Multicenter implementation of geriatric assessment in Belgian patients with cancer: A survey on treating physicians' general experiences and expectations.
; ; et al
in Journal of geriatric oncology (in press)
OBJECTIVES: The aim of this study is to identify treating physicians' general experiences and expectations regarding geriatric assessment (GA) in older patients with cancer. MATERIALS AND METHODS: A ... [more ▼]
OBJECTIVES: The aim of this study is to identify treating physicians' general experiences and expectations regarding geriatric assessment (GA) in older patients with cancer. MATERIALS AND METHODS: A survey was carried out in 9 Belgian hospitals, which participated in a national GA implementation project focusing on older patients with cancer. A newly developed questionnaire was completed by their treating physicians. Data collection comprised of reviewing hospital data, general respondent data, and treating physicians' general experiences and expectations regarding GA. Descriptive statistics were calculated. RESULTS: Eighty-two physicians from 9 hospitals participated. The GA team composition can vary substantially, with a nurse as core member. Ideally, all older patients with cancer in whom a treatment decision is necessary, should benefit from the GA. Nearly all GA domains are reported as very important. Availability of GA results can be improved. Treating physicians want geriatricians to coordinate geriatric recommendations related to the identified GA problems, and expect from trained healthcare workers (THCWs) to collect GA data, to report GA results, and to follow-up the implementation of geriatric recommendations. CONCLUSION: This study identifies relevant information for improving the implementation of GA in older patients with cancer in Belgium and reveals priorities for a THCW from the treating physician's point of view. To increase the effectiveness of GA, further efforts are needed to improve the implementation of geriatric recommendations. [less ▲]Detailed reference viewed: 28 (2 ULg)
High-Dose Cytarabine in Induction Treatment Improves the Outcome of Adult Patients Younger Than Age 46 Years With Acute Myeloid Leukemia: Results of the EORTC-GIMEMA AML-12 Trial
; ; et al
in Journal of Clinical Oncology (2014), 32(3), 219-228
Purpose : Cytarabine plays a pivotal role in the treatment of patients with acute myeloid leukemia (AML). Most centers use 7 to 10 days of cytarabine at a daily dose of 100 to 200 mg/m2 for remission ... [more ▼]
Purpose : Cytarabine plays a pivotal role in the treatment of patients with acute myeloid leukemia (AML). Most centers use 7 to 10 days of cytarabine at a daily dose of 100 to 200 mg/m2 for remission induction. Consensus has not been reached on the benefit of higher dosages of cytarabine. Patients and Methods : The European Organisation for Research and Treatment of Cancer (EORTC) and Gruppo Italiano Malattie Ematologiche dell’ Adulto (GIMEMA) Leukemia Groups conducted a randomized trial (AML-12; Combination Chemotherapy, Stem Cell Transplant and Interleukin-2 in Treating Patients With Acute Myeloid Leukemia) in 1,942 newly diagnosed patients with AML, age 15 to 60 years, comparing remission induction treatment containing daunorubicin, etoposide, and either standard-dose (SD) cytarabine (100 mg/m2 per day by continuous infusion for 10 days) or high-dose (HD) cytarabine (3,000 mg/m2 every 12 hours by 3-hour infusion on days 1, 3, 5, and 7). Patients in complete remission (CR) received a single consolidation cycle containing daunorubicin and intermediate-dose cytarabine (500 mg/m2 every 12 hours for 6 days). Subsequently, a stem-cell transplantation was planned. The primary end point was survival. Results : At a median follow-up of 6 years, overall survival was 38.7% for patients randomly assigned to SD cytarabine and 42.5% for those randomly assigned to HD cytarabine (log-rank test P = .06; multivariable analysis P = .009). For patients younger than age 46 years, survival was 43.3% and 51.9%, respectively (P = .009; multivariable analysis P = .003), and for patients age 46 to 60 years, survival was 33.9% and 32.9%, respectively (P = .91). CR rates were 72.0% and 78.7%, respectively (P = .001) and were 75.6% and 82.4% for patients younger than age 46 years (P = .01) and 68.3% and 74.8% for patients age 46 years and older (P = .03). Patients of all ages with very-bad-risk cytogenetic abnormalities and/or FLT3-ITD (internal tandem duplication) mutation, or with secondary AML benefitted from HD cytarabine. Conclusion : HD cytarabine produces higher remission and survival rates than SD cytarabine, especially in patients younger than age 46 years. [less ▲]Detailed reference viewed: 10 (1 ULg)
Guidelines of the Belgian Hematological Society for newly diagnosed and relapsed follicular lymphoma 2012
; ; et al
in Belgian Journal of Hematology (2012), 3(2), 41-50
Follicular lymphoma is an indolent lymphoma that has occurred more frequently over the last decades. In this article we present an overview of the diagnosis and initial work-up, prognostic scoring system ... [more ▼]
Follicular lymphoma is an indolent lymphoma that has occurred more frequently over the last decades. In this article we present an overview of the diagnosis and initial work-up, prognostic scoring system and choice of therapy. For limited stage disease radiotherapy is the treatment of choice, and may have a curative potential. For advanced stages treatment should be initiated upon certain criteria, and is essentially based on immunochemotherapy, rituximab plus chemotherapy. The choice of chemotherapy depends on age, frailty, and specific toxicities of chemotherapy. Maintenance therapy with rituximab after induction has become standard practice. Since virtually all patients relapse eventually, an overview of the treatment in the relapsed setting is given. The treatment is then again based on immunochemotherapy but there is also a place for radio-immunotherapy, or immunotherapy alone. For young patients, high dose chemotherapy with autologous stem cell rescue should be considered. A brief overview on novel agents, and agents that are in the pipeline, is given. We conclude with some recommendations for follow-up. [less ▲]Detailed reference viewed: 46 (1 ULg)
EORTC Leukemia Group achievements
; ; et al
in EJC Supplements (2012), I
The EORTC Leukemia Group (LG) has a long history of promoting the study of leukemias and related malignancies and reports here on three of their most significant achievements. In acute myelogenous ... [more ▼]
The EORTC Leukemia Group (LG) has a long history of promoting the study of leukemias and related malignancies and reports here on three of their most significant achievements. In acute myelogenous leukemia (AML), the LG and Italian group GIMEMA started their fruitful collaboration in 1986 with the AML-8 trial with 1519 inclusions. In the AML-8A trial, in patients who reached complete remission, without a HLA identical sibling, autograft provided longer disease-free survival than a second course of consolidation, whereas the best outcome was observed in patients with a donor, who had to be allografted. The AML-10 trial set a new standard of treatment for induction/consolidation with replacement of daunorubicin by either idarubicin or mitoxantrone. The AML-12 trial tested the effect of high-dose cytosinearabinoside during induction (2109 inclusions, data base locked in August 2011 for final analysis). Development of intergroup trials focusing on subgroups of AML bearing specific genetic abnormalities is now mandatory to validate the “targeted approach” of driving molecular events. In high-risk myelodysplastic syndrome (MDS), the phase III trial conducted by the LG in collaboration with the German MDS Study Group showed that the response rate of decitabine versus best supportive care was higher (complete or partial remissions, 19% versus 0%, and hematologic improvement, 15% versus 2%), progression-free survival was significantly prolonged (median 6.6 versus 3 months), cumulative incidence of AML was significantly decreased (22% versus 33% at one year), but the impact on OS was less evident (median 10.1 versus 8.5 months; hazard ratio 0.88). Quality of life had improved significantly in patients in the decitabine arm. The assessment of HDAC inhibitors, such as vorinostat, will probably be tested in the next trial. Also in MDS, relevant genetic lesions involved in the pathogenesis of this disease were identified using single nucleotide polymorphisms array-based genomic profiling and genomic sequencing in 102 patients with MDS. Acquired abnormalities of the TET2 gene were identified in 26% of the cases and in the EZH2 gene in 5−10% of the patients. TET2 mutations were detected in 96% of the bone marrow cells, including CD34+ progenitor cells, suggesting that TET2 mutations could be an early event during disease evolution. In normal bone marrow, TET2 expression was elevated in granulocytes, suggesting a role in myelopoiesis. Conclusion: during the last 25 years the EORTC LG in cooperation with GIMEMA made a considerable contribution to the improvement of treatment results of patients with acute leukemia or MDS. [less ▲]Detailed reference viewed: 20 (2 ULg)
Valproate synergizes with purine nucleoside analogues to induce apoptosis of B-chronic lymphocytic leukaemia cells.
Bouzar, Amel ; Boxus, Mathieu ; et al
in British journal of haematology (2009), 144(1),Detailed reference viewed: 54 (12 ULg)
Reduction of B cell turnover in chronic lymphocytic leukaemia.
; ; et al
in British Journal of Haematology (2008), 143(2), 240-7
Whether chronic lymphocytic leukaemia (CLL) is a latent or a proliferating disease has been intensively debated. Whilst the dogma that CLL results from accumulation of dormant lymphocytes is supported by ... [more ▼]
Whether chronic lymphocytic leukaemia (CLL) is a latent or a proliferating disease has been intensively debated. Whilst the dogma that CLL results from accumulation of dormant lymphocytes is supported by the unresponsiveness of leukaemic cells to antigens and polyclonal activators, recent in vivo kinetic measurements indicate that B lymphocytes do divide at significant rates in CLL. However, an important and still unanswered question is whether CLL cells proliferate faster or slower compared with their normal counterparts. This report addressed directly this point and compared B-cell kinetics in CLL subjects and healthy controls, using a pulse-chase approach based on incorporation of deuterium from 6,6-(2)H(2)-glucose into DNA. We confirmed that B cells proliferated at significant levels in CLL but found that the proliferation rates were reduced compared with healthy subjects (mean 0.47 vs. 1.31%/d respectively, P = 0.007), equivalent to an extended doubling time of circulating B cells (147 d vs. 53 d). In conclusion, CLL B cells proliferate at reduced levels compared with healthy controls. CLL is thus characterized by an aberrant B-cell kinetics with a decrease in cell turnover, an observation that may impact on elaboration of efficient therapeutic strategies. [less ▲]Detailed reference viewed: 47 (12 ULg)
Valproic acid induces apoptosis in chronic lymphocytic leukemia cells through activation of the death receptor pathway and potentiates TRAIL response.
; Gillet, Nicolas ; et al
in Experimental hematology (2007), 35(10), 1527-37
OBJECTIVE: Chronic lymphocytic leukemia (CLL) cells develop chemoresistance over time associated with defects in apoptosis pathway. Novel treatment strategies are required to overcome resistance of cells ... [more ▼]
OBJECTIVE: Chronic lymphocytic leukemia (CLL) cells develop chemoresistance over time associated with defects in apoptosis pathway. Novel treatment strategies are required to overcome resistance of cells to commonly used agents. The effects of valproic acid (VPA), an antiepileptic drug with histone deacetylase inhibitory activity, on mononuclear cells isolated from 40 CLL patients were evaluated. METHODS: CLL cells were treated with increasing doses of VPA (0.5, 1, 2, and 5 mM). The mode of cytotoxic drug action was determined by annexin binding, DNA fragmentation, and caspase activation. RESULTS: Exposure of CLL cells to VPA resulted in dose-dependent cytotoxicity and apoptosis in the 40 CLL patients. VPA treatment induced apoptotic changes in CLL cells including phosphatidylserine externalization and DNA fragmentation. The mean apoptotic rates were similar between IgV(H) mutated and unmutated patients, the latter presenting a more aggressive clinical course. VPA induced apoptosis via the extrinsic pathway involving engagement of the caspase-8-dependent cascade. Although CLL cells are commonly resistant to death receptor-induced apoptosis, VPA significantly increased sensitivity of leukemic cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and led to downregulation of c-FLIP (L) expression. VPA caused no potentialization of TRAIL-induced apoptosis on normal B cells. In addition, VPA overcame the prosurvival effects of bone marrow stromal cells. CONCLUSION: These findings point out that the combination of TRAIL and VPA, at clinically relevant concentration, may be valuable in the treatment of CLL. [less ▲]Detailed reference viewed: 50 (4 ULg)
Phase III randomized study comparing 5 or 10 microg per kg per day of filgrastim for mobilization of peripheral blood progenitor cells with chemotherapy, followed by intensification and autologous transplantation in patients with nonmyeloid malignancies.
; Baudoux, Etienne ; et al
in Transfusion (2003), 43(1), 50-7
BACKGROUND: It is not known whether increasing the dose of filgrastim after mobilizing chemotherapy improves collection of peripheral blood progenitor cells (PBPC) and leads to faster hematopoietic ... [more ▼]
BACKGROUND: It is not known whether increasing the dose of filgrastim after mobilizing chemotherapy improves collection of peripheral blood progenitor cells (PBPC) and leads to faster hematopoietic engraftment after autologous transplantation. STUDY DESIGN AND METHODS: A randomized, open-label, multicenter trial was carried out in patients with breast cancer, multiple myeloma, and lymphoma, in which patients were randomized to receive 5 or 10 microg per kg per day of filgrastim after standard chemotherapy to mobilize PBPCs. After high-dose chemotherapy, the components from the first two leukapheresis procedures were returned, and all patients received 5 microg per kg day of filgrastim after transplantation. RESULTS: A total of 131 patients were randomized, of whom 128 were mobilized (Group A, 5 microg/kg, n = 66; Group B, 10 microg/kg, n = 62) and 112 were transplanted. Only six patients were not transplanted because of insufficient CD34+ cell numbers. The median number of CD34+ cells collected in the first two leukapheresis procedures tended to be higher in Group B than in Group A (12.0 vs. 7.2 x 10(6)/kg, NS), but after transplantation there was no significant difference in median times to platelet (9 days in both groups) or neutrophil (8 days in both groups) engraftment or the number of platelet transfusions (three in both groups). A subsequent subgroup analysis separating patients transplanted after first- or second-line chemotherapy also showed no measurable impact of filgrastim dose on the median CD34+ cell yield or on platelet engraftment in either subgroup. CONCLUSION: PBPC mobilization with chemotherapy and 5 microg per kg of filgrastim is very efficient, and 10 microg per kg of filgrastim does not provide additional clinical benefit. [less ▲]Detailed reference viewed: 135 (6 ULg)
The belgian experience in unrelated donor bone marrow transplantation: identification of center experience as an important prognostic factor.
Dresse, Marie-Françoise ; ; et al
in Haematologica (1999), 84(7), 637-42
BACKGROUND AND OBJECTIVE: We reviewed all unrelated donor bone marrow transplants (UDBMT) performed in Belgium up to December 1995 to identify prognostic factors for relapse, transplant-related mortality ... [more ▼]
BACKGROUND AND OBJECTIVE: We reviewed all unrelated donor bone marrow transplants (UDBMT) performed in Belgium up to December 1995 to identify prognostic factors for relapse, transplant-related mortality and survival. DESIGN AND METHODS: A total of 163 UDBMT were performed in 92 males and 71 females aged 1-55 (median 26) years. Patients were transplanted for ALL (n=35), AML (n=34), CML (n=51), other myeloid malignancies (n=14), SAA (n=21) or miscellaneous other diseases (n=8). Most patients had advanced disease; a few patients were in CR1 (n=10) or early chronic phase (CP) of CML (n=5). RESULTS: Overall survival at 5 yrs was 17% (95% confidence interval: 8-32%), but survival was significantly better for patients with non-malignant disorders (55% at 4 yrs). The relapse rate +/-SE was projected to be 40 (28-54)% at 5 yrs, 36 (20-56)% for standard-risk and 68 (43-85)% for high-risk malignancies (p=0.0029). There was no relapse in CML patients transplanted in 1st CP compared to 68% at 4 yrs with more advanced CML (p=0.0033). Grade II-IV acute graft-versus-host disease (aGVHD) occurred in 55% by day 100 and was strongly modulated by age, ranging from 41% in <20-yr-old to 80% in >40-yr-old patients (p=0. 0021). Transplant-related mortality (TRM) was projected to be 72 (52-87)% at 5 yrs including 2 very late deaths from lung fibrosis and secondary cancer. Main causes of death were original disease in 27, secondary malignancy in 2, GVHD in 28, interstitial pneumonia in 21, other infections in 19, and miscellaneous toxic causes in 21 patients. In multivariate analysis, the relapse rate was strongly dependent on the disease status (p=0.0029), TRM being significantly worse with older age (p=0.0049), and overall survival being significantly worse in more advanced disease (p=0.0006), after a second transplant (p=0.0166), in centers of smaller size (p=0.0316) and in older patients (NS). INTERPRETATION AND CONCLUSIONS: Although results have improved somewhat in recent years, UDBMT remains a procedure with a high TRM. UDBMT should be performed in patients with less advanced diseases and in centers with more experience, particularly in the treatment of adult patients. [less ▲]Detailed reference viewed: 82 (6 ULg)