Severity predictors and new treatments for bone marrow neoplasms

• Grant number: 21/05132-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2021
• End date: May 31, 2022
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Sara Teresinha Olalla Saad
• Grantee: Mariana Pereira Pinto
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/21801-2 - Predictors of severity and new treatments for bone marrow neoplasias, AP.TEM

Abstract

Bone marrow neoplasias are aggressive disorders with low healing potential. Asthe incidence of cancer increases with age, a growing number of older individualsare receiving therapy for cancer and frequently in intensive modalities. As theseolder patients tend to present comorbidities, treatment decisions can often becomedifficult due to their fragile physical state which may affect therapy tolerability andefficiency against cancer. The toxicity related to the treatment and long periods ofhospitalization, often required, have a profound impact upon the quality of life ofthese patients. However, most elderly individuals and family members considerquality of life a priority. Additionally, extended treatments deplete the financialresources of both public and private health systems, and the extra costs alsodeplete the family´s financial reserves. In light of the foregoing, the present studywill address novel therapeutic forms and severity predictors which could aid intherapy decision taking of the following bone marrow neoplasias: acute myeloidleukemia (AML) myelodysplastic syndromes (MDS), multiple myeloma (MM) andprimary myelofibrosis (PMF). These disorders have a common characteristic whichis the fatal course of the disease and the lack of efficient therapeutic options,where bone marrow transplantation represents the only curative therapy ortherapy capable of extending survival, despite not being indicated for olderpatients or those with many comorbidities. Therefore, a number of issues could beclarified by this study: * What would be the effect of natural products, which havebeen demonstrated to be inductor agents of cell death or cell cycle arrest, uponthe treatment of these disorders? These compounds have a known action ofinducing or inhibiting reactive oxygen species (ROS) and/or nitric oxide and canhave a direct effect upon the induction of neoplasia cell death or modulate cellimmunity. *Would elderly patients have a better survival and quality of life werethey to be treated with less aggressive therapies with less side effects? *Couldmesenchymal cells or metformin reduce bone marrow fibrosis? *Would dendriticcell vaccines for AML and MM patients in remission, be an alternative for reducingdisease recurrence? * Could severity markers for the aforementioned disorders,identified in our previous studies, be the targets of specific therapies? *Would theproduction of universal in vitro platelets to improve the support therapy of thesepatients be possible? This choice of investigation is a result of our dissatisfaction inobserving that most patients with bone marrow neoplastic disorders are notcandidates for last-generation treatments. Furthermore, the lack of hospital bedsand the impossibility of using high cost antibiotics and immunobiologicals in theunified public health system (SUS) point to the need of performing high levelresearch to seek alternatives to enable us, in the short-term, to face the reality ofmany patients who have no access to clinical studies with new high cost drugs, notonly in Brazil, but throughout the World. For this investigation, we will carry outpre-clinical trials, using leukemia, myelodysplastic and xenogeneic tumor animalmodels, and phase I and II clinical studies. We will further standardize theproduction method of universal platelets, to enable better support for patients withsevere bone marrow failure in consequence of hematologic neoplasia. (AU)