| 1. |
- Albertsson-Lindblad, Alexandra, et al.
(author)
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Lenalidomide-bendamustine-rituximab in patients older than 65 years with untreated mantle cell lymphoma
- 2016
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 128:14, s. 1814-1820
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Journal article (peer-reviewed)abstract
- For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter, open-label phase 1/2 trial, we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment for elderly patients with MCL. Patients >65 years with untreated MCL, stages II-IV were eligible for inclusion. Primary end points were maximally tolerable dose (MTD) of LEN and progression-free survival (PFS). Patients received 6 cycles every four weeks of L-B-R (L D1-14, B 90 mg/m(2) IV, days 1-2 and R 375 mg/m(2) IV, day 1) followed by single LEN (days 1-21, every four weeks, cycles 7-13). Fifty-one patients (median age 71 years) were enrolled from 2009 to 2013. In phase 1, the MTD of LEN was defined as 10 mg in cycles 2 through 6, and omitted in cycle 1. After 6 cycles, the complete remission rate (CRR) was 64%, and 36% were MRD negative. At a median follow-up time of 31 months, median PFS was 42 months and 3-year overall survival was 73%. Infection was the most common nonhematologic grade 3 to 5 event and occurred in 21 (42%) patients. Opportunistic infections occurred in 3 patients: 2 Pneumocystis carinii pneumonia and 1 cytomegalovirus retinitis. Second primary malignancies (SPM) were observed in 8 patients (16%). LEN could safely be combined with R-B when added from the second cycle in patients with MCL, and was associated with a high rate of CR and molecular remission. However, we observed a high degree of severe infections and an unexpected high number of SPMs, which may limit its use. This trial is registered at www.Clinicaltrials.gov as #NCT00963534.
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| 2. |
- Albertsson-Lindblad, Alexandra, et al.
(author)
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Lenalidomide-bendamustine-rituximab in untreated mantle cell lymphoma > 65 years, the Nordic Lymphoma Group phase I+II trial NLG-MCL4
- 2016
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 128:14, s. 1814-1820
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Journal article (peer-reviewed)abstract
- For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter open-label phase I/II trial we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment to elderly MCL patients. Patients >65 years with untreated MCL, stage II-IV were eligible for inclusion. Primary endpoints were maximally tolerable dose (MTD) of LEN, and progression-free survival (PFS). Patients received six cycles q4w of L-B-R (L D1-14, B 90 mg/m(2) iv D1-2 and R 375 mg/m(2) iv D1) followed by single LEN (D1-21, q4w, cycles 7-13). 51 patients (median age 71 years) were enrolled 2009-2013. In phase I, the MTD of LEN was defined as 10 mg in cycles 2-6, and omitted in cycle 1. After six cycles, the complete remission rate (CRR) was 64% and 36% were MRD negative. At a median follow-up time of 31 months, median PFS was 42 months and 3 year overall survival was 73%. Infection was the most common non-hematological grade 3-5 event and occurred in 21 (42%) patients. Opportunistic infections occurred in three patients; 2 PCP and 1 CMV retinitis. Second primary malignancies (SPM) were observed in eight patients (16%). LEN could safely be combined with R-B, when added from the second cycle in patients with MCL, and was associated with a high rate of CR and molecular remission. However, we observed a high degree of severe infections and an unexpected high number of SPMs which may limit its use. http://clinicaltrials.gov: NCT00963534.
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| 3. |
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| 4. |
- Abalo, Kossi D., et al.
(author)
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Infections in patients with mantle cell lymphoma
- 2024
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In: HemaSphere. - : John Wiley & Sons. - 2572-9241. ; 8:7
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Journal article (peer-reviewed)abstract
- Advancements in treatments have significantly improved the prognosis for mantle cell lymphoma (MCL), and there is a growing population of survivors with an increased susceptibility to infections. We assessed the incidence of infections by clinical characteristics and treatment both before and after MCL diagnosis in Sweden. Patients with a diagnosis of MCL >= 18 years between 2007 and 2019 were included, along with up to 10 matched comparators. Infectious disease diagnosis and anti-infective drug dispensation were identified by the National Patient and the Prescribed Drug Registers, respectively. Patients and comparators were followed from the diagnosis/matching date until death, emigration, or June 30, 2020. Overall, 1559 patients and 15,571 comparators were followed for a median duration of 2.9 and 5 years, respectively. The infection rate among patients was twofold higher, RRadj = 2.14 (2.01-2.27), contrasted to the comparator group. There was a notable rise in infection rates already 4 years before MCL diagnosis, which reached a fourfold increase in the first year after diagnosis and persisted significantly increased for an additional 8 years. Among patients, 69% (n = 1080) experienced at least one infection during the first year of follow-up. Influenza, pneumonia, other bacterial infections, urinary tract infections, and acute upper respiratory infections were the most frequent. Notably, MCL remained to be the primary leading cause of death among patients (57%, n = 467/817). Infections as the main cause of death were rare (2.6%, n = 21). Our study highlights the importance of thoroughly assessing infectious morbidity when appraising new treatments. Further investigations are warranted to explore strategies for reducing infectious disease burden.
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| 5. |
- Abalo, Kossi, et al.
(author)
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Secondary malignancies among mantle cell lymphoma patients
- 2023
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In: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 195
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Journal article (peer-reviewed)abstract
- Purpose:With modern treatments, mantle cell lymphoma (MCL) patients more frequently experience long-lasting remission resulting in a growing population of long-term survivors. Follow-up care includes identification and management of treatment-related late-effects, such as secondary malignancies (SM). We conducted a populationbased study to describe the burden of SM in MCL patients.Methods:All patients with a primary diagnosis of MCL, aged >= 18 years and diagnosed between 2000 and 2017 in Sweden were included along with up to 10 individually matched population comparators. Follow-up was from twelve months after diagnosis/matching until death, emigration, or December 2019, whichever occurred first. Rates of SM among patients and comparators were estimated using the Anderson-Gill method (accounting for repeated events) and presented as hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age at diagnosis, calendar year, sex, and the number of previous events.Results:Overall, 1 452 patients and 13 992 comparators were followed for 6.6 years on average. Among patients, 230 (16%) developed at least one SM, and 264 SM were observed. Relative to comparators, patients had a higher rate of SM, HRadj= 1.6 (95%CI:1.4-1.8), and higher rates were observed across all primary treatment groups: the Nordic-MCL2 protocol, R-CHOP, R-bendamustine, ibrutinib, lenalidomide, and R-CHOP/Cytarabine. Compared to Nordic-MCL2, treatment with R-bendamustine was independently associated with an increased risk of SM, HRadj= 2.0 (95%CI:1.3-3.2). Risk groups among patients were those with a higher age at diagnosis (p < 0.001), males (p = 0.006), and having a family history of lymphoma (p = 0.009). Patients had preferably higher risk of melanoma, other neoplasms of the skin and other hematopoietic and lymphoid malignancies.Conclusions:MCL survivors have an increased risk of SM, particularly if treated with R-bendamustine. The intensive treatments needed for long-term remissions are a concern, and transition to treatment protocols with sustained efficacy but with a lower risk of SM is needed.
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| 6. |
- Abrahamsson, Anna, et al.
(author)
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Real world data on primary treatment for mantle cell lymphoma: a Nordic Lymphoma Group observational study.
- 2014
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 124:8, s. 1288-1295
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Journal article (peer-reviewed)abstract
- There is consensus that young patients with mantle cell lymphoma (MCL) should receive intensive immunochemotherapy regimens, but optimal treatment of elderly patients as well for as patients with limited or indolent disease is not defined. Our aim was to evaluate and compare outcome in relation to prognostic factors and first-line treatment in patients with MCL in a population-based data set. Data were collected from the Swedish and Danish Lymphoma Registries from the period of 2000-2011. A total of 1389 patients were diagnosed with MCL. During this period, age-standardized incidence MCL increased, most prominently among males. Furthermore, male gender was associated with inferior overall survival (OS) in multivariate analysis (HR 1.36; p=0.002). Forty-three (3.6%) patients with stage I-II disease received radiotherapy with curative intent, showing a 3 year OS of 93%. Twenty-nine (2.4%) patients followed a watch-and-wait approach and showed a 3 year OS of 79.8%. Among patients receiving systemic treatment, rituximab (n=766; HR 0.66; p=0.001) and autologous stem cell transplant (ASCT) (n=273; HR 0.55; p=0.004) were independently associated with improved overall survival in multivariate analysis. Hence, by a population-based approach, we were able to provide novel data on prognostic factors and primary treatment of MCL, applicable to routine clinical practice.
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| 7. |
- Acosta, Stefan, et al.
(author)
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Increasing incidence of ruptured abdominal aortic aneurysm : a population-based study
- 2006
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In: Journal of Vascular Surgery. - : Elsevier BV. - 0741-5214 .- 1097-6809. ; 44:2, s. 237-243
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Journal article (peer-reviewed)abstract
- Objective: The aim of the present population-based study was to assess the trends of age- and gender-specific incidence of ruptured abdominal aortic aneurysm (rAAA). Methods. Patients with rAAA from the city of Malmo, Sweden, were studied between 2000 and 2004. An analysis of trends of incidence and mortality of rAAA in Malmo was possible because of a previous population-based study on patients with rAAA between 1971 and 1986 (autopsy rate 85% compared with 25% for the time period 2000 to 2004). The in-hospital registry of Malmo University Hospital and the databases at the Department of Pathology, Malmo, and the Institution of Forensic Medicine, Lund, identified patients with rAAA, and the in-hospital registry identified all elective repairs for AAA. Results. Compared with the time period 1971 to 1986, the overall incidence of rAAA significantly increased from 5.6 (95 % confidence interval [CI], 4.9 to 6.3) to 10.6 (95% CI, 8.9 to 12.4) per 100,000 person-years (standardized mortality ratio, 1.6; 95% CI, 1.0 to 2.1). In men aged 60 to 69 and 70 to 79 years, the incidence increased significantly from 16 (95% CI, 11 to 21) and 56 (95% Cl, 43 to 69) to 46 (95% Cl, 28 to 63) and 117 (95% CI, 84 to 149) per 100,000 person-years, respectively, whereas no increase in the age-specific incidence in women could be demonstrated. The overall incidence of elective repair of AAA increased significantly from 3.4 (95% CI, 2.8 to 4.0) to 7.0 (95% CI, 5.6 to 8.4) per 100,000 person-years and increased most significantly from 12 (95% CI, 3.4 to 32) to 68 (95% CI, 34 to 102) per 100,000 person-years in men aged 80 to 89 years and from 5.1 (95% CI, 2.4 to 9.3) to 28 (95% CI, 15 to 41) per 100,000 person-years in women aged 70 to 79 years. The elective-acute repair ratio in women increased from 2.4 to 5.6 and decreased in men from 2.1 to 1.0. Conclusions: Between 1971 to 1986 and 2000 to 2004, the incidence of rAAA increased significantly, despite a 100% increase in elective repairs and notwithstanding a potential for bias towards underestimation due to lower autopsy rates in recent years. The reason behind this increase is unclear, and further studies are needed to identify risk groups for direction of effective prevention and screening.
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| 8. |
- Acosta, Stefan, 1967-
(author)
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On Acute Thrombo-Embolic Occlusion of the Superior Mesenteric Artery
- 2004
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Doctoral thesis (other academic/artistic)abstract
- Acute thrombo-embolic occlusion of the superior mesenteric artery (SMA) with intestinal infarction is a lethal disease, difficult to diagnose in time, with unknown incidence and cause-specific mortality. The aim of this thesis was to characterize the disease and to develop diagnostic methods. Two laboratory studies were conducted on patients with suspected acute SMA occlusion. A pilot-study showed that the fibrinolytic marker D-dimer was elevated in six patients with the disease. In the subsequent study including 101 patients, D-dimer was the only elevated coagulation marker in nine patients with the disease. In a prospective study 24 patients (median age 84 years) were identified, of whom four were diagnosed at autopsy, despite an autopsy-rate of 10%. One-fourth were initially nursed in non-surgical wards. Length of the intestinal infarction was a predictor for death. An analysis of patients from the three studies showed that D-Dimer was elevated in all 16 tested patients with the disease.Sixty patients with acute SMA occlusion underwent intestinal revascularisation and were registered in the Swedish Vascular Registry (SWEDVASC). One-year survival-rate was 40%. Previous vascular surgery was a negative risk-factor.A population-based study was conducted in Malmö, based on an autopsy-rate of 87%. Among 270 patients with the disease, 2/3 were diagnosed only at autopsy and 1/2 were managed in non-surgical wards. The incidence was 8.6 per 100000 person years. The age-standardized incidence increased exponentially without gender differences. The diagnosis was the cause of death in 1.2% among octogenarians and beyond. Thrombotic occlusions were located proximally within the SMA and associated with extensive intestinal infarctions. Synchronous embolism, often multiple, occurred in 2/3 of the patients with embolic occlusions.Conclusions: A normal D-dimer at presentation most likely excludes the diagnosis. Acute SMA occlusion was more frequent than previously estimated from clinical series. The patients were often nursed in non-surgical wards.
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| 9. |
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| 10. |
- Acosta, Stefan, et al.
(author)
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The Hardman index in patients operated on for ruptured abdominal aortic aneurysm: A systematic review.
- 2006
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In: Journal of Vascular Surgery. - : Elsevier BV. - 1097-6809 .- 0741-5214. ; 44:5, s. 949-954
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Research review (peer-reviewed)abstract
- Background. The aims of the present study were to (1) analyze preoperative predictors for outcome suggested by Hardman and surgical mortality after open repair and endovascular repair (EVAR) of ruptured abdominal aortic aneurysms (rAAA), and (2) further evaluate the Hardman index in a systematic review. Methods. Patients operated on for rAAA during a 5-year period between 2000 and 2004 were scored according to Hardman-1 point for either age > 76 years, loss of consciousness after presentation, hemoglobin < 90 g/L, serum creatinine > 190 mu mol/L or electrocardiographic (ECG) signs of ischemia-with blinded evaluation of ECGs by a specialist in clinical physiology. The results were included in a systematic review of studies evaluating the Hardman index. Results: In-hospital mortality after operation was 41% (67/162). There was no difference in in-hospital mortality between open repair (n=106) and EVAR (n=56), whereas the Hardman index was associated with operative mortality in our institution and in the systematic review of 970 patients (P <.001). Mortality rate in patients with Hardman index >= 3 was 77% in the pooled analysis. A full data set of all five scoring variables was obtained in 94 (58%) of 162 patients in our study, and potential underscoring was thus possible in 68 patients. Of the available ECGs, 12 (8.7%) of 138 were judged nondiagnostic. Five studies did not state their missing data on ECG and hemoglobin and serum creatinine concentrations, nor did they specify the criteria for ECG ischermia. Conclusions: A strong correlation between the Hardman index and mortality was found. A Hardman index >= 3 cannot be used as an absolute limit for denial of surgery. The utility of the Hardman index seems to be impeded by variability in scoring resulting from missing or nondiagnostic data.
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