: Objectives: Until recently, no prospective epidemiologic survey of lymphoma and multiple myeloma (L/MM) in European cancer patients had been conducted; furthermore, data on prevalence, incidence, ...and treatment patterns of L/MM were limited or unavailable. Here we define anemia prevalence, incidence, and treatment patterns, and identify anemia risk factors in European L/MM patients. Methods: Data for a subgroup of 2360 L/MM patients in the European Cancer Anaemia Survey (ECAS) were analyzed; variables included age, gender, tumor type/stage, cancer and anemia treatment, WHO performance status, and hemoglobin (Hb) levels. Results: 2316 patients were evaluable (1612 L and 704 MM). Anemia rate at enrollment was 52.5%. At enrollment, Hb levels correlated significantly with WHO scores (r = −0.306, P < 0.001). Anemia prevalence during ECAS was 72.9% (MM, 85.3%; non‐Hodgkin's lymphoma, 77.9%; Hodgkin's disease, 57.4%); incidence in chemotherapy patients was 55.4%. Only 47.3% of patients anemic any time during ECAS received anemia treatment; overall Hb nadir for initiating treatment was 8.9 g/dL (epoetin, 9.5 g/dL; transfusion, 8.2 g/dL). Factors found to significantly (P < 0.03) increase anemia risk were low initial Hb, female gender, persistent/resistant disease, and platinum chemotherapy. Conclusions: L/MM patients have a high prevalence and incidence of anemia; however, anemia is not optimally treated. Anemia is common in L/MM patients and, given its known adverse impact on physical functioning and quality‐of‐life variables including fatigue and cognitive function, anemia management should be an integral part of their care. Predictive factors identified by ECAS may help clinicians develop optimal anemia treatment strategies for L/MM patients.
Patients with myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, have a propensity to develop acute myeloid leukemia (AML) and ...myelodysplastic syndromes (MDSs). Using population-based data from Sweden, we assessed the role of MPN treatment and subsequent AML/MDS risk with special focus on the leukemogenic potential of hydroxyurea (HU).
On the basis of a nationwide MPN cohort (N = 11,039), we conducted a nested case-control study, including 162 patients (153 and nine with subsequent AML and MDS diagnosis, respectively) and 242 matched controls. We obtained clinical and MPN treatment data for all patients. Using logistic regression, we calculated odds ratios (ORs) as measures of AML/MDS risk.
Forty-one (25%) of 162 patients with MPNs with AML/MDS development were never exposed to alkylating agents, radioactive phosphorous (P(32)), or HU. Compared with patients with who were not exposed to HU, the ORs for 1 to 499 g, 500 to 999 g, more than 1,000 g of HU were 1.5 (95% CI, 0.6 to 2.4), 1.4 (95% CI, 0.6 to 3.4), and 1.3 (95% CI, 0.5 to 3.3), respectively, for AML/MDS development (not significant). Patients with MPNs who received P(32) greater than 1,000 MBq and alkylators greater than 1 g had a 4.6-fold (95% CI, 2.1 to 9.8; P = .002) and 3.4-fold (95% CI, 1.1 to 10.6; P = .015) increased risk of AML/MDS, respectively. Patients receiving two or more cytoreductive treatments had a 2.9-fold (95% CI, 1.4 to 5.9) increased risk of transformation.
The risk of AML/MDS development after MPN diagnosis was significantly associated with high exposures of P(32) and alkylators but not with HU treatment. Twenty-five percent of patients with MPNs who developed AML/MDS were not exposed to cytotoxic therapy, supporting a major role for nontreatment-related factors.
BACKGROUND: The Evaluation of Xagrid Efficacy and Long-term Safety (EXELS) study (NCT00567502) is the largest prospective observational cohort of high-risk patients (pts) with essential ...thrombocythemia (ET) reported to date.
OBJECTIVES: The primary objective was safety and pregnancy outcomes of anagrelide (ANA) compared with other cytoreductive therapies (CRT). Secondary objectives included efficacy, measured by the incidence of thrombohemorrhagic events and platelet reduction.
METHODS: High-risk pts (≥1 of age >60 yrs, previous thrombotic event, platelet count >1000 x 109/L) with ET were enrolled across 13 countries in Europe between 2005 and 2009. Pts were required to be receiving CRT. Data, including events predefined in the protocol (PDEs), were collected every 6 mo for 5 yrs for all patients. Event rates are presented as number of pts per 100 patient-years exposure and by treatment at time of event. Event rates are provided rather than p values due to the observational nature of the study. Preliminary final data are presented and final data, including platelet response and pregnancy results, will be available at ASH. Recently, results have remained stable and conclusions are not expected to change.
RESULTS: 3649 pts were categorized according to treatment at registration as follows: ANA (n=804), ANA + other CRT (n=141), other CRT (n=2666) and no CRT (n=38). Over 80% of pts received either hydroxycarbamide (HC) or ANA, and 69.8% of pts received anti-aggregatory therapy. At registration, median age was lower in the ANA (55.5 yrs, range 18‒89) and ANA + other CRT (59.0 yrs, range 22–88) groups vs the other CRT group (70.0 yrs, range 17‒95).
The arterial thrombotic event rate was similar in ANA (1.63) and other CRT (1.62) groups, whereas venous thrombotic event rates differed (0.35 vs 0.57). The major hemorrhagic event rate was highest in the ANA group, especially in pts also treated with anti-aggregatory therapy (1.24).
105 pts transformed to myelofibrosis (MF) and 62 to acute leukemia (AL). Transformation to MF rates were similar in the ANA (1.31), ANA + other CRT (1.27) groups, and lower in the other CRT (0.32) group. Rate of transformation to AL was 0.17, 0.46, and 0.33, respectively. In pts who had only ever received either ANA or HC, rate of transformation to MF was higher in the ANA vs HC group (0.78 vs 0.17) whereas transformation to AL was higher in the HC vs ANA group (0.22 vs 0). All pts who ever received ANA and transformed to AL had also received prior HC.
PDEs of greatest interest are displayed in Table 1. Non-hematological malignancy was the most frequent PDE in the other CRT group. 57.4% of deaths were attributed to a PDE; transformation (event rate, 1.9), most frequently to AL (1.3), and non-hematological malignancies (1.6) were the most frequent causes of PDE-related death. No unexpected side effects were noted.
The proportion of pts with a white blood cell (WBC) count >15 x 109/L at any time was higher in pts who died (12.5%) vs alive pts (6.1%) and in pts who had transformed (15.7%) vs those who did not transform (5.7%).
CONCLUSION: Pts receiving ANA were younger than those receiving other CRT. Thrombotic event rates were low; arterial events were similar between ANA and other CRT groups, and venous events were lower in the ANA vs other CRT group. Hemorrhage was most frequent in the ANA + anti-aggregatory therapy group, whereas non-hematological malignancy was most frequent in the other CRT group. Transformation to MF and AL were most frequent in the ANA and HC groups, respectively. The incidence of death and transformation was higher in pts with a WBC count >15 x 109/L.
Abstract 1846. Table 1Treatment at time of eventANA N=1127ANA + other CRTN=451Other CRT N=2909No CRT N=645PDEPts(events)nEvent ratePts(events)nEvent ratePts(events)nEvent ratePts(events)nEvent rateTotal thrombohemorrhagic events92 (113)2.7524 (29)2.86270 (326)2.6030 (33)4.91Arterial thrombotic events55 (65)1.6319 (21)2.25171 (200)1.6217 (19)2.74Venous thrombotic events12 (13)0.351 (1)0.1161 (67)0.577 (7)1.13Major hemorrhagic events30 (35)0.876 (7)0.6953 (59)0.497 (7)1.12Transformation to:Myelofibrosis45 (45)1.3111 (11)1.2735 (35)0.3214 (14)2.31Acute leukemia6 (6)0.174 (4)0.4636 (36)0.3316 (17)2.57Non-hematological malignancy17 (18)0.494 (5)0.46143 (161)1.3512 (13)1.95Non-PDE death22 (22)0.647 (7)0.8128 (128)1.1830 (30)4.80
ANA, anagrelide; CRT, cytoreductive therapy; PDE, predefined event; Pts, patients
Birgegard:Shire Pharmaceuticals: Consultancy, Honoraria, Research Funding. Besses:Shire Pharmaceuticals: honoraria for educational lectures Other. Griesshammer:Amgen: Honoraria; Sanofi: Honoraria; Shire: Honoraria; Novartis: Honoraria; Roche: Honoraria. Gugliotta:Shire Pharmaceuticals: Honoraria, Research Funding. Harrison:Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; S Bio: Honoraria; YMBioscience: Honoraria; CTI: Honoraria; Gilead: Honoraria; Sanofi: Honoraria, Speakers Bureau; Shire Pharmaceuticals: Honoraria, Speakers Bureau. Hamdani:Shire Pharmaceuticals: Employment. Achenbach:Shire Pharmaceuticals: Employee Other. Kiladjian:Shire Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees.
Background:An alumni study of graduates from the medical school in Uppsala, was performed to give input into an ongoing reform process.
Aims: This study aimed to investigate how medical interns view ...their undergraduate medical education and the extent to which they felt that the curriculum prepared them for their current positions.
Methods: A web-based questionnaire was sent out via mail in 2005 to all past graduates who had qualified in Uppsala in 2003.
Results: Replies were obtained from 69 of 102 students (68%). The most apparent suggested change of the education was increased integration of preclinical and clinical teaching.
Correlations were found between student satisfaction with the medical school and perceived teacher attitude, encouragement to reflect, and the graduates' perception of having sufficient practical abilities. Significant gender differences were found regarding perceived clinical ability and concerning feedback and encouragement from the teachers.
Conclusions: Our results suggest more direct feedback from the teachers and more integration between basic sciences and clinical education. Female and male students may have different needs. A key question is therefore to encourage teachers to learn about gender since female and male students should equally experience respectful encounters with teachers and doctors acting as role models.
Oral cryotherapy causes local vasoconstriction, which reduces blood flow and reduces the cytotoxic damage to the oral mucosa, has been shown to reduce oral mucositis after intense cytostatic ...treatment. The main object of this study was to investigate the effect of oral cryotherapy on the temperature in the oral mucosa, the level of proinflammatory cytokine interleukin-6 (IL-6) in saliva and the effect on blood pressure in healthy volunteers, before and after 1 h of cooling the oral cavity with crushed ice. Twelve healthy volunteers mean age 32.4 (SD 13.2) (20–56) years were treated with oral cryotherapy in the form of crushed ice. Temperature measurements were performed in the oral mucosa using infrared thermograph following a flowchart protocol. Blood pressure (BP) was measured with a sphygmomanometer. Saliva was analysed for inflammatory cytokine IL-6, using an enzyme-linked immunosorbent assay (ELISA). All participants fulfilled the cooling session. The temperature in the oral cavity decreased significantly (mean 12.9 °C,
p
< .002). The systolic BP was marginally but significantly higher after cooling (~5 mmHg,
p
= .019). We could not detect any differences in cytokine IL-6 levels before and after oral cooling. We conclude that cryotherapy during 1 h lowers the mucosal temperature as much as ~12.9 °C, which explains the significant protective effect against mucosal damage by cytostatic drugs. The cooling caused no increase in IL-6 levels. Systemic blood pressure was marginally increased.
Evaluation of Anagrelide (Xagrid
) Efficacy and Long-term Safety, a phase IV, prospective, non-interventional study performed in 13 European countries enrolled high-risk essential thrombocythemia ...patients treated with cytoreductive therapy. The primary objectives were safety and pregnancy outcomes. Of 3721 registered patients, 3649 received cytoreductive therapy. At registration, 3611 were receiving: anagrelide (Xagrid
) (n=804), other cytoreductive therapy (n=2666), or anagrelide + other cytoreductive therapy (n=141). The median age was 56
70 years for anagrelide
other cytoreductive therapy. Event rates (patients with events/100 patient-years) were 1.62
2.06 for total thrombosis and 0.15
0.53 for venous thrombosis. Anagrelide was more commonly associated with hemorrhage (0.89
0.43), especially with anti-aggregatory therapy (1.35
0.33) and myelofibrosis (1.04
0.30). Other cytoreductive therapies were more associated with acute leukemia (0.28
0.07) and other malignancies (1.29
0.44).
multivariate analyses identified increased risk for thrombosis with prior thrombohemorrhagic events, age ≥65, cardiovascular risk factors, or hypertension. Risk factors for transformation were prior thrombohemorrhagic events, age ≥65, time since diagnosis, and platelet count increase. Safety analysis reflected published data, and no new safety concerns for anagrelide were found. Live births occurred in 41/54 pregnancies (76%).
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