Intracarotid Chemotherapy with 1,3-Bis-(2-chloroethyl)-1-nitrosourea (BCNU) in 5% Dextrose in Water in the Treatment of Malignant Glioma

Neurosurgery ◽  
1987 ◽  
Vol 20 (4) ◽  
pp. 577-583 ◽  
Author(s):  
David W. Johnson ◽  
David Parkinson ◽  
Samuel M. Wolpert ◽  
David L. Kasdon ◽  
Eddie S. K. Kwan ◽  
...  

Abstract After radiotherapy, 20 patients, 18 with documented progression of malignant glioma and 2 with Grade II astrocytoma, received a total of 52 courses of intracarotid 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) at a dose of 150 mg/m2 dissolved in 5% dextrose in water. The patients were treated at 6-week intervals for a maximum of five courses of chemotherapy per patient. Response to treatment was analyzed on computed tomographic scans by measuring the volume of the enhancing tumor and any central low density. From these data, tumor doubling times ranging from 110 to 968 days were obtained. An 11 to 60% reduction in enhancing tumor volume was noted in 8 patients, 2 of whom had a greater than 50% decrease in tumor volume. One patient had no change in tumor volume 110 weeks after the initiation of BCNU chemotherapy. Four patients had tumor in more than one vascular territory; tumor growth was arrested in the perfused territory, but continued in the nonperfused area. In 1 of the 4 patients, tumor also grew along a shunt catheter tract and spread over the surface of the ipsilateral hemisphere. One patient developed clinically asymptomatic leukoencephalopathy after five courses of BCNU. Two patients had postradiation leukoencephalopathy before BCNU treatment. Seventeen patients had peritumoral low density with mass effect after BCNU; thus, the true incidence of BCNU-related leukoencephalopathy could not be determined. All patients experienced transient unilateral orbital pain during the infusion and scleral erythema that lasted for several hours afterward. Loss of vision was noted in 2 patients, although it seemed to be related to the therapy in only 1 patient. In our group of patients, there was no significant myelosuppression or indication of other systemic toxicity.

Neurosurgery ◽  
1984 ◽  
Vol 14 (2) ◽  
pp. 234-237 ◽  
Author(s):  
Lawrence Kulla ◽  
James A. Russell ◽  
Thomas W. Smith ◽  
Joseph L. Zito ◽  
Robin Davidson

Abstract A patient with subacute aphasia and hemiparesis was found to have a low density white matter lesion with mass effect on the computed tomographic (CT) scan. Serological examination and biopsy established the diagnosis of paretic neurosyphilis. This CT appearance has not previously been described in cases of neurosyphilis. Neurosyphilis should be considered as a potentially treatable cause of a cerebral mass lesion.


Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1969
Author(s):  
Aline Rangel-Pozzo ◽  
Pak Yu ◽  
Sadhana LaL ◽  
Yasmin Asbaghi ◽  
Luiza Sisdelli ◽  
...  

The prognosis of multiple myeloma (MM), an incurable B-cell malignancy, has significantly improved through the introduction of novel therapeutic modalities. Myeloma prognosis is essentially determined by cytogenetics, both at diagnosis and at disease progression. However, for a large cohort of patients, cytogenetic analysis is not always available. In addition, myeloma patients with favorable cytogenetics can display an aggressive clinical course. Therefore, it is necessary to develop additional prognostic and predictive markers for this disease to allow for patient risk stratification and personalized clinical decision-making. Genomic instability is a prominent characteristic in MM, and we have previously shown that the three-dimensional (3D) nuclear organization of telomeres is a marker of both genomic instability and genetic heterogeneity in myeloma. In this study, we compared in a longitudinal prospective study blindly the 3D telomeric profiles from bone marrow samples of 214 initially treatment-naïve patients with either monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or MM, with a minimum follow-up of 5 years. Here, we report distinctive 3D telomeric profiles correlating with disease aggressiveness and patient response to treatment in MM patients, and also distinctive 3D telomeric profiles for disease progression in smoldering multiple myeloma patients. In particular, lower average intensity (telomere length, below 13,500 arbitrary units) and increased number of telomere aggregates are associated with shorter survival and could be used as a prognostic factor to identify high-risk SMM and MM patients.


2021 ◽  
Vol 07 (02) ◽  
pp. 01-03
Author(s):  
Mezoun Almuhaimeed

A 22-year-old single female presented to primary care Wazarat Health Center at Prince Sultan Military Medical City in Riyadh, with a 3 weeks history of itchy erythematous papules and vesicles and papulo-vesicles over the neck, chest, and upper back and face, which started 4 to 5 days after bariatric surgery. The patient on daily multivitamin supplements, vitamin D (50,000 IU, weekly / 2 months). The patient has lost 4kg since the operation, family history of atopy was positive regarding the mother physical examination shows erythematous papules and vesicles and papulo-vesicles over the neck with crust, chest, and upper back, Based on medical history and clinical presentation a provisional diagnosis was Prurigo Pigmentosa. The patient was prescribed topical mometasone furoate cream (BID for one week). Two -week follow-up showed improvement of the eruption. The course of the disease was shorter than usual in such cases the patient response to treatment was reactive to the topical mometasone without taking the oral minocyline, which major of such cases need in the late course of the disease The patient starts to improve within 2 weeks compared to others who need an average of 6 weeks to improve in such cases


Blood ◽  
2019 ◽  
Vol 133 (10) ◽  
pp. 1020-1030 ◽  
Author(s):  
U. Platzbecker ◽  
P. Fenaux ◽  
L. Adès ◽  
A. Giagounidis ◽  
V. Santini ◽  
...  

Abstract The heterogeneity of myelodysplastic syndromes (MDSs) has made evaluating patient response to treatment challenging. In 2006, the International Working Group (IWG) proposed a revision to previously published standardized response criteria (IWG 2000) for uniformly evaluating clinical responses in MDSs. These IWG 2006 criteria have been used prospectively in many clinical trials in MDSs, but proved challenging in several of them, especially for the evaluation of erythroid response. In this report, we provide rationale for modifications (IWG 2018) of these recommendations, mainly for “hematological improvement” criteria used for lower-risk MDSs, based on recent practical and reported experience in clinical trials. Most suggestions relate to erythroid response assessment, which are refined in an overall more stringent manner. Two major proposed changes are the differentiation between “procedures” and “criteria” for hematologic improvement–erythroid assessment and a new categorization of transfusion-burden subgroups.


Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1259
Author(s):  
Gerard Anmella ◽  
Silvia Vilches ◽  
Jordi Espadaler ◽  
Andrea Murru ◽  
Isabella Pacchiarotti ◽  
...  

Several pharmacogenetic-based decision support tools for psychoactive medication selection are available. However, the scientific evidence of the gene-drug pairs analyzed is mainly based on pharmacogenetic studies in patients with major depression or schizophrenia, and their clinical utility is mostly assessed in major depression. This study aimed at evaluating the impact of individual genes, with pharmacogenetic relevance in other psychiatric conditions, in the response to treatment in bipolar depression. Seventy-six patients diagnosed with bipolar disorder and an index major depressive episode were included in an observational retrospective study. Sociodemographic and clinical data were collected, and all patients were genotyped using a commercial multigene pharmacogenomic-based tool (Neuropharmagen®, AB-Biotics S.A., Barcelona, Spain). Multiple linear regression was used to identify pharmacogenetic and clinical predictors of efficacy and tolerability of medications. The pharmacogenetic variables response to serotonin-norepinephrine reuptake inhibitors (SNRIs) (ABCB1) and reduced metabolism of quetiapine (CYP3A4) predicted patient response to these medications, respectively. ABCB1 was also linked to the tolerability of SNRIs. An mTOR-related multigenic predictor was also associated with a lower number of adverse effects when including switch and autolytical ideation. Our results suggest that the predictors identified could be useful to guide the pharmacological treatment in bipolar disorder. Additional clinical studies are necessary to confirm these findings.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 45-47
Author(s):  
Josu de la Fuente ◽  
Dirk-Jan Eikema ◽  
Paul Bosman ◽  
Robert F Wynn ◽  
Miguel Díaz ◽  
...  

Congenital sideroblastic anaemias (CSA) are a rare group of disorders characterized by the presence of pathologic iron deposits within the mitochondria of erythroid precursors (ring sideroblasts) in the bone marrow due to heterogenous germline mutations leading to defects in mitochondrial heme synthesis, iron-sulfur (Fe-S) cluster biogenesis, or protein synthesis. Patients present with anaemia and relative reticulocytopenia, and systemic iron overload secondary to chronic ineffective erythropoiesis, leading to end-organ damage. The disease is heterogenous underlying the genetic variability and the variable response to treatment. Although a number of CSA patients have received a bone marrow transplant, the outcomes and toxicities are not known. This status makes it very difficult to understand the role of BMT in the management of CSA. A search in the EBMT database identified 28 patients receiving a HSCT for CSA between 1998 to 2018 by 24 participating centres. The median year of transplantation was 2014 (IQR 2004-2016). The distribution was equal between males (n=14) and females (n=14). The median age at transplantation was 7 years of age (3-10 years). Fifteen patients had a sibling HSCT (88%), one a family matched donor HSCT (6%) and one an unrelated matched (6%), the type of transplant being unknown in others (n=11). The source of stem cells was bone marrow in 20 cases (74%), peripheral blood in 4 cases (15%), cord blood in 2 (7%) and combined bone marrow and cord in one (4%). Five cases had a Bu/Cy based conditioning regimen, 4 had Bu/fludarabine based regimen and three fludarabine/treosulfan based conditioning with the rest having a variety of approaches. Eighty-six percent of cases had serotherapy with ATG or alemtuzumab. The median follow-up was 31.6 months (95% CI, 12.2-74.1%). The overall survival at 12 and 24 months was 88% (76-100) and 82% (66-99), respectively (figure 1). The median neutrophil engraftment was 18 (15-21) days and platelet engraftment >20 x 109/L was 29 (20-51) days, with a graft failure incidence of 7% (0-17) at 12 months. Two patients suffered from VOD. There were four deaths, three of which were related to transplant complications. The event free survival (survival without graft failure, relapse and second transplant) at 12 and 24 months was 85% (72-99) (figure 2). Six patients developed acute GvHD grade II and one case grade III; giving a grade II/III incidence of 28% (10-46). There was one case of limited and one of chronic GvHD, giving an incidence of 11% (0-26%) at 12 months and 24 months. In conclusion, whilst HSCT for CSA is a rare occurrence, these data demonstrate that HSCT for this condition is feasible and the outcomes are in keeping with those obtained for transplantation for transfusion dependent anaemias during the same time-period. Disclosures Handgretinger: Amgen: Honoraria. Moraleda:Gilead: Consultancy, Other: Travel Expenses; Jazz Pharmaceuticals: Consultancy, Research Funding; Novartis: Consultancy, Other: Travel Expenses; Sandoz: Consultancy, Other: Travel Expenses; Takeda: Consultancy, Other: Travel Expenses. Risitano:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alnylam: Research Funding; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Jazz: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Samsung: Membership on an entity's Board of Directors or advisory committees; Amyndas: Consultancy; RA pharma: Research Funding; Biocryst: Membership on an entity's Board of Directors or advisory committees; Apellis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Achillion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Speakers Bureau. Peffault De Latour:Amgen: Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Apellis: Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.


Author(s):  
Dilek Hacer Cesme ◽  
Alpay Alkan ◽  
Lutfullah Sari ◽  
Ahmet Kaya ◽  
Ismail Yurtsever ◽  
...  

Background: The effectiveness of Diffusion Tensor Imaging (DTI) in demonstrating functional changes in the tumor in determining the response to treatment after radiosurgery in patients with vestibular schwannoma (VS) is not clear yet. Objective: The study aimed to determine the change total in tumor volume (TTV) in terms of radiological response in patients who had VS and were treated with radiosurgery and investigate the relationship between the TTV, follow-up times and DTI parameters. Methods: Thirty-one patients were assessed using DTI and MRI. TTV, apparent diffusion coefficient (ADC), and fractional anisotropy (FA) were calculated. Patients were divided into tree groups: those who responded to the treatment (group 1) (n=11), who did not (group 0) (n=9) and who remained stable (group 2) (n=11). Background: The effectiveness of Diffusion Tensor Imaging (DTI) in demonstrating functional changes in the tumor in determining the response to treatment after radiosurgery in patients with vestibular schwannoma (VS) is not clear yet. Objective: The study aimed to determine the change total in tumor volume (TTV) in terms of radiological response in patients who had VS and were treated with radiosurgery and investigate the relationship between the TTV, follow-up times and DTI parameters. Methods: Thirty-one patients were assessed using DTI and MRI. TTV, apparent diffusion coefficient (ADC), and fractional anisotropy (FA) were calculated. Patients were divided into tree groups: those who responded to the treatment (group 1) (n=11), who did not (group 0) (n=9) and who remained stable (group 2) (n=11). Results: The mean duration of follow-up was 28.81±14 months. ADC values increased in patients with VS after radiosurgery (p=0.004). There was no statistical difference in the FA values. A significant reduction in TTV after radiosurgery was detected in group 1 (p=0.003). ADC values increased significantly after radiosurgery in group 2 (p=0.04). Although there were no significant differences, ADC values after radiosurgery increased in group 1 and group 0. Conclusions: ADC values continuously increase due to radiation damage in the period before the tumor volume shrinks after radiosurgery. We think that it is not appropriate to diagnose inadequate treatment or progression only when TTV is evaluated in terms of response to treatment in the early period after radiosurgery.


2019 ◽  
Vol 50 (3) ◽  
pp. e36-e41
Author(s):  
Narges Ansari ◽  
Saeid Shahrabi ◽  
Abbas Khosravi ◽  
Reza Shirzad ◽  
Hadi Rezaeean

Abstract Breast cancer (BC) is one of the most common cancers among women; genetic mutations reflect the development of this disease. Mutations in cell signaling factors can be the main cause of BC development. In this study, we focused on mutations in checkpoint kinase 2 (CHEK2) and their impact as a prognostic factor in the pathogenesis of BC. CHEK2 is controlled in cell signaling pathways through the influence of upstream genes. Also, several downstream genes are regulated by CHEK2. In addition, mutations in CHEK2 lead to resistance of BC cells to chemotherapy and metastasis of cancer cells to other parts of the body. Finally, detection of mutations in CHEK2 can be used as a prognostic factor for patient response to treatment and for targeting downstream molecules of CHEK2 that are involved in the proliferation of breast tumor cells. Mutations such as c.1100delC and I157T can distinguish which patients are susceptible to metastasis.


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