Recent studies have shown that more than 80% of bone marrow (BM) samples from patients with myelodysplastic syndrome (MDS) harbor somatic mutations and/or genomic aberrations, which are of diagnostic and prognostic importance. We investigated the potential use of peripheral blood (PB) and serum to identify and monitor BM-derived genetic markers using high-resolution single nucleotide polymorphism array (SNP-A) karyotyping and parallel sequencing of 22 genes frequently mutated in MDS. This pilot study showed a 100% SNP-A karyotype concordance and a 97% mutation concordance between the BM and PB. In contrast, mutation analysis using Sanger sequencing of PB and serum-derived DNA showed only 65% and 42% concordance to BM, respectively. Our results show the potential utility of PB as a surrogate for BM for MDS patients, thus avoiding the need for repeated BM aspirates particularly in elderly patients and those with fibrotic or hypocellular marrows.

Barrier chemicals are used for coating a substrate fabric surface when air-proofness or water-proofness is desired in military operations. The properties of the base fabric changes depending upon the barrier chemical employed for coating. In this study, authors selected inherently flame retardant Kevlar as base fabric and coating was done using four chemicals viz: Natural rubber (NR), Polyurethane (PU), Neoprene, and Hypalon. While NR and PU readily burn, Neoprene and Hypalon resist ignition due to the presence of chlorine atom. The resultant flame retardant properties were studied using UL-94 V and NFPA-701 methods. Although Kevlar is flame retardant in nature, it was observed that some coatings burned readily leaving behind charred base fabric.

The research examines the outcomes of shear and flexure testing on reinforced concrete beams made from steel and polypropylene fibre. As well as assessing the impact of fibre in this structural integrity with shear strengthening ratios, certain elements in the characteristics of the cement that is both new and hardened are presented. 14 square beams being put into practice. Tests were made. There were beams produced from 7 distinct mixing dimensions, depending on the kind and the fibre content. For each composite mix there were two beams: one with and the other without stirrups. The primary changes caused by the introduction of fibres were enhanced shear strength, rigidity (especially after the first breaking stage) and ductility. The characteristics of hard concrete (tensile strength, compressive strength and elasticity modules), longitudinal reinforcement concrete, stresses in stirrups, were other factors utilized for the analysis of performance (at the compression and web zone).

Background: One third of patients with myelodysplastic syndrome (MDS) relapse after allogeneic stem cell transplantation (HCT). Early detection of impending relapse would enable pre-emptive treatment and potentially reduce relapse risk but is limited by the lack of sensitive markers for measurable residual disease (MRD). We developed a pipeline where patient-specific mutations, as determined by a myeloid next generation sequencing (NGS) panel are tracked using digital droplet PCR (ddPCR). Aims: To evaluate if personalized MRD detection by ddPCR can predict clinical relapse earlier than conventional methods. Methods: The prospective study (NCT02872662) enrolled patients with MDS, MDS/MPN or MDS-AML with < 30% marrow blasts undergoing HCT. Patients were included before HCT, and serial bone marrow (BM) samples were collected every third month post-HCT for 2 years. Peripheral blood (PB) samples were collected monthly. MRD results were not available for the treating physician. Results: We screened 286 pts between 2016 and 2020, whereof 20 were excluded mainly due to lack of genetic aberration or no HCT performed. 266 pts were included from 12 HCT centers. Median age was 64 (18-78) years and 59% were male. Myeloid panel NGS screening identified a median of 2 (0-9) mutations. The most common mutations were TET2 (n=85), ASXL1 (n=73) and SRSF2 (n=59). Median time of follow up was 886 (4-1934) days. Sixty pts relapsed after a median of 189 (53-1281) days and 46 died due to non-relapse mortality after a median of 121 (4-1036) days. Remaining pts (n=160) were in continuous complete remission (CCR) after a median follow-up of 1053 (479-1934) days. Estimated 1 and 2y overall survival was 79%, and 71%, respectively, while estimated 1 and 2y relapse-free survival (RFS) was 75% and 66%, respectively. MRD data was missing in 46 pts; no post-HCT samples available (n=15), no mutation detected (n=14) and difficulties to design ddPCR primers (n=11). 221 pts were available for MRD analysis with a median number of 4 (0-13) and 5 (0-23) samples from BM and PB, respectively. Of 53 clinical relapses with MRD results available, 42 were preceded by pos MRD (>0.1%) with a median of 70 (range 20-425) days between first pos MRD and clinical relapse. For the 11 remaining pts, 8 were inadequately sampled with a median time of 189 (82-397) days between last sampling and clinical relapse. One patient had an extramedullary relapse only. Of 31 pts who died without relapse, 19 were consistently MRD neg, while 5 were borderline positive (MRD > 0.1% and <0.5%) during the first 100 days but negative thereafter. Four MRD+ patients died without clinical relapse. Three pts were initially MRD+ but turned negative, all of which had chronic GVHD (cGVHD). Of 136 CCR patients, 94 were consistently MRD neg; 26 were borderline pos (MRD > 0.1% and <0.5%) during the first 100 days followed by neg samples; 16 were MRD positive (either > 0.5% during the first 100d or > 0.1% after 100d) of which 10 had a transition from pos to neg samples (all had cGVHD); one patient was treated for a molecular relapse detected by clinical routine method (FISH) and five patients were MRD positive at time of last follow-up. MRD used as a time-dependent co-variate was negatively associated with RFS (HR 7.1, p<0.01). Estimated cumulative incidence of relapse and non-relapse mortality 2y after pos MRD was 60% and 7% respectively (see figure). Image:Summary/Conclusion: We report the development of a highly functional personalized MRD pipeline based on patient-specific mutations showing a high sensitivity to predict relapse and relapse-free survival.

The only potential cure for patients with myelodysplastic syndrome (MDS) is allogeneic hematopoietic stem cell transplantation (HCT). However, a proportion of patients who are HCT candidates do not finally get transplanted. This population-based study aimed to characterize HCT candidates were attempting to reach HCT fail and to identify causes and risk factors for failure. Data were collected from (1) the national Swedish registry, enrolling 291 transplant candidates between 2009–2018, and (2) Karolinska University Hospital, enrolling 131 transplantation candidates between 2000 and 2018. Twenty-five % (nation-wide) and 22% (Karolinska) failed to reach HCT. Reasons for failure to reach HCT were progressive and refractory disease (47%), no donor identified (22%), identification of comorbidity (18%), and infectious complications (14%). Factors associated with failure to reach HCT were IPSS-R cytogenetic risk-group very poor, mixed MDS/MPN disease, low blast count (0–4.9%), and low hemoglobin levels (≤7.9 g/dL). Transplanted patients had a longer overall survival (OS) compared to patients who failed to reach transplantation (83 months versus 14 months; p < 0.001). The survival advantage was seen for the IPSS-R risk groups intermediate, high, and very high. This study demonstrated that a high proportion of HCT-candidates fail to reach HCT and underlines the difficulties associated with bridging MDS patients to HCT.

In patients with chronic myelogenous leukemia (CML), point mutations in the BCR-ABL1 kinase domain are the most common cause of treatment failure with a tyrosine kinase inhibitor (TKI). It is not clear whether the splice variant BCR-ABL135INS is also associated with treatment failure.We reviewed all CML patients who had BCR-ABL1 kinase mutation analysis performed between August 1, 2007, and January 15, 2014. Patients who had BCR-ABL135INS detected had their medical records reviewed to determine response to TKI therapy.Two hundred and eighty four patients had kinase mutation testing performed; of these, 64 patients (23%) had BCR-ABL135INS detected. Forty-five patients were in chronic phase (70%), 10 were in accelerated phase (16%), 6 were in blastic phase (9%), and 3 were in other settings (5%). Of the 34 chronic phase patients who began therapy with imatinib, 23 patients (68%) failed therapy: 8 patients (24%) had primary refractory disease, 11 patients (32%) progressed, and 4 patients (12%) had disease progression after dose interruption. In contrast to the patients with disease progression or lack of response, none of 23 patients who were responding to imatinib had BCR-ABL135INS detected. DNA sequencing of commonly mutated spliceosomal genes SF3B1, U2AF1, SRSF2, ZRSR2, SFA31, PRPF408, U2A565, and SF1 did not reveal mutations in seven BCR-ABL135INS –positive patients tested.The splice variant BCR-ABL135INS is frequently found in patients who are resistant to imatinib. Mutations in the commonly mutated spliceosomal proteins do not contribute to this association.

METHYLATION AGE IN MPN PATIENTS AS A CORRELATE FOR DISEASE STATUS, ALLELE BURDEN AND THERAPEUTIC RESPONSE

Validation Of Prognostic Scoring Systems For Myelodysplastic Syndromes In The Swedish Mds-Register

Influence of IL-28B and IL-6 Genetic Polymorphism on IFN-ALFA Treatment Outcome in Patients with Polycythemia Vera and Essential Trombocythemia