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Validation of novel low-dose CT methods for quantifying bone marrow in the appendicular skeleton of patients with multiple myeloma: initial results from the [18F]FDG PET/CT sub-study of the Phase 3 GMMG-HD7 Trial.

PURPOSE: The clinical significance of medullary abnormalities in the appendicular skeleton detected by computed tomography (CT) in patients with multiple myeloma (MM) remains incompletely elucidated. This study aims to validate novel low-dose CT-based methods for quantifying myeloma bone marrow (BM) volume in the appendicular skeleton of MM patients undergoing [1⁸F]FDG PET/CT. MATERIALS AND METHODS: Seventy-two newly diagnosed, transplantation eligible MM patients enrolled in the randomised phase 3 GMMG-HD7 trial underwent whole-body [18F]FDG PET/CT prior to treatment and after induction ther

[The significance of rare chromosomal abnormalities and fetoplacental mosaicism in prenatal diagnosis in the non-invasive prenatal testing era].

UNLABELLED: Összefoglaló. Bevezetés és célkitűzés: A gyakori autoszomális trisomiák és a nemi kromoszómaeltérések a mikroszkóppal észlelhető kromoszóma-rendellenességek kb. 80-85%-át képviselik. A ritka kromoszóma-rendellenességek klinikai következménye jelentős, kimutatásukat a jelenlegi szűrővizsgálatok ugyan nem célozzák, de a teljes kromoszómaszerelvényt vizsgáló, nem invazív praenatalis tesztelés új lehetőséget nyitott a korai felismerésükre. Módszer: Retrospektív analízis (2014-2019) a mikroszkóppal kimutatható kromoszóma-rendellenességek eloszlására, a fetoplacentaris mozaikosság előfor

PD-L1-armored CD19/CD22 dual-targeted CAR-T cell co-infusion bridging to allogeneic hematopoietic stem cell transplantation achieves 7-year sustained remission in an adult patient with early relapsed, chemorefractory B-cell acute lymphoblastic leukemia: a case report.

BACKGROUND: Antigen escape and PD-L1/PD-1 axis-mediated immunosuppression in the tumor microenvironment (TME) are the predominant drivers of … p for B-ALL was performed using 8-color multiparameter flow cytometry (MFC), conventional G-banding cytogenetic analysis, and multiplex leukemia fusion gene screening. Serial lumbar punctures with triple intrathecal chemotherapy (dexamethasone 5 mg + methotrexate 10 mg + cytarabine 30 mg) were performed throughout the treatment course; no abnormalities were detected i …

Role of Sirt3 in mitochondrial biogenesis and developmental competence of human in vitro matured oocytes.

STUDY QUESTION: Does Sirt3 dysfunction result in poor developmental outcomes for human oocytes after in vitro maturation (IVM)? SUMMARY ANS … n embryos was performed with an array comparative genomic hybridization method, and that of ESCs by cytogenetic analysis. The function of the Sirt3 gene was investigated using siRNA and in vitro transcribed mRNA injection. Markers of ESCs were identified using immunofluorescence. MAIN RESULTS AND THE ROLE OF CHANCE: A retrospective analysis revealed a higher spontane …

Romiplostim in patients with refractory aplastic anaemia previously treated with immunosuppressive therapy: a dose-finding and long-term treatment phase 2 trial.

BACKGROUND: Aplastic anaemia is a rare, life-threatening condition, characterised by pancytopenia with hypocellular bone marrow. Haematopoietic stem cells and most progenitor cells express thrombopoietin receptor (c-MPL). Romiplostim is a peptibody with c-MPL agonist activity that stimulates endogenous thrombopoietin production and leads to promoting the proliferation and differentiation of megakaryocytes in the bone marrow. In this phase 2 trial we aimed to assess the activity and safety of romiplostim in patients with aplastic anaemia who were previously treated with immunosuppressive therap

Bortezomib, thalidomide, and dexamethasone with or without daratumumab and followed by daratumumab maintenance or observation in transplant-eligible newly diagnosed multiple myeloma: long-term follow-up of the CASSIOPEIA randomised controlled phase 3 trial.

BACKGROUND: CASSIOPEIA part 1 demonstrated superior depth of response and prolonged progression-free survival with daratumumab in combination with bortezomib, thalidomide, and dexamethasone (D-VTd) versus bortezomib, thalidomide, and dexamethasone (VTd) alone as an induction and consolidation regimen in transplant-eligible patients newly diagnosed with myeloma. In CASSIOPEIA part 2, daratumumab maintenance significantly improved progression-free survival and increased minimal residual disease (MRD)-negativity rates versus observation. Here, we report long-term study outcomes of CASSIOPEIA. ME

Chromosomal changes detected by fluorescence in situ hybridization in patients with acute lymphoblastic leukemia.

OBJECTIVES: To investigate patients with acute lymphoblastic leukemia (ALL) for TEL/AML1 fusion, BCR/ABL fusion, MLL gene rearrangements, and numerical changes of chromosomes 4, 10, 17 and 21 by fluorescence in situ hybridization (FISH) and to determine the relationship and the significance of those findings. METHODS: Fifty-one American patients (34 men and 17 women) were included in this study. Of them there were 41 patients with pro-B cell type ALL, 9 with B cell type ALL and 1 with T cell type ALL. Chromosome metaphases of each sample were prepared according to standard protocols. Fluoresc

Real-world outcomes for multiple myeloma patients after apheresis for planned chimeric antigen receptor T-cell therapy.

BACKGROUND: Chimeric antigen receptor T-cell (CAR-T) therapy is highly active in relapsed/refractory multiple myeloma (RRMM), but manufacturing creates an obligatory waiting period between apheresis and infusion. Patients may deteriorate, progress or die during this window. Analyses that begin follow-up at infusion exclude these patients entirely and cannot describe the experience of all patients who enter the CAR-T pathway. AIM: To describe, in an intention-to-collect fashion, the outcomes of all RRMM patients who underwent T-cell apheresis for planned CAR-T therapy; to characterise the apher

Stem Cell Mobilization Yields with Daratumumab (Dara) and Lenalidomide (Len)-Containing Quadruplet Induction Therapy in Patients with Newly Diagnosed Multiple Myeloma (NDMM): A Real-World Experience at 2 Institutes.

BACKGROUND: Quadruplet therapy has become standard frontline therapy in transplant eligible NDMM patients. Using data from the MASTER and GRIFFIN trials, Chhabra et al. reported that Dara-Len containing quadruplet therapies had minimal impact on stem cell harvesting and engraftment. It is unclear if this remains true in a real-world setting where heterogeneity exists among patients and in institutional practices. Herein, we describe our experience of stem cell mobilization and collection in NDMM patients receiving DRVd at Levine Cancer Institute (LCI) and Emory Winship Cancer Institute. METHO

Case Report: The diagnostic and therapeutic crossroads: when myelofibrosis transforms into mixed phenotype acute leukemia.

BACKGROUND: Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by the proliferation of fibrous tissue in the bone marrow. Transformation to acute leukemia, typically acute myeloid leukemia, represents a terminal event in its natural history; however, transformation to mixed phenotype acute leukemia (MPAL) is exceedingly rare. The diagnosis and treatment of MPAL are particularly challenging, especially in elderly patients with underlying MF. The clinical characteristics, treatment response, and prognosis of such cases remain unclear and are rarely reported. CASE PRESENTATION: Th

Inotuzumab ozogamicin in paediatric very high risk first B-cell acute lymphoblastic leukaemia relapse (ITCC-059): a multicentre, single-arm, phase 2 trial.

BACKGROUND: Children with very high-risk first relapse of B-cell acute lymphoblastic leukaemia have very poor outcomes with conventional chemotherapy. Inotuzumab ozogamicin has shown high antitumoral activity in second or higher relapsed or refractory B-cell acute lymphoblastic leukaemia. We aimed to evaluate the preliminary activity of inotuzumab ozogamicin single-agent in children with very high risk first B-cell acute lymphoblastic leukaemia relapse. METHODS: ITCC-059 was a multicentre, international, single-arm, phase 1-2 trial, designed to identify the recommended dose of inotuzumab ozog

Preimplantation genetic testing is not a preferred recommendation for patients with X chromosome abnormalities.

STUDY QUESTION: Should women with X chromosome abnormalities (XCAs) be recommended to have embryos selected by both morphological and cytogenetic assessment through preimplantation genetic testing (PGT) rather than morphological assessment only in conventional IVF/ICSI treatment? SUMMARY ANSWER: PGT is not a preferred recommendation for women with XCAs in the absence of other PGT indications. WHAT IS KNOWN ALREADY: XCAs are the most frequent sort of chromosomal aberrations in infertile women. Patients with a complete or partial absence of one X chromosome, diagnosed as Turner Syndrome (TS),

NTP technical report on the toxicity studies of Methyl Ethyl Ketone Peroxide (CAS No. 1338-23-4) in Dimethyl Phthalate (CAS No. 131-11-3) (45:55) Administered Topically in F344/N Rats and B6C3F1 Mice.

Methyl ethyl ketone peroxide (MEKP) is an unstable organic peroxide used in the manufacture of acrylic resins, as a hardening agent for fiberglass-reinforced plastics, and as a curing agent for unsaturated polyester resins. It is commercially available as a 40% to 60% solution in dimethyl phthalate (DMP). Because exposure to MEKP is typically through dermal contact, 2-week and 13-week toxicity studies were conducted by topical application of MEKP in DMP (45:55 w/w) to the clipped dorsal region of male and female Fischer 344/N rats and mice. Animals were evaluated for histopathology and for rep

Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study.

BACKGROUND: Elderly patients (aged ≥65 years) with acute myeloid leukaemia have poor outcomes and no effective standard-of-care therapy exists. Treatment with hypomethylating agents such as azacitidine and decitabine is common, but responses are modest and typically short-lived. The oral anti-apoptotic B-cell lymphoma 2 protein inhibitor, venetoclax, has shown promising single-agent activity in patients with relapsed or refractory acute myeloid leukaemia and preclinical data suggested synergy between hypomethylating agents and venetoclax, which led to this combination phase 1b study. METHODS:

Prenatal screening for fetal aneuploidy in singleton pregnancies.

OBJECTIVE: To develop a Canadian consensus document on maternal screening for fetal aneuploidy (e.g., Down syndrome and trisomy 18) in singl … invasive prenatal screening for aneuploidy is available. (II-2A) 4. Invasive prenatal diagnosis for cytogenetic analysis should not be performed without multiple marker screening results except for women who are at increased risk of fetal aneuploidy (a) because of ultrasound findings, (b) because the pregnancy was conceived by in vitro fertilization with intracytoplas …

Abstracts from the 3rd International Genomic Medicine Conference (3rd IGMC 2015) : Jeddah, Kingdom of Saudi Arabia. 30 November - 3 December 2015.

O1 Regulation of genes by telomere length over long distances Jerry W. Shay O2 The microtubule destabilizer KIF2A regulates the postnatal establishment of neuronal circuits in addition to prenatal cell survival, cell migration, and axon elongation, and its loss leading to malformation of cortical development and severe epilepsy Noriko Homma, Ruyun Zhou, Muhammad Imran Naseer, Adeel G. Chaudhary, Mohammed Al-Qahtani, Nobutaka Hirokawa O3 Integration of metagenomics and metabolomics in gut microbiome research Maryam Goudarzi, Albert J. Fornace Jr. O4 A unique integrated system to discern pathoge

Variability of definition of high-risk multiple myeloma across phase III clinical trials.

The definition of high-risk multiple myeloma (HRMM) is evolving. Use of a clear definition of HRMM in clinical trials was not previously studied. We explored the definition of HRMM in completed phase III clinical trials. There is extreme variability in the definition and cutoffs used to define HRMM, with a significant number of studies lacking a clear definition. Our study provides a quantification of the variability in defining HRMM and suggests a need to better define HRMM in future clinical trials to enable more consistent treatment recommendations.

Daratumumab у поддающихся трансплантации пациентов с недавно диагностированным множественным миэломой: окончательный анализ клинических подгрупп в ГРИФФИН.

Случайный, фазы 2 Исследование ГРИФФИНNCT02874742) оценивалась " даратумумаб " плюс " линалидомид " / " бортезомиб "/дексаметасон " (D-RVD) в недавно диагностированной миеломе (NDMM). Мы представляем окончательный послекризисный анализ (средняя последующая деятельность, 49.6 - месяцев) подгрупп, имеющих отношение к клиническим заболеваниям, включая пациентов с повышенным риском цитогенетических аномалий (СПЧ) в соответствии с пересмотренным определением (del[17p], t[4;14], t[14;16], t[14;20], и/или прирост/и/или[1q21]). Полученные пациенты 4 индукционные цикл

A concise revised Myeloma Comorbidity Index as a valid prognostic instrument in a large cohort of 801 multiple myeloma patients.

With growing numbers of elderly multiple myeloma patients, reliable tools to assess their vulnerability are required. The objective of the analysis herein was to develop and validate an easy to use myeloma risk score (revised Myeloma Comorbidity Index) that allows for risk prediction of overall survival and progression-free survival differences in a large patient cohort. We conducted a comprehensive comorbidity, frailty and disability evaluation in 801 consecutive myeloma patients, including comorbidity risks obtained at diagnosis. The cohort was examined within a training and validation set.

Use of Curcumin in Multiple Myeloma patients intolerant of steroid therapy.

Curcumin, when used in a combination regimen in multiple myeloma patients, has comparable progression-free survival without the adverse effects of steroid-based combination therapies that is curcumin may be a viable alternative to corticosteroids in combination with an immunomodulatory drug or proteasome inhibitor.

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… Conventional cytogenetic analysis for each patient was performed at intervals as well as fluorescent in situ hybridization (FISH). Data are expressed as a mean (±1 SD). RESULTS There were fifteen MM patients intolerant of Dex in whom curcumin was used in combination with IMiD’s or PI’s. …