Long-lived immunity to canine core vaccine antigens in UK dogs as assessed by an in-practice test kit.

OBJECTIVES: To determine the utility of an in-practice test kit to detect protective serum antibody against canine distemper virus, canine adenovirus and canine parvovirus type 2 in a sample of the UK dog population. MATERIALS AND METHODS: Serum samples from 486 dogs, last vaccinated between less than 1 month and 124 months previously, were tested with the VacciCheck™ test kit for protective antibodies against distemper, adenovirus and parvovirus type 2. RESULTS: A high proportion of the dogs tested (93·6%) had protective antibody against all three of the core vaccine antigens: 95·7% of the dogs were seropositive against canine distemper virus, 97·3% against canine adenovirus and 98·5% against canine parvovirus type 2. The small number of dogs that were seronegative for one or more of the antigens (n = 31) may have had waning of previous serum antibody or may have been rare genetic non-responders to that specific antigen. CLINICAL SIGNIFICANCE: UK veterinarians can be reassured that triennial revaccination of adult dogs with core vaccines provides long-lived protective immunity. In-practice serological test kits are a valuable tool for informing decision-making about canine core revaccination.

Graphene gas sensing using a non-contact microwave method.

We report a non-contact CVD graphene gas sensing method that utilises a high Q microwave dielectric resonator perturbation technique. A graphene sample is coupled to the evanescent field of a dielectric resonator whereupon nitrogen dioxide (NO2), a p-doping gas, is detected by monitoring the change in the linewidth and frequency of the resonant mode. The resonant peak shape is dependent on the number of carriers in the graphene sheet. Therefore, the linewidth perturbation can be converted to a measurement of the graphene sheet resistance. To demonstrate the strength of this technique, sensor response curves for NO2 at different concentrations and temperatures are measured showing sub ppm sensitivity. This technique eliminates interactions between the trace gas and metal contacts that otherwise effect the sensor response of the graphene device.

Allogeneic stem cell transplantation for refractory acute myeloid leukemia in pediatric patients: the UK experience.

We report outcomes for 44 children who underwent stem cell transplantation (SCT) for refractory AML in the UK between 2000 and 2012. Median age at SCT was 11.5 years. Twenty-three patients had primary refractory and 21 relapsed refractory AML. Refractory disease was confirmed by cytogenetics/molecular genetics in 24 cases. Median follow-up of the whole cohort is 6.8 years (2.1-14.9 years). Thirty patients (68%) achieved a CR following SCT. Transplant-related mortality at 1 year was 18%. Acute GVHD incidence was 52% (grade ⩾III 19%), chronic 7%. Relapse was the major cause of treatment failure and occurred in 32% of patients at a median of 61 days post SCT. Five-year overall survival and leukemia-free survival (LFS) were 43% (95% CI 31-61%). All patients with favorable cytogenetics (n=6) are alive in CR. Outcomes in patients with primary refractory disease were equivalent to those with relapsed refractory AML. Blast percentage ⩽30% in the BM pre-SCT, myeloablative conditioning and acute GVHD proved to be favorable prognostic features. We could stratify patients according to age ⩾10 years and >30% blasts in BM pre-SCT. Patients with none/one of these risk factors were highly salvageable (5 years LFS 53%) whereas those with both factors had a very poor prognosis (5 years LFS 10%). This may facilitate decision making on whether it is appropriate to consider transplant in such patients.

Impact of pre-transplant co-morbidities on outcome after alemtuzumab-based reduced intensity conditioning allo-SCT in elderly patients: a British Society of Blood and Marrow Transplantation study.

The advent of reduced intensity conditioning (RIC) regimens has permitted the extension of allo-SCT to selected patients into their eighth decade but GVHD remains a major cause of morbidity and mortality. Alemtuzumab is increasingly used to reduce the risk of severe GVHD, but there are concerns that T-cell depletion may compromise outcome particularly in older patients. We therefore studied the impact of pre-transplant factors on the outcome of 187 patients with a haematological malignancy over the age of 60 transplanted using an alemtuzumab-based RIC regimen of whom co-morbidity scoring was possible in 169. Of the patients, 120 had a haematopoietic cell transplantation co-morbidity index (HCT-CI) of 0 or 1 and 49 had a score of 2 or more. The 5-year OS was 33%. In multivariable analysis, OS was determined by co-morbidity score (P=0.001) and disease status at transplant (P=0.004) but not by patient age. Non-relapse mortality was determined by co-morbidity score (P=0.001). Two-year OS for patients with a HCT-CI of 0-1 was 59 versus 6% for patients with a higher score. Alemtuzumab-based RIC allografts can be delivered safely in patients aged over 60 but co-morbidity scoring is mandatory to identify patients who will benefit.

Retrospective study of alemtuzumab vs ATG-based conditioning without irradiation for unrelated and matched sibling donor transplants in acquired severe aplastic anemia: a study from the British Society for Blood and Marrow Transplantation.

This retrospective national study compared the use of alemtuzumab-based conditioning regimens for hematopoietic SCT (HSCT) in acquired severe aplastic anemia with antithymocyte globulin (ATG)-based regimens. One hundred patients received alemtuzumab and 55 ATG-based regimens. A matched sibling donor (MSD) was used in 87 (56%), matched unrelated donor (MUD) in 60 (39%) and other related or mismatched unrelated donor (UD) in 8 (5%) patients. Engraftment failure occurred in 9% of the alemtuzumab group and 11% of the ATG group. Five-year OS was 90% for the alemtuzumab and 79% for the ATG groups, P=0.11. For UD HSCT, OS of patients was better when using alemtuzumab (88%) compared with ATG (57%), P=0.026, although smaller numbers of patients received ATG. Similar outcomes for MSD HSCT using alemtuzumab or ATG were seen (91% vs 85%, respectively, P=0.562). A lower risk of chronic GVHD (cGVHD) was observed in the alemtuzumab group (11% vs 26%, P=0.031). On multivariate analysis, use of BM as stem cell source was associated with better OS and EFS, and less acute and cGVHD; young age was associated with better EFS and lower risk of graft failure. This large study confirms successful avoidance of irradiation in the conditioning regimens for MUD HSCT patients.

Evidence for a GVL effect following reduced-intensity allo-SCT in ALL: a British Society of Blood and Marrow Transplantation study.

Myeloablative allo-SCT decreases relapse incidence (RI) in ALL. Reduced intensity conditioning (RIC) may extend allo-SCT to older and less fit patients. Sixty-nine ALL patients reported to the BSBMT underwent fludarabine-based RIC allo-SCT, 38 from unrelated donors (UD). Forty-four patients received alemtuzumab. ALL was in CR in 64 patients (93%). This was a second or third SCT in 23 patients. Two-year OS and PFS were 36% and 32%, respectively. In multivariate analysis male recipients demonstrated better OS and PFS (hazard ratio (HR) = 0.42, P = 0.008 and HR = 0.45, P = 0.012, respectively). Two-year TRM was 29%: higher with younger age (HR = 0.97/year, P = 0.041), female recipient (HR = 2.55, P = 0.049) and increasing grade of acute GVHD (HR = 1.87, P = 0.001). Two-year RI was 38% and was lower in patients with acute and chronic GVHD (HR = 0.62 per increasing grade, P = 0.035 and HR = 0.52, P = 0.025, respectively). Long-term ALL-free survival is achievable following fludarabine-based RIC allo-SCT. The association between GVHD and decreased RI suggests the presence of a GVL effect.

Markers of circulating tumour cells in the peripheral blood of patients with melanoma correlate with disease recurrence and progression.

BACKGROUND: Multimarker quantitative real-time polymerase chain reaction (qRT-PCR) represents an effective method for detecting circulating tumour cells in the peripheral blood of patients with melanoma. OBJECTIVES: To investigate whether the phenotype of circulating melanoma cells represents a useful indicator of disease stage, recurrence and treatment efficacy. METHODS: Peripheral blood was collected from 230 patients with melanoma and 152 healthy controls over a period of 3years and 9months. Clinical data and blood samples were collected from patients with primary melanoma (early stages, 0-II, n=154) and metastatic melanoma (late stages, III-IV, n=76). Each specimen was examined by qRT-PCR analysis for the expression of five markers: MLANA, ABCB5, TGFß2, PAX3d and MCAM. RESULTS: In total, 212 of the patients with melanoma (92%) expressed markers in their peripheral blood. Two markers, MLANA and ABCB5, had the greatest prognostic value, and were identified as statistically significant among patients who experienced disease recurrence within our study period, being expressed in 45% (MLANA) and 49% (ABCB5) of patients with recurrence (P=0·001 and P=0·031, respectively). For patients administered nonsurgical treatments, MCAM expression correlated with poor treatment outcome. CONCLUSIONS: Circulating tumour cells were detectable at all stages of disease and long after surgical treatment, even when patients were considered disease free. Specifically, expression of ABCB5 and MLANA had significant prognostic value in inferring disease recurrence, while MCAM expression was associated with poor patient outcome after treatment, confirming multimarker qRT-PCR as a potential technique for monitoring disease status.

The clinical features and outcome of 2009 H1N1 influenza infection in allo-SCT patients: a British Society of Blood and Marrow Transplantation study.

The clinical course of 2009 H1N1 influenza in Allo-SCT patients is unknown. Data were collected in the UK from October 2009 to April 2010 on laboratory-confirmed cases of H1N1 influenza in Allo-SCT recipients. H1N1 infection was diagnosed in 60 patients, median age 42 years, at a median of 10 months post-SCT. Twenty-one patients (35%) developed pneumonia and nine (15%) required admission to intensive care units. Actuarial mortality was 7% at 28 days and 19% 4 months post-diagnosis of 2009 H1N1 influenza. Increasing age and pre-existing lung disease were risk factors for pneumonia (P=0.006 and 0.037, respectively); older age was a risk factor for death (P=0.012). Morbidity and mortality from 2009 H1N1 influenza in SCT patients exceeds that of immunocompetent patients, but parallels that in other critically ill hospitalised cohorts; the elderly and those with chronic pulmonary disease are at greatest risk.

The management of complex acetabular fractures in the elderly with fracture fixation and primary total hip replacement.

Osteoporosis and associated fragility fractures are an increasing problem across the developed world. The elderly osteoporotic acetabular fracture presents a difficult problem due to high failure rates and poor outcomes. Standard management may or may not include fracture fixation, but generally includes a period of protected weight bearing, even if total hip replacement has been performed. We present a series of 12 cases of complex osteoporotic acetabular fractures in elderly patients, managed successfully using primary fracture fixation and total hip replacement with trabecular metal technology. Immediate weight bearing was allowed in all cases, few complications have been seen, and no component migration has been identified in any case.

Minimally invasive partial or total nephrectomy in children: a comparison between transperitoneal and retroperitoneal approaches.

INTRODUCTION AND OBJECTIVES: We present data from a single surgeon experience of paediatric transperitoneal (TP) and retroperitoneal (RP) minimally invasive approaches for partial (PN) and total nephrectomy (TN). METHODS: A retrospective review was conducted in the patients undergoing nephrectomy between 2003 and 2008. Patients were divided depending on PN or TN and the approach (RP or TP). Primary outcome was the need to convert to an open procedure. Secondary outcomes included operation time, length of stay (LOS) and complications. Statistical analysis included Fisher's exact test. RESULTS: 68 patients underwent minimally invasive TN/PN, 49 (72%) RP versus 19 (28%) TP. There were no differences between the groups in terms of sex, age, pathology, LOS, complication rate and conversion rate. Neither group recorded mortality. Conversion occurred because of difficult anatomy or the kidney size rather than an adverse event. Overall, there was no difference in operative time between the RP and TP. This was also the case for TN only. However, the PN subgroup demonstrated a decreased operative time with RP (p = 0.049) possibly due to better anatomical delineation. There were no complications. CONCLUSIONS: Minimally invasive TN or PN can be performed via retroperitoneal or transperitoneal routes with minimal morbidity. With training, PN via retroperitoneal approach can be achieved with significantly reduced operative time.

Partial nephroureterectomy in a duplex system in children: the need for additional bladder procedures.

INTRODUCTION AND OBJECTIVES: Heminephroureterectomy (HN) is our treatment of choice in a duplex system with non-functioning moiety. We examined the need for endoscopic incision (EI)/bladder reconstructive surgery (BRS) and whether ureteroceles and/or vesicoureteric reflux (VUR) influenced management options. METHODS: Retrospective study of patients undergoing HN by a single surgeon (2003-2008). Patients were classified according to the presence (Group 1) or absence (Group 2) of ureterocele. The groups were subdivided with coexisting dilating VUR (a) or not (b). Statistical analysis included Fisher's exact test. RESULTS: Thirty-one children were identified. Seventeen (54.8%) had ureterocele (Group 1) and 14 patients had no ureterocele (Group 2). Group 1 had eight with VUR (1a) and nine without (1b). Group 2 had seven with VUR (2a) and seven without (2b). Significantly more patients with ureterocele required EI/BRS (p = 0.006). Five (29%) in Group 1 required BRS versus none in Group 2 (p = 0.04). Six (75%) in Group 1a underwent EI/BRS versus three (33%) in Group 1b (p = 0.15). Significantly more in Group 1a required EI prior to HN versus Group 1b (p = 0.04). Similar numbers of patients required BRS in Groups 1a and 1b (p = 0.61). CONCLUSIONS: In the absence of ureterocele, there is minimal likelihood of requiring surgery apart from HN, independent of VUR. Presence of ureterocele is an indicator for additional procedure within the bladder. There is a higher incidence of EI when ureterocele co-exists with dilating VUR.

Genetic factors in metastatic progression of cutaneous melanoma: the future role of circulating melanoma cells in prognosis and management.

The greatest potential for improvement of outcome for patients with Cutaneous Malignant Melanoma lies in the prevention of systemic metastasis. Despite extensive investigation, current prognostic indicators either alone or in combination, although related to melanoma progression, are not sufficient to accurately predict the pattern of progression and outcome for any individual patient. Metastasis related death has been recorded in patients initially diagnosed with early stage tumour as well as in patients many years after initial tumour removal. The trouble finding a predictable pattern in the puzzle of melanoma progression may be linked to the fact that most of the material studied for prognosis is either, cutaneous primaries or metastatic deposits, rather than the melanoma cells in the circulatory system which are responsible for disease progression. In this review article we discuss the potential use of circulating tumour cell (CTC) detection and quantification for identifying patients at risk of metastatic deposits. We also discuss current therapies for the treatment of metastatic melanoma and analyse how CTCs may be used to evaluate the effectiveness of current therapies and to pinpoint patients who require further treatment.

Outcomes of acetabular fracture fixation with ten years' follow-up.

We report the outcome of 161 of 257 surgically fixed acetabular fractures. The operations were undertaken between 1989 and 1998 and the patients were followed for a minimum of ten years. Anthropometric data, fracture pattern, time to surgery, associated injuries, surgical approach, complications and outcome were recorded. Modified Merle D'Aubigné score and Matta radiological scoring systems were used as outcome measures. We observed simple fractures in 108 patients (42%) and associated fractures in 149 (58%). The result was excellent in 75 patients (47%), good in 41 (25%), fair in 12 (7%) and poor in 33 (20%). Poor prognostic factors included increasing age, delay to surgery, quality of reduction and some fracture patterns. Complications were common in the medium- to long-term and functional outcome was variable. The gold-standard treatment for displaced acetabular fractures remains open reduction and internal fixation performed in dedicated units by specialist surgeons as soon as possible.

Open reduction and internal fixation of a traumatic diastasis of the pubic symphysis: one-year radiological and functional outcomes.

The aim of this study was to review the number of patients operated on for traumatic disruption of the pubic symphysis who developed radiological signs of movement of the anterior pelvic metalwork during the first post-operative year, and to determine whether this had clinical implications. A consecutive series of 49 patients undergoing internal fixation of a traumatic diastasis of the pubic symphysis were studied. All underwent anterior fixation of the diastasis, which was frequently combined with posterior pelvic fixation. The fractures were divided into groups using the Young and Burgess classification for pelvic ring fractures. The different combinations of anterior and posterior fixation adopted to stabilise the fractures and the type of movement of the metalwork which was observed were analysed and related to functional outcome during the first post-operative year. In 15 patients the radiographs showed movement of the anterior metalwork, with broken or mobile screws or plates, and in six there were signs of a recurrent diastasis. In this group, four patients required revision surgery; three with anterior fixation and one with removal of anterior pelvic metalwork; the remaining 11 functioned as well as the rest of the study group. We conclude that radiological signs of movement in the anterior pelvic metalwork, albeit common, are not in themselves an indication for revision surgery.

The outcome of high-dose chemotherapy and auto-SCT in patients with multiple myeloma: a UK/Ireland and European benchmarking comparative analysis.

Auto-SCT is the standard first-line consolidative therapy in patients with multiple myeloma (MM). We performed a national benchmarking outcome analysis for patients with MM who underwent a single auto-SCT in 1999 and 2005. They were identified from the British Society of Blood and Marrow Transplantation (BSBMT) (n=211 and n=453) and EBMT (n=1311 and n=1978) registries. An improvement in Day+100 and D+365 non-relapsed mortality (NRM) was shown between years 1999 and 2005 (P=0.0495). The 4-year relapse rate (RR) was significantly higher in 2005 (P=0.0003) and was associated with a shorter time to next treatment (TTNT) (P=0.025). The 4-year PFS was significantly lower in 2005 (P=0.0012), with the year of auto-SCT (P=0.001) and status at auto-SCT (P=0.02) being independently significant. The 4-year OS was similar between the year cohorts (P=0.266). In the 'benchmarking' comparison, the European Group for Blood and Marrow Transplantation (EBMT) 1999 cohort demonstrated the best PFS, although no year-of-transplant effect could be demonstrated on the 4-year OS rates (P=0.760). An improvement in supportive care resulting in reduced NRM is evident between the decades. The main cause of treatment failure remains disease progression. The similarity in OS between the years may reflect the introduction of novel agents in salvage therapy. The reduced PFS in 2005 is as yet not fully explained, but may represent recent disease response criterion standardization.

The role of allogeneic SCT in primary myelofibrosis: a British Society for Blood and Marrow Transplantation study.

Fifty-one patients with primary myelofibrosis (PMF) received allogeneic haematopoietic stem cell transplants from related (n=33) or unrelated (n=18) donors. Twenty-seven patients, 19-54 years old, were prepared with myeloablative regimens including CY plus BU (n=4) or TBI (n=23). Twenty-four patients, 40-64 years old, received reduced-intensity conditioning (RIC) regimens. All RIC regimens contained fludarabine, combined with melphalan (n=19) or BU (n=5), and alemtuzumab or anti-thymocyte globulin (ATG) in the majority (n=19). Four patients (17%) in the RIC group had primary graft failure. Previous splenectomy reduced time to engraftment in the RIC group (13 versus 20 days; P=0.008). For MA and RIC groups, respectively, at 3 years, overall survival rates were 44 and 31% (P=0.67), progression-free survival 44 and 24% (P=0.87), and actuarial relapse rates 15 and 46% (P=0.06). Non-relapse mortality at 3 years was 41% for the myeloablative and 32% for the RIC group. Acute GVHD occurred in 29 and 38% of patients in the myeloablative and RIC groups, respectively. Extensive chronic GVHD developed in 30 and 35% of evaluable patients, respectively.

Alemtuzumab markedly reduces chronic GVHD without affecting overall survival in reduced-intensity conditioning sibling allo-SCT for adults with AML.

By retrospective analysis of 88 patients from the British Society of Blood and Marrow Transplantation registry, we investigated the effect of in vivo T-cell depletion in HLA-identical sibling reduced-intensity conditioning (RIC) allografts for adult AML by comparing patients who received alemtuzumab with those without alemtuzumab conditioning. Both groups were equivalent for age, sex, karyotype and disease status at transplant. With a median follow-up of 27 months (3-72 months) and 48 months (7-72 months), the 2- and 5-year overall survival, with or without alemtuzumab, is 60 and 60% (P=0.80) and 61 and 53%, respectively (P=0.85). The 2-year non-relapse mortality is 12% with alemtuzumab, and 17% without alemtuzumab (P=0.49). The 2-year relapse rate is 35% with alemtuzumab compared with 19% without alemtuzumab (P=0.28). Grades II-IV acute GVHD occurred in 22% (8/37) without alemtuzumab compared with 14% (7/51) given alemtuzumab (P=0.25). Extensive chronic GVHD occurred in 47% (14/30) not given alemtuzumab compared with 4% (2/45) who were given alemtuzumab (P=0.001). Among evaluable patients, the risk of infections was higher in those treated with alemtuzumab compared with those not treated with alemtuzumab (79 vs 57%, respectively, P=0.02). In conclusion, alemtuzumab has a beneficial effect by reducing chronic GVHD without affecting overall survival. Further studies are warranted before alemtuzumab can be recommended as standard in RIC allografts for AML.