A revised prognostic model for patients with acute myeloid leukemia and first relapse.

Most patients with acute myeloid leukemia (AML) may obtain remission upon induction chemotherapy, but relapse is frequent and associated with poor survival. Previous prognostic models for outcomes after relapse lacked analysis of comprehensive molecular data. A validated prognostic model integrating clinical, cytogenetic, and molecular variables may support treatment decisions.

Different features of acute myeloid leukemia stem cell quantification in intensively treated patients.

In acute myeloid leukemia, the burden of CD34+CD38- leukemia stem cells (LSC) has prognostic value at diagnosis and after induction chemotherapy. Since different methods of LSC quantification have been proposed, we determined the prognostic value on overall survival and incidence of relapse of these methods across ELN2017 risk groups, using data from the HOVON-SAKK132 trial. In addition, we have evaluated the optimal number of acquired white blood cells for accurate LSC detection and the prognostic value of individual LSC markers.

A data management system for precision medicine.

Precision, or personalised medicine has advanced requirements for medical data management systems (MedDMSs). MedDMS for precision medicine should be able to process hundreds of parameters from multiple sites, be adaptable while remaining in sync at multiple locations, real-time syncing to analytics and be compliant with international privacy legislation. This paper describes the LogiqSuite software solution, aimed to support a precision medicine solution at the patient care (LogiqCare), research (LogiqScience) and data science (LogiqAnalytics) level.

Computational assessment of measurable residual disease in acute myeloid leukemia using mixture models.

Background: The proportion of residual leukemic blasts after chemotherapy assessed by multiparameter flow cytometry, is an important prognostic factor for the risk of relapse and overall survival in acute myeloid leukemia (AML). This measurable residual disease (MRD) is used in clinical trials to stratify patients for more or less intensive consolidation therapy. However, an objective and reproducible analysis method to assess MRD status from flow cytometry data is lacking, yet is highly anticipated for broader implementation of MRD testing.

The role of the primitive marker CD133 in CD34-negative acute myeloid leukemia for the detection of leukemia stem cells.

The most important reason for dismal outcomes in acute myeloid leukemia (AML) is the development of relapse. Leukemia stem cells (LSCs) are hypothesized to initiate relapse, and high CD34+CD38- LSC load is associated with poor prognosis. In 10% of AML patients, CD34 is not or is low expressed on the leukemic cells (<1%), and CD34+CD38- LSCs are absent.

Bayesian interim analysis for prospective randomized studies: reanalysis of the acute myeloid leukemia HOVON 132 clinical trial.

Randomized controlled trials (RCTs) are the gold standard to establish the benefit-risk ratio of novel drugs. However, the evaluation of mature results often takes many years. We hypothesized that the addition of Bayesian inference methods at interim analysis time points might accelerate and enforce the knowledge that such trials may generate.

Prognostic Value of -Internal Tandem Duplication Residual Disease in Acute Myeloid Leukemia.

Purpose: The applicability of -internal tandem duplications (-ITD) for assessing measurable residual disease (MRD) in acute myeloid leukemia (AML) in complete remission (CR) has been hampered by patient-specific duplications and potential instability of -ITD during relapse. Here, we comprehensively investigated the impact of next-generation sequencing (NGS)-based -ITD MRD detection on treatment outcome in a cohort of patients with newly diagnosed AML in relation to established prognostic factors at diagnosis and other MRD measurements, ie, mutant and multiparameter flow cytometry.

Methods: In 161 patients with de novo -ITD AML, NGS was performed at diagnosis and in CR after intensive remission induction treatment.

Concordance in measurable residual disease result after first and second induction cycle in acute myeloid leukemia: An outcome- and cost-analysis.

Measurable residual disease (MRD) measured using multiparameter flow-cytometry (MFC) has proven to be an important prognostic biomarker in acute myeloid leukemia (AML). In addition, MRD is increasingly used to guide consolidation treatment towards a non-allogenic stem cell transplantation treatment for MRD-negative patients in the ELN-2017 intermediate risk group. Currently, measurement of MFC-MRD in bone marrow is used for clinical decision making after 2 cycles of induction chemotherapy.

A systematic review and meta-analysis of adjuvant chemotherapy after chemoradiation for locally advanced cervical cancer.

We investigated whether the addition of adjuvant chemotherapy to chemoradiation improves overall survival (OS) and progression-free survival (PFS) by conducting a systematic review and meta-analysis. Systematic searches in the databases of PubMed, Embase and Web of Science yielded 881 articles. Two reviewer authors independently selected 31 articles for full text review and deemed eight studies eligible for inclusion.

Molecular characterization of mutant TP53 acute myeloid leukemia and high-risk myelodysplastic syndrome.

Substantial heterogeneity within mutant TP53 acute myeloid leukemia (AML) and myelodysplastic syndrome with excess of blast (MDS-EB) precludes the exact assessment of prognostic impact for individual patients. We performed in-depth clinical and molecular analysis of mutant TP53 AML and MDS-EB to dissect the molecular characteristics in detail and determine its impact on survival. We performed next-generation sequencing on 2200 AML/MDS-EB specimens and assessed the TP53 mutant allelic status (mono- or bi-allelic), the number of TP53 mutations, mutant TP53 clone size, concurrent mutations, cytogenetics, and mutant TP53 molecular minimal residual disease and studied the associations of these characteristics with overall survival.

Adjuvant Systemic Therapy after Chemoradiation and Brachytherapy for Locally Advanced Cervical Cancer: A Systematic Review and Meta-Analysis.

Background: Standard of care for locally advanced cervical cancer is chemoradiation and brachytherapy. The addition of adjuvant systemic treatment may improve overall survival. A systematic review and meta-analysis was conducted to summarize evidence on survival outcomes, treatment completion and toxicity.

Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial.

Lenalidomide, an antineoplastic and immunomodulatory drug, has therapeutic activity in acute myeloid leukemia (AML), but definitive studies about its therapeutic utility have been lacking. In a phase 3 study, we compared 2 induction regimens in newly diagnosed patients age 18 to 65 years with AML: idarubicine-cytarabine (cycle 1) and daunorubicin and intermediate-dose cytarabine (cycle 2) without or with lenalidomide (15 mg orally on days 1-21). One final consolidation cycle of chemotherapy or autologous stem cell transplantation (auto-SCT) or allogeneic SCT (allo-SCT) was provided according to a prognostic risk and minimal residual disease (MRD)-adapted approach.

Radiation Exposure From Pediatric CT Scans and Subsequent Cancer Risk in the Netherlands.

Background: Computed tomography (CT), a strong diagnostic tool, delivers higher radiation doses than most imaging modalities. As CT use has increased rapidly, radiation protection is important, particularly among children. We evaluate leukemia and brain tumor risk following exposure to low-dose ionizing radiation from CT scans in childhood.

Molecular Minimal Residual Disease in Acute Myeloid Leukemia.

Background: Patients with acute myeloid leukemia (AML) often reach complete remission, but relapse rates remain high. Next-generation sequencing enables the detection of molecular minimal residual disease in virtually every patient, but its clinical value for the prediction of relapse has yet to be established.

Methods: We conducted a study involving patients 18 to 65 years of age who had newly diagnosed AML.

Comparative Cistromics Reveals Genomic Cross-talk between FOXA1 and ERα in Tamoxifen-Associated Endometrial Carcinomas.

Tamoxifen, a small-molecule antagonist of the transcription factor estrogen receptor alpha (ERα) used to treat breast cancer, increases risks of endometrial cancer. However, no parallels of ERα transcriptional action in breast and endometrial tumors have been found that might explain this effect. In this study, we addressed this issue with a genome-wide assessment of ERα-chromatin interactions in surgical specimens obtained from patients with tamoxifen-associated endometrial cancer.