Estimativa da produtividade da água para o milho irrigado em Minas Gerais.

CONBEA 2014

Determinação da produtividade para diferentes épocas de semeadura do milho irrigado em Minas Gerais utilizando modelagem computacional.

CONBEA 2014

Physicians’ Perceptions of Clinical Utility of a Digital Health Tool for Electronic Patient-Reported Outcome Monitoring in Real-Life Hematology Practice. Evidence From the GIMEMA-ALLIANCE Platform

Digital health tools are increasingly being used in cancer care and may include electronic patient-reported outcome (ePRO) monitoring systems. We examined physicians’ perceptions of usability and clinical utility of a digital health tool (GIMEMA-ALLIANCE platform) for ePRO monitoring in the real-life practice of patients with hematologic malignancies. This tool allows for the collection and assessment of ePROs with real-time graphical presentation of results to medical staff. Based on a predefined algorithm, automated alerts are sent to medical staff. Participating hematologists completed an online survey on their experience with the platform. Of the 201 patients invited to participate between December 2020 and June 2021 (cut-off date for current analysis), 180 (90%) agreed to enter the platform and had a median age of 57 years. Twenty-three hematologists with a median age of 42 years and an average of 17 years of experience in clinical practice were surveyed. All hematologists agreed or strongly agreed that the platform was easy to use, and 87%, agreed or strongly agreed that ePROs data were useful to enhance communication with their patients. The majority of physicians (78%) accessed the platform at least once per month to consult the symptom and health status profile of their patients. The frequency of access was independent of physician sex (p=0.393) and years of experience in clinical practice (p=0.404). In conclusion, our preliminary results support the clinical utility, from the perspective of the treating hematologist, of integrating ePROs into the routine cancer care of patients with hematologic malignancies

Cerebrospinal fluid xanthochromia after pegasparaginase hepatotoxicity in B-cell acute lymphoblastic leukemia

Patients with B-lineage acute lymphoblastic leukemia treated with pegasparaginase-containing regimens can develop hepatotoxicity related to it. The systemic hyperbilirubinemia due to hepatotoxicity can lead to the development of CSF xanthochromia

Targeting p53 in chronic lymphocytic leukemia

Introduction: Genomic studies have allowed to identify molecular predictors for chronic lymphocytic leukemia (CLL) treatment tailoring. TP53 disruption is the strongest predictor of chemo-refractoriness and its assessment is the first decisional node in the disease treatment algorithm. Areas covered: The review covers the p53 biological pathway, its genetic alterations and clinical implications in CLL, and its druggable targets. The potential therapeutic options for TP53 disrupted patients are described, including: i) agents circumventing TP53 disruption; ii) targeted therapies restoring the physiological function of mutant p53; and iii) medicines potentiating p53 function. Expert opinion: The key approach to improve CLL outcome is treatment tailoring in individual patients. BCR and BCL2 inhibitors have significantly improved CLL survival, however TP53 disrupted patients still have a less favorable outcome than wild type cases, possibly because these novel drugs do not directly target p53 and do not restore the function of the disrupted p53 pathway. Emerging innovative molecules in cancer are able to restore the p53 mutant protein and/or potentiate the activity of the p53 wild type protein. If these compounds were confirmed as efficacious also for CLL, they would represent another step forward in the care of high risk CLL patients with TP53 abnormalities

Genetic predisposition to myelodysplastic syndromes: A challenge for adult hematologists

Myelodysplastic syndromes (MDS) arising in the context of inherited bone marrow failure syndromes (IBMFS) differ in terms of prognosis and treatment strategy compared to MDS occurring in the adult population without an inherited genetic predisposition. The main molecular pathways affected in IBMFS involve telomere maintenance, DNA repair, biogenesis of ribosomes, control of proliferation and others. The increased knowledge on the genes involved in MDS pathogenesis and the wider availability of molecular diagnostic assessment have led to an improvement in the detection of IBMFS genetic predisposition in MDS patients. A punctual recognition of these disorders implies a strict surveillance of the patient in order to detect early signs of progression and promptly offer allogeneic hematopoietic stem cell transplantation, which is the only curative treatment. Moreover, identifying an inherited mutation allows the screening and counseling of family members and directs the choice of donors in case of need for transplantation. Here we provide an overview of the most recent data on MDS with genetic predisposition highlighting the main steps of the diagnostic and therapeutic management. In order to highlight the pitfalls of detecting IBMFS in adults, we report the case of a 27-year-old man affected by MDS with an underlying telomeropathy

Inducible T-cell co-stimulator (ICOS) and ICOS ligand are novel players in the multiple-myeloma microenvironment

The inducible T-cell co-stimulator (ICOS) is a T-cell receptor that, once bound to ICOS ligand (ICOSL) expressed on several cell types including the B-cell lineage, plays a decisive role in adaptive immunity by regulating the interplay between B and T cells. In addition to its immunomodulatory functions, we have shown that ICOS/ICOSL signalling can inhibit the activity of osteoclasts, unveiling a novel mechanism of lymphocyte–bone cells interactions. ICOS and ICOSL can also be found as soluble forms, namely sICOS and sICOSL. Here we show that: (i) levels of sICOS and sICOSL are increased in multiple myeloma (MM) compared to monoclonal gammopathy of undetermined significance and smouldering MM; (ii) levels of sICOS and sICOSL variably correlate with several markers of tumour burden; and (iii) sICOS levels tend to be higher in Durie–Salmon stage II/III versus stage I MM and correlate with overall survival as an independent variable. Moreover, surface ICOS and ICOSL are expressed in both myeloma cells and normal plasma cells, where they probably regulate different functional stages. Finally, ICOSL triggering inhibits the migration of myeloma cell lines in vitro and the growth of ICOSL+ MOPC-21 myeloma cells in vivo. These results suggest that ICOS and ICOSL represent novel markers and therapeutic targets for MM

Lymphocyte Doubling Time As A Key Prognostic Factor To Predict Time To First Treatment In Early-Stage Chronic Lymphocytic Leukemia

The prognostic role of lymphocyte doubling time (LDT) in chronic lymphocytic leukemia (CLL) was recognized more than three decades ago when the neoplastic clone\u2019s biology was almost unknown. LDT was defined as the time needed for the peripheral blood lymphocyte count to double the of the initial observed value. Herein, the LDT prognostic value for time to first treatment (TTFT) was explored in our prospective O-CLL cohort and validated in in two additional CLL cohorts. Specifically, newly diagnosed Binet stage A CLL patients from 40 Italian Institutions, representative of the whole country, were prospectively enrolled into the O-CLL1-GISL protocol (clinicaltrial.gov identifier: NCT00917540). Two independent cohorts of newly diagnosed CLL patients recruited respectively at the Division of Hematology in Novara, Italy, and at the Hospital Clinic in Barcelona, Spain, were utilized as validation cohorts. In the training cohort, TTFT of patients with LDT >12 months was significantly longer related to those with a shorter LDT. At Cox multivariate regression model, LDT 64 12 months maintained a significant independent relationship with shorter TTFT along with IGHV unmutated (IGHVunmut) status, 11q and 17p deletions, elevated \u3b22M, Rai stage I-II, and NOTCH1 mutations. Based on these statistics, two regression models were constructed including the same prognostic factors with or without the LDT. The model with the LTD provided a significantly better data fitting (\u3c72 = 8.25, P=0.0041). The risk prediction developed including LDT had better prognostic accuracy than those without LDT. Moreover, the Harrell\u2019C index for the scores including LDT were higher than those without LDT, although the accepted 0.70 threshold exceeded in both cases. These findings were also confirmed when the same analysis was carried out according to TTFT\u2019s explained variation. When data were further analyzed based on the combination between LDT and IGHV mutational status in the training and validation cohorts, IGHVunmut and LDT>12months group showed a predominant prognostic role over IGHVmut LTD 64 12 months (P=0.006) in the O-CLL validation cohort. However, this predominance was of borden-line significance (P=0.06) in the Barcelona group, while the significant prognostic impact was definitely lost in the Novara group. Overall, in this study, we demonstrated that LDT could be re-utilized together with the more sophisticated prognostic factors to manage the follow-up plans for Binet stage A CLL patients