ABSTRACT
Geological education plays a major role in the social, economic, and cultural growth and development of any coun-try. India is a vast diversified country with wide-ranging geological features, consisting of rocks of all geological ages with well-developed physiographic divisions. The Indian lithospheric plate is a storehouse of vast georesources and also serves as a natural field laboratory for developing and testing numerous geological principles. The exploration of Indian georesources began in the past;with the organized exploration began way back in the 1830s. The number of institutions offering geological education is, however, comparatively low. Thus, Geology as a science discipline is less popular in comparison with other science subjects such as Physics, Chemistry, Zoology, Botany, and Environmental science, based on enrolment data of the learners enrolled in academic sessions from 2011-2012 to 2018-2019 of the Master's degree programs. Analysis indicates that teaching-learning resources of foreign origin are dominantly being adopted as learning resources in the teaching-learning pedagogy of degree programs in Geology, and are over-riding those of Indian origin. The COVID-19 pandemic is affecting geological education in two ways namely, the disruption of conventional (face-to-face) teaching together with not allowing learners of Geology programs to complete their compulsory out-door geological fieldwork assignments. The analysis of data gathered by an online questionnaire survey shows that the use of indigenous open educational resources in Geology appears as a plausible solution to overcome the learning barriers created by the COVID-19 pandemic, and also to enrich teaching-learning resources of Indian origin. This article provides an up-to-date detailed account of the necessity and evolution of geological education, the current popularity of Geology as a science discipline, the nature of available geological teaching-learning resources, the impact of the COVID-19 on geological education, and the role of open educational resources in providing quality and equita-ble geological education, whilst removing educational barriers created by COVID-19 in India. © 2022, Universidad Nacional de Colombia. All rights reserved.
ABSTRACT
Genetic and Clinical Background: The clinical outcome of Core Binding Factor Leukemia (CBFL) seems influenced by the mutational status of KIT. In fact, several retrospective studies, in addition to our own, as well as a systematic review, indicate that KIT mutations have a negative prognostic impact in AML with t(8;21) or, to a lesser extent, with inv(16)/t(16;16). In addition, gene expression studies found KIT to be highly expressed in CBFL regardless of its mutational status. Furthermore, recent studies have identified novel recurrent somatic mutations co-occurring with KITmut. In-vitro studies revealed that Midostaurin (Mido) is effective in inhibiting both wild type (WT) and a range of KIT mutants. In addition, it is proven to be effective in KIT-positive malignancies such as Aggressive Systemic Mastocytosis (ASM), Mast Cell Leukemia (MCL), and SM with Associated Hematological Neoplasm (SM-AHN). With this background, we designed a Phase II trial to evaluate the safety and efficacy of Mido in association with Intensive Chemotherapy (IC), in CBFL regardless of KIT mutational status. Methods: The inclusion criteria were the following: age 18 to 60 years, diagnosis of de-novo CBFL, adequate organ function, signed informed consent. The exclusion criteria were: central nervous system involvement, uncontrolled infections, other active malignancies, a Qtc value greater than 470 ms (according to Bazett formula) at the electrocardiogram, significant uncontrolled or active cardiovascular diseases. Patients received standard induction therapy with an anthracycline containing regimen (“7+3”-like) + Mido, three cycles of post-remission consolidation chemotherapy with high-dose cytarabine + Mido, and 12 months of Mido as Maintenance. The Mido dosage was: 50 mg orally twice a day, on days 8-21, in association with IC, and 50 mg orally twice a day as single agent maintenance. In order to attain a reduction in 2 years Relapse Incidence (RI), from the historical value of 48% to 28% (Primary Objective of the Study), we plan to enrol 39 patients (power 82%, alpha error 4,6%). At diagnosis all patients were studied by a comprehensive NGS panel targeting 40 DNA genes and 29 RNA fusion driver genes. MRD status was assessed by qPCR and high-resolution multicolor flow cytometry at established check-points during consolidation and maintenance therapy. Results: 17 patients were enrolled between December 2018 to April 2020 (table1). Overall, the CR rate was 94.2%. At a median follow-up of 9 months (range 3-19 months), we recorded a RI of 12.5%, an OS of 93.7%, and a DFS of 81.2%. 16 patients continue on study and 14 patients are in 1st CR, MRD-negative by flow cytometry and qPCR. Six patients (35.2 %) experienced 12 Treatment Emergent Adverse Event (TEAE), 10 out of whom were infections, with grade 3-4 neutropenia (Table 2). We only recorded one death from SARS-Cov2 infection (Interstitial Pneumonia) in a patient in MRD-negative complete remission. There were no treatment-related deaths. Conclusion: In patients with CBFL, the regimen consisting of intensive chemotherapy and consolidation chemotherapy in association with Mido, followed by Mido maintenance, had an acceptable safety profile and excellent response rates with a significant proportion of patients in MRD-negative complete remission. Trial is continuing to accrue (EudraCT Number 2017-002094-18;ClinicalTrials ID: NCT 03686345). This work was supported by a grant from Fondazione Regionale per la Ricerca Biomedica (FRRB 2015). [Formula presented] Disclosures: Krampera: Janssen: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees. Todisco: Jannsen, Abbvie, Jazz: Membership on an entity's Board of Directors or advisory committees. Veronese: Novartis: Other: Travel Expenses;Bayer: Honoraria;AstraZeneca: Other: Travel Expenses;Janssen Cilag: Honoraria. OffLabel Disclosure: Midostaurin for treatment of Core Binding Factor Leukemia. The drug has been used as KIT inhibitor.