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BACKGROUND: The use of spinal cord stimulation (SCS) in patients with refractory angina pectoris (RAP) is still under debate. Studies up to date have shown a positive effect with an improvement in quality of life. However, no double blinded randomized controlled trials have been performed. HYPOTHESIS & METHODS: The objective of this trial is to investigate if high density SCS leads to a significant reduction in the amount of myocardial ischemia in patients with RAP. Eligible patients must meet the criteria for RAP, have proven ischemia and a positive transcutaneous electrical nerve stimulator treadmill test. Patients who meet the inclusion criteria will receive an implanted spinal cord stimulator. Patients receive 6 months of high density SCS and 6 months of no stimulation using a cross-over design. The order of the treatment options is determined using randomization. The primary endpoint is the effect of SCS measured by the change in percentage of myocardial ischemia using myocardial perfusion positron emission tomography scan. Key secondary endpoints are patient related outcome measures, major cardiac adverse events and safety endpoints. The follow-up period is 1 year for the primary and key secondary endpoints. RESULTS: The SCRAP trial began enrollment on December 21, 2021 and is set to complete the primary assessments in June 2025. To date, January 2, 2023, 18 patients have been enrolled in the study and 3 patients have completed the 1-year follow-up. CONCLUSIONS: The SCRAP trial is an investigator-initiated, single-center, double-blind, placebo-controlled, and cross-over randomized controlled trial investigating the efficacy of SCS in patients with RAP. (ClinicalTrials. gov Identifier: NCT04915157).
Subject(s)
Coronary Artery Disease , Spinal Cord Stimulation , Humans , Angina Pectoris/diagnosis , Angina Pectoris/therapy , Heart , Quality of Life , Randomized Controlled Trials as Topic , Spinal Cord Stimulation/methods , Treatment OutcomeABSTRACT
INTRODUCTION: In a Dutch heart centre, a dedicated chronic total occlusion (CTO) team was implemented in June 2017. The aim of this study was to the evaluate treatment success and clinical outcomes before and after this implementation. METHODS: A total of 662 patients who underwent percutaneous coronary intervention (PCI) for a CTO between January 2013 and June 2020 were included and divided into pre- and post-CTO team groups. The primary endpoint was the angiographic success rate of CTO-PCI. Secondary endpoints included angiographic success stratified by complexity using the JCTO score and the following clinical outcomes: in-hospital complications and myocardial infarction, target vessel revascularisation, all-cause mortality, quality of life (QoL) and major adverse cardiac events (MACE) at 30-day and 1year follow-up. RESULTS: Compared with the pre-CTO team group, the success rate in the post-CTO team group was higher after the first attempt (81.4% vs 62.7%; pâ¯< 0.001) and final attempt (86.7% vs 73.8%; pâ¯= 0.001). This was mainly driven by higher success rates for difficult and very difficult CTO lesions according to the JCTO score. The MACE rate at 1 year was lower in the post-CTO team group than in the pre-CTO team group (6.4% vs 16.0%; pâ¯< 0.01), while it was comparable at 30-day follow-up (0.1% vs 1.7%; pâ¯= 0.74). Angina symptoms were significantly reduced at 30-day and 1year follow-up, and QoL scores were higher after 1 year. CONCLUSION: This study demonstrated higher success rates of CTO-PCI and improved clinical outcomes and QoL at 1year follow-up after implementation of a dedicated CTO team using the hybrid algorithm.
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BACKGROUND: The presence of mesorectal fascia (MRF) invasion, grade 4 extramural venous invasion (EMVI), tumour deposits (TD) or extensive or bilateral extramesorectal (lateral) lymph nodes (LLN) on MRI has been suggested to identify patients with indisputable, extensive locally advanced rectal cancer (LARC), at high risk of treatment failure. The aim of this study is to evaluate whether or not intensified chemotherapy prior to neoadjuvant chemoradiotherapy improves the complete response (CR) rate in these patients. METHODS: This multicentre, single-arm, open-label, phase II trial will include 128 patients with non-metastatic high-risk LARC (hr-LARC), fit for triplet chemotherapy. To ensure a study population with indisputable, unfavourable prognostic characteristics, hr-LARC is defined as LARC with on baseline MRI at least one of the following characteristics; MRF invasion, EMVI grade 4, enlarged bilateral or extensive LLN at high risk of an incomplete resection, or TD. Exclusion criteria are the presence of a homozygous DPD deficiency, distant metastases, any chemotherapy within the past 6 months, previous radiotherapy within the pelvic area precluding standard chemoradiotherapy, and any contraindication for the planned treatment. All patients will be planned for six two-weekly cycles of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) prior to chemoradiotherapy (25 × 2 Gy or 28 × 1.8 Gy with concomitant capecitabine). A resection will be performed following radiological confirmation of resectable disease after the completion of chemoradiotherapy. A watch and wait strategy is allowed in case of a clinical complete response. The primary endpoint is the CR rate, described as a pathological CR or a sustained clinical CR one year after chemoradiotherapy. The main secondary objectives are long-term oncological outcomes, radiological and pathological response, the number of resections with clear margins, treatment-related toxicity, perioperative complications, health-related costs, and quality of life. DISCUSSION: This trial protocol describes the MEND-IT study. The MEND-IT study aims to evaluate the CR rate after intensified chemotherapy prior to concomitant chemoradiotherapy in a homogeneous group of patients with locally advanced rectal cancer and indisputably unfavourable characteristics, defined as hr-LARC, in order to improve their prognosis. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04838496 , registered on 02-04-2021 Netherlands Trial Register: NL9790. PROTOCOL VERSION: Version 3 dd 11-4-2022.
Subject(s)
Neoplasms, Second Primary , Rectal Neoplasms , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Camptothecin/analogs & derivatives , Chemoradiotherapy/methods , Clinical Trials, Phase II as Topic , Fluorouracil/therapeutic use , Humans , Leucovorin , Multicenter Studies as Topic , Neoadjuvant Therapy/methods , Neoplasm Staging , Neoplasms, Second Primary/pathology , Organoplatinum Compounds , Quality of Life , Rectal Neoplasms/pathology , Treatment OutcomeABSTRACT
INTRODUCTION: Efficiency and safety are important features in the selection of lead extraction tools. We report our experience with different endovascular techniques to extract individual pacing and defibrillator leads. METHODS: This is a single-centre study of consecutive lead extraction procedures from 1997 until 2019. A total of 1725 leads were extracted in 775 patients. Direct traction sufficed for 588 leads, and 22 leads were primarily removed by surgery. The endovascular techniques used in the remainder were a laser sheath (190 leads), the femoral approach (717 leads) and rotating mechanical sheaths (208 leads). RESULTS: The three approaches were comparably effective in completely removing the leads (pâ¯= 0.088). However, there were more major complications with the laser sheath than with the femoral approach or rotating mechanical sheaths (8.4%, 0.5% and 1.2%, respectively). Therefore, the procedural result-extraction without major complications-was significantly better with both the femoral approach and rotating mechanical sheaths than with the laser sheath (pâ¯< 0.001). This result was confirmed after propensity score matching to compensate for differences between lead cohorts (pâ¯= 0.007). Cross-over to another endovascular tool was necessary in 7.9%, 7.1% and 8.2% of laser, femoral and rotating mechanical attempts, respectively. CONCLUSION: All three endovascular lead extraction techniques showed comparable efficacy. However, there were significantly more major complications using the laser sheath compared to the femoral approach or rotating mechanical sheaths, leading us to abandon the laser technique. Importantly, no single endovascular technique sufficed to successfully extract all leads.
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AIMS: Percutaneous coronary intervention (PCI) of bifurcation lesions can be performed using various techniques. The aim of this study was to analyse the outcome of various techniques of bifurcation stenting in all patients undergoing bifurcation stenting at one large intervention centre in 2013, taking into account that more complex lesions might more often warrant a two-stent technique. METHODS AND RESULTS: This retrospective study included 260 consecutive patients who underwent non-primary PCI of a bifurcation lesion at the Catharina Hospital, Eindhoven, in 2013. Patients were classified into two groups: one-stent technique (provisional stenting), and two-stent techniques (culotte, crush and Tstenting). The primary endpoint was the rate of restenosis at 1 year. The secondary endpoints were procedural complications (side branch occlusion, periprocedural infarction, and death) and major adverse cardiac events (MACE) at 1 year. Periprocedural complications occurred in 15 patients (5.8 %) with no difference between the groups (p = 0.27). After 1 year, restenosis occurred in 3.2 % of the patients in the one-stent technique group and 7.3 % in the two-stent technique group (p = 0.20). MACE at 1 year did not differ between the groups at 11.9 % and 12.2 % respectively (p = 1.00). CONCLUSIONS: This study shows that there is no significant difference between restenosis rate, or any other outcome parameter, with the different techniques of bifurcation stenting. Since provisional stenting is the simplest, most straightforward and cheapest approach, if technically feasible this technique has our preference as the initial approach, and an upgrade can be considered if the result is insufficient.
Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Cytarabine/therapeutic use , Lymphoma, Mantle-Cell/therapy , Whole-Body Irradiation , Adult , Aged , Antimetabolites, Antineoplastic/administration & dosage , Chemoradiotherapy , Cytarabine/administration & dosage , Dose-Response Relationship, Drug , Humans , Middle Aged , Stem Cell TransplantationABSTRACT
BACKGROUND: Cardiovascular diseases are the most common nonmalignant cause of death in Hodgkin lymphoma (HL) survivors, especially after mediastinal irradiation. We investigated the role of computed tomographic coronary angiography (CTA) as a screening tool for coronary artery disease (CAD) in asymptomatic HL survivors, and related CTA findings to exercise testing and subsequent interventions. PATIENTS AND METHODS: Patients were eligible for this phase II study if at least 10 years disease-free and treated with mediastinal radiotherapy. Screening consisted of electrocardiogram, exercise testing and CTA. Primary end point was significant CAD (stenosis >50%) on CTA. CTA screening was considered to be indicated for testing in a larger population if ≥6 of 50 CTA scanned patients (12%) would need revascularization. Screening was evaluated with a questionnaire before and after screening. RESULTS: Fifty-two patients were included, and 48 patients underwent CTA. Median age was 47 years, time since HL diagnosis 21 years. There were 45 evaluable scans. Significant CAD on CTA was found in 20% (N = 9), significantly increased compared with the 7% expected abnormalities (P = 0.01, 95% confidence interval 8.3% to 31.7%). In 11% (N = 5), significant stenosis was confirmed at coronary angiography, and revascularization was carried out. Additionally, two patients were treated with optimal medical therapy. Ninety percent of patients were content with screening, regardless whether the CTA showed abnormalities. CONCLUSIONS: Prevalence of significant CAD among HL survivors is high, while asymptomatic even in the presence of life-threatening CAD. This might justify screening by CTA in asymptomatic HL survivors who had mediastinal radiotherapy, but needs to be evaluated in a larger cohort. The trial protocol was approved by the Ethics Committee of the LUMC and registered with ClinicalTrials.gov, NCT01271127.
Subject(s)
Coronary Angiography , Coronary Artery Disease/diagnosis , Coronary Artery Disease/epidemiology , Hodgkin Disease/radiotherapy , Radiotherapy/adverse effects , Adult , Coronary Artery Disease/etiology , Electrocardiography , Exercise Test , Female , Humans , Male , Mediastinum/radiation effects , Middle Aged , Prevalence , SurvivorsABSTRACT
BACKGROUND: Recent evidence questions the role of intra-aortic balloon counterpulsation (IABP) in the treatment of acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). An area of increasing interest is the use of IABP for persistent ischaemia (PI). We analysed the use of IABP in patients with AMI complicated by CS or PI. METHODS: From 2008 to 2010, a total of 4076 patients were admitted to our hospital for primary percutaneous coronary intervention (PCI) for AMI. Out of those, 239 patients received an IABP either because of CS or because of PI. Characteristics and outcome of those patients are investigated. RESULTS: The mean age of the study population was 64 ± 11 years; 75 % were male patients. Of the patients, 63 % had CS and 37 % had PI. Patients with CS had a 30-day mortality rate of 36 %; 1-year mortality was 41 %. Patients with PI had a 30-day mortality rate of 7 %; 1-year mortality was 11 %. CONCLUSIONS: Mortality in patients admitted for primary PCI because of AMI complicated by CS is high despite IABP use. Outcome in patients treated with IABP for PI is favourable and mandates further prospective studies.
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OBJECTIVES: The aim of our study was to investigate the circadian and weekly variation and assess the influence of environmental variables on the occurrence of acute myocardial infarction (AMI). METHODS: Our study population consisted of 2983 consecutive patients admitted with AMI between January 2006 and May 2008. Data were abstracted from hospital records and partially from an electronic database. In patients with a known time of onset of AMI, circadian variation was analysed. In all patients, weekly variation of onset of AMI was analysed. Information on daily mean temperature, sunny hours, rainy hours, maximal humidity and mean atmospheric pressure was obtained from the KNMI database and the influence of these environmental variables on the incidence of AMI was analysed. RESULTS AND CONCLUSION: Incidence of AMI shows a circadian pattern with an increase in occurrence during daylight. AMI occurs equally on each day of the week and no relation was found between environmental variables and the occurrence of AMI.
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Background/objectives. To investigate the procedural and long-term outcome of primary percutaneous coronary intervention (PCI) in octogenarians with an acute myocardial infarction.Methods. We performed a retrospective analysis of all consecutive octogenarian patients (n=98) with an acute myocardial infarction treated with primary PCI in the Catharina Hospital in the year 2006. We compared procedural results and outcome with a matched control group composed of non-octogenarians undergoing primary PCI. Follow-up period was one year.Results. The initial success rate of PCI was similar in the two groups but short-term mortality was higher among the elderly patients: 30-day mortality 26.3 vs. 9.6%. Age-adjusted mortality between 30 days and one year was comparable in the two groups and similar to natural survival in the Netherlands. Octogenarians were less likely to have a normal left ventricular function during follow-up (48.3 vs. 66.7%). New York Heart Association (NYHA) class and recurrence rate of myocardial infarction was higher among octogenarians.Conclusion. Technical success rate during primary PCI was as good for octogenarians as in younger patients, but 30-day mortality, though acceptable, was higher among the elderly. After 30 days, age-adjusted mortality was comparable in both groups. (Neth Heart J 2010;18:129-34.).
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Currently the transverse diameter is the primary decision criterion to assess rupture risk in patients with an abdominal aortic aneurysm (AAA). To obtain a measure for more patient-specific risk assessment, aneurysm wall stress, calculated using finite element analysis (FEA), has been evaluated in literature. In many cases, initial stress, present in the AAA wall during image acquisition, is not taken into account. In the current study the effect of initial stress incorporation (ISI) is determined by directly comparing wall displacements extracted from FEA and dynamic MRI. Ten patients with an aneurysm diameter >5.5 cm were scanned with cardiac triggered MRI. Semi-automatic segmentation of the AAA was performed on the diastolic phase. The segmented in-slice contours were propagated through the remaining cardiac phases using an active contour model as to track wall displacements on MRI. Consequently, FEA with and without ISI (no-ISI) was performed using the diastolic geometry with simultaneously measured intra-aneurysm pressure values as boundary condition. Contours extracted from FEA were compared with MRI contours at corresponding cardiac phases by distance and relative area differences. The wall displacements from FEA with ISI show significant better correspondence with wall motion from MRI data in comparison with the no-ISI FEA (deviation in wall displacement 1.7% vs. 12.4%; p<0.001). Based on these results it can be concluded that incorporation of initial stress significantly improves wall displacement accuracy of FEA and therefore it should be incorporated in future analyses.
Subject(s)
Aorta, Abdominal/pathology , Aorta, Abdominal/physiopathology , Aortic Aneurysm, Abdominal/pathology , Aortic Aneurysm, Abdominal/physiopathology , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Models, Cardiovascular , Computer Simulation , Elastic Modulus , Finite Element Analysis , Humans , Male , Motion , Shear Strength , Stress, MechanicalSubject(s)
Chromosome Deletion , Chromosomes, Human, Pair 17/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , MicroRNAs/genetics , Aged , Aged, 80 and over , Down-Regulation , Exons/genetics , Female , Gene Expression Regulation, Leukemic , Genes, p53 , Humans , Male , Middle Aged , Sequence Analysis, DNA , Tumor Suppressor Protein p53/deficiencyABSTRACT
To asses the quality of bone marrow cytology of hospital laboratories in the south-west Netherlands a proficiency testing program was implemented. Two sets of bone marrow and blood smears from two patients were sent to 20 hospital laboratories using a tight time schedule biannually. Required results consisted of differential counts of 500 bone marrow cells and 100 peripheral blood cells, together with the description of morphological abnormalities and final conclusions. Twice a year the collected review data were discussed in a plenary session which was also used for continuous education. Over the past 7 years 30 bone marrow samples were evaluated. The coefficient of variations of specific cells counts was large. The amount of correct conclusions ranged from 12% to 100% (median: 61%). Participant attendance of the meetings was 90-100%. The total cost of this scheme of proficiency testing approximately amounted euro7000 per year. The presented formulae for both proficiency testing and haematopathological/cytological education is feasible and fulfilled the need of the participants.
Subject(s)
Bone Marrow/pathology , Cytological Techniques/standards , Hematologic Diseases/pathology , Hematologic Diseases/diagnosis , Humans , Laboratories, Hospital/standards , Netherlands , Quality Control , Reproducibility of ResultsSubject(s)
Antimetabolites, Antineoplastic/pharmacokinetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Methotrexate/pharmacokinetics , Piperazines/pharmacology , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Pyrimidines/pharmacology , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/analysis , Benzamides , Chromosomes, Human, Pair 22/ultrastructure , Chromosomes, Human, Pair 9/ultrastructure , Cytarabine/administration & dosage , Drug Interactions , Edema/chemically induced , Edema/drug therapy , Etoposide/administration & dosage , Female , Humans , Imatinib Mesylate , Leucovorin/therapeutic use , Methotrexate/administration & dosage , Methotrexate/analysis , Middle Aged , Piperazines/administration & dosage , Piperazines/adverse effects , Pleural Effusion, Malignant/chemically induced , Pleural Effusion, Malignant/chemistry , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Pyrimidines/administration & dosage , Pyrimidines/adverse effects , Sodium Potassium Chloride Symporter Inhibitors/therapeutic use , Translocation, GeneticABSTRACT
Leptomeningeal involvement in patients with CLL is relatively rare and the prognosis is usually considered to be poor. The authors reviewed all CLL patients treated in a tertiary referral center to assess the incidence and outcome of leptomeningeal involvement (LI) in CLL. They found an incidence of 1-2% of LI. Most of the patients with LI had a longterm survival, despite failure to clear the cerebrospinal fluid from tumor cells.
Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Meningeal Neoplasms/mortality , Meningeal Neoplasms/secondary , Meninges/pathology , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Arachnoid/drug effects , Arachnoid/pathology , Arachnoid/radiation effects , Cohort Studies , Comorbidity , Dementia, Vascular/etiology , Humans , Incidence , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/radiotherapy , Male , Meningeal Neoplasms/drug therapy , Meningeal Neoplasms/radiotherapy , Meninges/drug effects , Meninges/radiation effects , Middle Aged , Pia Mater/drug effects , Pia Mater/pathology , Pia Mater/radiation effects , Radiotherapy/adverse effects , Radiotherapy/methods , Retrospective Studies , Survival Rate , Treatment OutcomeABSTRACT
Several miRNAs have been reported to be associated with immunoglobulin heavy chain (IgH) mutation and ZAP-70 expression status in blood samples of B-cell chronic lymphocytic leukaemia/small lymphocytic lymphoma (B-CLL/SLL). In the bone marrow and lymphoid tissues, proliferation centres (PCs) represent an important site of activation and proliferation of the neoplastic cells, suggesting that these tissues better reflect the biology of CLL than circulating blood cells. We collected 33 lymph nodes and 37 blood CLL samples and analysed IgH mutation status and ZAP-70 expression status. Expression of 15 miRNAs was analysed by qRT-PCR and RNA-ISH. Sixty-three per cent of the lymph node cases contained mutated IgH genes and 49% of the lymph node cases were ZAP-70-positive, and a significant correlation was observed between ZAP-70 expression and IgH mutation status. Of the blood CLL samples, 49% contained mutated IgH sequences. The miRNA expression pattern in CLL lymph node and blood samples was very similar. Three of 15 miRNAs (miR-16, miR-21, and miR-150) showed a high expression level in both blood and lymph node samples. No difference was observed between ZAP-70-positive or -negative and between IgH-mutated or unmutated cases. No correlation was found between miR-15a and miR-16 expression levels and 13q14 deletion in the blood CLL samples. RNA in situ hybridization (ISH) revealed strong homogeneous staining of miR-150 in the tumour cells outside the PCs. In reverse BIC/pri-miR-155 expression was observed mainly in individual cells including prolymphocytes of the PCs. This reciprocal pattern likely reflects the different functions and targets of miR-150 and miR-155.
Subject(s)
Leukemia, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , MicroRNAs/genetics , Cell Proliferation , Chi-Square Distribution , Gene Expression , Genes, Immunoglobulin , Humans , Immunoglobulin Heavy Chains/genetics , Immunohistochemistry , In Situ Hybridization/methods , Leukemia, B-Cell/metabolism , Leukemia, B-Cell/pathology , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Lymph Nodes/chemistry , Lymph Nodes/pathology , MicroRNAs/blood , Mutation , Reverse Transcriptase Polymerase Chain Reaction , ZAP-70 Protein-Tyrosine Kinase/analysis , ZAP-70 Protein-Tyrosine Kinase/bloodABSTRACT
BACKGROUND: Protein kinase C beta (PKCbeta), a pivotal enzyme in B-cell signaling and survival, is overexpressed in most cases of mantle cell lymphoma (MCL). Activation of PI3K/AKT pathway is involved in pathogenesis of MCL. Enzastaurin, an oral serine/threonine kinase inhibitor, suppresses signaling through PKCbeta/PI3K/AKT pathways, induces apoptosis, reduces proliferation, and suppresses tumor-induced angiogenesis. PATIENTS AND METHODS: Patients with relapsed/refractory MCL, and no more than four regimens of prior therapy, received 500 mg enzastaurin, orally, once daily. RESULTS: Sixty patients, median age 66 years (range 45-85), Eastern Cooperative Oncology Group performance status of zero to two (48% had baseline International Prognostic Index of 3-5), were enrolled. Most patients had prior CHOP-like chemotherapy and/or rituximab (median = 2 regimens). No drug-related deaths occurred. There was one case each of grade 3 anemia, diarrhea, dyspnea, vomiting, hypotension, and syncope. Fatigue was the most common toxicity. Although no objective tumor responses occurred, 22 patients (37%, 95% CI 25% to 49%) were free from progression (FFP) for > or =3 cycles (one cycle = 28 days); 6 of 22 were FFP for >6 months. Two patients remain on treatment and FFP at >23 months. CONCLUSION: Freedom from progression for >6 months in six patients and a favorable toxicity profile with minimal hematological toxicity indicate that enzastaurin warrants evaluation as maintenance therapy and combination chemotherapy in MCL.
Subject(s)
Indoles/administration & dosage , Lymphoma, Mantle-Cell/drug therapy , Lymphoma, Mantle-Cell/mortality , Protein Kinase C/antagonists & inhibitors , Administration, Oral , Aged , Aged, 80 and over , Disease-Free Survival , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Resistance, Neoplasm , Female , Humans , Indoles/adverse effects , Kaplan-Meier Estimate , Lymphoma, Mantle-Cell/pathology , Male , Maximum Tolerated Dose , Middle Aged , Prognosis , Protein Kinase C/administration & dosage , Protein Kinase C beta , Protein Kinase Inhibitors/administration & dosage , Recurrence , Survival Analysis , Treatment OutcomeSubject(s)
Bone Marrow/parasitology , Hematopoietic Stem Cell Transplantation/adverse effects , Leishmania donovani/pathogenicity , Leishmaniasis, Visceral/etiology , Travel , Animals , Endemic Diseases , Humans , Immunocompromised Host , Leishmaniasis, Visceral/diagnosis , Male , Mediterranean Region , Middle Aged , Transplantation, HomologousABSTRACT
OBJECTIVE: To assess the diagnostic accuracy of flow cytometric immunophenotyping in comparison with classic cytomorphology for diagnosing CNS localizations of hematologic malignancies, and to evaluate the implications of CSF pleocytosis and protein content in this context. METHODS: We reviewed the results of diagnostic evaluations of all CSF samples analyzed for localization of a hematologic malignancy between 2001 and 2004 at our center. RESULTS: A total of 1,054 samples from 219 patients were available for analysis. Sixty patients had a CSF localization diagnosed by positive flow cytometry, cytomorphology, or both. The first sample was positive by flow cytometry in 44 (73%) patients, by cytomorphology in 19 (32%). Four first samples were positive by cytomorphology but negative by flow cytometry. Patients with positive cytomorphology had more frequent clinical symptomatology (95% vs 58%) and CSF pleocytosis (84% vs 25%), and tended to a poorer progression-free survival than patients with positive flow cytometry only. OR for CNS localization in case of CSF pleocytosis was 10.1 (95% CI 4.9 to 20.8); OR for CNS localization in case of elevated protein content was 2.9 (95% CI 1.5 to 5.4). Nevertheless, 26 of 137 (19%) patients with normal cell count and protein concentration had a CNS localization. CONCLUSIONS: The diagnostic value of flow cytometry is more than twice that of cytomorphology. However, cytomorphologic examination of the CSF has additional diagnostic and possibly prognostic value, and should still be performed in conjunction with flow cytometry.