16 results on '"Unell Riley"'
Search Results
2. Clinical profile and outcome of urotheliotropic viral haemorrhagic cystitis following haematopoietic stem cell transplantation: a 7-year tertiary centre analysis
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Unell Riley, Radovan Saso, Jennie Treleaven, Bronwen E. Shaw, Simon Littlewood, Faith E. Davies, Gareth J. Morgan, Donna Lancaster, Kabir Mohammed, A Atra, Michael Potter, Mary Taj, Mark Ethell, and Parameswaran Anoop
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Cyclophosphamide ,medicine.medical_treatment ,Hemorrhage ,Hematopoietic stem cell transplantation ,Gastroenterology ,Young Adult ,Risk Factors ,Internal medicine ,Cystitis ,Humans ,Medicine ,Child ,Aged ,business.industry ,Data Collection ,Incidence ,Incidence (epidemiology) ,Hematopoietic Stem Cell Transplantation ,Infant ,Hematology ,Middle Aged ,Total body irradiation ,Transplantation ,Treatment Outcome ,Child, Preschool ,Immunology ,Alemtuzumab ,Female ,business ,Complication ,Viral load ,medicine.drug - Abstract
Viral haemorrhagic cystitis (HC) is a significant complication after haematopoietic stem cell transplantation (HSCT), with a potential for major morbidity. The aim of this 7-year analysis of 1160 HSCT patients was to evaluate risk factors for the incidence, severity, toxicity of therapy, clinical course, and outcome of this condition. The overall incidence of HC was 5·8%, with most cases occurring after allogeneic HSCT. Unrelated donors (P = 0·001), non-peripheral blood stem cell source (P = 0·005), myeloablative conditioning (P0·001), use of alemtuzumab in conditioning (P = 0·001), and severe acute graft versus host disease (P0·001) were independent risk factors for an increased incidence of HC post-allogeneic transplant on multivariate analysis. Severe forms of HC were associated with grades II-IV acute graft versus host disease and a longer duration of haematuria. Contrary to previous studies which were carried out on smaller patient populations, busulphan, cyclophosphamide, anti-thymocyte globulin, and total body irradiation were not found to independently increase the risk of viral HC, unless used in a myeloablative combination. Neither duration of viriuria nor peak viral load in urine influenced the severity of HC on multivariate analysis. Severe HC contributed to the deaths of two patients. Overall survival was not statistically different between patient subgroups with non-severe and severe HC.
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- 2011
3. An early CT-diagnosis-based treatment strategy for invasive fungal infection in allogeneic transplant recipients using caspofungin first line: an effective strategy with low mortality
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C Dearden, Faith E. Davies, Jennifer Treleaven, Fiona L Dignan, Bronwen E. Shaw, Michael Potter, Mark Ethell, Unell Riley, Stephen O Evans, and Gareth J. Morgan
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Adult ,Male ,medicine.medical_specialty ,Antifungal Agents ,Time Factors ,Allogeneic transplantation ,Adolescent ,Neutropenia ,law.invention ,Echinocandins ,Lipopeptides ,chemistry.chemical_compound ,Pharmacotherapy ,Randomized controlled trial ,Caspofungin ,law ,Internal medicine ,Humans ,Transplantation, Homologous ,Medicine ,Mycosis ,Aged ,Transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,medicine.disease ,Surgery ,Mycoses ,chemistry ,Hematologic Neoplasms ,Female ,Tomography, X-Ray Computed ,business ,Febrile neutropenia - Abstract
Empirical antifungal therapy is frequently used in allogeneic transplant patients who have persistent febrile neutropenia and can be associated with high cost, toxicity and breakthrough infections. There are limited reports of strategies for early diagnosis of invasive fungal infection (IFI) and, to our knowledge, no reports of treatment strategies based only on high-resolution computerized tomography (HRCT) scans. We used an early treatment strategy for IFI in 99 consecutive patients undergoing allogeneic transplantation. Patients received caspofungin if they had antibiotic-resistant neutropenic fever for more than 72 h and a positive HRCT scan. Fifty-three of 99 patients (54%) had antibiotic-resistant neutropenic fever at 72 h and would have received parenteral antifungal treatment if an empirical approach had been used. The HRCT-based strategy reduced the use of parenteral antifungal agents to 17/99 patients (17%), a 68% reduction. No subsequent diagnoses of IFI occurred within 100 days in patients with a negative HRCT. Only one patient died from IFI within 100 days. These data suggest that this non-empirical strategy may be feasible and that caspofungin may be effective in this setting. A randomized controlled trial is warranted to further assess these results.
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- 2009
4. Amphotericin B lipid complex (ABLC) for the treatment of confirmed or presumed fungal infections in immunocompromised patients with hematologic malignancies
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Seema Singhal, Jennie Treleaven, C. Evans, Patrick Chu, Unell Riley, Jayesh Mehta, Stephen M. Kelsey, Adrian C. Newland, Ray Powles, and Dena L. Hazel
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Adult ,Male ,medicine.medical_specialty ,Antifungal Agents ,Adolescent ,medicine.medical_treatment ,Aspergillosis ,Transplantation, Autologous ,Gastroenterology ,Nephrotoxicity ,Immunocompromised Host ,Amphotericin B ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Mycosis ,Aged ,Bone Marrow Transplantation ,Transplantation ,Chemotherapy ,business.industry ,Phosphatidylglycerols ,Immunosuppression ,Hematology ,Middle Aged ,medicine.disease ,Surgery ,Drug Combinations ,Mycoses ,Hematologic Neoplasms ,Concomitant ,Phosphatidylcholines ,Female ,business ,medicine.drug - Abstract
Sixty-four adult patients (median age 43) with hematologic malignancies who were immunocompromised after allogeneic (n = 23) or autologous (n = 9) blood/marrow transplantation, or chemotherapy (n = 32) received 68 courses of amphotericin B lipid complex (ABLC, Abelcet) at the daily dose of 5 mg/kg for presumed (n = 52) or proven (n = 16) fungal infection. The major indications for ABLC were failure of previous antifungal therapy and/or renal dysfunction. Fifty-three treatment courses in 49 patients comprising 4-58 doses (median 10) were considered evaluable. Fourteen courses administered for confirmed infections resulted in nine complete and one partial responses, and four failures (71% response). Thirty-nine empiric courses resulted in 18 complete and six partial responses, and 14 failures (64% response). The overall response rate was 66%. Five of seven evaluable patients with aspergillus pneumonia responded. Response rates were comparable for chemotherapy, autograft and allograft recipients. The change in serum creatinine from the beginning to the end of therapy was -284 to +277 mumol/l (median +24). The creatinine doubled during seven evaluable courses of therapy, five of which were associated with concomitant nephrotoxic therapy. Nephrotoxicity was comparable for transplant and chemotherapy patients. Renal dysfunction necessitated discontinuation of ABLC in only four patients. These data suggest that ABLC is effective in presumed or confirmed fungal infections in immunocompromised patients after transplantation or chemotherapy.
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- 1997
5. Antimicrobial Prophylaxis to Prevent Opportunistic Infections in Patients with Chronic Lymphocytic Leukemia after Allogeneic Blood or Marrow Transplantation
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Seema Singhal, Daniel Catovsky, Jayesh Mehta, Unell Riley, Jennifer Treleaven, and R. L. Powles
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Cancer Research ,Chronic lymphocytic leukemia ,chemical and pharmacologic phenomena ,Opportunistic Infections ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Humans ,Transplantation, Homologous ,In patient ,neoplasms ,Bone Marrow Transplantation ,Marrow transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Antimicrobial ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Toxoplasmosis ,Anti-Bacterial Agents ,Fludarabine ,Leukemia ,surgical procedures, operative ,Oncology ,Immunology ,Drug Therapy, Combination ,business ,Allogeneic transfusion ,medicine.drug - Abstract
Opportunistic infections have been a problem after BMT in CLL. We have allografted seven patients with B-CLL (n = 6) or B-prolymphocytic leukemia (n = 1) from matched siblings (n = 6) or a mismatched unrelated donor (n = 1). Amongst the first six, we saw two cases of recurrent or prolonged cytomegaloviremia and CMV disease, one listeria meningitis, and one fatal toxoplasma encephalitis. The latter two developed in the setting of steroid therapy of GVHD with extensive prior fludarabine therapy. Prophylaxis for opportunistic infections was developed on an ongoing basis as new infectious complications were seen. The current drug prophylaxis, which has been successful for eight months in the last patient despite pretreatment with fludarabine and steroid therapy for GVHD, is directed against pneumocystis, toxoplasma, fungi, and pneumococci. It includes immunoglobulin (for 3 1/2 months), pyrimethamine-sulfadiazine (for 4 months and during steroids), fluconazole (for 2 1/2 months), cotrimoxazole or pentamidine (for 2 years) and penicillin (lifelong). Dietary precautions are followed for 4 months and during steroids to prevent listeriosis. Four patients are alive in remission with no active infectious problems 8-44 months (median 29) after BMT. We recommend adoption of these or similar prophylactic measures for BMT in CLL as a baseline which can be modified if new infections are identified and according to individual needs.
- Published
- 1997
6. High readmission rates are associated with a significant economic burden and poor outcome in patients with grade III/IV acute GvHD
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Fiona L Dignan, L. Lewis, Louise McNamara, Unell Riley, Mark Ethell, Bronwen E. Shaw, Gareth J. Morgan, Claire Dearden, Faith E. Davies, Steve O. Evans, Michael Potter, Joy Brennan, and Matthew Taylor
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Graft vs Host Disease ,Gastroenterology ,Patient Readmission ,Young Adult ,Postoperative Complications ,Cost of Illness ,immune system diseases ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,In patient ,Aged ,Retrospective Studies ,Transplantation ,Hospital readmission ,business.industry ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,Readmission rate ,medicine.disease ,Prognosis ,Surgery ,Clinical trial ,Survival Rate ,surgical procedures, operative ,Graft-versus-host disease ,Hematologic Neoplasms ,Transplant patient ,Female ,business ,Complication ,Follow-Up Studies - Abstract
Graft-versus-host disease (GvHD) is a common complication following haematopoietic stem cell transplant but little is published about the impact of this condition on hospital readmission rates. We report a retrospective analysis of readmission rates and associated costs in 187 consecutive allogeneic transplant patients to assess the impact of GvHD. The overall readmission rate was higher in patients with GvHD (86% (101/118) vs. 59% (41/69), p < 0.001). The readmission rate was higher both in the first 100 d from transplant (p = 0.02) and in the first year following transplant (p < 0.001). 151/455 (33%) of all readmission episodes occurred within 100 d of transplant. The mean number of inpatient days was significantly higher in patients with grade III/IV acute GvHD (101 d) compared with those with grade I/II GvHD (70 d; p = 0.003). The mean cost of readmission was higher in patients with GvHD (28 pound 860) than in non-GvHD patients (13 pound 405; p = 0.002) and in patients with grade III/IV GvHD (40 pound 012) compared with those patients with grade I/II GvHD (24 pound 560; p = 0.038). Survival was higher in those with grade I/II GvHD (55%) compared to grade III/IV GvHD (14%; p < 0.001). This study shows the high economic burden and poor overall survival associated with grade III/IV GvHD.
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- 2012
7. First report of fatal human infections with the cactophilic yeast Sporopachydermia cereana
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Mark Ethell, Elizabeth M. Johnson, Jennie Treleaven, Unell Riley, Gareth J. Morgan, Michael Potter, and Parameswaran Anoop
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Microbiology (medical) ,Identification methods ,Adult ,Male ,Antifungal Agents ,Neutropenia ,Human pathogen ,Fungus ,Biology ,Microbiology ,Immunocompromised Host ,Fatal Outcome ,Amphotericin B ,medicine ,Humans ,Middle Aged ,biology.organism_classification ,medicine.disease ,Yeast ,Infectious Diseases ,Mycoses ,Saccharomycetales ,Fungal sepsis ,Sporopachydermia cereana ,medicine.drug - Abstract
Sporopachydermia cereana is a cactophilic yeast, which is not recognised as a human pathogen. We describe two fatal infections with this fungus in profoundly neutropenic patients. S. cereana escapes detection by conventional mycological identification methods. This organism may be an under-recognised cause of fatal fungal sepsis among immunocompromised patients.
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- 2011
8. List of contributors
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Douglas R Adkins, Jane Apperley, Andrew S Artz, Smita Bahtia, Kristin Baird, A John Barrett, Michael R Bishop, Andrew Bodenham, Charles Bolan, Alan K Burnett, Kenneth Carson, Richard Childs, Susan Cleaver, Robin P Corbett, Michele Cottler-Fox, Charles Craddock, H Joachim Deeg, Josu de la Fuente, William B Ershler, Stephen O Evans, Suzanne Fanning, Jürgen Finke, Mary E D Flowers, H Bobby Gaspar, Duncan Gilbert, Eliane Gluckman, Nicola Gökbuget, John M Goldman, John G Gribben, Vikas Gupta, Rupert Handgretinger, Nancy M Hardy, Carolyn Hemsley, Louise Henry, Helen E Heslop, Dieter Hoelzer, Mary Horowitz, Alan Horwich, Edwin Horwitz, Gabor Illei, Armand Keating, Hanna Jean Khoury, Chris Kibbler, Steven Knapper, Samar Kulkarni, Rifca Le Dieu, Zi Yi Lim, Gayle Loader, Chrystal U Louis, Andreas Lundqvist, Judith Marsh, Jayesh Mehta, Simon Meller, Stephan Mielke, Matthew Montgomery, Ghulam J Mufti, Tariq I Mughal, Paolo Muraro, Bijay Nair, John Oram, Steven Pavletic, Gavin D Perkins, Michael Potter, Barry Quinn, Unell Riley, Irene A G Roberts, Vanderson Rocha, James A Russell, Bipin N Savani, Anthony P Schwarer, Bronwen E Shaw, Seema Singhal, Gérard Socié, Shivani Srivastava, John W Sweetenham, Lochie Teague, John Theus, André Tichelli, Jennifer Treleaven, Jaap van Laar, Frits van Rhee, Sumithira Vasu, Paul Veys, Phyllis Warkentin, Alan S Wayne, Daniel Weisdorf, and Robert Wynn
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- 2009
9. Barrier precautions, prophylaxis and neutropenic fever
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Unell Riley
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Pediatrics ,medicine.medical_specialty ,business.industry ,Neutropenic fever ,Medicine ,business - Published
- 2009
10. Parainfluenza type 3 infection post stem cell transplant: high prevalence but low mortality
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Unell Riley, Fiona L Dignan, Michael Potter, Caroline L. Alvares, J. Bendig, David Cunningham, Mark Ethell, Gareth J. Morgan, Stanley W. Ashley, and Jennifer Treleaven
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Microbiology (medical) ,Adult ,Male ,medicine.medical_specialty ,Pediatrics ,Adolescent ,Antiviral Agents ,Respirovirus Infections ,Transplantation, Autologous ,chemistry.chemical_compound ,Lower respiratory tract infection ,Ribavirin ,Prevalence ,Medicine ,Infection control ,Humans ,Transplantation, Homologous ,Intensive care medicine ,Cause of death ,Retrospective Studies ,Cross Infection ,Infection Control ,business.industry ,Incidence (epidemiology) ,Mortality rate ,Retrospective cohort study ,General Medicine ,Middle Aged ,medicine.disease ,Parainfluenza Virus 3, Human ,Transplantation ,Infectious Diseases ,chemistry ,England ,Female ,business ,Stem Cell Transplantation - Abstract
Parainfluenza type 3 (PIV 3) is a well-recognized cause of respiratory illness after stem cell transplantation (SCT), with an estimated incidence of 2-7% and a high mortality rate associated with lower respiratory tract infection (LRTI). A 12-month retrospective study was undertaken in which 23 positive cases of PIV 3 occurred in SCT recipients. The frequency of infection was 36.1% in matched unrelated donor SCT recipients, 23.8% in sibling allogeneic SCT recipients and 2.3% in autologous transplant recipients. Seventeen cases were outpatient or community acquired despite standard infection control measures. Eleven patients only developed upper respiratory tract symptoms. LRTI symptoms developed in 12 patients, of whom eight had a new infiltrate on chest X-ray. Overall mortality at 30 days from PIV 3 diagnosis was 4% (one patient). Four patients died within 100 days of PIV 3 diagnosis, but PIV 3 was not believed to be the primary cause of death in any of these patients. Early ribavirin was used in eight patients and only one patient who received ribavirin died. These results suggest a higher prevalence of PIV 3 but a lower mortality than documented previously, particularly in allogeneic transplant recipients. The authors propose that the high prevalence reflects the unit's policy of active surveillance for respiratory viruses and the difficulty in preventing transmission of PIV 3, especially in the outpatient setting during an outbreak period. Ribavirin treatment may improve outcome in patients with LRTI but is not required in all patients with PIV 3.
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- 2006
11. High Rates of Passive CMV Antibody Acquisition Pre-Allograft in Patients Receiving Plasma-Rich CMV Unselected and Leukodepleted Blood Components: A Caution for Donor Selection
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Unell Riley, Michael Potter, Mark Ethell, and Robert N Lown
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medicine.medical_specialty ,Blood transfusion ,biology ,business.industry ,Donor selection ,medicine.medical_treatment ,Immunology ,virus diseases ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Total body irradiation ,Biochemistry ,Gastroenterology ,Platelet transfusion ,Immunoglobulin M ,Internal medicine ,medicine ,biology.protein ,Alemtuzumab ,Seroconversion ,business ,medicine.drug - Abstract
For many years there has been ongoing debate in the United Kingdom (UK) about the necessity of using blood components from cytomegalovirus IgG seronegative (CMV neg) donors for CMV neg patients undergoing allogeneic hematopoietic stem cell transplantation, in the era of universal leukodepletion. From June 2012, our centre followed the guidance of the Advisory Committee on the Safety of Blood Tissues and Organs (SaBTO) in the United Kingdom, using CMV unselected leucodepleted components for all patients regardless of CMV serostatus. As part of an ongoing biovigilance commitment, we assessed the impact this policy had on rates of CMV seroconversion and viremia. 137 patients were included in the study, each allografted between March 2012 and December 2013. The median age was 49 years (range 2-71) and 62% were male. Diseases transplanted included acute leukemia or myelodysplastic syndrome (73.0%), lymphoma (11.0%), chronic leukemias (7.3%) and others (8.7%). 42 patients (30.7%) received myeloablative conditioning, 43 (31.4%) received total body irradiation, and 112 (81.7%) received in-vivo T-cell depletion with alemtuzumab. 119 (86.9%) received peripheral blood stem cells, 8 (5.8%) bone marrow, and 10 (7.3%) cord blood. 35 donors (25.5%) were siblings. 78 patients (56.9%) were CMV neg when first documented, of which 62 (79.5%) had a CMV neg donor. 59 patients (43.1%) were CMV IgG seropositive (CMV pos) when first documented, of which 36 (64.3%) had a CMV pos donor. All patients had CMV serology checked again within 28 days pre-transplant: of the 78 CMV neg patients, 14 (17.9%) were found to have changed their CMV status to seropositive. Of note, these patients had received significantly more platelet transfusions in the three months prior to transplant than those who did not seroconvert pre-transplant (median 13 vs 0 adult doses, p Conclusion In 78 CMV IgG negative patients, there were only four incidences of proven primary CMV infection, all in patients receiving CMV pos stem cell donations. Excluding these cases, there were no cases of primary CMV infection associated with transfusion of CMV unselected blood components. However, we found a significant incidence of probable passive transfer of CMV IgG antibody, which was strongly associated with the use of platelet transfusions. Whilst this has no direct impact on the patient, it has significant implications for donor selection if it is incorrectly interpreted as representing prior CMV infection. It is conceivable that a CMV na•ve patient could be incorrectly ascribed as CMV positive due to detectable passive antibody: by selecting a CMV positive donor in these circumstances, the patient is thus subjected to a significant risk of primary CMV infection. Transplant centres must remain vigilant of this possibility, and be aware of the CMV selection policy for blood components in referring hospitals. Pre-transfusion CMV status should be obtained in all potential transplant candidates and, in those who appear to seroconvert, CMV IgM and DNA should be considered as indicators of recent seroconversion. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
- Published
- 2014
12. An early computed tomography-guided antifungal treatment strategy is safe and efficacious in patients undergoing chemotherapy for high-risk acute leukemia
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Fiona L Dignan, Gareth J. Morgan, Faith E. Davies, Mark Ethell, Michael N. Potter, Unell Riley, Steve O. Evans, Bronwen E. Shaw, and Kabir Mohammed
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Antifungal ,Cancer Research ,medicine.medical_specialty ,Antifungal Agents ,medicine.drug_class ,medicine.medical_treatment ,Antineoplastic Agents ,Computed tomography ,Biology ,High Risk Acute Leukemia ,medicine ,Humans ,In patient ,Fungemia ,Chemotherapy ,medicine.diagnostic_test ,Hematology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Prognosis ,medicine.disease ,Surgery ,Leukemia, Myeloid, Acute ,Tomography x ray computed ,Oncology ,Treatment strategy ,Radiology ,Tomography, X-Ray Computed - Published
- 2011
13. Systemic candidiasis with candida vasculitis due to Candida kruzei in a patient with acute myeloid leukaemia
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PS Mortimer, Unell Riley, Jennifer Treleaven, Andrew Wotherspoon, ML Smith, RK Gregory, and R. L. Powles
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Male ,Vasculitis ,medicine.medical_specialty ,Antifungal Agents ,Itraconazole ,Gastroenterology ,Internal medicine ,Candida krusei ,Amphotericin B ,medicine ,Humans ,Mycosis ,Transplantation ,Drug Carriers ,biology ,business.industry ,Vascular disease ,Candidiasis ,Induction chemotherapy ,Hematology ,Middle Aged ,Triazoles ,medicine.disease ,biology.organism_classification ,Leukemia, Myeloid ,Immunology ,Chemoprophylaxis ,Acute Disease ,Liposomes ,Systemic candidiasis ,business ,medicine.drug - Abstract
Candida kruzei-related systemic infections are increasing in frequency, particularly in patients receiving prophylaxis with antifungal triazoles. A Caucasian male with newly diagnosed acute myeloid leukaemia (AML M1) developed severe and persistent fever associated with a micropustular eruption scattered over the trunk and limbs during induction chemotherapy. Blood cultures grew Candida kruzei, and biopsies of the skin lesions revealed a candida vasculitis. He responded to high doses of liposomal amphotericin B and was discharged well from hospital.
- Published
- 1999
14. An Early CT-Diagnosis Based Treatment Strategy for Invasive Fungal Infection in Allogeneic Transplant Recipients Using Caspofungin First Line: An Effective Strategy with Low Mortality
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Faith E. Davies, Mark Ethell, Michael Potter, Gareth J. Morgan, Stephen O Evans, Unell Riley, Fiona L Dignan, Bronwen E. Shaw, Claire Dearden, and Jennifer Treleaven
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Voriconazole ,medicine.medical_specialty ,Itraconazole ,business.industry ,Standard treatment ,Immunology ,Cell Biology ,Hematology ,Aspergillosis ,medicine.disease ,Biochemistry ,Surgery ,Transplantation ,chemistry.chemical_compound ,chemistry ,Internal medicine ,medicine ,Absolute neutrophil count ,Caspofungin ,business ,Febrile neutropenia ,medicine.drug - Abstract
Empirical antifungal therapy is the standard treatment in allogeneic transplant patients who have persistent febrile neutropenia. This approach can be associated with increased cost, toxicity and breakthrough infections. There are limited reports to date of strategies for the early diagnosis of invasive fungal infection (IFI). These include either invasive investigations or serum testing. (Oshima K et al, J Antimicrobial Chemother2007 Aug; 60(2): 350–5, Maertens J et al, Clin Infect Dis2005; 41:1242–50). To our knowledge, there are no reports to date of treatment strategies based only on high resolution computerised tomography (HRCT) scans. We used a CT-diagnosis based treatment strategy for early invasive aspergillosis in 99 consecutive patients undergoing allogeneic transplantation over a two year time period. A retrospective review of the electronic patient record, notes and drug charts was undertaken in all patients receiving an allogeneic transplant in our unit from 1st January 2006 to 31st December 2007. The study protocol was approved by the Royal Marsden Hospital audit committee. Patients received primary antifungal prophylaxis with itraconazole or secondary prophylaxis with voriconazole from day + 1. Patients had a HRCT scan performed if they had antibiotic resistant fever for > 72 hours. Parenteral antifungal treatment with caspofungin was commenced in patients with a positive HRCT result. Cavitation, air crescent sign and halo sign were classified as major changes. Nodules and new infiltrates including consolidation and effusions were classified as minor changes. Serum testing was not used due to the possibility of false positive results with tazobactampiperacillin antimicrobials and low sensitivity in patients receiving mould active azoles as prophylaxis. Neutropenic fever developed in 89/99 patients (90%). Fifty-four percent (53/99) of patients developed antibiotic resistant fever for > 72 hours and would have received parenteral antifungal treatment if an empiric strategy had been used. The HRCT-based strategy reduced the use of parenteral antifungal treatment to 17% of patients (17/99). Four of these patients had engrafted (absolute neutrophil count >0.5x109 cells/L for 3 days) at time of commencing caspofungin following a period of persistent neutropenic fever. Fifteen patients had a positive HRCT scan and 2 were treated empirically until a HRCT could be performed. The remaining 36/53 patients (68%) did not receive antifungal treatment although they would have met criteria for standard empirical therapy. Our nonempiric strategy reduced the use of parenteral antifungal treatment from 54% to 17% of allogeneic transplant patients. These findings represent a 68% reduction in use of parenteral antifungal agents Caspofungin (70mg once daily IV on day 1 and 50mg once daily IV thereafter) was given for a median of 13 days (3–34 days) and 11 patients responded to treatment. Six patients required second line antifungal therapy. Only one patient died from IFI after 100 days of follow-up. No patients had to stop caspofungin due to toxicity. Three of the 36 patients who did not receive initial antifungal treatment went on to receive empiric caspofungin within 100 days. One of these 3 patients died of enterococcal septicaemia. The other 2 patients recovered. None of this group had probable or proven IFI. During the extended follow-up period of 3–27 months (median 13 months) only 3/99 patients (3%) died of IFI. These results suggest that this non-empiric strategy of parenteral antifungal treatment based on HRCT scanning is feasible and may help to reduce toxicity, cost and breakthrough infections associated with the use of antifungal agents. Caspofungin may be a useful first line agent in this setting. A randomised controlled trial is warranted to further evaluate these results.
- Published
- 2008
15. High Dose Methylprednisolone and Rituximab Is an Effective Therapy in Advanced Refractory Chronic Lymphocytic Leukaemia Resistant to Fludarabine Therapy
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Steve O. Evans, Pamala Kanagasabapathy, Daniel Catovsky, Samar Kulkarni, M. Dungarwalla, Unell Riley, Gareth J. Morgan, Estella Matutes, and Claire Dearden
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medicine.medical_specialty ,Cytopenia ,business.industry ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Haemolysis ,Biochemistry ,Gastroenterology ,Fludarabine ,Surgery ,Refractory ,hemic and lymphatic diseases ,Internal medicine ,Medicine ,Alemtuzumab ,Rituximab ,Progression-free survival ,Stage (cooking) ,business ,medicine.drug - Abstract
The management of refractory advanced chronic lymphocytic leukaemia (CLL) continues to pose a considerable challenge to the clinician. CLL patients who are refractory or become resistant to fludarabine containing regimens currently have a poor prognosis. High dose methylprednisolone (HDMP) has been shown to be an effective therapeutic option in patients who are resistant to fludarabine particularly those with bulky lymphadenopathy or refractory cytopenias who are unsuitable for alemtuzumab therapy. We have used HDMP in combination with the anti-CD20 monoclonal antibody, Rituximab, to treat 14 patients with advanced refractory CLL. Eight of fourteen patients were male. The median age was 62.5 years (range 30–71). Twelve patients had bulky lymphadenopathy with nodal masses greater than 5 centimetres in diameter. Nine patients had Binet stage C and the remainder were stage B. Autoimmune manifestations were present in five of the patients, and in one of them fludarabine therapy was contraindicated due to active autoimmune haemolysis. FISH analysis was performed to detect 17p, 11q and 13q deletions and showed 11q23 deletions in five patients. The overall response rate was 93% with a median progression free survival (PFS) of seven months. Two patients achieved a CR, another a nodular PR and 10 patients had a PR. Responses were seen in all 4 patients who had not responded to alemtuzumab as a single agent. Only one patient failed to respond. The median survival was 20 months. All five patients with 11q23 deletions responded, and the mean progression free survival in this subgroup was 10.5 months. These results compare extremely favourably with our own previous study (Thornton et al, 1998) that used HDMP alone in the management of advanced/refractory CLL where only 43% of patients responded and no patients achieved a CR. We have demonstrated that the combination of HDMP with rituximab is more effective than HDMP alone (p
- Published
- 2007
16. Parainfluenza Virus Type 3 Post Stem Cell Transplant: High Prevalence but Low Mortality
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David Cunningham, Caroline L. Alvares, Jennifer Treleavan, Mark Ethell, Fiona L Dignan, Unell Riley, and Michael Potter
- Subjects
education.field_of_study ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Ribavirin ,Incidence (epidemiology) ,Immunology ,Population ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Post-transplant lymphoproliferative disorder ,Surgery ,Transplantation ,chemistry.chemical_compound ,chemistry ,Lower respiratory tract infection ,Internal medicine ,medicine ,education ,business ,Cause of death - Abstract
Parainfluenza virus type 3 (PIV 3) is a well recognised cause of respiratory illness after stem cell transplant (SCT) with an estimated incidence of 2–7%.(Wendt et al. N Engl J Med1992; 326: 921–926, Nichols et al. Blood2001; 98: 573–578). Persistently high mortality rates have been documented in this population. The largest series to date reported 75% mortality from PIV 3 lower respiratory tract infection.(Nichols et al). Treatment options are limited. There are anecdotal reports of successful use of ribavirin treatment but no randomised controlled trials have been undertaken.We undertook a retrospective review of 23 cases of PIV 3 occurring in adult SCT recipients over a 12 month period. A total of 145 patients had received a SCT in the same time period and 20 developed PIV3 infection (13.8%). The frequency of infection was 36.1% (13 of 36) in matched unrelated donor SCT recipients, 23.8% (5 of 21) in sibling allogenic SCT recipients and only 2.3% (2of 88) in autologous transplant recipients. Fourteen patients had received Campath 1-H as part of their conditioning regimen. The remaining three PIV 3 cases had a transplant date prior to the 12 month period. The median time from transplant to PIV 3 diagnosis was 54 days (range −7 to 2037 days). Only 6 cases were inpatients at diagnosis. Seventeen cases were outpatient or community acquired despite standard infection control procedures. Cases were identified by nasopharyngeal aspirate taken at the first sign of coryzal symptoms. Immunofluorescence (IF) identified PIV 3 in 13 patients and the virus was cultured in the remaining 10 cases. Eleven patients developed only upper respiratory tract symptoms and all survived. Lower respiratory tract symptoms and signs developed in 12 patients, of which 8 had a new infiltrate on chest X-ray. Four patients required invasive ventilation and one required non-invasive ventilation. Overall mortality at 30 days from PIV3 diagnosis was 4% (1 of 23). Three patients died in total but PIV 3 was not believed to be the primary cause of death in any of these patients. Autopsy confirmed post transplant lymphoproliferative disorder in one patient. The second case had septicaemia from a multiresistant coliform. Bronchoscopy in the remaining patient revealed invasive aspergillosis but IF and culture were negative for PIV 3. Early ribavirin treatment was administered in 8 patients. The primary indication for ribavirin treatment was lower respiratory tract infection. Six cases received aerosolised treatment, one intravenous and one patient received both aerosolised and IV therapy. Only one patient who received ribavirin treatment died. These results suggest a higher prevalence of PIV 3 but lower mortality than previously documented particularly in allogenic transplant recipients. We propose that the high prevalence reflects our unit policy of active surveillance for respiratory viruses and the difficulty in preventing transmission of PIV 3 especially in the outpatient setting. Ribavirin treatment may improve outcome in patients with lower respiratory tract infection but is not required in all patients with PIV 3 infection.
- Published
- 2005
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