Real‐world experience in treating pediatric relapsed/refractory or therapy‐related myeloid malignancies with decitabine, vorinostat, and FLAG therapy based on a phase 1 study run by the TACL consortium

alexandrossfakianakis shared this article with you from Inoreader Real‐world experience in treating pediatric relapsed/refractory or therapy‐related myeloid malignancies with decitabine, vorinostat, and FLAG therapy based on a phase 1 study run by the TACL consortium via Pediatric Blood & Cancer Abstract Current therapies for relapsed/refractory (R/R) pediatric myeloid neoplasms are inadequately effective. Real-world data (RWD) can improve care by augmenting traditional studies and include individuals not eligible for clinical trials. The Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) consortium recently completed T2016-003, a phase 1 study of decitabine, vorinostat, fludarabine, cytarabine, and granulocyte colony-stimulating factor (G-CSF) in R/R acute myeloid leukemia (AML), which added epigenetic drugs to a cytotoxic backbone. We report results of RWD from six centers that treated 28 pediatric patients (26 with AML, two with other myeloid neoplasms) identically to the TACL study but who were not enrolled. This allowed unique analyses and the ability to compare data with the 35 TACL study patients. The overall response rate (ORR) (complete response [CR] plus CR with incomplete count recovery) among 26 RWD evaluable patients was 65%. The ORR of 13 patients with re lapsed AML with epigenetic alterations was 69% (T2016-003 + RWD: 68%, n = 25), of eight patients with refractory AML was 38% (T2016-003 + RWD: 41%, n = 17) and of five patients with therapy-related AML (t-AML) was 80% (T2016-003 + RWD: 75%, n = 8). The mean number of Grade 3/4 toxicities experienced by the T2016-003-eligible RWD population (n = 22) (one per patient-cycle) was not meaningfully different than those (n = 6) who would have been TACL study-ineligible secondary to comorbidities (two per patient-cycle). Overall, this therapy was well tolerated and effective in pediatric patients with R/R myeloid neoplasms, particularly those with epigenetic alterations, t-AML, and refractory disease. View on Web

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A sensitive and inexpensive HRM‐based testing algorithm for diagnosis of TAM and myeloid leukemia of Down syndrome

alexandrossfakianakis shared this article with you from Inoreader A sensitive and inexpensive HRM‐based testing algorithm for diagnosis of TAM and myeloid leukemia of Down syndrome via Pediatric Blood & Cancer ABSTRACT Patients with Down syndrome (DS) are commonly affected by a pre-leukemic disorder known as transient abnormal myelopoiesis (TAM). This condition usually undergoes spontaneous remission within the first two months after birth, however in children under 5, 20 – 30% of cases evolve to myeloid leukemia of DS (ML-DS). TAM and ML-DS are caused by co-operation between trisomy 21 and acquired mutations in the GATA1 gene. Currently, only NGS-based methodologies are sufficiently sensitive for diagnosis in samples with small GATA1 mutant clones (≤ 10% blasts). Alternatively, this article presents research on a new, fast, sensitive and inexpensive HRM-based diagnostic approach that allows the detection of most cases of GATA1 mutations, including silent TAM. The algorithm first uses flow cytometry for blast count, followed by high resolution melting (HRM) and Sanger sequencing to search for mutations on exons 2 and 3 of GATA1. We analyzed 138 samples of DS patie nts: 110 of asymptomatic neonates, 10 suspected of having TAM, and 18 suspected of having ML-DS. Our algorithm enabled the identification of 33 mutant samples, among them 5 cases of silent TAM (5/110) and 7 cases of ML-DS (7/18) with blast count ≤ 10%, in which GATA1 alterations were easily detected by HRM. Depending on the type of genetic variation and its location, our methodology reached sensitivity similar to that obtained by NGS (0.3%) at a considerably reduced time and cost thus making it accessible worldwide. This article is protected by copyright. All rights reserved View on Web

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Preoperative hemoglobin A1c and perioperative blood glucose in patients with diabetes mellitus undergoing spinal cord stimulation surgery: a literature review of surgical site infection risk

alexandrossfakianakis shared this article with you from Inoreader Preoperative hemoglobin A1c and perioperative blood glucose in patients with diabetes mellitus undergoing spinal cord stimulation surgery: a literature review of surgical site infection risk via Pain Practice Abstract Aims The aim of our study was to review the surgical literature regarding the relationship between hemoglobin A1c (HbA1c), diagnosis of diabetes mellitus (DM), and risk of post-operative surgical site infection (SSI). Methods A librarian-assisted literature search was performed with two goals: 1) identify surgical publications related to SSI and HbA1c values, and 2) identify publications reporting infection risk with DM in spinal cord stimulation (SCS), intrathecal drug delivery systems (IDDS), and cardiovascular implantable electronic device (CIED) implantation surgeries. Published guidelines on perioperative management of DM are reviewed. Results We identified 30 studies reporting SSI and HbA1c values. The literature review indicated that for many surgical procedures elevated HbA1c is not correlated to rate of SSI. We identified 16 studies reporting infection rates within DM cohorts following SCS, IDDS, and CIED implantation surgeries. The data reviewed did not indicate DM as an independent risk factor for SSI. Conclusion Preoperative HbA1c levels in patients with a history of DM is not a singularly sufficient tool to estimate risk of perioperative infection in SCS implantation surgery. Published guidelines on perioperative management of DM do not suggest a specific HbA1c above which surgery should be delayed; intentional perioperative glycemic control is recommended. View on Web

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Systematic review and meta‐analysis of celiac plexus neurolysis for abdominal pain associated with unresectable pancreatic cancer

alexandrossfakianakis shared this article with you from Inoreader Systematic review and meta‐analysis of celiac plexus neurolysis for abdominal pain associated with unresectable pancreatic cancer via Pain Practice Abstract Introduction Celiac plexus neurolysis (CPN) has been developed as adjunctive therapy to medical management (MM) of abdominal pain associated with unresectable pancreatic cancer. We aimed to conduct a systematic review and meta-analysis to obtain updated and more accurate evidence on the efficacy of additional types of CPN, including endoscopic ultrasound-guided CPN (EUS-CPN). Methods On March 16, 2021, we performed searches of PubMed, Web of Science, and CENTRAL for original randomized controlled trials (RCTs). We defined the primary outcome as a standardized pain intensity score with a range of 0-10, and evaluated the mean difference between the CPN+MM and MM groups at 4, 8, and 12 weeks after the initiation of treatment. We used a random-effects model to synthesize the mean differences across RCTs. Results We selected 10 RCTs involving 646 individuals. The synthesized mean difference in the pain intensity score between the CPN+MM and MM groups was -0.58 (95% confidence interval [CI]: -1.09 to -0.07) (P = 0.034) in favor of CPN+MM at 4 weeks, -0.46 (95%CI: -1.00 to 0.08) (P = 0.081) at 8 weeks, and -1.35 (95%CI: -3.61 to 0.92) (P = 0.17) at 12 weeks. Conclusions This updated meta-analysis of CPN demonstrates its efficacy for managing abdominal pain at 4 weeks. Although there are various limitations, when abdominal pain in patients with unresectable pancreatic cancer is poorly controlled with MM alone, CPN should be an option even if the duration of effect is short-lived, taking into account the absence of serious adverse events. View on Web

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Increased local concentrations of growth factors from leucocyte‐ and platelet‐rich fibrin do not translate into improved alveolar ridge preservation: an intraindividual mechanistic randomized controlled trial

alexandrossfakianakis shared this article with you from Inoreader Increased local concentrations of growth factors from leucocyte‐ and platelet‐rich fibrin do not translate into improved alveolar ridge preservation: an intraindividual mechanistic randomized controlled trial via Journal of Clinical Periodontology Abstract Aims Leucocyte- and platelet-rich fibrin (L-PRF) has been tested for enhancing alveolar ridge preservation (ARP), but little is known about the local release profile of growth factors (GF) and the clinical equipoise related to its efficacy remains. This study compared the patterns of GF release, early soft tissue healing and alveolar ridge resorption following unassisted healing and L-PRF application in non-molar extraction sockets. Materials and Methods Atraumatic tooth extraction of two hopeless teeth per patient was followed by unassisted healing or L-PRF placement to fill the socket in 18 systemically healthy, nonsmoking subjects. This intraindividual trial was powered to assess changes in horizontal alveolar ridge dimensions 1 mm below the crest of alveolar bone. GF concentrations in wound fluid were assessed with a multiplex assay at 6, 24, 72 and 168 hours. Early healing was evaluated with the wound-healing index and changes in soft tissue volumes on serial digital scans. Hard tissue changes were measured on superimposed CBCT images after 5 months of healing. Results L-PRF resulted in higher GF concentrations in WF as compared to the control, but no differences in release patterns or time of peak were observed. No intergroup differences in early healing parameters were observed. Alveolar bone resorption was observed in both groups. No significant intergroup differences were observed in hard tissue healing 1, 3 or 5 mm apical to the original bone crest, or in ability to digitally plan a prosthetically guided implant with or without bone augmentation. Conclusions L-PRF increased the GF concentrations in wound fluid of extraction sockets without shifting the pattern observed in unassisted healing, while the increased delivery did not translate into clinical benefits in early wound healing or ARP. The current findings question the assumption that increased local concentrations of GF by L-PRF translate into improved clinical outcomes. Additional definitive studies are needed to establish the benefits of L-PRF in ARP. (clinicaltrials.gov NCT03985033) View on Web

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Dose of deferasirox correlates with its effects, which differ between low‐risk myelodysplastic syndrome and aplastic anaemia

alexandrossfakianakis shared this article with you from Inoreader Dose of deferasirox correlates with its effects, which differ between low‐risk myelodysplastic syndrome and aplastic anaemia via Journal of Clinical Pharmacy and Therapeutics This study retrospectively evaluated the efficacy, safety and dose–effect relationships of deferasirox (DFX) in patients with low-risk myelodysplastic syndrome (MDS) and aplastic anaemia (AA) who were refractory to regular treatment in a real-world setting. We found that a significant decrease in serum ferritin (SF) and an improvement in haematologic parameters, organ function and even overall survival (OS) can be achieved if the accumulated DFX dose reaches a certain level. Patients with low-risk MDS need a higher dose than those with AA. Abstract What is known and objective Patients with low-risk myelodysplastic syndrome (MDS) and aplastic anaemia (AA) often need transfusions, which may accelerate iron overload. The aim of this study was to evaluate the efficacy, safety and dose–effect relationships of deferasirox (DFX) in patients with low-risk MDS and AA who were refractory to regular treatment in a real-world setting. Methods Patient data were recorded, and dose–effect relationships of DFX were calculated after the first 6 months. Total annual exposure to DFX was calculated after 12 months and expressed as the accumulated exposure time at a dosage of 20 mg/kg/day. Results and discussion Sixty-one patients with low-risk MDS and 51 with AA were enrolled. The minimum dosage of DFX needed for a significant serum ferritin (SF) decrease was 20 mg/kg/day at 6 months, and the minimum accumulation of DFX had to reach 9 months at 20 mg/kg/day by 12 months for patients with low-risk MDS. For patients with AA, the minimum dosage was 10 mg/kg/day at 6 months, and the minimum accumulation had to reach 3 months at 20 mg/kg/day by 12 months. With the same exposure, significant improvements in haematological parameters were also observed in AA. Lower liver enzymes compared with baseline were observed. Gastrointestinal disorders and elevated serum creatinine were the most common side effects. Higher exposure to DFX correlated with longer overall survival (OS). What is new and conclusion A significant decrease in SF and an improvement in haematologic parameters, organ function and even OS can be achieved if the accumulated DFX dose reaches a certain level. Patients with low-risk MDS need a higher dose than those with AA. View on Web

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Comparative effectiveness and stage‐shift effect of endoscopic exam among newly diagnosed oral cancer patients with different stages in Taiwan

alexandrossfakianakis shared this article with you from Inoreader Comparative effectiveness and stage‐shift effect of endoscopic exam among newly diagnosed oral cancer patients with different stages in Taiwan via Head & Neck Abstract Background Patients with oral cancer are at higher risk of developing second primary esophageal cancer (SPEC) and the consensus for screening strategies remains unclear. This study aimed to examine comparative effectiveness and the stage-shift effect of endoscopic exam among patients with oral cancer. Method A population-based longitudinal retrospective observational matched case and control cohort study with at least 5 years follow-up was conducted. We identified 45 457 newly diagnosed patients with oral cancer, 2004–2013, and the eligible patient with oral cancer was 39 401. Propensity score matching was used to match comparable groups, and the two groups (screening vs. nonscreening) was 5941, individually. The study primary endpoints were to compare detection of incident SPEC and the stage-shift effect of endoscopic screening between screened and nonscreened incident oral cancer patients. Cox proportional hazard and competing risk models were analyzed. Statistical analyses were conducted in 2020–2021. Result Detection of incident SPEC in the screened group was significantly higher than in the nonscreened group (hazard ratio: 2.92, 95% confidence interval [CI]: 2.29–3.72). The stage-shift effect from endoscopic screening was found overall in patients with oral cancer (odds ratio [OR]: 0.39, 95%CI: 0.21–0.70), in particular in advanced-stage patients (OR: 0.25, 95%CI: 0.11–0.61), but not in early-stage patients (OR: 0.60, 95%CI: 0.26–1.40). Conclusion This study confirmed that endoscopic screening achieved early detection of SPEC among patients with oral cancer. To improve the screening stage-shift effect, patients with oral cancer are encouraged to undergo routine endoscopic screening. View on Web

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Kidney transplant from hepatitis C viremic donors into aviremic recipients and risk for post‐transplant BK and CMV infection

alexandrossfakianakis shared this article with you from Inoreader Kidney transplant from hepatitis C viremic donors into aviremic recipients and risk for post‐transplant BK and CMV infection via Transplant Infectious Disease Abstract Background kidney transplantation from HCV-viremic donors to uninfected recipients is associated with excellent short-term outcomes. However, HCV viremia might be associated with an increased risk for post-transplant viral complications. Methods We designed a retrospective study of HCV-negative kidney-only transplant recipients between 2018 and 2020. Recipients were grouped into group 1; HCV-negative donors, and group 2; HCV-viremic donors. Patients were matched 1:1 using propensity score. Primary objectives were to compare the incidence of CMV viremia ≥ 200 ml/IU, and BK viremia ≥1000 copies/ml between the groups. Secondary outcomes included group comparison of CMV disease, BK viremia ≥10,000 copies/ml, and one year patient and allograft survival. Results The study included 634 patients in group 1, and 71 patients in group 2. 65 pairs of patients were matched. Incidence of CMV viremia (33.3% vs 40.0%, p = 0.4675), and BK viremia (15.9% vs 27.7%, P = 0.1353) did not differ significantly between groups in the matched cohort. Incidence of CMV disease (81.0% Vs 76.9%; p = 1.000), and BK viremia ≥10,000 copies/ml (9.5% vs 16.9%, p = 0.2987) were comparable between groups. There was no difference in the one-year patient or allograft survival between groups. Conclusion kidney transplant from HCV-viremic donors is not associated with increased risk for BK or CMV viremia. This article is protected by copyright. All rights reserved View on Web

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