Median Followup (median + followup)

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Selected Abstracts

Mixed chimerism and graft failure following conditioning with the fludarabine and cyclophosphamide nonablative regimen; Conversion to full donor chimerism

Anand P. Jillella
Abstract Twenty-one patients with hematologic malignancies were treated with the fludarabine (120,125 mg/m2) and cyclophosphamide (120 mg/kg) nonmyeloablative conditioning regimen. Graft versus host disease (GVHD) and graft rejection prophylaxis was with tacrolimus and mycophenolate mofetil. Thirteen of the 21 patients (62%) had mixed chimerism (,,90% donor cells) at day 60 and 11 (52%) of these patients had mixed chimerism which persisted until day 100. Immunosuppression was discontinued in 12 of 13 patients and two of them converted to full chimerism by day 100. Eight patients received a donor lymphocyte infusion (DLI) and five of them converted to full donor chimerism with DLI alone. Two patients were given GM-CSF in addition to a DLI with conversion to full donor chimerism. Three patients (14%) had graft failure requiring a second transplant using fludarabine (125 mg/m2) and melphalan (140 mg/m2). With a median followup of 2.8 years, 15 patients are alive,one with disease and 14 with no disease. Two patients died of acute GVHD, one of chronic GVHD, and three due to progressive disease. We conclude that the nonmyeloablative fludarabine/cyclophosphamide regimen results in a significant incidence of mixed chimerism and graft rejection but is well tolerated. We suggest a more intense regimen, such as fludarabine and melphalan, be used in patients with a high risk of early disease progression to establish early engraftment and graft versus tumor effect. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc. [source]

Long-term remission after cessation of interferon-, treatment in patients with severe uveitis due to Behçet's disease

Christoph M. E. Deuter
Objective To retrospectively assess the development of visual acuity and the frequency and duration of relapse-free periods in patients who were treated with interferon-, (IFN,) for severe uveitis due to Behçet's disease (BD) and who completed a followup period of ,2 years. Methods IFN alfa-2a was administered at an initial dosage of 6 million IU per day, then tapered to a maintenance dosage of 3 million IU twice per week, and finally discontinued, if possible. In case of a relapse, IFN treatment was repeated. Visual acuity at the end of followup was compared with visual acuity when ocular disease was in remission. Results Of 53 patients (96 eyes), 52 (98.1%) responded to IFN. In 47 patients (88.7%), IFN could be discontinued when the disease was in remission. Twenty of these 47 (42.6%) needed a second treatment course during a median followup of 6.0 years (range 2.0,12.6 years). Visual acuity improved or remained unchanged in 91 eyes (94.8%). Ocular disease was still in remission in 50% of the patients 45.9 months after cessation of the first IFN course. The relapse rate tended to be lower in women than in men. The BD activity score decreased significantly during followup, but long-term remission of nonocular BD manifestations was not achieved. However, since local treatments were sufficient, no systemic treatment was administered. Conclusion Our findings indicate that IFN, induces long-lasting remission in patients with severe ocular BD, resulting in a notable improvement in visual prognosis. [source]

Mortality in Behçet's disease

D. Saadoun
Objective To report the long-term mortality in patients with Behçet's disease (BD). Methods A cohort of 817 patients fulfilling the international criteria for BD from a single center in France were analyzed for causes of death, the standardized mortality ratio (SMR), and the factors associated with mortality. Results Among the 817 patients with BD, 41 (5%) died after a median followup of 7.7 years, of whom 95.1% were male. The mean ± SD age at death was 34.8 ± 11.9 years. Main causes of death included major vessel disease (mainly, arterial aneurysm and Budd-Chiari syndrome) (43.9%), cancer and malignant hemopathy (14.6%), central nervous system involvement (12.2%), and sepsis (12.2%). The mortality rate at 1 year and 5 years was 1.2% and 3.3%, respectively. There was an increased mortality among patients ages 15,24 years (SMR 2.99, 95% confidence interval [95% CI] 1.54,5.39) and those ages 25,34 years (SMR 2.90, 95% CI 1.80,4.49) as compared with age-and sex-matched healthy controls. The mortality decreased in patients older than age 35 years (SMR 1.23, 95% CI 0.75,1.92). In multivariate analyses, male sex (hazard ratio [HR] 4.94, 95% CI 1.53,16.43), arterial involvement (HR 2.51, 95% CI 1.07,5.90), and a high number of BD flares (HR 2.37, 95% CI 1.09,5.14) were independently associated with the risk of mortality. Conclusion The overall mortality in our BD cohort was 5% after a median followup of 7.7 years. Male sex, arterial involvement, and the number of flares were associated with mortality in BD. [source]

Value of anti,modified citrullinated vimentin and third-generation anti,cyclic citrullinated peptide compared with second-generation anti,cyclic citrullinated peptide and rheumatoid factor in predicting disease outcome in undifferentiated arthritis and rheumatoid arthritis

Michael P. M. van der Linden
Objective Autoantibodies such as rheumatoid factor (RF) and anti,citrullinated protein autoantibodies (ACPAs) determined by testing with second-generation anti,cyclic citrullinated peptide (anti,CCP-2) are frequently measured in clinical practice because of their association with disease outcome in undifferentiated arthritis (UA) and rheumatoid arthritis (RA). Recently, 2 new ACPA tests were developed: third-generation anti-CCP (anti,CCP-3) and anti,modified citrullinated vimentin (anti-MCV) autoantibody tests. To facilitate the decision on which autoantibody to test in daily practice, this study evaluated the capability of these autoantibodies and combinations of them to predict 3 outcome measures: progression from UA to RA, the rate of joint destruction in RA, and the chance of achieving sustained disease-modifying antirheumatic drug (DMARD),free remission in RA. Methods Patients with UA (n = 625) were studied for whether UA progressed to RA after 1 year. Patients with RA (n = 687) were studied for whether sustained DMARD-free remission was achieved and for the rate of joint destruction during a median followup of 5 years. Positive predictive values (PPVs) for RA development and for associations with the disease course in RA were compared between single tests (anti,CCP-2, anti,CCP-3, anti-MCV, and RF) and between combinations of these tests. Results Among the single tests performed in patients with UA, anti,CCP-2 tended to have the highest PPV for RA development (67.1%), but the 95% confidence intervals of the other tests overlapped. Among the single tests in patients with RA, all 4 tests showed comparable associations with the rate of joint destruction and with the achievement of remission. In both ACPA-positive and ACPA-negative RA, the presence of RF was not associated with more joint destruction. For all outcome measures, performing combinations of 2 or 3 autoantibody tests did not increase the predictive accuracy compared with performing a single test. Conclusion For clinical practice, a single autoantibody test is sufficient for risk estimation in UA and RA. [source]

Association of a single-nucleotide polymorphism in CD40 with the rate of joint destruction in rheumatoid arthritis

Michael P. M. van der Linden
Objective The severity of joint destruction in rheumatoid arthritis (RA) is highly variable from patient to patient and is influenced by genetic factors. Genome-wide association studies have enormously boosted the field of the genetics of RA susceptibility, but risk loci for RA severity remain poorly defined. A recent meta-analysis of genome-wide association studies identified 6 genetic regions for susceptibility to autoantibody-positive RA: CD40, KIF5A/PIP4K2C, CDK6, CCL21, PRKCQ, and MMEL1/TNFRSF14. The purpose of this study was to investigate whether these newly described genetic regions are associated with the rate of joint destruction. Methods RA patients enrolled in the Leiden Early Arthritis Clinic were studied (n = 563). Yearly radiographs were scored using the Sharp/van der Heijde method (median followup 5 years; maximum followup 9 years). The rate of joint destruction between genotype groups was compared using a linear mixed model, correcting for age, sex, and treatment strategies. A total of 393 anti,citrullinated protein antibody (ACPA),positive RA patients from the North American Rheumatoid Arthritis Consortium (NARAC) who had radiographic data available were used for the replication study. Results The TT and CC/CG genotypes of 2 single-nucleotide polymorphisms, rs4810485 (CD40) and rs42041 (CDK6), respectively, were associated with a higher rate of joint destruction in ACPA-positive RA patients (P = 0.003 and P = 0.012, respectively), with rs4810485 being significant after Bonferroni correction for multiple testing. The association of the CD40 minor allele with the rate of radiographic progression was replicated in the NARAC cohort (P = 0.021). Conclusion A polymorphism in the CD40 locus is associated with the rate of joint destruction in patients with ACPA-positive RA. Our findings provide one of the first non,HLA-related genetic severity factors that has been replicated. [source]

No increased risk of valvular heart disease in adult poststreptococcal reactive arthritis

J. M. van Bemmel
Objective Poststreptococcal reactive arthritis (ReA) is a (poly)arthritis presenting after a Streptococcus group A infection. Acute rheumatic fever (ARF), albeit caused by the same pathogen, has different risk characteristics and is considered to be a separate entity. Whereas ARF is known to cause carditis, the risk of carditis in adult poststreptococcal ReA is unknown. Consequently, the prevailing recommendations regarding long-term antibiotic prophylaxis in poststreptococcal ReA are imprecise and derived from the data on ARF. This study was undertaken to investigate the development of valvular heart disease in an unselected cohort of adult patients with poststreptococcal ReA who did not receive antibiotic prophylaxis and were followed up prospectively. Methods All patients presenting with early arthritis to an inception cohort of >2,000 white patients were evaluated. Patients presenting with poststreptococcal ReA (n = 75) were selected. After a median followup of 8.9 years, the occurrence of valvular heart disease was evaluated by transthoracic echocardiography in 60 patients. Controls were matched for age, sex, body surface area, and left ventricular function, with a patient-to-control ratio of 1:2. Results No differences were seen in left ventricular dimensions. Morphologic abnormalities of the mitral or aortic valves were not more prevalent among patients than among controls. Mild mitral regurgitation was present in 23% and 21% of patients and controls, respectively. Mild aortic regurgitation was present in 10% and 11%, and mild tricuspid regurgitation in 43% and 39%, respectively, revealing no significant differences. Conclusion Our findings indicate that there is no increased risk of valvular heart disease in adult poststreptococcal ReA. Based on these data, routine long-term antibiotic prophylaxis is not recommended in adult poststreptococcal ReA. [source]

Sjögren's syndrome and localized nodular cutaneous amyloidosis: Coincidence or a distinct clinical entity?

Jiska M. Meijer
Objective To report 8 patients with Sjögren's syndrome (SS) and localized nodular cutaneous amyloidosis and to examine serologic and immunohistologic findings that may link the 2 diseases. Methods The databases for 3 amyloidosis centers were searched for patients with localized nodular cutaneous amyloidosis and SS. Eight patients with this combination were identified, and clinical, serologic, and histologic parameters were retrospectively evaluated. Results Among the 8 patients with a clinical diagnosis of SS, 6 fulfilled the American,European Consensus Group criteria for SS. All of the patients were women in whom SS had been diagnosed at a median age of 47 years (range 30,61 years) and amyloid had been diagnosed at a median age of 60 years (range 42,79 years). The presence of the immunoglobulin light chain type of amyloid (AL amyloid) was confirmed in 4 patients. In 3 of these 4 patients as well as 2 other patients, a light chain,restricted plasma cell population was observed near the amyloid deposits. Progression to systemic amyloidosis was not observed in any patient during a median followup of 3.5 years. Conclusion SS should be considered in patients with cutaneous amyloidosis. The combination of cutaneous amyloidosis and SS appears to be a distinct disease entity reflecting a particular and benign part of the polymorphic spectrum of lymphoproliferative diseases related to SS. [source]

Morbidity and mortality in rheumatoid arthritis patients with prolonged therapy-induced lymphopenia: Twelve-year outcomes

Alice R. Lorenzi
Objective To assess immunologically relevant outcomes in a cohort of rheumatoid arthritis (RA) patients with prolonged therapy-induced lymphopenia. Methods Morbidity (infection or malignancy) and mortality were assessed in 53 RA patients who were treated with the lymphocytotoxic monoclonal antibody alemtuzumab between 1991 and 1994. Data were obtained by interview, medical record review, and Office for National Statistics mortality monitoring. Lymphocyte subsets were enumerated by flow cytometry. A retrospective, matched-cohort study of mortality was performed with 102 control subjects selected from the European League Against Rheumatism database of patients with rheumatic disorders. Results Lymphopenia persisted in the patients: median CD3+CD4+, CD3+CD8+, CD19+, and CD56+ lymphocyte counts measured at a median followup of 11.8 years from the first administration of alemtuzumab were 0.50 × 109/liter, 0.26 × 109/liter, 0.11 × 109/liter, and 0.09 × 109/liter, respectively. Twenty-seven of 51 cases and 46 of 101 controls with available data had died, yielding a mortality rate ratio of 1.20 (95% confidence interval 0.72,1.98). Causes of death were similar to those that would be expected in a hospital-based RA cohort. No opportunistic infections were noted, and only 3 infections were documented following 36 elective orthopedic procedures. Conclusion Despite continued lymphopenia 11.8 years after therapy, our patient cohort did not exhibit excess mortality or unusual infection-related morbidity, and surgery was well tolerated. These data should be reassuring for clinicians and patients who are considering lymphocytotoxic or other immunomodulatory therapy for RA. [source]

High N-terminal pro,brain natriuretic peptide levels and low diffusing capacity for carbon monoxide as independent predictors of the occurrence of precapillary pulmonary arterial hypertension in patients with systemic sclerosis

Y. Allanore
Objective To evaluate predictors of pulmonary arterial hypertension (PAH) in a prospective cohort of patients with systemic sclerosis (SSc). Methods Routine clinical assessments as well as measurements of the diffusing capacity for carbon monoxide/alveolar volume (DLCO/VA) ratio and N-terminal pro,brain natriuretic peptide (NT-proBNP) level were performed in a prospective cohort of 101 SSc patients who did not have PAH or severe comorbidities. After a planned 36-month followup, we evaluated the predictive value of these parameters for the development of precapillary PAH, as demonstrated by cardiac catheterization, disease progression, and death. Criteria for cardiac catheterization were a systolic pulmonary artery pressure (PAP) of >40 mm Hg on echocardiography, a DLCO value of <50% without pulmonary fibrosis, and unexplained dyspnea. Results Eight patients developed PAH, 29 had disease progression, and 10 died during a median followup of 29 months. Kaplan-Meier analysis identified the following baseline parameters as being predictors of PAH: DLCO/VA ratio <70% or <60% (P < 0.01 for each comparison), elevated plasma NT-proBNP level (>97th percentile of normal; P = 0.005), echocardiographically estimated systolic PAP >40 mm Hg (P = 0.08), and erythrocyte sedimentation rate >28 mm/hour (P = 0.015). In multivariate analyses, an elevated baseline NT-proBNP level (hazard ratio [HR] 9.97 [95% confidence interval (95% CI) 1.69,62.42]) and a DLCO/VA ratio <60% (HR 36.66 [95% CI 3.45,387.6]) were predictors of the occurrence of PAH during followup. An increased NT-proBNP level together with a decreased DLCO/VA ratio of <70% was highly predictive of the occurrence of PAH during followup (HR 47.20 [95% CI 4.90,450.33]). Conclusion This prospective study identified a decreased DLCO/VA ratio and an increased NT-proBNP as predictors of PAH in SSc. Use of these markers should result in improved PAH risk stratification and allow earlier initiation of therapy. [source]

Echogenicity of liver metastases from colorectal carcinoma is an independent prognostic factor in patients treated with regional chemotherapy

CANCER, Issue 6 2002
Thomas Gruenberger M.D.
Abstract BACKGROUND Echogenicity of liver metastases was found to be a predictive biologic factor influencing long-term outcome after curative liver resection. The current analysis focuses on the influence of echogenicity on survival in patients treated with intraarterial chemotherapy for unresectable colorectal carcinoma liver metastases. METHODS A retrospective analysis of prospectively collected data at the Department of Surgery at the University of New South Wales-affiliated St. George Hospital was performed. Two hundred twelve consecutive patients with unresectable hepatic metastases from colorectal carcinoma treated between May 1992 and September 2000 were analyzed. Echogenicity of metastases was measured intraoperatively using a 5 MHz probe. Overall survival difference was compared between hyper- and hypoechoic metastases on an intention-to-treat basis. RESULTS At a median followup of 15.1 months, 47 patients (22%) were alive and 165 (78%) had died. A significant survival benefit was observed in patients having hyperechoic lesions (median survival 16.2 months, 95% confidence interval [CI] 13.9,18.5) compared to hypoechoic lesions (median survival 11.6 months, 95% CI 8,15.2), P < 0.01. Other prognostic factors were differentiation of the primary tumor (P < 0.02), percentage hepatic replacement (P < 0.05) and carcinoembryonic antigen decrease (P < 0.03). Echogenicity was identified as an independent prognostic factor in multivariate analysis (P < 0.009). CONCLUSIONS Echogenicity is an important prognostic survival parameter. Cancer 2002;94:1753,9. © 2002 American Cancer Society. DOI 10.1002/cncr.10386 [source]