• Rituximab prevents steroidrequiring chronic graft-vs-host disease when given after peripheral blood stem cell transplantation.• Overall survival is improved with rituximab after allogeneic peripheral blood stem cell transplantation when compared with a control cohort.B cells are implicated in the pathophysiology of chronic graft-vs-host disease (GVHD), and phase 2 trials suggest that B cell depletion can treat established chronic GVHD. We hypothesized that posttransplantation B cell depletion could prevent the occurrence of chronic GVHD. We performed a 65-patient phase 2 trial of rituximab (375 mg/m 2 IV), administered at 3, 6, 9, and 12 months after transplantation. Rituximab administration was safe without severe infusional adverse events. The cumulative incidences of chronic GVHD and systemic corticosteroid-requiring chronic GVHD at 2 years from transplantation were 48% and 31%, respectively, both lower than the corresponding rates in a concurrent control cohort (60%, P 5 .1, and 48.5%, P 5 .015). There was no difference in relapse incidence, but treatment-related mortality at 4 years from transplantation was significantly lower in treated subjects when compared with controls (5% vs 19%, P 5 .02), and overall survival was superior at 4 years (71% vs 56%, P 5 .05). At 2 years from transplantation, the B-cell activating factor/B-cell ratio was significantly higher in subjects who developed chronic GVHD in comparison with those without chronic GVHD (P 5 .039). Rituximab can prevent systemic corticosteroid-requiring chronic GVHD after peripheral blood stem cell transplantation and should be tested in a prospective randomized trial. This trial was registered at www.clinicaltrials.gov as NCT00379587. (Blood. 2013;122(8):1510-1517
• Under current treatment approaches, patients with LA GVHD have poor overall and failure-free survival.• Levels of AREG are elevated in LA GVHD, and the AREG/ EGF ratio is predictive of overall survival and nonrelapse mortality in LA GVHD.Late acute (LA) graft-versus-host disease (GVHD) is persistent, recurrent, or new-onset acute GVHD symptoms occurring >100 days after allogeneic hematopoietic cell transplantation (HCT). The aim of this analysis is to describe the onset, course, morbidity, and mortality of and examine angiogenic factors associated with LA GVHD. A prospective cohort of patients (n 5 909) was enrolled as part of an observational study within the Chronic GVHD Consortium. Eighty-three patients (11%) developed LA GVHD at a median of 160 (interquartile range, 128-204) days after HCT. Although 51 out of 83 (61%) achieved complete or partial response to initial therapy by 28 days, median failure-free survival was only 7.1 months (95% confidence interval, 3.4-19.1 months), and estimated overall survival (OS) at 2 years was 56%. Given recently described alterations of circulating angiogenic factors in classic acute GVHD, we examined whether alterations in such factors could be identified in LA GVHD. We first tested cases (n 5 55) and controls (n 5 50) from the Chronic GVHD Consortium and then validated the findings in 37 cases from Mount Sinai Acute GVHD International Consortium. Plasma amphiregulin (AREG; an epidermal growth factor [EGF] receptor ligand) was elevated, and an AREG/EGF ratio at or above the median was associated with inferior OS and increased nonrelapse mortality in both cohorts. Elevation of AREG was detected in classic acute GVHD, but not chronic GVHD. These prospective data characterize the clinical course of LA GVHD and demonstrate alterations in angiogenic factors that make LA GVHD biologically distinct from chronic
Individuals with monoclonal gammopathy of undetermined significance (MGUS) develop multiple myeloma and related malignancies at the rate of 1% per year. Given differences in ethnicity, data on prevalence and risk factors of MGUS in Thai population will be helpful in understanding the pathogenesis of plasma cell disorders and designing an early cancer detection strategy. Subjects of 50 years or older were included. Demographic data and suspected risk factors were collected. Monoclonal proteins were detected using serum protein electrophoresis. Serum was obtained from 3,260 participants; 1,104 males (33.9%) and 2,156 females (66.1%). The median age was 57 years (range 50-93 years). Monoclonal proteins were detectable in 2.3% (95% confidence interval [CI] 1.8-2.8). M spikes were found in gamma- and beta-globulin regions in 50 (1.5%) and 25 (0.8%) subjects, respectively. The prevalence of MGUS in subjects 50-59, 60-69, and 70 years or older was 2.0% (41/1,975), 2.6% (22/851), and 2.8% (12/434), respectively. By multivariate analysis, MGUS was associated with living outside Bangkok (odds ratio 2.25, 95% CI 1.11-4.58). The overall prevalence of MGUS in the Thai population was 2.3%, which was lower than that in Western countries, but comparable to that in Japan.
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