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  • 1
    Online Resource
    Online Resource
    American Society of Hematology ; 2006
    In:  Blood Vol. 108, No. 11 ( 2006-11-16), p. 5059-5059
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 5059-5059
    Abstract: Multiple myeloma is a clonal lymphoproliferative disorder characterised by proliferation of plasma cells in marrow and is associated with an unbalanced bone remodelling leading to osteolytic lesions. Bone marrow interstitial fibrosis is common in myeloma. Correlation of marrow fibrosis with clinical parameters and survival in patients with myeloma is conflicting. We have analysed the impact of marrow fibrosis at presentation in 83 (F: 45; M: 38) patients with median age 67 yrs on osteolytic lesions and survival. Reticulin silver impregnation is employed as standard matrix stain. H & E slides were reviewed for degree and pattern of plasma cell infiltration. Marrow reticulin was quantified from Grade 0–4. 50 had IgG myeloma, 15 had Ig A myeloma, 13 had LC myeloma, 2 had Ig D myeloma and PCL and one had Ig M myeloma. Median marrow plasma cell count was 60%. 42% had increased marrow reticulin ( & gt; grade2). 33 received VAD, 16 melphalan and prednisolone, 7 dexamethasone, 6 cyclophosphamide, thalidomide, dexamethasone, 6 cyclophosphamide, 4 thalidomide, 1 dexamethasone and thalidomide combination and 10 only bisphosphonates as initial therapy. Haemoglobin & lt; 10 gms/dl was in 47% patients. 67% were positive for BJP. 33% had hypercalcaemia. 51% had & gt;2 osteolytic lesions at diagnosis. 55% had β2-microglobulin & gt;4mg/L and 22% had renal failure at diagnosis. 47% needed more than one line of therapy. Marrow reticulin was a negative predictor for osteolytic lesions (Fisher’s Exact test; p: 0.001). Marrow reticulin didn’t correlate with other laboratory parameters. Marrow reticulin, sex, BJP & number of osteolytic lesions at diagnosis did not impact on OS (Log Rank test p values: 0.6, 0.07, 0.6 & 0.4 respectively). Known poor prognostic markers Hb & lt;10gm/dl, hypercalcaemia, renal failure and elevated β2-microglobulin were associated with poor OS (Log Rank test p values: 0.02, 0.04, 0.004 & 0.002 respectively) with median follow-up 27 months. Number of osteolytic lesions and anaemia at diagnosis had impact on progression free survival (Log Rank test; p values: 0.01 & 0.02 respectively) where as raised β2-microglobulin, marrow reticulin, hypercalcaemia and renal failure (Log Rank test; p values: 0.07, 0.7, 0.9 & 0.35 respectively) had no impact. Marrow reticulin also had no effect on requirement for more than one line of therapy (p value: 0.17). Marrow reticulin is a negative predictor for osteolytic lesions, even though it does not appear to impact on survival in patients with myeloma. Our study also confirms the poor prognostic role of anaemia, hypercalcaemia, renal failure and raised β2-microglobulin in patients with myeloma. Further study of the hepatocyte growth factor/c-Met interaction may identify the negative correlation between marrow fibrosis and osteolytic lesions. This may enhance understanding of skeletal prophylaxis in patients with myeloma.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
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  • 2
    Online Resource
    Online Resource
    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 21 ( 2011-11-18), p. 4779-4779
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 4779-4779
    Abstract: Abstract 4779 Objective: To describe the epidemiology of bacterial organisms in a level 4 haematology centre and to investigate the prevalence of positive blood cultures at various time points in a febrile patient Methodology: A retrospective review was performed on 138 haematology patients who had blood cultures taken on ward 19 for febrile episodes at Heartlands Hospital, a BCSH Level 4 centre over a 6 month period from 1/5/2009 until 30/11/2009. Results: There were 704 blood cultures performed on 138 patients for 246 ‘febrile’ episodes. There were 59 positive blood cultures. Patients with AML and DLBCL are most likely to require blood cultures as a result of febrile neutropenia. Coagulase Negative Staphylococcus is the most common organism isolated from blood cultures in neutropenic patients during ‘febrile’ episodes. There was only one pathogen cultured that was resistant to the first line antibiotic (Pipercillin/Tazobactam) that was used at this Trust. The incidence of positive blood cultures at onset of fever is 15% is comparable to that seen in other institutions of similar patient populations. This decreased to 1.5 % at 24 hours, 1.7% at 48 hours and 6.3% at 72 hours. Conclusion: Based on the results above, it appears reasonable in stable patients to reduce the number of blood cultures done to 72 hours after the initial culture. At the time of this review, the antibiotic policy in place at HOE NHS trust is appropriate for the pathogens that normally affect this patient population. There should be regular audits to observe the epidemiology of microbials that affect haematology patients in this region and also to monitor their antimicrobial resistance to ensure appropriate first line antibiotics are in use. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
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  • 3
    In: Thrombosis and Haemostasis, Georg Thieme Verlag KG, Vol. 101, No. 04 ( 2009), p. 791-794
    Type of Medium: Online Resource
    ISSN: 0340-6245 , 2567-689X
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2009
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  • 4
    In: Thrombosis and Haemostasis, Georg Thieme Verlag KG, Vol. 103, No. 02 ( 2010), p. 338-343
    Abstract: Venous thromboembolism (VTE) is a clinically important complication for both hospitalised and ambulatory cancer patients. In the current study, the frequency, demographics and risk (according to tumour site) of VTE were examined among patients seen at outpatient DVT (deep-vein thrombosis) clinics. Of 10,015 VTE cases, 1,361 were diagnosed with cancer, for an overall rate of cancer-associated VTE of 13.6% in this outpatient population. Patients with cancer-associated VTE were significantly older than cancer-free VTE cases (66.4 ± 12.7 vs. 58.8 ± 18.5 years; p 〈 0.0001). The frequency of cancer-associated VTE peaked earlier among females than males, occurring in the sixth (137/639, 21.4% vs. 98/851, 11.3%; p 〈 0.001) and seventh decades (213/980, 21.7% vs. 197/1096, 18%; p=0.036). VTE was described most frequently in common cancers – breast, prostate, colorectal and lung (56.1% of cases). The risk of VTE varied widely across 17 cancer types. Calculating odds ratios (OR) to assess the effect size of cancer type on VTE risk, the highest odds were observed for patients with pancreatic cancer (OR 9.65, 95% confidence interval [CI] (5.51–16.91). Tumours of the head and neck had higher odds than previously reported (OR 8.24, 95% CI 5.06–13.42). Reduced risk estimates were observed for skin cancers (melanoma and non-melanoma: OR 0.89, 95% CI 0.42–1.87; OR 0.74, 95% CI, 0.32–1.69, respectively). We conclude that outpatients have a similar rate of cancer-associated VTE as VTE patient populations previously reported, that cancer-associated VTE occurs in an older age group and earlier in females and that outpatients exhibit distinct tumour site-specific risk from that described among hospitalised cancer patients.
    Type of Medium: Online Resource
    ISSN: 0340-6245 , 2567-689X
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2010
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  • 5
    In: British Journal of Haematology, Wiley, Vol. 150, No. 5 ( 2010-09), p. 640-641
    Type of Medium: Online Resource
    ISSN: 0007-1048
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    Language: English
    Publisher: Wiley
    Publication Date: 2010
    detail.hit.zdb_id: 1475751-5
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  • 6
    Online Resource
    Online Resource
    American Society of Hematology ; 2006
    In:  Blood Vol. 108, No. 11 ( 2006-11-16), p. 4020-4020
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 4020-4020
    Abstract: Use of D-dimer levels along with clinical probability scores in the diagnosis of venous thrombosis is well established. Recently it has been shown that high quantitative D-dimer levels at presentation are predictor for poor survival and underlying malignancy in patients with VTE. Do quantitative D-dimer levels in patients without VTE have a similar predictive role? Materials and Methods This study included 2263 (F: 1518; M: 745) consecutive patient episodes from the prospectively maintained database of patients without venous thrombosis at a University Teaching Hospital, between February 2001 and December 2005. All patients with suspected venous thrombosis underwent a Doppler ultrasound examination to rule out venous thrombosis. D-dimer assays were done using Bio-Merieux kit containing mouse monoclonal antibody. The database was regularly updated (6 monthly) using hospital information systems, questionnaires and clinical review. Statistical analysis was carried out using SPSS 13.0 for Windows and GraphPad InStat ® Version 3.06 for Windows software’s. Overall survival (OS) was estimated by the Kaplan-Meier method. Cox regression analysis by forward Likelihood Ratio was subsequently used to explore the independent effect of variables that showed a significant influence on OS. Results Median age at diagnosis was 69 yrs (range: 18–105 yrs). Median D-dimer level was 1000ug FEU/ml (range: 300–35500ug FEU/ml). 1165 patients (51.7%) had a D-dimer level of & gt;1000ug FEU/ml and 40 (2%) had a D-dimer level of & gt;8000ug FEU/ml at presentation. 1472 patients (65.4%) were aged above 60 years. Median follow up was 22 months (range: 0–65 months). D-dimer level & gt;1000ug FEU/ml, & gt;4000ug FEU/ml and & gt;8000ug FEU/ml were associated with decreased overall survival (Log rank test: p value: 0.002, & lt; 0.001 and & lt;0.001 respectively). Age & gt;60 yr is also associated with decreased overall survival (Log rank test: p value: & lt;0.001). D-dimer & gt;8000ug FEU/ml and age & gt;60yr were an independent poor prognostic factor for overall survival on Cox regression analysis (p value: & lt;0.001). 27.5% of patients with a D-dimer level & gt;8000ug FEU/ml had cancer (Fisher’s exact test; p value: 0.003). 17% of patients with a D-dimer level & gt;4000ug FEU/ml had cancer (Fisher’s exact test; p value: 0.04). 12.4% of patients with a D-dimer level & gt;1000ug FEU/ml had cancer (Fisher’s exact test; p value: 0.02). Conclusions This study show elevated D-dimer levels at presentation in patients without venous thrombosis is a marker of poor survival and a predictor for underlying malignancy. We have previously shown that D-dimer & gt;8000ug FEU/ml is a predictor for poor survival and underlying malignancy in patients with proven venous thrombosis. This suggests heightened fibrinolytic activity in the absence or presence of established venous thrombosis is associated with poor prognosis. Further studies are warranted to establish in different medical conditions the presence or absence of increased fibrinolysis and impact on clinical outcome.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 1991-1991
    Abstract: Bone marrow transplantation is frequently used as a consolidation therapy in patients with haematological malignancies to improve outcome. Obese individuals have larger absolute lean body and fat masses than non-obese individuals of the same age, gender and height, which might lead to altered pharmacokinetics of chemotherapeutic agents. Data on the impact of body mass on transplant outcome is conflicting. This study included 254 patients (M: 151; F: 103) with 283 transplant episodes (Autograft: 178, Allograft: 105). 81 patients had myeloma, 61 non Hodgkin’s lymphoma, 38 Hodgkin’s lymphoma, 34 acute myeloid leukaemia, 28 chronic lymphocytic leukaemia, 15 acute lymphoblastic leukaemia, 9 T cell non Hodgkin’s lymphoma, 6 each myelodysplasia and aplastic leukaemia and 1 each acute promyelocytic leukaemia and myelofibrosis. Statistical analysis was carried out using SPSS 13.0 for Windows. Overall survival (OS) and event free survival (EFS) were estimated by the Kaplan-Meier method. At transplantation 47% patients had normal & 52% high BMI. After a median follow-up of 14 month (range:0–75), mean OS in patients undergoing autograft with normal BMI was 52 months as compared to 54 with high BMI. Mean OS in patients undergoing allograft with normal BMI was 27 months as compared to 39 with high BMI (log rank test p value; autograft: 0.74 & allograft: 0.09). Odds Ratio for survival in autograft patients was 1.305 (95% CI: 0.611–2.786). For normal BMI patients OR for survival was 1.175(95% CI: 0.73–1.891), where as for high BMI patients 0.901 (95% CI: 0.678–1.197). Odds Ratio for survival in allograft patients was 0.512 (95% CI: 0.23–1.136). For normal BMI patients OR for survival was 0.751 (95% CI: 0.534–1.057), where as for high BMI patients 1.468 (95% CI: 0.921–2.341). Mean EFS in patients undergoing autograft with normal BMI was 42 months as compared to 50 with high BMI. Mean EFS in patients undergoing allograft with normal BMI was 26 months as compared to 48 with high BMI (log rank test p value; autograft: 0.4 & allograft: 0.3). This study shows that high BMI does not adversely impact on either OS or EFS in patients undergoing both autologous and allogeneic transplantation for haematological malignancies. On the contrary, the trend for OS appears to better in patients undergoing allograft with high BMI. We recommend patients with high BMI should not be excluded from having autologous transplantation. Studies with greater number of patients are needed to establish the potential beneficial impact of high BMI on survival in patients undergoing allogeneic transplantation. Figure Figure
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 4348-4348
    Abstract: R-CHOP is the standard of care for patients with diffuse large B cell lymphoma (DLBCL) however poor risk patients (IPI 3-5) still have an inadequate outcome. Neither first remission high dose chemotherapy and peripheral blood stem cell transplantation (HDC+PBSCT) nor selection of cases for intensification by interim PET scanning have demonstrated a proven benefit. In the case of Burkitts lymphoma (BL) there is a paucity of data on the addition of Rituximab to the CODOX-M and IVAC regimen. Patients and Methods 113 patients with DLBCL and 37 with BL were recruited from 53 UK sites between May 2008 and April 2013. Median age was 49 years (18-65). For DLBCL patients IPI scores were 3 – 72 ( 64%), 4 -40 (35%) and 5 – 1 (1%). All patients received the modified CODOX-M and IVAC regimen including all CNS directed therapy( Mead et al Ann Oncol. 2002 Aug;13(8):1264-74) and 8 doses of rituximab. The primary end point of the study was Progression Free survival (PFS) and secondary endpoints included toxicity and CR rate. Results The main toxicities reported were neutropenia ( 89% grade 3 or 4), thrombocytopenia (84.2% grade 3 or 4), infection 61.6% grade 3 or 4 and mucositis (30.1% grade 3 or 4). 4 patients were excluded from toxicity assessment as they did not start therapy after registration. There were 8 treatment related deaths observed (infection with neutropenia (5), GI haemorrhage (1), acute cerebral haemorrhage (1) and bowel perforation (1) ). 78 patients with DLBCL and 31 with BL have completed all therapy ( 78.5 % of patients with available data) with an overall response rate of 92 % for DLBCl and 94% for BL. In patients who completed all therapy CR was achieved in 34 (44%), CR (u) in 8 (10%) and PR in 30 (38%) for DLBCL patients and CR was achieved in 21 (68%), CR (u) in 6 (19%) and PR in 2 (6%) in BL patients. 3 patients ( 2 DLBCL and 1 BL) who progressed during therapy have been included in the response analysis. End of treatment PET scanning was not obligatory. 80 patients with DLBCL and 30 patients with BL remain alive and without progression at a median follow up of 18.6 and 19.3 months respectively. Conclusion The R-CODOX-M -R-IVAC regimen can be delivered to patients with poor risk DLBCL in a multicentre setting. High rates of haematological toxicity and consequent infection are inevitable with treatment of this intensity but appear acceptable when compared with other treatments such as HDC+PBSCT. Response rates are encouraging in view of the very poor risk IPI profile of the patients included in this study. Burkitts lymphoma patients also achieved an excellent response rate with no apparent additional toxicity attributable to the addition of rituximab to the regimen. We currently plan the first analysis for the primary endpoint of PFS in 2015. The Trial was supported by Leukaemia and Lymphoma Research (LLR). Disclosures: McMillan: Roche: Consultancy, Honoraria; Amgen: Research Funding. Off Label Use: Rituximab usage in Burkitts Lymphoma. Ardeshna:Roche: Honoraria, Research Funding. Jack:Roche/Genentech: Research Funding. Patmore:Roche: Consultancy, Honoraria. Pettengell:Roche: Honoraria; Amgen: Honoraria. Linch:Roche: Honoraria, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 5553-5553
    Abstract: PAM score is a simple tool for predicting mortality risk in patients undergoing allogeneic bone marrow transplantation. Originally developed and validated at Fred Hutchinson Cancer Research Center, Seattle, this has recently been validated in 276 patients from Japan. We retrospectively evaluated this in our cohort of T deplete myeloablative allogeneic transplants as there are no published studies validating PAM score in T deplete myeloablative setting. Results After a median follow up of 63 months 51% of the patients are alive. The predicted mortality for category 2, 3 and 4 patients via PAM score was 28%, 48% and 28% respectively. This was concordant with the predicted mortality at 2yrs for category 2 and 3. Category 4 was not concordant (Chi-square test, P=0.0035). Disclosures: Milligan: Celgene: unrestricted educational grant Other.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    Online Resource
    Online Resource
    American Society of Hematology ; 2006
    In:  Blood Vol. 108, No. 11 ( 2006-11-16), p. 1500-1500
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 1500-1500
    Abstract: Association between VTE and cancer has been recognised for over a century. The incidence of occult or overt malignancy in patients with thrombosis is 7–26%. VTE has been shown to impart poor prognosis in patients with cancer and cancer also adversely impacts on the survival of patients with VTE. It is desirable to identify patients with thrombosis at increased risk of malignancy or those with minimal risk, thus avoiding unnecessary investigations. We propose here a predictive model using age and quantitative D-dimer level at presentation along with site of thrombosis. Materials and Methods This study included 696 (M: 358; F: 338) consecutive patients from the prospectively maintained database of patients with venous thrombosis at a University Teaching Hospital, between February 2001 and December 2005. All patients underwent a Doppler ultrasound examination to confirm the diagnosis and determine the extent of venous thrombosis. At presentation, D-dimer assays were done using Bio-Merieux kit containing mouse monoclonal antibody. The database was regularly updated (6 monthly) using hospital information systems, questionnaires and clinical review Thrombosis recurrence was always confirmed by Doppler ultrasound examination. All Patients with thrombosis received standard treatment with low molecular weight heparin and warfarin. Statistical analysis was carried out using SPSS 13.0 for Windows software. A logistic multivariate regression model was fitted using complete data records from 621 patients with an indicator variable for a subsequent cancer as the response and age, the natural logarithm of the quantitative D-dimer level and the site of the thrombosis as explanantory variables. The fitted model was validated using an additional set of independent data. Results The model correctly identified the VTE patients without malignancy in 473 out of 480 cases (98.5% accuracy). But the model was ineffective in identifying VTE patients with malignancy (13 out of 141; 9% accuracy). The area under the receiver operating characteristic (ROC) curve was 0.72, indicating that the test developed for predicting cancer for the model data was reasonably good. Our model shows that below a predicted probability of 0.10 less than 5% of the patients actually developed cancer (9/190) whereas for a predicted probability of 0.19 less than 10% of patients actually developed cancer (27/276). In the validation dataset of 93 patients with VTE, the model correctly identified the number of patients without malignancy in 72 out of 73 cases (98.6% accuracy). One-sample binomial tests revealed that there was no significant difference in the number VTE patients with cancer between the model and the validation dataset for the predicted probabilities of 0.10 and 0.19 (p-values of 0.650 and 0.246 respectively). Conclusions This suggests that our model is useful for identifying patients at minimal risk of developing cancer with VTE. This predictive model has been validated by an independent dataset demonstrating reproducibility. This model will enable a focused and a cost-effective strategy of screening for a malignancy in patients with VTE.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
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    detail.hit.zdb_id: 80069-7
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