Incidence, outcomes, and risk factors of pleural effusion in patients receiving dasatinib therapy for Philadelphia chromosome-positive leukemia.

Dasatinib, a second-generation BCR-ABL1 tyrosine kinase inhibitor, is approved for the treatment of chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia, both as first-line therapy and after imatinib intolerance or resistance. While generally well tolerated, dasatinib has been associated with a higher risk for pleural effusions. Frequency, risk factors, and outcomes associated with pleural effusion were assessed in two phase 3 trials (DASISION and 034/Dose-optimization) and a pooled population of 11 trials that evaluated patients with chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia treated with dasatinib (including DASISION and 034/Dose-optimization). In this largest assessment of patients across the dasatinib clinical trial program (N=2712), pleural effusion developed in 6-9% of patients at risk annually in DASISION, and in 5-15% of patients at risk annually in 034/Dose-optimization. With a minimum follow up of 5 and 7 years, drug-related pleural effusion occurred in 28% of patients in DASISION and in 33% of patients in 034/Dose-optimization, respectively. A significant risk factor identified for developing pleural effusion by a multivariate analysis was age. We found that overall responses to dasatinib, progression-free survival, and overall survival were similar in patients who developed pleural effusion and in patients who did not. clinicaltrials.gov identifier 00481247; 00123474

Sequenze sismiche: La nuova struttura di Pronto Intervento dell’Istituto Nazionale di Geofisica e Vulcanologia

Fin dai primi anni ‘70, l’Istituto Nazionale di Geofisica e Vulcanologia (INGV, ex ING) si avvale di una struttura di Pronto Intervento in occasione di eventi sismici rilevanti garantendo in tempi relativamente brevi il monitoraggio di dettaglio in area epicentrale. Dal suo primo intervento (terremoto di Ancona 1972) ad oggi, la struttura di Pronto Intervento si è evoluta costantemente implementando migliorie tecnologiche e logistiche. In questo lavoro prensentiamo la nuova struttura impiegata per la prima volta durante l’ ”Operazione Blue Mountains 2008”, l'esercitazione di Protezione Civile sul rischio sismico organizzata dalla Regione Marche il 23-25 maggio 2008

Continuous Flooding or Alternate Wetting and Drying Differently Affect the Accumulation of Health-Promoting Phytochemicals and Minerals in Rice Brown Grain

Climate changes impose adoption of water-saving techniques to improve the sustainability of irrigated rice systems. This study was aimed, by a two-years side-by-side comparison, at verifying the hypothesis whether \u201cAlternate Wetting and Drying\u201d (AWD) affects the concentrations of health-related compounds and minerals in brown grains of three japonica rice (Oryza sativa L.) cvs (\u2018Baldo\u2019, \u2018Gladio\u2019, and \u2018Loto\u2019) usually grown in temperate areas in continuous flooding (CF). Due to the rotational turns in water distribution imposed by local authorities and to the weather behavior, different AWD timing and severity occurred in the two years of the study. AWD induced in both seasons yield losses in \u2018Baldo\u2019 and \u2018Gladio\u2019 but not in \u2018Loto\u2019. In the brown grains of \u2018Loto\u2019, AWD increased the concentrations of total tocols, \u3b3-oryzanol, flavonoids, and the antioxidant activity. AWD affected the concentrations of minerals, particularly increasing copper, cadmium and nickel, and decreasing manganese, arsenic and zinc. In the sensitive cultivars, \u2018Baldo\u2019 and \u2018Gladio\u2019, AWD seems to affect plant yield, rather than for severity of the dry period, for prolonged absence of ponded water that exposes plants to cooler temperatures. The selection of suitable cultivars, like \u2018Loto\u2019, tolerant to AWD-related stresses, could combine environmental, yield-related, and nutritional benefits improving the product quality

Telomere length shortening is associated with treatment-free remission in chronic myeloid leukemia patients

We studied telomere length in 32 CML patients who discontinued imatinib after achieving complete molecular remission and 32 age-sex-matched controls. The relative telomere length (RTL) was determined by q-PCR as the telomere to single copy gene (36B4) ratio normalized to a reference sample (K-562 DNA). Age-corrected RTL (acRTL) was also obtained. The 36-month probability of treatment-free remission (TFR) was 59.4 %. TFR patients showed shorter acRTL compared to relapsed (mean ± SD = 0.01 ± 0.14 vs 0.20 ± 0.21; p = 0.01). TFR was significantly higher in CML patients with acRTL ≤0.09 (78.9 vs 30.8 %, p = 0.002). CML stem cells harboring longer telomeres possibly maintain a proliferative potential after treatment discontinuation

Next-generation sequencing for BCR-ABL1 kinase domain mutation testing in patients with chronic myeloid leukemia: A position paper

BCR-ABL1 kinase domain (KD) mutation status is considered to be an important element of clinical decision algorithms for chronic myeloid leukemia (CML) patients who do not achieve an optimal response to tyrosine kinase inhibitors (TKIs). Conventional Sanger sequencing is the method currently recommended to test BCR-ABL1 KD mutations. However, Sanger sequencing has limited sensitivity and cannot always discriminate between polyclonal and compound mutations. The use of next-generation sequencing (NGS) is increasingly widespread in diagnostic laboratories and represents an attractive alternative. Currently available data on the clinical impact of NGS-based mutational testing in CML patients do not allow recommendations with a high grade of evidence to be prepared. This article reports the results of a group discussion among an ad hoc expert panel with the objective of producing recommendations on the appropriateness of clinical decisions about the indication for NGS, the performance characteristics of NGS platforms, and the therapeutic changes that could be applied based on the use of NGS in CML. Overall, these recommendations might be employed to inform clinicians about the practical use of NGS in CML

Cerebral relapse of metastatic gastrointestinal stromal tumor during treatment with imatinib mesylate: Case report

BACKGROUND: The management of unresectable or metastatic gastrointestinal stromal tumors (GISTs) has previously been difficult as they are resistant to conventional chemotherapy and radiation. The development of imatinib mesylate has made a major impact on the management of advanced GISTs. It is apparent that there are sanctuary sites such as the central nervous system where imatinib does not achieve adequate concentrations. We describe the case of a man with metastatic GIST who experienced multiple cerebral relapses of disease while systemic disease progression appeared to be controlled by imatinib. CASE PRESENTATION: A 47-year-old man presented in July 1999 with a jejunal GIST with multiple hepatic metastases. The jejunal primary was resected and after unsuccessful cytoreductive chemotherapy, the liver metastases were also resected in December 1999. The patient subsequently relapsed in August 2001 with symptomatic hepatic, subcutaneous gluteal, left choroidal and right ocular metastases all confirmed on CT and PET scanning. Biopsy confirmed recurrent GIST. MRI and lumbar puncture excluded central nervous system involvement. The patient was commenced on imatinib 400 mg bd in September 2001 through a clinical trial. The symptoms improved with objective PET and CT scan response until December 2002 when the patient developed a right-sided foot drop. MRI scan showed a left parasagittal tumor which was resected and confirmed histologically to be metastatic GIST. Imatinib was ceased pre-operatively due to the trial protocol but recommenced in February 2003 on a compassionate use program. The left parasagittal metastasis recurred and required subsequent re-excision in September 2003 and January 2004. Control of the systemic GIST was temporarily lost on reduction of the dose of imatinib (due to limited drug supply) but on increasing the dose back to 800 mg per day, systemic disease was stabilized for a period of time before generalised progression occurred. CONCLUSION: This case illustrates that the brain can be a sanctuary site to treatment of GISTs with imatinib. Maintaining dosing of imatinib in the face of isolated sites of disease progression is also important, as other metastatic sites may still be sensitive

Next-generation sequencing for BCR-ABL1 kinase domain mutation testing in patients with chronic myeloid leukemia: A position paper

BCR-ABL1 kinase domain (KD) mutation status is considered to be an important element of clinical decision algorithms for chronic myeloid leukemia (CML) patients who do not achieve an optimal response to tyrosine kinase inhibitors (TKIs). Conventional Sanger sequencing is the method currently recommended to test BCR-ABL1 KD mutations. However, Sanger sequencing has limited sensitivity and cannot always discriminate between polyclonal and compound mutations. The use of next-generation sequencing (NGS) is increasingly widespread in diagnostic laboratories and represents an attractive alternative. Currently available data on the clinical impact of NGS-based mutational testing in CML patients do not allow recommendations with a high grade of evidence to be prepared. This article reports the results of a group discussion among an ad hoc expert panel with the objective of producing recommendations on the appropriateness of clinical decisions about the indication for NGS, the performance characteristics of NGS platforms, and the therapeutic changes that could be applied based on the use of NGS in CML. Overall, these recommendations might be employed to inform clinicians about the practical use of NGS in CML

The serological prevalence of SARS-CoV-2 infection in patients with chronic myeloid leukemia is similar to that in the general population

Background: Patients with hematological malignancies are at an increased risk of SARS-CoV-2 disease (COVID-19) and adverse outcome. However, a low mortality rate has been reported in patients with chronic myeloid leukemia (CML). Preclinical evidence suggests that tyrosine kinase inhibitors (TKIs) may have a protective role against severe COVID-19. Methods: We conducted a cross-sectional study of 564 consecutive patients with CML who were tested for anti-SARS-CoV-2 IgG/IgM antibodies at their first outpatient visit between May and early November 2020 in five hematologic centers representative of three Italian regions. Results: The estimated serological prevalence of SARS-CoV-2 infection in patients with CML after the first pandemic wave was similar to that in the general population (about 2%), both at national and regional levels. CML patients with positive anti-SARS-CoV-2\ua0serology were more frequently male (p\ua0=\ua00.027) and active workers (p\ua0=\ua00.012), while there was no significant association with TKI treatment type. Only 3 out of 11 IgG-positive patients had previously received a molecular diagnosis of COVID-19, while the remainders were asymptomatic or with mild symptoms. Conclusions: Our data confirm that the course of SARS-CoV-2 infection in patients with CML is generally mild and reassure about the safety of continuing TKIs during the COVID-19 pandemic. Furthermore, we suggest that patients with CML succeed to mount an antibody response after exposure to SARS-CoV-2, similar to the general population

Being Grateful for My Stupid Little Life : Why We Need Movies

More and more I’m convinced the current cultural paradigm leaves us too thin. The practical and objective approach to reality doesn’t attend to the complexity and mystery of the created world; it doesn’t attend to the complexity and mystery of our humanity. Posting about how movies help make sense of our experiences from In All Things - an online hub committed to the claim that the life, death, and resurrection of Jesus Christ has implications for the entire world. http://inallthings.org/being-grateful-for-my-stupid-little-life-why-we-need-movies