Characterization of a thermoplastic polyimidesulfone

The detailed characterization of an experimental thermoplastic polyimidesulfone adhesive based on 3,3 prime-diaminodiphenylsulfone and 3,3 prime,4,4 prime-benzophenone tetracarboxylic dianhydride was studied. Model compounds were also examined. Thermal cyclization of the amide-acid to the imide was studied by a variety of techniques including DSC, TGA, MS, in situ diffuse reflectance-FTIR, and flow mearsurement. Characterizations were continued during the processing of adhesive tapes and the fabrication, bonding, and testing of lap shear specimens. Results provide fundamental insights into the role of cure chemistry, and the effects of residual solvent and volatile produces on processing and performance. These insights and the resulting chemical models should lead to more efficient processing cycles for these and other related thermoplastic adhesive systems

Initial adhesive screening of novel polyamide-imides and their copolymers

Continued interest by the research community in thermally stable, tough, high temperature adhesives has resulted in the investigation by Langley Research Center of two linear aromatic polyamide-imide (PAI) homopolymers and two linear aromatic PAI copolymers. The homopolymers were made with either 3,3'=DABA or 4,4'-DABA and BTDA. The two polymers were prepared with a monomer ratio of 0.75 DABP:0.25 DABA:1.00 BTDA. These aromatic PAIs possess high thermal stability because of intermolecular hydrogen bonding and chain stiffness. Lap shear strength (LSS) was the main criteria used to evaluate the polymers as adhesives. LSS of bonded Ti-6Al-4V was determined at room temperature (RT), 177, 204 and 232 C. The glass transition temperature and the type of bond failure were also determined. The best LSS values of the four adhesive systems investigated were obtained with the PAI copolymer identified in the report as LARC-TPI (25 percent 3,3'-DABA); however, it did not produce LSSs nearly as high as LARC-TPI. The poor flow properties observed appear to be due to a combination of high molecular weight and the increased interchain electronic interactions associated with the amide group

Special considerations in the management of adult patients with acute leukaemias and myeloid neoplasms in the COVID-19 era: recommendations from a panel of international experts

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 is a global public health crisis. Multiple observations indicate poorer post-infection outcomes for patients with cancer than for the general population. Herein, we highlight the challenges in caring for patients with acute leukaemias and myeloid neoplasms amid the COVID-19 pandemic. We summarise key changes related to service allocation, clinical and supportive care, clinical trial participation, and ethical considerations regarding the use of lifesaving measures for these patients. We recognise that these recommendations might be more applicable to high-income countries and might not be generalisable because of regional differences in health-care infrastructure, individual circumstances, and a complex and highly fluid health-care environment. Despite these limitations, we aim to provide a general framework for the care of patients with acute leukaemias and myeloid neoplasms during the COVID-19 pandemic on the basis of recommendations from international experts

Optimal Treatment Order of Lenalidomide and Hypomethylating Agents for Lower-Risk Myelodysplastic Syndromes: A Report on Behalf of the MDS Clinical Research Consortium

Abstract Introduction While lenalidomide (LEN) is the standard of care for treatment of red blood cell (RBC) transfusion-dependent (TD) lower-risk myelodysplastic syndromes (LR-MDS) with chromosome 5q deletion (del 5q), it is widely used off-label in the non-del5q setting. In the MDS-002 and MDS-005 studies, 26% of TD non-del5q LR-MDS patients became RBC transfusion independent after LEN treatment. National Comprehensive Cancer Network (NCCN) clinical guidelines list LEN as a second line treatment option for TD anemia in lower-risk non-del 5q MDS after hypomethylating agents (HMAs). Thatrecommendationhas led to wide use of HMAs as frontline therapy after erythroid stimulating agents (ESA) failure in LR-MDS. The response rate to LEN after HMA failure, however, is not known, as MDS-002 and MDS-005 excluded patients previously treated with HMAs. To assess the best order of LEN and HMA in optimizing response potential in lower-risk MDS, we examined response rates to each drug when treatment order (LEN followed by HMA or HMA followed by LEN) differed. Methods We identified patients with LR- MDS (International Prognostic Scoring System (IPSS) low or intermediate-1 (int-1) risk groups) within the MDS Clinical Research Consortium database who received both LEN and HMA as first or second line therapy after ESA failure or patients who had low chance of response to ESA. We excluded patients with isolated del5q or del q + one additional cytogenetic abnormality. The primary objective was to compare rates of erythroid hematological improvement (HI-E), defined using 2006 International Working Group criteria (IWG 2006), between patients who received LEN as first line therapy followed by HMA as second line (LEN 1st line group) versus those who received LEN as second line therapy after HMA (LEN 2nd line group). Results We identified 144 patients who received both HMA and LEN as first and second line therapies: 80 patients were in group 1 (LEN 1st line) and 64 patients were in group 2 (LEN 2nd line). Baseline characteristics between the two groups are summarized in Table 1. There were no statistically significant differences between the 2 groups. The rate of HI-E was 20% (16/80) for the LEN 1st line group compared to 11% (7/64) in the LEN 2nd line group. (p=.046). There were no differences in response rates to HMA between the two groups: In the LEN 1st line group, response to 2nd line HMA was 30% (24/78) compared to 39% (25/64) for those who received HMA as first line (p=.2). There was no difference in overall survival (OS) between the two groups, The median OS was 79 months (mo) the LEN 1st line group compared to 61 mo in Len 2nd line group (p= .4). The rate of AML transformation was 9% in Len 1st line group compared to 22% in Len 2nd line group rate (p=.03). There was no difference in AML free survival (78mo versus 61mo respectively, p=0.4). In multivariable analyses adjusting for age, sex, and IPSS-R order of treatment still did not impact overall survival. Conclusion LEN yields a higher rate of HI-E in LR- MDS when used as first line therapy, but responses to HMAs were similar when used before or after LEN. The rate of AML transformation was lower when LEN was used as first line. The order of treatment does not impact overall survival. Lenalidomide should be used prior to HMA if it is to be considered for treatment of anemia in non-del5q LR-MDS. Table 1 Baseline characteristics Table 1. Baseline characteristics Disclosures Komrokji: Novartis: Consultancy, Speakers Bureau; Incyte: Consultancy; Boehringer-Ingelheim: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Roboz:Agios, Amgen, Amphivena, Astex, AstraZeneca, Boehringer Ingelheim, Celator, Celgene, Genoptix, Janssen, Juno, MEI Pharma, MedImmune, Novartis, Onconova, Pfizer, Roche/Genentech, Sunesis, Teva: Consultancy; Cellectis: Research Funding

Importance of Complete Remission on Predicting Overall Survival in Patients with Lower-Risk Myelodysplastic Syndromes (MDS)

Abstract Background Lower-risk (LR) MDS (Low/Int-1 per International Prognostic Scoring System (IPSS)) are a heterogeneous group of disorders characterized mainly by refractory anemia and transfusion dependency. As survival of this patient (pt) population is measured in years. Goals of therapy focus on decreasing blood transfusions, improving quality of life, while minimizing treatment toxicities. While achieving complete remission (CR) in higher-risk MDS correlates with improved overall survival (OS), its relationship to OS in LR MDS is not well defined. We evaluated the impact of achieving CR on OS in LR MDS and defined the clinical characteristics that may predict for this response in this pt population. Method Included pts were diagnosed with MDS (per 2008 WHO criteria) and had LR disease with clinical and pathologic data collected from MDS Clinical Research Consortium institutions. Only pts with bone marrow blasts of 5-9% who would thus qualify both as having LR MDS and for being eligible to assess CR were included. Responses (including CR, PR, HI, stable disease and progressive disease) were defined per International Working Group 2006 criteria. OS was calculated from the time of achievement of best response to time of death or last follow-up. Cox proportional hazard analysis that included all clinical variables and treatment characteristics was used to identify independent prognostic factors. Results Of 1470 pts included in the database, 999 identified with LR disease, and 174 had bone marrow blasts of 5-9%. The median age was 60 years (range, 22-87), and 37% were female. Median neutrophil count was 1.25 X 109\L (range, .10-51.0), hemoglobin was 9.8 g/dl, platelets were 109 k/ml (range, 18-562), and bone marrow blasts were 6% (range, 5-9%). Best responses to therapy included: 26 pts (15%) with CR, 10 pts (6%) with PR, and 13 pts (7%) with HI. Among pts who achieved CR/PR/HI, 27 received HMA (25 with azacidtine +/- combination and 2 with single agent decitabine), 16 intensive chemotherapy, 2 lenalidomide, and 4 received other therapies. With a median follow up from diagnosis of 31.2 months, the median time from diagnosis to best response was 11.9 months (range, .69-81.0) and was similar in pts who achieved CR compared to PR/HI (11.5 vs. 12.4 months, respectively, p = .74). The median OS from time of CR/PR/HI for the entire cohort was 21.3 months. The median OS for pts who achieved a CR was longer compared to pts with PR/HI (46.5 vs. 18.5 months, respectively, p = .03). In multivariate analyses that included clinical variables and treatment history, achieving CR remained an independent prognostic factor for longer OS (HR .32, p = .03) but no individual demographic, clinical or treatment variables were predictive of CR. Conclusions Similar to pts with higher-risk MDS, LR MDS pts who achieve CR to therapy have improved OS compared to those with PR or HI. CR is thus an important endpoint in LR MDS, though is difficult to predict. As OS is measured in years in LR MDS, CR may be used as a surrogate endpoint for OS in clinical trials in this pt population. Disclosures Komrokji: Novartis: Consultancy, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Roboz:Cellectis: Research Funding; Agios, Amgen, Amphivena, Astex, AstraZeneca, Boehringer Ingelheim, Celator, Celgene, Genoptix, Janssen, Juno, MEI Pharma, MedImmune, Novartis, Onconova, Pfizer, Roche/Genentech, Sunesis, Teva: Consultancy. Sekeres:Millenium/Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees

What Is the Optimal Time to Initiate Hypomethylating Agents (HMA) in Higher Risk Myelodysplastic Syndromes (MDS)?

Abstract Background: Hypomethylating agents (HMA) are the standard of care for higher risk MDS patients (pts). Fewer than one-half will respond to therapy for an average duration of one year, thereby emphasizing the necessity to optimize the use of these disease modifying agents. HMA clinical trials have not addressed the optimal time in the disease course to initiate treatment to maximize disease-modifying potential. The current dogma is to begin HMA therapy in all higher risk MDS pts at the time of initial diagnosis. Nevertheless, a subset of higher risk MDS pts will have adequate hematopoiesis at the time of diagnosis regardless of disease risk, and for these pts therapy may be delayed and reserved for a later time when symptomatic cytopenias develop. We investigated the impact of the timing of HMA initiation on outcomes among higher risk MDS pts presenting with adequate blood counts to discern the possible benefit of early treatment based solely on disease risk. Methods: We identified MDS pts with intermediate-2 and high risk IPSS (higher risk) MDS treated with HMA among the Moffitt Cancer Center database. We included patients with adequate hematopoiesis defined for the purpose of this study as platelets >50 x 109/L, Hgb > 9 g/dl and ANC > 0.5 x 109/L and being transfusion independent to exclude those pts in need of HMA treatment for cytopenias. We divided patients into 4 groups based on the time of HMA initiation (within 30, 31-60 , 61-90 and greater than 90 days from time of diagnosis). We compared baseline characteristics, best response rate to treatment using international working group criteria (IWG 2006), leukemia free survival (LFS) and overall survival (OS) among the 4 groups. Results: We identified 320 higher risk MDS pts with adequate hematopoiesis who were treated with HMA. Baseline characteristics for the 4 groups based upon time of HMA therapy initiation are summarized in Table-1. Pts receiving treatment within 30 days had higher marrow myeloblast percentage at time of diagnosis. There was no difference in mean blood counts at time of diagnosis between the 4 groups; however, mean platelet count was lower at time of initiating HMA therapy in patients treated after 90 days from diagnosis. Table-2 summarizes somatic gene mutation data among 110 patients tested. TET-2 mutations were more common among those treated within 60 days, whereas U2AF1 mutations were more common among those treated after 60 days from diagnosis. The complete response rates were 21%, 26%, 23% and 7%, respectively for pts treated within 30 , 31-60 , 61-90 and greater than 90 days from time of diagnosis (p=0.046). The overall response rates (defined as hematological improvement or better) were 43%, 41%, 43% and 34%, respectively for pts treated within 30, 31-60 , 61-90 and greater than 90 days from date of diagnosis (p .70). There was no difference in mean duration of treatment with HMA among the groups with mean durations of 267, 204, 224 and 215 days, respectively, (p .35). The median OS from the date of diagnosis was 641, 550, 979 and 806 days, respectively for pts treated within 30, 31-60, 61-90 and greater than 90 days from date of diagnosis (p .2). There was no impact of timing for HMA initiation when adjusted for Revised-IPSS risk groups in Cox regression analysis. There was no difference in OS based on HMA initiation time when adjusted for myeloblasts % or karyotype. Further, there was no difference between groups in rate of AML transformation or LFS (p =.7 and .16, respectively). Conclusions A delay in initiating HMA therapy in higher risk MDS pts with adequate blood counts is not associated with worsened overall survival or increased frequency of leukemia transformation. Complete response rates were higher when treatment was started earlier in the disease course, however, there was no difference in overall response rate. Close observation to initiate treatment upon development of clinically significant cytopenias appears to be a safe and equally effective strategy among pts with higher risk MDS. Disclosures Komrokji: Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding. Sallman:Celgene: Research Funding, Speakers Bureau. Nazha:MEI: Consultancy. Steensma:Takeda: Consultancy; Syros: Research Funding; Otsuka: Membership on an entity's Board of Directors or advisory committees; Onconova: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Kura: Research Funding; Janssen: Consultancy, Research Funding; H3 Biosciences: Research Funding; Celgene: Research Funding; Amphivena: Membership on an entity's Board of Directors or advisory committees; Acceleron: Consultancy. Roboz:AbbVie: Consultancy; Daiichi Sankyo: Consultancy; Jazz Pharmaceuticals: Consultancy; Cellectis: Research Funding; Novartis: Consultancy; Celltrion: Consultancy; Astex Pharmaceuticals: Consultancy; Sandoz: Consultancy; Celgene Corporation: Consultancy; Otsuka: Consultancy; Janssen Pharmaceuticals: Consultancy; Aphivena Therapeutics: Consultancy; Daiichi Sankyo: Consultancy; Orsenix: Consultancy; Bayer: Consultancy; Aphivena Therapeutics: Consultancy; Argenx: Consultancy; Orsenix: Consultancy; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy; Eisai: Consultancy; Celgene Corporation: Consultancy; AbbVie: Consultancy; Roche/Genentech: Consultancy; Cellectis: Research Funding; Otsuka: Consultancy; Bayer: Consultancy; Pfizer: Consultancy; Astex Pharmaceuticals: Consultancy; Argenx: Consultancy; Sandoz: Consultancy; Celltrion: Consultancy; Janssen Pharmaceuticals: Consultancy; Pfizer: Consultancy; Eisai: Consultancy; Roche/Genentech: Consultancy. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees. List:Celgene: Research Funding