Publications by authors named "Simon D J Gibbs"

22 Publications

  • Page 1 of 1

Australian and New Zealand consensus statement on the management of lymphoma, chronic lymphocytic leukaemia and myeloma during the COVID-19 pandemic.

Intern Med J 2020 06 15;50(6):667-679. Epub 2020 May 15.

Department of Haematology, St Vincent's Hospital, Sydney, New South Wales, Australia.

The COVID-19 pandemic poses a unique challenge to the care of patients with haematological malignancies. Viral pneumonia is known to cause disproportionately severe disease in patients with cancer, and patients with lymphoma, myeloma and chronic lymphocytic leukaemia are likely to be at particular risk of severe disease related to COVID-19. This statement has been developed by consensus among authors from Australia and New Zealand. We aim to provide supportive guidance to clinicians making individual patient decisions during the COVID-19 pandemic, in particular during periods that access to healthcare resources may be limited. General recommendations include those to minimise patient exposure to COVID-19, including the use of telehealth, avoidance of non-essential visits and minimisation of time spent by patients in infusion suites and other clinical areas. This statement also provides recommendations where appropriate in assessing indications for therapy, reducing therapy-associated immunosuppression and reducing healthcare utilisation in patients with specific haematological malignancies during the COVID-19 pandemic. Specific decisions regarding therapy of haematological malignancies will need to be individualised, based on disease risk, risks of immunosuppression, rates of community transmission of COVID-19 and available local healthcare resources.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/imj.14859DOI Listing
June 2020

Lenalidomide and dexamethasone for systemic AL amyloidosis following prior treatment with thalidomide or bortezomib regimens.

Br J Haematol 2014 Sep 13;166(6):842-8. Epub 2014 Jun 13.

National Amyloidosis Centre, University College London Medical School, Royal Free Hospital Campus, London, UK.

The outcomes and responses to treatment remain poorly studied among patients with systemic AL amyloidosis who require further treatment following prior novel agent-based therapy. We report here treatment with lenalidomide-dexamethasone in 84 AL amyloidosis patients with relapsed/refractory clonal disease following prior treatment with thalidomide (76%) and/or bortezomib (68%). On an intention-to-treat (ITT) basis, the overall haematological response rate was 61%, including 20% complete responses. The median overall survival (OS) has not been reached; 2-year OS and progression-free survival (PFS) was 84% and 73%, respectively. Achieving a free light chain (FLC) response was an independent good prognostic factor for OS in multivariate analysis. There was no impact of prior thalidomide or bortezomib therapy on response rate, OS or PFS. 16% achieved an organ response at 6 months, with a marked improvement in organ responses in patients on long term therapy (median duration 11 months) and 55% achieving renal responses by 18 months. Lenalidomide/dexamethasone therapy achieves good haematological responses in patients with AL amyloidosis with relapsed/refractory clonal disease. The rate of renal responses among patients who received prolonged treatment was unexpectedly high, raising the possibility that immunomodulatory effects of lenalidomide therapy might enhance the otherwise slow natural regression of amyloid deposits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bjh.12973DOI Listing
September 2014

A rare case of localised oral amyloid of the labial mucosa.

Br J Oral Maxillofac Surg 2014 Apr 18;52(4):e24-5. Epub 2014 Feb 18.

Oral and Maxillofacial Surgery, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK.

Amyloidosis is often a systemic process, and localised oral amyloidosis is rare. We present the case of a young woman with amyloid deposition in the labial mucosa of her lower lip. Systemic involvement was excluded by comprehensive assessment at the UK Amyloidosis Centre. Of 40 previously reported cases of localised oral amyloidosis we found only one that was limited to the labial mucosa.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bjoms.2014.01.014DOI Listing
April 2014

CMR-based differentiation of AL and ATTR cardiac amyloidosis.

JACC Cardiovasc Imaging 2014 Feb 8;7(2):133-42. Epub 2014 Jan 8.

Cardiovascular Sciences, St. George's University of London, London, United Kingdom.

Objectives: This study was devised to describe the different cardiac magnetic resonance (CMR) appearances in light chain amyloid (AL) and transthyretin-related amyloidosis (ATTR).

Background: CMR is increasingly used to investigate patients with suspected amyloidosis. Global subendocardial late gadolinium enhancement (LGE) has been reported as typical of AL amyloidosis, whereas different patterns have been noted in ATTR amyloidosis.

Methods: We performed de novo analyses on original DICOM magnetic resonance imaging in 46 patients with cardiac AL amyloidosis and 51 patients with ATTR type who had been referred to a specialist amyloidosis center between 2007 and 2012 after CMR. Histological examination was performed in all cases, with immunohistochemistry, to confirm systemic amyloidosis.

Results: Patients' median age was 68 ± 10 years, and 74% were male. Left ventricular mass was markedly increased in ATTR amyloidosis (228 g [202 to 267 g]) compared with AL type (167 g [137 to 191 g]) (p < 0.001). LGE was detected in all but 1 cardiac amyloidosis patient (AL type) and was substantially more extensive in ATTR compared with AL amyloidosis. Ninety percent of ATTR patients demonstrated transmural LGE compared with 37% of AL patients (p < 0.001). Right ventricular LGE was apparent in all ATTR patients but in only 33 AL patients (72%) (p < 0.001). Despite these findings, survival was significantly better in cardiac ATTR amyloidosis compared with AL type. We derived an LGE scoring system (Query Amyloid Late Enhancement) that independently differentiated ATTR from AL amyloidosis and, when incorporated into a logistic regression model with age and wall thickness, detected ATTR type with 87% sensitivity and 96% specificity.

Conclusions: Transmural patterns of LGE distinguished ATTR from AL cardiac amyloidosis with high accuracy in this real-world analysis of CMR. Precise diagnosis of cardiac amyloidosis is crucial given the role of chemotherapy in AL type and with novel therapies for ATTR type currently in development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcmg.2013.08.015DOI Listing
February 2014

Retinal microangiopathy as an initial manifestation of familial amyloid cardiomyopathy associated with transthyretin e89k mutation.

Retin Cases Brief Rep 2013 ;7(3):271-5

*Medical Retina Service, Moorfields Eye Hospital, London, United Kingdom; and †National Amyloidosis Centre, UCL Division of Medicine, Royal Free Hospital, London, United Kingdom.

Purpose: To report a rare case of transthyretin (TTR) familial amyloid cardiomyopathy with retinal microangiopathy and vitreous amyloid as the initial manifestation.

Methods: A 54-year-old woman presented with bilateral retinal microangiopathy, presumed idiopathic retinal vasculitis. She subsequently developed retinal ischemia associated vitreous hemorrhage and was treated with panretinal laser photocoagulation. Clinical eye signs remained stable for 6 years with the absence of overt inflammation. However, the patient developed chest pain and atrial flutter and underwent echocardiography, cardiac magnetic resonance imaging, and Tc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy to investigate possible cardiac amyloidosis. Sequencing of the TTR gene was conducted and a rectal biopsy performed for tissue diagnosis. A full neurologic screen was also conducted.

Results: Cardiac investigations were highly suggestive of an amyloid cardiomyopathy. The rectal biopsy stained positive for Congo red with demonstration of apple green birefringence, confirming amyloid, and immunostaining confirmed the TTR subtype. Gene sequencing revealed heterozygous TTR mutation encoding E89K variant. No significant neuropathy could be detected.

Conclusion: Amyloid should be considered as a masquerade diagnosis in cases of retinal microangiopathy, especially in the absence of inflammation. Liaising with physicians for systemic evaluation and TTR gene sequencing is essential for early diagnosis and management of this rare condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/ICB.0b013e31828eefa2DOI Listing
January 2015

Senile systemic amyloidosis: clinical features at presentation and outcome.

J Am Heart Assoc 2013 Apr 22;2(2):e000098. Epub 2013 Apr 22.

National Amyloidosis Centre, UCL Medical School, Royal Free Hospital, London, UK.

Background: Cardiac amyloidosis is a fatal disease whose prognosis and treatment rely on identification of the amyloid type. In our aging population transthyretin amyloidosis (ATTRwt) is common and must be differentiated from other amyloid types. We report the clinical presentation, natural history, and prognostic features of ATTRwt compared with cardiac-isolated AL amyloidosis and calculate the probability of disease diagnosis of ATTRwt from baseline factors.

Methods And Results: All patients with biopsy-proven ATTRwt (102 cases) and isolated cardiac AL (36 cases) seen from 2002 to 2011 at the UK National Amyloidosis Center were included. Median survival from the onset of symptoms was 6.07 years in the ATTRwt group and 1.7 years in the AL group. Positive troponin, a pacemaker, and increasing New York Heart Association (NYHA) class were associated with worse survival in ATTRwt patients on univariate analysis. All patients with isolated cardiac AL and 24.1% of patients with ATTRwt had evidence of a plasma cell dyscrasia. Older age and lower N-terminal pro-B-type natriuretic peptide (NT pro-BNP) were factors significantly associated with ATTRwt. Patients aged 70 years and younger with an NT pro-BNP <183 pmol/L were more likely to have ATTRwt, as were patients older than 70 years with an NT pro-BNP <1420 pmol/L.

Conclusions: Factors at baseline associated with a worse outcome in ATTRwt are positive troponin T, a pacemaker, and NYHA class IV symptoms. The age of the patient at diagnosis and NT pro-BNP level can aid in distinguishing ATTRwt from AL amyloidosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.113.000098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3647259PMC
April 2013

Systemic amyloidosis in England: an epidemiological study.

Br J Haematol 2013 May 11;161(4):525-32. Epub 2013 Mar 11.

Department of Medicine, UK National Amyloidosis Centre, Royal Free and University College Medical School, London, UK.

Epidemiological studies of systemic amyloidosis are scarce and the burden of disease in England has not previously been estimated. In 1999, the National Health Service commissioned the National Amyloidosis Centre (NAC) to provide a national clinical service for all patients with amyloidosis. Data for all individuals referred to the NAC is held on a comprehensive central database, and these were compared with English death certificate data for amyloidosis from 2000 to 2008, obtained from the Office of National Statistics. Amyloidosis was stated on death certificates of 2543 individuals, representing 0·58/1000 recorded deaths. During the same period, 1143 amyloidosis patients followed at the NAC died, 903 (79%) of whom had amyloidosis recorded on their death certificates. The estimated minimum incidence of systemic amyloidosis in the English population in 2008, based on new referrals to the NAC, was 0·4/100 000 population. The incidence peaked at age 60-79 years. Systemic AL amyloidosis was the most common type with an estimated minimum incidence of 0·3/100 000 population. Although there are various limitations to this study, the available data suggest the incidence of systemic amyloidosis in England exceeds 0·8/100 000 of the population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bjh.12286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296340PMC
May 2013

Inflammatory bowel disease and systemic AA amyloidosis.

Dig Dis Sci 2013 Jun 31;58(6):1689-97. Epub 2013 Jan 31.

Department of Medicine, Centre for Amyloidosis and Acute Phase Proteins, National Amyloidosis Centre, University College London, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK.

Background: Systemic AA amyloidosis is a recognised complication of inflammatory bowel disease. AA amyloidosis is a potential cause of end-stage renal failure and mortality but little is known of the natural history of this condition in inflammatory bowel disease.

Methods: We evaluated the clinical phenotype, disease progression and outcome amongst 26 patients with inflammatory bowel disease and AA amyloidosis followed prospectively at a single center between 1989 and 2010.

Results: Twenty-two patients had Crohn's disease and four had ulcerative colitis. Fistulae and abscesses occurred in ten cases, all of whom had Crohn's disease. Amyloidotic proteinuric renal dysfunction occurred in all of the cases. It resolved in five patients with well-controlled inflammation, but was progressive in all of the other patients. Fifteen patients reached end-stage renal disease after a median time of 6.3 years from development of renal dysfunction (by Kaplan-Meier estimate), six of whom subsequently proceeded to renal transplantation. There were five functioning grafts at census 0.8, 3.2, 4.2, 20.1 and 24.6 years after transplantation. One graft failed 14.5 years after renal transplantation because of amyloid recurrence in a patient with sustained chronic inflammatory activity.

Conclusions: AA amyloidosis remains a serious complication of both Crohn's disease and ulcerative colitis, and is characterized by proteinuric renal dysfunction that may resolve following suppression of inflammatory activity. Patient and graft survival are excellent in patients who undergo renal transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10620-012-2549-xDOI Listing
June 2013

Quantification of myocardial extracellular volume fraction in systemic AL amyloidosis: an equilibrium contrast cardiovascular magnetic resonance study.

Circ Cardiovasc Imaging 2013 Jan 28;6(1):34-9. Epub 2012 Nov 28.

The Heart Hospital, London, UK.

Background: Cardiac involvement predicts outcome in systemic AL amyloidosis and influences therapeutic options. Current methods of cardiac assessment do not quantify myocardial amyloid burden. We used equilibrium contrast cardiovascular magnetic resonance (EQ-CMR) to quantify the cardiac interstitial compartment, measured as myocardial extracellular volume (ECV) fraction, hypothesizing it would reflect amyloid burden.

Methods And Results: Sixty patients with systemic AL amyloidosis (65% men, median age 65 years) underwent conventional clinical cardiovascular magnetic resonance, including late enhancement, equilibrium contrast cardiovascular magnetic resonance, and clinical cardiac evaluation, including ECG, echocardiography, assays of N-terminal pro-brain natriuretic peptide and Troponin T, and functional assessment comprising the 6-minute walk test in ambulant individuals. Cardiac involvement in the amyloidosis patients was categorized as definite, probable, or none, suspected by conventional criteria. Findings were compared with 82 healthy controls. Mean ECV was significantly greater in patients than healthy controls (0.25 versus 0.40, P<0.001) and correlated with conventional criteria for characterizing the presence of cardiac involvement, the categories of none, probable, definite corresponding to ECV of 0.276 versus 0.342 versus 0.488, respectively (P<0.001). ECV was correlated with cardiac parameters by echocardiography (eg, Tissue Doppler Imaging [TDI] S-wave R=0.52, P<0.001) and conventional cardiovascular magnetic resonance (eg, indexed left ventricular mass R=0.56, P<0.001). There were also significant correlations with N-terminal pro-brain natriuretic peptide (R=0.69, P<0.001) and Troponin T (R=0.53, P=0.006). ECV was associated with smaller QRS voltages (R=0.57, P<0.001) and correlated with poorer performance in the 6-minute walk test (R=0.36, P=0.03).

Conclusions: Myocardial ECV measurement has potential to become the first noninvasive test to quantify cardiac amyloid burden.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCIMAGING.112.978627DOI Listing
January 2013

A prospective study of nutritional status in immunoglobulin light chain amyloidosis.

Haematologica 2013 Jan 14;98(1):136-40. Epub 2012 Sep 14.

National Amyloidosis Centre, Centre for Amyloidosis & Acute Phase Proteins, University College London, UK.

Weight loss is common in systemic immunoglobulin light chain amyloidosis but there are limited data on the impact of nutritional status on outcome. Using the Patient-Generated Subjective Global Assessment (PG-SGA) score, we prospectively examined nutritional status in 110 consecutive newly-diagnosed, treatment-naïve patients with immunoglobulin light chain amyloidosis attending the UK National Amyloidosis Centre. At study entry, 72 of 110 (66%) patients had a PG-SGA score of 4 or over, indicating malnutrition requiring specialist nutritional intervention. Number of amyloidotic organs, elevated alkaline phosphatase, presence of autonomic neuropathy and advanced Mayo disease stage were independently associated with poor nutritional status (P<0.05). Quality of life was substantially poorer among those with higher PG-SGA scores (P<0.001). Furthermore, PG-SGA score was a powerful independent predictor of patient survival (P=0.02). Malnutrition is prevalent and is associated with poor quality of life and reduced survival among patients with systemic immunoglobulin light chain amyloidosis. The PG-SGA score would be an appropriate tool to evaluate whether nutritional intervention could improve patient outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3324/haematol.2012.070359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533675PMC
January 2013

The electrocardiographic features associated with cardiac amyloidosis of variant transthyretin isoleucine 122 type in Afro-Caribbean patients.

Am Heart J 2012 Jul;164(1):72-9

National Amyloidosis Centre, UCL Medical School, Royal Free Campus, London, United Kingdom.

Background: About 4% of African Americans possess the isoleucine 122 (V122I) variant of transthyretin, associated with cardiac amyloidosis beyond ages of 55 to 60 years. Transthyretin amyloidosis associated with variant V122I (ATTR V122I) is likely to be an important cause of heart failure in Afro-Caribbean populations, but the high prevalence of left ventricular hypertrophy (LVH) and lack of awareness of this genetic disorder pose diagnostic hurdles. We report the electrocardiographic (ECG) features of ATTR V122I in the largest clinical series to date.

Methods: Patients with ATTR V122I were identified in collaboration with the UK National Amyloidosis Centre. The ECG at presentation was assessed for cardiac rhythm, axis, and voltage complex size.

Results: We include 64 patients with ATTR V122I, with a median age of 74 years (range, 57-88 years). Normal or increased ECG voltage was present in 44.3% of patients, and overall 25% met the criteria for LVH. A significant negative correlation between voltage complex size and duration of illness was seen (P < .05). First-degree heart block was evident in 56% of patients in sinus rhythm. During follow-up (n = 17; median, 28 months), 50% of patients with initial first-degree heart block required pacing.

Conclusion: Electrocardiographic voltages meet the criteria for LVH in one quarter of patients with ATTR V122I cardiac amyloidosis. The widely held belief that cardiac amyloidosis is associated with low-voltage complexes is likely to contribute to underdiagnosis of ATTR V122I. First-degree heart block is common at diagnosis and identifies patients at high risk for subsequent pacing requirement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ahj.2012.04.013DOI Listing
July 2012

Cyclophosphamide, bortezomib, and dexamethasone therapy in AL amyloidosis is associated with high clonal response rates and prolonged progression-free survival.

Blood 2012 May 13;119(19):4387-90. Epub 2012 Feb 13.

National Amyloidosis Centre, University College London Medical School, Royal Free Hospital Campus, London, United Kingdom.

Bortezomib has shown great promise in the treatment of amyloid light-chain (AL) amyloidosis. We present our experience of 43 patients with AL amyloidosis who received cyclophosphamide, bortezomib, and dexamethasone (CVD) upfront or at relapse. Of these, 74% had cardiac involvement and 46% were Mayo Cardiac Stage III. The overall hematologic response rate was 81.4%, including complete response (CR) in 41.9% and very good partial response with >90% decrease in difference between involved/uninvolved light chain (VGPR-dFLC) in 51.4%. Patients treated upfront had higher rates of CR (65.0%) and VGPR-dFLC (66.7%). The estimated 2-year progression-free survival was 66.5% for patients treated upfront and 41.4% for relapsed patients. Those attaining a CR or VGPR-dFLC had a significantly better progression-free survival (P=.002 and P=.026, respectively). The estimated 2-year overall survival was 97.7% (94.4% in Mayo Stage III patients). CVD is a highly effective regimen producing durable responses in AL amyloidosis; the deep clonal responses may overcome poor prognosis in advanced-stage disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2011-10-388462DOI Listing
May 2012

Cardiac phenotype and clinical outcome of familial amyloid polyneuropathy associated with transthyretin alanine 60 variant.

Eur Heart J 2012 May 11;33(9):1120-7. Epub 2011 Oct 11.

National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK.

Aims: Familial amyloid polyneuropathy (FAP) is a dominantly inherited multi-system disease associated with transthyretin (TTR) mutations. Previous series have predominantly described patients with the TTR variant Val30Met (V30M), which is the most prevalent cause of FAP worldwide. Here, we report the dominant cardiac phenotype and outcome of FAP associated with TTR Thr60Ala (T60A), the most common UK variant.

Methods And Results: Sixty consecutive patients with FAP associated with TTR T60A (FAP T60A) were prospectively evaluated in two centres between 1992 and 2009. Median (range) age of symptom development was 63 (45-78) years. A family history of amyloidosis was present in only 37%. Autonomic and peripheral neuropathy were present in 44 and 32 patients, respectively, at diagnosis. Cardiac involvement was evident on echocardiography at diagnosis in 56 patients, but was associated with reduced QRS voltages on electrocardiography in only 16% evaluable cases. Seventeen patients received implantable anti-arrhythmic devices. Median survival was 6.6 years following onset of symptoms and 3.4 years from diagnosis, and correlated with serum N-terminal prohormone brain natriuretic peptide (NT-proBNP) concentration and certain echocardiographic parameters at the latter. Orthotopic liver transplantation (OLT), performed to eliminate the predominant hepatic source of variant TTR T60A protein, was performed in eight patients including one who received a concomitant cardiac transplant. Cardiac amyloidosis progressed in all lone OLT recipients, of whom four died within 5 years.

Conclusion: Cardiac amyloidosis is almost always present at diagnosis in FAP T60A, and is a major determinant of its poor prognosis. Outcome of liver transplantation in FAP T60A has been discouraging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehr383DOI Listing
May 2012

Amyloidogenicity and clinical phenotype associated with five novel mutations in apolipoprotein A-I.

Am J Pathol 2011 Oct 5;179(4):1978-87. Epub 2011 Aug 5.

National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, Royal Free Campus, University College London, London, England.

The phenotype of hereditary apolipoprotein A-I amyloidosis is heterogeneous with some patients developing extensive visceral amyloid deposits and end-stage renal failure as young adults and others having only laryngeal and/or skin amyloid, which may be of little clinical consequence. Clinical management and prognosis of patients with systemic amyloidosis depend entirely on correct identification of the fibril protein, such that light chain amyloidosis (AL, previously referred to as "primary"), the most frequently diagnosed type, is treated with chemotherapy, which has absolutely no role in hereditary apolipoprotein A-I amyloidosis. We report five novel apolipoprotein A-I variants, four of which were amyloidogenic and one of which was incidental in a patient with systemic AL amyloidosis. Interestingly, only one of four patients with apolipoprotein A-I amyloidosis had a family history of similar disease. Laser microdissection and tandem mass spectrometry-based proteomics were used to confirm the amyloid fibril protein and, for the first time in apolipoprotein A-I amyloidosis, demonstrated that only mutated protein as opposed to wild-type apolipoprotein A-I was deposited as amyloid. The clinical spectrum and outcome of hereditary apolipoprotein A-I amyloidosis are reviewed in detail and support the need for sequencing of the apolipoprotein A-I gene among patients with apparent localized amyloidosis in whom IHC is nondiagnostic of the fibril protein, even in the absence of a family history of disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajpath.2011.06.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181365PMC
October 2011

Outcome in renal Al amyloidosis after chemotherapy.

J Clin Oncol 2011 Feb 10;29(6):674-81. Epub 2011 Jan 10.

National Amyloidosis Centre, Division of Medicine, University College London Medical School, Rowland Hill St, London NW3 2PF, United Kingdom.

Purpose: Chemotherapy in AL (primary or light chain) amyloidosis is associated with improved survival, but its effect on renal outcome has not been examined systematically. The purpose of this study was to evaluate the effect of chemotherapy on clinical outcome among patients with renal AL amyloidosis.

Patients And Methods: We evaluated factors influencing survival among 923 patients with renal AL amyloidosis observed during a 21-year period, including 221 patients who became dialysis dependent. Factors associated with renal outcome were analyzed, including serum free light chain (FLC) response to chemotherapy using a simple subtraction formula applicable to all stages of chronic kidney disease. Patient survival and graft survival were analyzed in 21 renal transplantation recipients.

Results: Median survival from diagnosis for the whole cohort was 35.2 months. Magnitude of FLC response with chemotherapy was strongly and independently associated with overall survival (P < .001) and renal outcome. Evaluable patients achieving more than 90% FLC response had a significantly higher rate of renal responses and lower rate of renal progression compared with patients achieving a 50% to 90% response, whose renal outcomes were, in turn, better than patients achieving less than 50% FLC response (P < .001). Median survival from dialysis dependence was 39.0 months, and median survival from renal transplantation was 89.0 months.

Conclusion: Renal outcome and overall outcome in AL amyloidosis are strongly associated with FLC response to chemotherapy and are best among patients achieving more than 90% suppression of the amyloidogenic monoclonal component. Survival on dialysis was substantially superior to that previously reported, and renal transplantation should be considered in selected patients with AL amyloidosis with end-stage renal disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2010.30.5235DOI Listing
February 2011

You can't have your cake and eat it too.

Gut 2011 Jun 14;60(6):852, 860. Epub 2010 May 14.

National Amyloidosis Centre, University College London Medical School, Royal Free Hospital, London, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/gut.2009.188649DOI Listing
June 2011

Biochemical basis of the amyloid diseases.

Br J Hosp Med (Lond) 2010 Feb;71(2):70-5

UCL Medical School, Royal Free Hospital Campus, London.

Amyloidosis is a heterogeneous group of diseases characterized by normally soluble proteins deposited extracellularly in an abnormally folded, insoluble fibrillar form. This can lead to organ impairment and premature death. This article discusses the pathogenesis, classification system and means of diagnosis of the amyloid diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12968/hmed.2010.71.2.46483DOI Listing
February 2010

Bisphosphonate-induced osteonecrosis of the jaw requires early detection and intervention.

Med J Aust 2005 Nov;183(10):549-50

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5694/j.1326-5377.2005.tb07172.xDOI Listing
November 2005

Severe and prolonged myeloid haematopoietic toxicity with myelodysplastic features following alemtuzumab therapy in patients with peripheral T-cell lymphoproliferative disorders.

Br J Haematol 2005 Jul;130(1):87-91

Haematology Service, Peter MacCallum Cancer Centre, Victoria, Australia.

Alemtuzumab is effective therapy for B- and T-cell lymphoproliferative disorders (LPD) but is associated with prolonged lymphopenia. Myeloid haematological toxicities are less well described, especially in T-cell disorders, and are usually transient. We report myeloid toxicities in a phase II trial of alemtuzumab for T-cell LPD. Five of 11 patients treated developed severe neutropenia and thrombocytopenia. Three cases had prolonged cytopenias (32-88+ weeks), including two with severe marrow hypoplasia. We observed three incidences of trilineage morphological myelodysplasia, two with new clonal cytogenetic abnormalities. Alemtuzumab can be associated with prolonged severe multilineage cytopenias, marrow hypoplasia and myelodysplasia in T-cell LPD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1365-2141.2005.05570.xDOI Listing
July 2005

Alemtuzumab: effective monotherapy for simultaneous B-cell chronic lymphocytic leukaemia and Sézary syndrome.

Eur J Haematol 2004 Dec;73(6):447-9

Haematology Service, Peter MacCallum Cancer Centre, Melbourne, Australia.

The simultaneous presentation of chronic lymphocytic leukaemia (CLL) and cutaneous T-cell lymphoma (CTCL) is a very rare occurrence where optimal treatment is unknown. We present the case of a 65-yr-old man who was successfully treated with alemtuzumab monotherapy for both disorders, but at a cost of severe infectious morbidity and prolonged pancytopenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1600-0609.2004.00332.xDOI Listing
December 2004