Browsing by Subject "RELAPSE"

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  • Halaburda, Kazimierz; Labopin, Myriam; Houhou, Mohamed; Niederwieser, Dietger; Finke, Juergen; Volin, Liisa; Maertens, Johan; Cornelissen, Jan J.; Milpied, Noel; Stuhler, Gernot; Kroeger, Nicolaus; Esteve, Jordi; Mohty, Mohamad; Nagler, Arnon (2018)
    Acute myeloid leukemia with inv(3)(q21;q26.2)/t(3;3)(q21;q26.2) (3q26 AML) is a rare disease with poor prognosis and median survival of
  • Koenecke, Christian; Goehring, Gudrun; de Wreede, Liesbeth C.; van Biezen, Anja; Scheid, Christof; Volin, Liisa; Maertens, Johan; Finke, Juergen; Schaap, Nicolaas; Robin, Marie; Passweg, Jakob; Cornelissen, Jan; Beelen, Dietrich; Heuser, Michael; de Witte, Theo; Kroeger, Nicolaus; MDS Subcomm Chronic Malignancies (2015)
    The aim of this study was to determine the impact of the revised 5-group International Prognostic Scoring System cytogenetic classification on outcome after allogeneic stem cell transplantation in patients with myelodysplastic syndromes or secondary acute myeloid leukemia who were reported to the European Society for Blood and Marrow Transplantation database. A total of 903 patients had sufficient cytogenetic information available at stem cell transplantation to be classified according to the 5-group classification. Poor and very poor risk according to this classification was an independent predictor of shorter relapse-free survival (hazard ratio 1.40 and 2.14), overall survival (hazard ratio 1.38 and 2.14), and significantly higher cumulative incidence of relapse (hazard ratio 1.64 and 2.76), compared to patients with very good, good or intermediate risk. When comparing the predictive performance of a series of Cox models both for relapse-free survival and for overall survival, a model with simplified 5-group cytogenetics (merging very good, good and intermediate cytogenetics) performed best. Furthermore, monosomal karyotype is an additional negative predictor for outcome within patients of the poor, but not the very poor risk group of the 5-group classification. The revised International Prognostic Scoring System cytogenetic classification allows patients with myelodysplastic syndromes to be separated into three groups with clearly different outcomes after stem cell transplantation. Poor and very poor risk cytogenetics were strong predictors of poor patient outcome. The new cytogenetic classification added value to prediction of patient outcome compared to prediction models using only traditional risk factors or the 3-group International Prognostic Scoring System cytogenetic classification.
  • Schmaelter, Ann-Kristin; Labopin, Myriam; Socie, Gerard; Itälä-Remes, Maija; Blaise, Didier; Yakoub-Agha, Ibrahim; Forcade, Edouard; Cornelissen, Jan; Ganser, Arnold; Beelen, Dietrich; Labussiere-Wallet, Helene; Passweg, Jakob; Savani, Bipin N.; Schmid, Christoph; Nagler, Arnon; Mohty, Mohamad (2020)
    Following chemotherapy, secondary acute myeloid leukemia (sAML), occurring after antecedent hematologic diseases, previous chemotherapy or radiation, has an inferior prognosis compared with de novo AML. To define the outcome of sAML in the context of allogeneic stem cell transplantation (alloSCT), a retrospective, registry-based comparison was performed, including 11,439 patients with de novo and 1325 with sAML. Among transplants in first complete remission (CR1) (n = 8,600), the 3-year cumulative incidence of relapse (RI) and non-relapse mortality (NRM) was 28.5% and 16.4% for de novo, and 35% and 23.4% for sAML. Three-year overall survival (OS), leukemia-free survival (LFS) and Graft-versus-Host Disease/relapse-free survival (GRFS) was 60.8%, 55.1%, and 38.6% for de novo, and 46.7%, 41.6%, and 28.4% for sAML, respectively. In multivariate analysis, sAML was associated with a lower OS (HR = 1.33 [95% CI = 1.21-1.48]; p <10(-5)), LFS (HR = 1.32 [95% CI = 1.19-1.45]; p <10(-5)) and GRFS (HR = 1.2 [95% CI = 1.1-1.31]; p <10(-4)) and higher NRM (HR = 1.37 [95% CI = 1.17-1.59]; p <10(-4)) and RI (HR = 1.27 [95% CI = 1.12-1.44]; p <10(-3)). Results of the Cox model were confirmed in a matched-pair analysis. In contrast, results did not differ between de novo and sAML after alloSCT in induction failure or relapse. Hence, this analysis identified sAML as an independent risk factor for outcome after alloSCT in CR1.
  • Puolanne, Anna-Maija; Kolho, Kaija-Leena; Alfthan, Henrik; Färkkilä, Martti (2019)
    Objectives: The aim of this prospective study was to evaluate the home monitoring with a rapid fecal calprotectin test combined with a symptom questionnaire in patients with colonic IBD in real-life setting. Methods: We randomized 180 patients with colonic IBD in a study or a control group. The home monitoring patients performed the fecal calprotectin test and filled in a symptom questionnaire every second month and in cases with increasing symptoms. The control patients filled in the symptom questionnaire at baseline and at 6 and 12 months as well as for the appointment at the outpatient clinic. The study duration was 12 months. Results: The patient adherence to the self-monitoring program was low. Patients with a higher disease burden were more adherent than patients with better health-related quality of life, but otherwise, there were no significant factors predicting the adherence. The home monitoring patients had fewer contacts with the outpatient clinic, but otherwise, the disease course between the home monitoring and the control group were similar. Conclusions: The self-monitoring of IBD activity with a combination of a rapid fecal calprotectin home test and a symptom questionnaire provides an option for individualized care for IBD patients. However, adherence to the self-monitoring program remains a challenge.
  • Molander, Pauliina; Farkkila, Martti; Kemppainen, Helena; Blomster, Timo; Jussila, Airi; Mustonen, Harri; Sipponen, Taina (2017)
    Background: Little data exist on the long-term prognosis of patients with inflammatory bowel disease (IBD) after stopping TNF alpha-blocking therapy in deep remission. Existing data indicate that approximately 50% of patients on combination therapy who discontinued TNF alpha-blockers are still in remission 24 months later. The aims of this follow-up analysis were to evaluate the long-term remission rate after cessation of TNF alpha-blocking therapy, the predicting factors of a relapse and the response to restarting TNF alpha-blockers. Methods: The first follow-up data of 51 IBD patients (17 Crohn's disease [CD], 30 ulcerative colitis [UC] and four inflammatory bowel disease type unclassified [IBDU]) in deep remission at the time of cessation of TNF alpha-blocking therapy have been published earlier. The long-term data was collected retrospectively after the first follow-up year to evaluate the remission rate and risk factors for the relapse after a median of 36 months. Results: After the first relapse-free year, 14 out of the remaining 34 IBD patients relapsed (41%; 5/12 [42%] CD and 9/22 [41%] UC/IBDU). Univariate analysis indicated no associations with any predictive factors. Re-treatment was effective in 90% (26/29) of patients. Conclusion: Of IBD patients in deep remission at the time of cessation of TNF alpha-blocking therapy, up to 60% experience a clinical or endoscopic relapse after a median follow-up time of 36 months (95% CI 31-41 months). No individual risk factors predicting relapse could be identified. However, the initial response to a restart of TNF alpha-blockers seems to be effective and well tolerated.
  • Economides, Marcos; Ranta, Kristian; Nazander, Albert; Hilgert, Outi; Goldin, Philippe R.; Raevuori, Anu; Forman-Hoffman, Valerie (2019)
    Background: Depression is one of the most common mental health disorders and severely impacts one's physical, psychological, and social functioning. To address access barriers to care, we developed Ascend-a smartphone-delivered, therapist-supported, 8-week intervention based on several evidence-based psychological treatments for depression and anxiety. A previous feasibility study with 102 adults with elevated depression reported that Ascend is associated with a postintervention reduction in depression symptoms. Objective: We aimed to examine whether Ascend is associated with a reduction in symptoms of anxiety, and importantly, whether reductions in symptoms of depression and anxiety are maintained up to 12-months postintervention. Methods: We assessed whether the previously reported, end-of-treatment improvements seen in the 102 adults with elevated symptoms of depression extended up to 12 months posttreatment for depression symptoms (measured by the Patient Health Questionnaire-9 [PHQ-9]) and up to 6 months posttreatment for anxiety symptoms (added to the intervention later and measured using the Generalized Anxiety Disorder-7 [GAD-7] scale). We used linear mixed effects models with Tukey contrasts to compare time points and reported intention-to-treat statistics with a sensitivity analysis. Results: The intervention was associated with reductions in symptoms of depression that were maintained 12 months after the program (6.67-point reduction in PHQ-9 score, 95% CI 5.59-7.75; P= 10) reported clinically significant improvement at the 12-month follow-up (at least 50% reduction in PHQ-9 score and postprogram score Conclusions: There is limited evidence on whether outcomes associated with smartphone-based interventions for common mental health problems are maintained posttreatment. Participants who enrolled in Ascend experienced clinically significant reductions in symptoms of depression and anxiety that were maintained for up to 1 year and 6 months after the intervention, respectively. Future randomized trials are warranted to test Ascend as a scalable solution to the treatment of depression and anxiety.
  • Laajala, Teemu D.; Seikkula, Heikki; Sadat, Fatemeh Seyednasrollah; Mirtti, Tuomas; Bostrom, Peter J.; Elo, Laura L. (2016)
    Ultrasensitive prostate-specific antigen (u-PSA) remains controversial for follow-up after radical prostatectomy (RP). The aim of this study was to model PSA doubling times (PSADT) for predicting biochemical recurrence (BCR) and to capture possible discrepancies between u-PSA and traditional PSA (t-PSA) by utilizing advanced statistical modeling. 555 RP patients without neoadjuvant/adjuvant androgen deprivation from the Turku University Hospital were included in the study. BCR was defined as two consecutive PSA values > 0.2 ng/mL and the PSA measurements were log(2)-transformed. One third of the data was reserved for independent validation. Models were first fitted to the post-surgery PSA measurements using cross-validation. Major trends were then captured using linear mixed-effect models and a predictive generalized linear model effectively identified early trends connected to BCR. The model generalized for BCR prediction to the validation set with ROC-AUC of 83.6% and 95.1% for the 1 and 3 year follow-up censoring, respectively. A web-based tool was developed to facilitate its use. Longitudinal trends of u-PSA did not display major discrepancies from those of t-PSA. The results support that u-PSA provides useful information for predicting BCR after RP. This can be beneficial to avoid unnecessary adjuvant treatments or to start them earlier for selected patients.
  • Vähämurto, Pauli; Pollari, Marjukka; Clausen, Michael R.; d'Amore, Francesco; Leppä, Sirpa; Mannisto, Susanna (2020)
    Low absolute lymphocyte counts (ALC) and high absolute monocyte counts (AMC) are associated with poor survival in patients with diffuse large B-cell lymphoma (DLBCL). We studied the prognostic impact of the ALC and AMC in patients with testicular DLBCL (T-DLBCL). T-DLBCL patients were searched using Southern Finland University Hospital databases and the Danish lymphoma registry. The progression free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier and Cox proportional hazards methods. We identified 178 T-DLBCL patients, of whom 78 (44%) had a low ALC at diagnosis. The ALC did not correlate with survival in the whole cohort. However, among the patients treated with rituximab (R) containing regimen, a pre-therapeutic low ALC was associated with an increased risk of progression (HR 1.976, 95% CI 1.267-3.086,p= 0.003). Conversely, intravenous (iv) CNS directed chemotherapy translated to favorable outcome. In multivariate analyses, the advantage of an iv CNS directed chemotherapy was sustained (PFS, HR 0.364, 95% CI 0.175-0.757,p= 0.007). The benefit of R and intravenous CNS directed chemotherapy was observed only in non-lymphopenic patients. The AMC did not correlate with survival. A low ALC is an adverse prognostic factor in patients with T-DLBCL. Alternative treatment options for lymphopenic patients are needed.
  • Kiiskinen, Tuomo; Korpi, Esa R.; Aitta-aho, Teemu (2019)
    Extinction and reinstatement of morphine-induced conditioned place preference were studied in glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-receptor GluA1 subunit-deficient mice (global GluA1-KO mice). In line with previous findings, both acquisition and expression of conditioned place preference to morphine (20 mg/kg, subcutaneously) were fully functional in GluA1 KO mice compared with wild-type littermate controls (GluA1-WT), thus enabling the study of extinction. With a 10-session extinction paradigm, the GluA1 KO mice showed complete extinction similar to that of the GluA1-WT mice. Morphine-induced reinstatement (10 mg/kg, subcutaneously) was detected in both mouse lines. GluA1 KO mice moved more during all the phases of the experiment, including the place conditioning trials, extinction sessions, and place preference tests. The results suggest that the GluA1 subunit may be dispensable or prone to compensation at the neural circuitries delineating extinction and reinstatement. The GluA1 KO mice show altered long-term between-session habituation, which extends longer than previously anticipated.
  • Malin, Maarit; Jaakkola, Nina; Luukkonen, Ritva; Heloma, Antero; Lamminpaa, Anne; Reijula, Kari (2020)
    Objectives: Occupational health (OH) professionals could play a prominent role in smoking cessation treatment and support (SCTS) and help individuals and workplaces become smoke free. However, their role has not been evaluated. The aim of this study was to assess differences between OH professionals' perceptions of their role in SCTS by measuring three groups of OH professionals' attitudes, knowledge, and motivation concerning SCTS. Methods: We collected data through an online survey completed by a cross-sectional sample of OH professionals: OH physicians (n = 182), OH nurses (n = 296), and OH physiotherapists (n = 96), collected from national trade union registers. The differences between the OH professional groups were analyzed using ANOVA, the Kruskal-Wallis, and chi-square tests. Results: The OH professionals had a positive attitude toward offering SCTS and were highly motivated to enhance their knowledge of this topic and acquire further training. The OH physicians and OH nurses assessed their current knowledge as sufficient. Conversely, the OH physiotherapists' level of knowledge was seen as insufficient. Traditionally, OH physicians and OH nurses have been responsible for carrying out SCTS, but the majority of the OH physiotherapists thought that SCTS should also be included in their job description. Conclusions: All the OH professionals were highly motivated to deepen their knowledge of SCTS. The barriers between different professionals need to be recognized in occupational health services (OHS). OHS should organize its SCTS more effectively, strengthen their contributions to smoking cessation programs, and recognize the potential of OH physiotherapists for providing SCTS and enable them to expand their training.
  • Canaani, Jonathan; Labopin, Myriam; Itälä-Remes, Maija; Blaise, Didier; Socie, Gerard; Forcade, Edouard; Maertens, Johan; Wu, Depei; Malladi, Ram; Cornelissen, Jan J.; Huynh, Anne; Bourhis, Jean Henri; Esteve, Jordi; Mohty, Mohamad; Nagler, Arnon (2019)
    Baseline cytogenetic studies at diagnosis remain the single most important determinant of outcome in patients with acute myeloid leukemia (AML). However, the prognostic role of the complete gamut of cytogenetic aberrations in AML patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently undefined. In addition, their significance in conjunction with FLT3-ITD status has not been addressed thus far. Using the ALWP/EBMT registry we conducted a retrospective analysis to determine the clinical outcomes of AML patients undergoing allo-HSCT with respect to specific recurring cytogenetic abnormalities complemented with FLT3-ITD status. We analyzed a cohort consisting of 8558 adult AML patients who underwent allo-HSCT from either a matched sibling or a matched unrelated donor. Patients with inv(3)(q21q26)/t(3;3)(q21;q26), del(5q), monosomy 7, chromosome 17p abnormalities, t(10;11)(p11-14;q13-23), t(6;11)(q27;q23), as well as those patients with a monosomal or complex karyotype experienced significantly inferior leukemia-free survival (LFS) compared to patients with a normal karyotype. Trisomy 14, del(9q), and loss of chromosome X were associated with improved LFS rates. A novel prognostic model delineating 5 distinct groups incorporating cytogenetic complexity and FLT3-ITD status was constructed with significant prognostic implications. Our analysis supports the added prognostic significance of FLT3-ITD to baseline cytogenetics in patients undergoing allo-HSCT.
  • Af Björkesten, C. -G.; Jussila, A.; Kemppainen, H.; Hallinen, T.; Soini, E.; Mankinen, P.; Valgardsson, S.; Veckman, V.; Nissinen, R.; Naessens, D.; Molander, P. (2019)
    Background and Aims: A retrospective non-interventional, multi-centre patient chart review study was conducted to investigate the association of faecal calprotectin (FC) 1 year (+/- 2 months) after biological therapy initiation with composite event-free survival (CEFS) consisting of surgical procedures, corticosteroid initiation, treatment failure or dose increase in patients with Crohn's disease (CD). In addition, the correlations of FC and other tests of disease activity were assessed. Materials and methods: Data on Finnish CD patients initiating a biological therapy between 2010 and 2016, were collected. The association of FC and CEFS was analysed with Kaplan-Meier and Cox proportional hazard modelling. The correlations were tested with Pearson's test. Results: Biological therapy was initiated in 186 patients, of which 87 (46.8%) had FC results available at 1 year and 80 had follow-up exceeding 14 months. The characteristics of patients with and without FC results were similar. Patients with elevated FC (>250 mu g/g) had a significantly increased risk of experiencing composite event (HR 3.4, 95% CI: 1.3-8.9; p = .013) when compared to patients with normal FC (FC
  • Poire, Xavier; Labopin, Myriam; Polge, Emmanuelle; Volin, Liisa; Finke, Juergen; Ganser, Arnold; Blaise, Didier; Yakoub-Agha, Ibrahim; Beelen, Dietrich; Forcade, Edouard; Lioure, Bruno; Socie, Gerard; Niederwieser, Dietger; Labussiere-Wallet, Helene; Maertens, Johan; Cornelissen, Jan; Craddock, Charles; Mohty, Mohamad; Esteve, Jordi; Nagler, Arnon (2020)
    Monosomy 7 or deletion 7q (-7/7q-) is the most frequent adverse cytogenetic features reported in acute myeloid leukemia (AML), and is a common indication for allogeneic stem cell transplantation (SCT). Nevertheless, -7/7q- occurs frequently with other high-risk cytogenetic abnormalities such as complex karyotype (CK), monosomal karyotype (MK), monosomy 5 or deletion 5q (-5/5q-), 17p abnormalities (abn(17p)) or inversion of chromosome 3 (inv(3)), the presence of which may influence the outcomes after SCT. A total of 1109 patients were allocated to this study. Two-year probability of leukemia-free survival (LFS) and overall survival (OS) were 30% and 36%, respectively. Two-year probability of non-relapse mortality (NRM) was 20%. We defined five different cytogenetic subgroups: the "-7/7q- +/- CK group- designated group1," the "MK group-designated group 2," the "-5/5q- group- designated group 3," the "abn(17p) group- designated group 4" and the "inv(3) group- designated group 5." The 2-year probability of LFS in first remission was 48% for group 1, 36.4% for group 2, 28.4% for group 3, 19.1% for group 4 and 17.3% for group 5, respectively (P <.001). Multivariate analysis confirmed those significant differences across groups. Note, SCT in -7/7q- AML provides durable responses in one third of the patients. The presence of -7/7q- with or without CK in the absence of MK, abn(17p) or inv (3) is associated with a better survival after SCT. On the contrary, addition of MK, -5/5q-, abn(17p) or inv(3) identifies a sub-group of patients with poor prognosis even after SCT.
  • Tuovinen, Eeva-Liisa; Saarni, Suoma E.; Kinnunen, Taru H.; Ollila, Hanna; Ruokolainen, Otto; Patja, Kristiina; Männistö, Satu; Jousilahti, Pekka; Kaprio, Jaakko; Korhonen, Tellervo (2018)
    Background: Nicotine-dependent smokers find it difficult to quit smoking. Additionally, smoking-specific weight concerns may affect smoking cessation although the evidence is controversial. We investigated whether smoking-specific weight concerns predict the probability of cessation and, if so, whether the effect varies according to the level of nicotine dependence. Methods: The study was conducted with a population-based sample of 355 adult daily smokers who participated in the baseline examination in 2007 and in the 2014 follow-up. Baseline nicotine dependence was classified as low or high (Fagerstrom Test for Nicotine Dependence; 0-3 vs. 4-10 points). Within these groups, we examined whether baseline weight concerns predict smoking status (daily, occasional, ex-smoker) at follow-up by using multinomial logistic regression with adjustment for multiple covariates. Results: Among low-dependent participants at baseline, 28.5% had quit smoking, while among highly dependent participants 26.1% had quit smoking. The interaction between weight concerns and nicotine dependence on follow-up smoking status was significant. Among participants with low nicotine dependence per the fully adjusted model, greater weight concerns predicted a lower likelihood of both smoking cessation (relative risk ratio 0.93 [95% CI 0.87-1.00]) and smoking reduction to occasional occurrence (0.89 [95% CI 0.81-0.98]). Weight concerns were not associated with follow-up smoking status among participants with high nicotine dependence. Conclusions: Weight concerns are associated with a smaller likelihood of quitting among smokers with low nicotine dependence. Weight concerns should be addressed in smoking cessation interventions, especially with smokers who have low nicotine dependence.