The use of interferon-alfa and allogeneic-stem cell transplantation, and more recently of tyrosine-kinase inhibitors (TKIs) has improved the outcome of patients with chronic myeloid leukemia (CML). We performed a population-based study of CML to evaluate relative survival (RS) trend by treatment eras. All instances of CML diagnosed between 1975 and 2009 reported in the Surveillance, Epidemiology, and End Results databases were reviewed. The incidence of CML was 1.75/100,000 persons per-year and increased with age. The incidence was highest in Detroit and lowest among Asians. The 5-year RS ratios increased from 0.26 in patients diagnosed in 1975–1989 to 0.36 in 1990–2000 and 0.56 in 2001–2009. There was a significant improvement in 5-year RS ratios in 2005–2009 calendar period compared to 2001–2004 period (P<0.05) corresponding to the introduction of second generation of TKIs. Age was the most important prognostic factor for RS, but the improvement in 5-year RS ratios was observed in all age groups except the group aged <15 years (P>0.05) including adolescent and young adults and elderly patient groups. There are ethnic and geographic variations in the incidence of CML. The RS improved with each treatment era, with the greatest improvement in all age groups occurring during the TKI era.

BACKGROUND: Waldenstrom macroglobulinemia (WM) is a non-Hodgkin lymphoma (NHL) subtype. Little is known about the incidence and trends for this disease in the United States. METHODS: Twenty-year data from the Surveillance, Epidemiology, and End Results (SEER) program were used for this study. SEER*Stat was used for data analysis. RESULTS: Of the 95,797 cases of NHL diagnosed between 1988 and 2007 in 9 SEER registries, 1835 (1.9%) were new cases of WM. Median age at diagnosis of WM was 73 years. The overall annual age-adjusted incidence was 0.38 per 100,000 persons per year, which increased with age, ranging from 0.03 in patients aged <50 years to 2.85 in patients aged !80 years. The incidence of WM was higher in men (0.54) than in women (0.27; P < .001) and was higher in whites (0.41) than in African Americans (0.18) or other races (0.21; P < .05). The annual percentage change for the whole population was 1.01% (P > .05). The annual percentage change was 1.21% for whites (P < .05) and 0.80% (P > .05) for nonwhites. Significant annual percentage change increases were seen in the group aged 70 to 79 years (1.24%; P < .05) and in 3 geographic registries (P < .001). CONCLUSIONS: Although the overall incidence of WM remained steady over time, significant increases in incidence were seen over the past 20 years in whites, in those aged 70 to 79 years, and in 3 geographic registry areas.

BACKGROUND: With the introduction of all‐trans retinoic acid and arsenic trioxide, the management of acute promyelocytic leukemia (APL) has changed dramatically. We performed a population‐based study of APL in the United States to determine its incidence and relative survival (RS) during a 34‐year period. METHODS: We identified 1397 patients diagnosed with APL between 1975 and 2008 in the Surveillance, Epidemiology, and End Results database. Patients were categorized into 4 age groups and 3 calendar periods. As a comparison, we also reviewed the outcome of APL patients treated at our institution during approximately the same time interval. RESULTS: The incidences of APL increased with time period and patient age. Short‐ and long‐term RS improved with each calendar period, with the greatest improvement occurring between 1991 and 1999; 5‐year RS rates were 0.18 for patients diagnosed in 1975‐1990, 0.52 in 1991‐1999, and 0.64 in 2000‐2008. Age was an important predictor of survival. For example, the 5‐year RS rate in patients diagnosed in 2000‐2008 was 0.38 for patients aged ≥60 years and 0.73 and 0.75 for patients aged <20 years and 20‐39 years, respectively. Similar treads of improvements in the survival were observed in APL patients treated at our institution. CONCLUSIONS: The incidence of APL has increased, especially in the last decade. Clinical outcome improved remarkably in patients with APL diagnosed from 1991 to 1999, mainly because of the increased use of all‐trans retinoic acid. Cancer 2012;. © 2012 American Cancer Society.

A B S T R A C T PurposeTo determine the prognostic impact of persistent cytogenetic abnormalities at complete remission (CR) on relapse-free survival (RFS) and overall survival (OS) in patients with acute myeloid leukemia (AML) and to examine the potential role of allogeneic stem-cell transplantation (SCT) in this setting. Patients and MethodsData from 254 adult patients with AML (excluding acute promyelocytic leukemia) who achieved CR after induction chemotherapy on various first-line protocols were examined. ResultsMedian follow-up for surviving patients was 43 months. Patients with cytogenetic abnormalities at CR (n ϭ 71) had significantly shorter RFS (P ϭ .001) and OS (P Ͻ .001) compared with patients with normal cytogenetics at CR (n ϭ 183); 3-year RFS was 15% and 45%, and 3-year OS was 15% and 56%, respectively. Among the patients with persistent cytogenetic abnormalities at CR, those who underwent SCT in first CR (CR1; n ϭ 15) had better RFS and OS compared to those without SCT (n ϭ 56; P ϭ .04 and .06, respectively). In multivariate analysis, persistent cytogenetic abnormalities at CR was an independent predictor for RFS (P Ͻ .001) and OS (P ϭ .001), but among patients with persistent cytogenetic abnormalities at CR, no significant differences in OS (P ϭ .25) was observed between those who did or did not receive SCT with a trend favoring SCT for RFS (P ϭ .08). ConclusionPersistent cytogenetically abnormal cells at CR predict a significantly shorter RFS and OS. SCT in CR1 may improve the clinical outcome of patients lacking cytogenetic remission after induction although this depends on patient selection.

The emergence of active tuberculosis follows a biphasic pattern. Persistently high levels of released IFNγ or QFT-G conversion strongly indicate the development of active tuberculosis in patients undergoing long-term anti-TNFα therapy.

IntroductionThe goal of this study was to investigate (1) the associations of rheumatoid arthritis (RA)-related inflammation or rheumatoid factor/anti-cyclic citrullinated peptide (anti-CCP) positivity with lipid profiles and insulin resistance (IR), (2) the effects of biologic therapy on lipid profiles and IR, and (3) potential predictors for the presence of subclinical atherosclerosis.MethodsSerum levels of lipid profiles were determined by enzymatic methods in 32 adalimumab-treated patients, 16 etanercept-treated patients, 24 tocilizumab-treated patients, and 20 biologic-naïve patients. Atherogenic index, which corresponds to the ratio of total cholesterol to high-density lipoprotein cholesterol (HDL-C), was calculated. IR was measured by homeostasis model assessment. Pro-inflammatory cytokine levels were examined by enzyme-linked immunosorbent assay. Common carotid artery intima-media thickness was determined by using sonography.ResultsThere was an inverse correlation between disease activity (disease activity score for 28 joints, or DAS28) and low-density lipoprotein cholesterol (LDL-C) levels (r = −0.226, P <0.05) and a positive correlation between DAS28 and IR (r = 0.361, P <0.005). Anti-CCP-positive patients had significantly higher DAS28 and IR compared with anti-CCP-negative patients. There was also a positive correlation between IR and levels of interleukin-6 or tumor necrosis factor-alpha (TNF-α). HDL-C levels significantly increased in patients receiving 6-month anti-TNF-α therapy, and levels of total cholesterol, LDL-C, and triglyceride increased in tocilizumab-treated patients. IR significantly decreased in patients under biologic therapy but was unchanged in biologic-naïve patients. Age, IR, and DAS28 were significant predictors of severe subclinical atherosclerosis (odds ratios of 1.08, 2.77, and 2.52, respectively).ConclusionsSignificant associations of RA-related inflammation with lipid profiles and IR indicate the involvement of RA in atherosclerosis pathogenesis. Biologic therapies were associated with IR reduction without change in atherogenic index, but their beneficial effects on atherosclerosis reduction need to be verified in the future.

We aimed to investigate the association of gut microbiota with disease activity, inflammatory parameters, and auto-antibodies profile in rheumatoid arthritis (RA). A total of 138 RA patients and 21 healthy controls (HC) were enrolled. Fecal samples were collected for bacterial DNA extraction and 16S ribosome (r)RNA sequencing, followed by analyses of gut microbiota composition. Serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-17A were determined by using ELISA. Our results indicated that RA patients had lower diversity index, which reflects both evenness and richness of gut microbiota, compared to HC. The alpha-diversity was lower in anti-citrullinated peptide antibodies (ACPA)-positive patients than in HC. The phylum Verrucomicrobiae and genus Akkermansia were more abundant in patients compared to HC. There was increased relative abundance of Enterobacteriaceae as well as Klebsiella, and less abundance of Bifidobacterium in patients with high levels of TNF-α or IL-17A compared to those who had low levels of these cytokines. In addition, ACPA-positive patients had higher proportions of Blautia, Akkermansia, and Clostridiales than ACPA-negative patients. Gut dysbiosis in RA patients was presented as different microbial composition and its association with inflammatory parameters as well as ACPA seropositivity. These findings support the involvement of gut microbiota in RA pathogenesis.

ADA dose-halving is feasible for patients who have achieved remission and sufficient drug levels. Drug level monitoring may help clinicians optimize the dosing regimen and prevent overtreatment for patients receiving anti-TNF-α therapy.