Azacitidine (Onureg)

CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec. This review assesses azacitidine (Onureg), tablet 300 mg, oral. Indication: Maintenance therapy in adult patients with acute myeloid leukemia who achieved complete remission or complete remission with incomplete blood count recovery following induction therapy with or without consolidation treatment, and who are not eligible for hematopoietic stem cell transplantation.

Successful Case of Resin-Based Chemical Sand Consolidation as a Remedial Sand Control Treatment

The Mahakam delta in east Kalimantan, Indonesia, yields gas as the main hydrocarbon production with giant reservoirs ranging from shallow to very deep zones. Reservoirs consists of clean sandstone with high permeability. Due to the field maturity, production gradually moved from the deep, consolidated zones into very shallow, unconsolidated zones. Sand production often causes significant problems at the surface when the well is online. The best approach to sand control is to keep it inside the reservoir, because it could create problems not only at surface but within the wellbore as well. Sand consolidation has been a common approach applied in Mahakam field for more than a decade. Several products have been utilized, including laboratory testing and field trials. The case history is based on a well that had been treated using 2 different sand consolidation products in the past, but both eventually produced inadequate results. Sand continued to break through after each treatment, hence the reserves could not be drained in full. Since the reservoir still had promising reserves, another remedial sand consolidation treatment was planned. This treatment was executed by utilizing a tension packer with a J-slot mechanism in order to focus injection of the resin into the zone of interest. Additionally, there was a challenge with another open zone above the subject interval. The remedial sand consolidation treatment using a resin-based chemical delivered excellent results. Even though this reservoir had been exposed to 2 different chemical treatments in the past, by using the resin-based sand consolidation product, the well was still able to be produced at target rates without sand production. In conclusion, resin-based sand consolidation solutions can unlock prolific reserves that may have been a significant challenge with traditional methods.

High-Dose Melphalan in 1 Day Versus over 2 Days Followed By Autologous Stem Cell Transplantation As Consolidation Treatment in Patients with Multiple Myeloma

Background High-dose melphalan (HDM) at 200 mg/m2 is a myeloablative consolidation treatment prior to autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM) and is administered in 1-day or divided over 2-days. Although the 1-day regimen (lower AUC) has been shown to result in significantly less gastro-intestinal toxicity, it is not completely clear whether this administration strategy has any deleterious effects on efficacy, compared to the 2-day regimen. In this retrospective cohort study, we aimed to evaluate the effects of 1- or 2-day dosing of HDM on disease remission, progression-free survival (PFS) and overall survival (OS) in patients with MM. Methods Data from two academic centers in Amsterdam that have recently merged were used for the analysis, with one of the centers using the 1-day regimen and the other the 2-days regimen. A total of 265 patients with MM divided over the 1-day group (n=174) and 2-day group (n=91) treated between July 2017 and February 2020, were included in the study. The primary endpoint was the proportion of patients with at least very good partial remission (≥VGPR) at day ±90 post-ASCT. Secondary endpoints were overall survival (OS), progression-free survival (PFS), duration of hospitalization post-ASCT, engraftment period of neutrophils and platelets, and complications (other than mucositis) during hospitalization. Results Patient characteristics are summarized in Table 1. Remission status of ≥VGPR was comparable between the 1-day and 2-day groups (84% vs. 80% respectively). After a median follow-up of 21 months, OS (92% vs. 91%) and PFS (80% vs. 81%) were comparable in the 1-day and 2-day group respectively. There were no differences in the incidence of hematologic adverse events between the 1-day and 2-day groups (neutropenia; 98% vs. 100%, thrombocytopenia; 90% vs. 96% respectively). Median time to neutrophil engraftment (ANC >0.5 x10 9 L -1) was significantly shorter in the 2-day group than in the 1-day group (14 days vs. 18 days, p = 0.002). Median time to platelet engraftment (platelets >20 x10 9 L -1) was comparable between the groups. Lower CD34+ cell counts were administered in the 1-day group compared to the 2-day group (2.6 vs. 3.4 x10 6/kg, p <0.0001). A significant negative correlation between the reinfused CD34+ cell counts and time to neutrophil engraftment was found (R= - 0.244). Table 2 shows the number of hospitalization days after ASCT. The median number was 18 days in the 1-day group and 15 days in the 2-day group (OR 1.22, 95% C.I. (1.10-1.35), p <0.0001). Incidences of infectious complications, febrile neutropenia and intensive care unit (ICU) admissions were not different between the groups. Conclusion The use of 1-day HDM as consolidation treatment in MM patients resulted in equal disease response, progression-free survival and overall survival as compared to 2-day HDM. Based on the results of this study showing comparable efficacy and earlier findings of reduced toxicity with the 1-day HDM administration, we recommend the 1-day protocol for HDM. Interestingly, our results also confirmed that patients might benefit from higher counts of reinfused CD34+/enucleated cells. Figure 1 Figure 1. Disclosures Wondergem: Novartis: Honoraria. de Leeuw: Takeda: Membership on an entity's Board of Directors or advisory committees. Biemond: Sanquin: Research Funding; Celgene: Honoraria; CSL Behring: Honoraria; Novo Nordisk: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; Global Blood Therapeutics: Honoraria, Research Funding, Speakers Bureau. van de Donk: Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Cellectis: Research Funding. Zweegman: Sanofi: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Nur: Roche: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Research Funding, Speakers Bureau.

The effect of consolidation treatment on selected mechanical properties of sandstone

An investigation was made into selected mechanical properties of sandstone of Božanov mining site in Czechia using both natural specimens of the sandstone and specimens impregnated with consolidants – liquid products aimed at improving strength and durability of degraded stones. Experiments in three-point bending of notched and cracked specimens made it possible to determine (i) the quasi-static notch toughness as well as the fracture toughness of specimens when they were subjected to static loading, and (ii) the impact fracture toughness and total energy of fracture when specimens were subjected to impact loading. The results of the tests are presented and are discussed with a view to the effects of consolidants.

PARAQUAT INDUCED BILATERAL SPONTANEOUS PNEUMOTHORAX-DAISLEY BARTON SYNDROME – A CASE REPORT

Paraquat (1,1-dimethyl-4, 4-bipyridylium dichloride) is an effective herbicide which is widely used all over the world and India is no exception. It is toxic to humans due to its redox activity which produces superoxide anions. Accidental or suicidal poisoning causes ulceration over the mouth and gastrointestinal tract and the majority of patients die of acute renal failure, hepatic failure and acute lung injury causing mainly lung brosis and consolidation. Treatment of paraquat poisoning is extremely difcult as it does not have any specic antidote. Treatment is mainly symptomatic. Very few patients may develop spontaneous pneumothorax, known as Daisley Barton syndrome, which further impairs survival of the patient Here we present a patient of paraquat induced spontaneous bilateral pneumothorax who survived with conservative treatment.

Consolidation and Maintenance in Newly Diagnosed Multiple Myeloma

PURPOSE To address the role of consolidation treatment for newly diagnosed, transplant eligible patients with multiple myeloma in a controlled clinical trial. PATIENTS AND METHODS The EMN02/HOVON95 trial compared consolidation treatment with two cycles of bortezomib, lenalidomide, and dexamethasone (VRD) or no consolidation after induction and intensification therapy, followed by continuous lenalidomide maintenance. Primary study end point was progression-free survival (PFS). RESULTS Eight hundred seventy-eight eligible patients were randomly assigned to receive VRD consolidation (451 patients) or no consolidation (427 patients). At a median follow-up of 74.8 months, median PFS with adjustment for pretreatment was prolonged in patients randomly assigned to VRD consolidation (59.3 v 42.9 months, hazard ratio [HR] = 0.81; 95% CI, 0.68 to 0.96; P = .016). The PFS benefit was observed across most predefined subgroups, including revised International Staging System (ISS) stage, cytogenetics, and prior treatment. Revised ISS3 stage (HR, 2.00; 95% CI, 1.41 to 2.86) and ampl1q (HR, 1.67; 95% CI, 1.37 to 2.04) were significant adverse prognostic factors. The median duration of maintenance was 33 months (interquartile range 13-86 months). Response ≥ complete response (CR) after consolidation versus no consolidation before start of maintenance was 34% versus 18%, respectively ( P < .001). Response ≥ CR on protocol including maintenance was 59% with consolidation and 46% without ( P < .001). Minimal residual disease analysis by flow cytometry in a subgroup of 226 patients with CR or stringent complete response or very good partial response before start of maintenance demonstrated a 74% minimal residual disease–negativity rate in VRD-treated patients. Toxicity from VRD was acceptable and manageable. CONCLUSION Consolidation treatment with VRD followed by lenalidomide maintenance improves PFS and depth of response in newly diagnosed patients with multiple myeloma as compared to maintenance alone.