, Umbilical Cord Blood Cytomegalovirus Serostatus Does Not Have an Impact on Outcomes of Umbilical Cord Blood Transplantation for Acute Leukemia, BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, Vol: 23, Pages: 1729-1735, ISSN: 1083-8791
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Pavlu J, Auner H, Szydlo RM, et al., 2017, Analysis of hematopoietic recovery after autologous transplantation as method of quality control for long-term progenitor cell cryopreservation., Bone Marrow Transplantation, Vol: 52, Pages: 1599-1601, ISSN: 1476-5365
Hematopoietic precursor cells (HPC) are able to restore hematopoiesis after high-dose chemotherapy and their cryopreservation is routinely employed prior to the autologous hematopoietic cell transplantation (AHCT). Although previous studies showed feasibility of long-term HPC storage, concerns remain about possible negative effects on their potency. To study the effects of long-term cryopreservation, we compared time to neutrophil and platelet recovery in 50 patients receiving two AHCT for multiple myeloma at least 2 years apart between 2006 and 2016, using HPC obtained from one mobilization and collection attempt before the first transplant. This product was divided into equivalent fractions allowing a minimum of 2 × 106 CD34+ cells/kg recipient’s weight. One fraction was used for the first transplant after median storage of 60 days (range, 17–165) and another fraction was used after median storage of 1448 days (range, 849–3510) at the second AHCT. Neutrophil recovery occurred at 14 days (median; range, 11–21) after the first and 13 days (10–20) after the second AHCT. Platelets recovered at a median of 16 days after both procedures. Considering other factors, such as disease status, conditioning and HPC dose, this single institution data demonstrated no reduction in the potency of HPC after long-term storage.
Claudiani S, Apperley J, Gale RP, et al., 2017, E14a2 BCR-ABL1 transcript is associated with a higher rate of treatment-free remission in persons with chronic myeloid leukemia after stopping tyrosine kinase-inhibitor therapy., Haematologica, Vol: 102, Pages: e297-e299, ISSN: 0390-6078
Shaw BE, Mayor NP, Szydlo RM, et al., 2017, Recipient/donor HLA and CMV matching in recipients of T-cell-depleted unrelated donor haematopoietic cell transplants, BONE MARROW TRANSPLANTATION, Vol: 52, Pages: 717-725, ISSN: 0268-3369
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- Citations: 40
Pluta A, Robak T, Wrzesien-Kus A, et al., 2017, Addition of cladribine to the standard induction treatment improves outcomes in a subset of elderly acute myeloid leukemia patients. Results of a randomized Polish Adult Leukemia Group (PALG) phase II trial, AMERICAN JOURNAL OF HEMATOLOGY, Vol: 92, Pages: 359-366, ISSN: 0361-8609
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- Citations: 21
Patel A, Szydlo RM, Auner HW, et al., 2016, C-reactive protein prior to myeloablative allogeneic haematopoietic cell transplantation identifies patients at risk of early- and long-term mortality, British Journal of Haematology, Vol: 180, Pages: 889-892, ISSN: 1365-2141
Anthias C, Billen A, Arkwright R, et al., 2016, Harvests from bone marrow donors who weigh less than their recipients are associated with a significantly increased probability of a suboptimal harvest yield, TRANSFUSION, Vol: 56, Pages: 1052-1057, ISSN: 0041-1132
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- Citations: 13
Nasilowska-Adamska B, Czyz A, Markiewicz M, et al., 2016, Mild chronic graft-versus-host disease may alleviate poor prognosis associated with <i>FLT3</i> internal tandem duplication for adult acute myeloid leukemia following allogeneic stem cell transplantation with myeloablative conditioning in first complete remission: a retrospective study, EUROPEAN JOURNAL OF HAEMATOLOGY, Vol: 96, Pages: 236-244, ISSN: 0902-4441
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- Citations: 8
Bain BJ, Littlewood TJ, Szydlo RM, 2016, The finer points of writing and refereeing scientific articles, BRITISH JOURNAL OF HAEMATOLOGY, Vol: 172, Pages: 350-359, ISSN: 0007-1048
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- Citations: 4
Paul DS, Jones A, Sellar RS, et al., 2015, A donor-specific epigenetic classifier for acute graft-versus-host disease severity in hematopoietic stem cell, Genome Medicine, Vol: 7, ISSN: 1756-994X
BackgroundAllogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for many hematological conditions. Acute graft-versus-host disease (aGVHD) is a prevalent immune-mediated complication following HSCT. Current diagnostic biomarkers that correlate with aGVHD severity, progression, and therapy response in graft recipients are insufficient. Here, we investigated whether epigenetic marks measured in peripheral blood of healthy graft donors stratify aGVHD severity in human leukocyte antigen (HLA)-matched sibling recipients prior to T cell-depleted HSCT.MethodsWe measured DNA methylation levels genome-wide at single-nucleotide resolution in peripheral blood of 85 HSCT donors, matched to recipients with various transplant outcomes, with Illumina Infinium HumanMethylation450 BeadChips.ResultsUsing genome-wide DNA methylation profiling, we showed that epigenetic signatures underlying aGVHD severity in recipients correspond to immune pathways relevant to aGVHD etiology. We discovered 31 DNA methylation marks in donors that associated with aGVHD severity status in recipients, and demonstrated strong predictive performance of these markers in internal cross-validation experiments (AUC = 0.98, 95 % CI = 0.96–0.99). We replicated the top-ranked CpG classifier using an alternative, clinical DNA methylation assay (P = 0.039). In an independent cohort of 32 HSCT donors, we demonstrated the utility of the epigenetic classifier in the context of a T cell-replete conditioning regimen (P = 0.050).ConclusionsOur findings suggest that epigenetic typing of HSCT donors in a clinical setting may be used in conjunction with HLA genotyping to inform both donor selection and transplantation strategy, with the ultimate aim of improving patient outcome.
Patel A, Stroud T, Breen D, et al., 2015, Patient age predicts the delay before survivors of cancer utilise their cryopreserved sperm for assisted reproductive technology., Blood, Vol: 126, Pages: 4481-4481, ISSN: 0006-4971
Objective: Sperm cryopreservation (sperm banking) is the recommended standard of care for fertility preservation for men with cancer. Men can utilise their sperm for assisted reproductive technology (ART) when they are ready to become fathers. However, the duration of sperm cryopreservation that should be offered to men is unknown. We hypothesised that younger men with cancer require a longer duration of sperm storage before readiness to utilise their samples for ART, compared with older patients. To test this hypothesis, we investigated whether age at sperm harvest predicts the time of sperm storage necessary before ART.Design: A retrospectively analysed cohort study spanning 37 years using prospectively acquired routine clinical data.Setting: A specialist andrology facility in the UK, that provides unlimited storage of sperm as part of NHS treatment free-of-charge to the patient.Participants: Adolescent boys and men with a confirmed diagnosis of cancer were identified by cross-referencing and verifying patient records: Human Fertility & Embryology Authority (HEFA), Department of Andrology, and the NHS Spine Services Portal database, part of the Health and Social Care Information Centre.Main outcome measures: The primary outcome measures were the effect of age on the time from sperm cryopreservation to use for ART, and the specificity and sensitivity of age at predicting the requirement of >10 years sperm storage.Results: 4305 men harvested and cryopreserved their sperm between 1976 and 2013. Men with cancer comprised 3191 and were included in the study. The cancer types that indicated sperm cryopreservation comprised testicular (1130, 35.4%), lymphoma (762, 23.9%), leukaemia (462, 14.5%), and others (838, 26.3%). At sperm harvesting, their median age was 30.3 years (IQR 24.6 to 36.2). Sperm from 217 (6.8%) patients with a median age of 31.3 (IQR 26.5 to 36.7) were utilized for ART after a median of 7.8 years (interquartile range (IQR) 3.5 to 14.3).Increasin
Auner HW, Szydlo R, Hoek J, et al., 2015, Trends in autologous hematopoietic cell transplantation for multiple myeloma in Europe: increased use and improved outcomes in elderly patients in recent years, Bone Marrow Transplantation, Vol: 50, Pages: 209-215, ISSN: 0268-3369
Autologous hematopoietic cell transplantation (AHCT) is a standard of care in multiple myeloma (MM) patients aged <65 years. To understand age-related trends in utilisation and outcome of AHCT, we analysed 53 675 MM patients who underwent a first AHCT in 31 European countries between 1991 and 2010. The number of patients undergoing AHCT increased for all age groups (<40, 40–49, 50–59, 60–64, 65–69 and ⩾70 years) throughout the observation period. The highest increase was observed for patients aged ⩾65 years, who accounted for 3% of AHCTs in 1991–1995 and for 18.8% of AHCTs in 2006–2010. Risk factors associated with survival over the entire observation period (P<0.001) were calendar period, remission status at AHCT, gender, disease duration before AHCT and age. Survival improved considerably more in older than in younger patients in recent years. In 2006–2010, median 2- and 5-year post-transplant survival ranged from 85.9 and 61.5% in patients <40 years to 80.2 and 49.7% in those ⩾70 years. All-cause day-100 mortality decreased throughout the observation period to ⩽2.4% for all age groups in 2006–2010. The results of this study demonstrate increased utilisation and safety of AHCT with improved post-transplant survival particularly in elderly MM patients in recent years in Europe.
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