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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The impact of pre‐transplant serum ferritin on haploidentical hematopoietic stem cell transplant for acquired severe aplastic anemia in children and adolescents

alexandrossfakianakis shared this article with you from Inoreader The impact of pre‐transplant serum ferritin on haploidentical hematopoietic stem cell transplant for acquired severe aplastic anemia in children and adolescents via Pediatric Blood & Cancer Abstract Haploidentical hematopoietic stem cell transplant (haplo-HSCT) provides an important alternative for children and adolescents with acquired severe aplastic anemia (SAA) lacking of matched donors. To test whether pre-transplant serum ferritin (SF) represents a candidate predictor for survival and a potential biomarker for graft-versus-host disease (GvHD) in pediatric haplo-HSCT, we retrospectively evaluated 147 eligible patients with SAA who underwent haplo-HSCT. The patients were divided into the low-SF group (< 1000 ng/ml) and the high-SF group (≥ 1000 ng/ml). We found that SF ≥1000 ng/ml independently increased the risk of grade II-IV aGvHD (HR = 2.596, 95% CI 1.304-5.167, p = .007) and grade III-IV aGvHD (HR = 3.350, 95% CI 1.162-9.658, p = .025). Similar probabilities of transplant-related mortality at 100 days were observed in the two groups (6.19 ± 2.45% vs 8.00 ± 3.84%, p = .168). The 2-year overall survival (85.29 ± 3.89% vs 92.00 ±3.84%, p = .746) and fai lure-free survival (83.23% ± 4.08% vs 83.37 ± 6.27%, p = .915) were comparable. GvHD-/failure-free survival were 60.06 ± 5.10% and 75.56 ± 6.87%, respectively (p = .056). In conclusion, the elevated pre-transplant SF level is associated with higher incidences of grade II-IV aGvHD and grade III-IV aGvHD. However, it is not associated with worse survival after haplo-HSCT for children and adolescent patients with SAA. This article is protected by copyright. All rights reserved View on Web

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High‐frequency temperature monitoring at home using a wearable device: A case series of early fever detection and antibiotic administration for febrile neutropenia with bacteremia

alexandrossfakianakis shared this article with you from Inoreader High‐frequency temperature monitoring at home using a wearable device: A case series of early fever detection and antibiotic administration for febrile neutropenia with bacteremia via Pediatric Blood & Cancer Abstract We present a case series of three febrile episodes in neutropenic pediatric cancer patients who wore a Food and Drug Administration approved high-frequency temperature monitoring (HFTM) wearable device (WD) at home. The WD detected fever events when temperature monitoring by thermometer did not detect fever or was not feasible to perform. Two of the episodes were associated with bloodstream infections and the WD detected fevers 5 and 12 h prior to fevers detected by thermometer, triggering earlier medical evaluation and more prompt administration of antibiotics. These observations provide a basis for future investigation of home-based HFTM to improve infection-related outcomes in pediatric oncology. View on Web

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Asphericity of tumor [123I]mIBG uptake as a prognostic factor in high‐risk neuroblastoma

alexandrossfakianakis shared this article with you from Inoreader Asphericity of tumor [123I]mIBG uptake as a prognostic factor in high‐risk neuroblastoma via Pediatric Blood & Cancer Abstract Background In recent years, many research groups have attempted to identify a subgroup of "ultra-high risk" patients within the high-risk neuroblastoma (NB) category. The aim of our study was to evaluate the prognostic significance of parameters derived from pretherapeutic 123I-meta-iodobenzylguanidine ([123I]mIBG) integrated single photon emission computed tomography and computed tomography in high-risk patients with NB. Methods The established parameters metabolic tumor volume (MTV), maximal standardized uptake value (SUVmax) and the novel parameter tumor asphericity as well as clinical (age, stage) and genetic factors (1p/11q deletions and MYCN amplification) were analyzed in this single-center retrospective study of high-risk patients with newly diagnosed NB. Univariate/multivariable Cox regression and propensity score matching were performed for clinical and radiological parameters. Results Twenty-eight high-risk patients with NB were included (14 males, median age 28.8 (11.3–41.0), range 3–74 months). Multivariable analysis of "full" cohort identified high asphericity (≥65%, adjusted hazard ratio [HR] 5.32, 95% confidence interval [CI]: 1.18–24.07, p = .03) and MTV (≥50 ml, adjusted HR 4.31, 95% CI: 1.18–15.80, p = .027) as the only factors associated with worse event-free survival. In matched cohort, tumor asphericity was a significant predictor of relapse/progression (HR 3.83, 95% CI: 1.03–14.26, p = .046). Conclusion In this exploratory study, imaging parameters related to tumor metabolic activity, tumor asphericity and MTV, provided prognostic value for event-free survival in high-risk NB patients. Asphericity ≥65% and MTV ≥50 ml may serve as additional prognostic factors to those already used. View on Web

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Prospective registration of symptoms and times to diagnosis in children and adolescents with central nervous system tumors: A study of the Swedish Childhood Cancer Registry

alexandrossfakianakis shared this article with you from Inoreader Prospective registration of symptoms and times to diagnosis in children and adolescents with central nervous system tumors: A study of the Swedish Childhood Cancer Registry via Pediatric Blood & Cancer Abstract Background The elapsed time taken to diagnose tumors of the central nervous system in children and adolescents varies widely. The aim of the present study was to investigate such diagnostic time intervals at a national level in Sweden as they correlate with clinical features. Methods Data prospectively accumulated over a 4-year period in the Swedish Childhood Cancer Registry from patients aged 0–18 years were pooled, and diagnostic time intervals were analyzed considering tumor location, tumor type, patient age and sex, initial symptoms, and clinical timelines. All six pediatric oncology centers in Sweden contributed to collection of data. Time points for calculating the total diagnostic interval (TDI) defined as the time from symptom onset to diagnosis were reported in 257 of 319 patients (81%). Results The time from symptom onset to the first healthcare consultation, median 2.6 weeks, did not vary significantly between patients categorized according to tumor type or location. The median TDI was 8.3 weeks for the 4-year study period. Patients with optic pathway glioma (TDI 26.6 weeks), those with tumors of the spinal cord (TDI 25.9 weeks), and those with midline tumors (TDI 24.6 weeks) had the longest lead times. Additionally, older age, too few initial symptoms, and seeking initial redress outside an emergency ward were factors associated with a longer time to diagnosis. Conclusion This study identified several factors associated with delayed diagnosis of central nervous system tumors among Swedish children and adolescents. These novel data ought to help direct future efforts toward clinical improvement. 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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