Bone Marrow Transplantation or Hematopoietic Stem Cell Transplantation (HSCT) is a therapeutic modality widely used to cure hematological or other tissue diseases, bone marrow insufficiencies and congenital disorders of hematopoiesis. Despite recent advances, allogeneic HSCT – one in which the bone marrow or hematopoietic progenitor cells come from a compatible donor – is not free from complications. Around 80% of patients undergoing allogeneic HSCT present oral complications, which can be classified as acute and late, according to the moment they appear and the type of sequelae generated.

The most common acute oral complications include oral mucositis (mouth sores), recurrent infections, pain, and bleeding. Late oral complications include Graft-Versus-Host Disease, progressive cavities, the development of new tumors in the mouth, as well as changes in the composition and flow of saliva, which can generate serious and irreversible problems.

Several oral complications are related to salivary changes found in patients undergoing allogeneic HSCT, such as hyposalivation; xerostomia (dry mouth sensation); changes in taste; progressive and generalized cavities; recurrent fungal, viral and bacterial infections, among others. These complications significantly impact the quality of life of these patients, generating significant morbidity.

Although studies have correlated the presence of damage of varying extent to the salivary glands and, consequently, to the saliva of these patients as a late sequelae of allogeneic HSCT, its influence on early changes in salivary flow, thus considered those that occur earlier than expected, are not completely elucidated. Added to this is the lack of standardized criteria for the clinical assessment of hyposalivation (decreased saliva excretion) for this group of patients, which makes early diagnosis difficult and delays measures that help minimize its harmful effects.

The Dentistry and Oral Medicine Group of the Hematopoietic Stem Cell Transplantation Unit, of the Hematology and Hemotherapy Center of the Hospital de Clínicas/Hemocentro da Unicamp, has been studying, over the last two decades, oral changes related to allogeneic HSCT, with the objective of better understanding them and managing them in the most appropriate way.

Given this scenario, dental surgeon Vinicius Rabelo Torregrossa evaluated in his master's thesis the influence of allogeneic HSCT on early changes in salivary flow, correlating the results obtained from salivary flow with clinical data from the transplant. Furthermore, clinical criteria for diagnosing hyposalivation in these patients were also validated, through the development of a scoring system that allows dry mouth situations to be characterized.

Postgraduate student at the Faculty of Dentistry of Piracicaba (FOP-Unicamp), where the dissertation was presented, he carried out the work at the University's Blood Center, under the guidance of also a dental surgeon and professor Maria Elvira Pizzigatti Correa, coordinator of the dentistry outpatient clinic from Hemocentro Campinas. 

Maria Elvira remembers that after chemotherapy, the mouth and saliva change, causing consequences that can last for the rest of your life. For her, “an early diagnosis of quantitative salivary changes, combined with individual analysis of the risk of oral complications, can allow adequate preventive management, essential for the support of patients undergoing HSCT”.

The work of the dentist in the oncohematological multidisciplinary team aims to provide the patient with comprehensive holistic care, where treatments are carried out that he or she would have difficulty obtaining outside the Blood Center.

SLAVE-LIKE LABOR.

In the first chapter of the publication, the author presents a prospective and retrospective study, based on patient collection and use of a database available at the unit, which involved 69 adult patients undergoing the first allogeneic HSCT, between 2010 and 2014, in Unicamp Clinical Hospital/Hemocentro. During this period, saliva samples were collected and salivary flow was determined, in addition to the assessment of the patients' oral health condition and degree of mucositis.

Specific clinical criteria for the diagnosis of hyposalivation were also applied, before the start of the conditioning regimen, and after 8 to 10 days of marrow infusion, for the purpose of systematic and comparative monitoring. The results showed that hyposalivation was not a common finding during the period evaluated. Furthermore, the increase in salivary flow found during the mucositis phase may have been influenced by the synergistic effect caused by the presence of more viscous saliva combined with difficulty in swallowing, responsible for generating an increase in the residual volume of saliva in the oral cavity of these patients. , giving a false impression of hypersalivation between days 8 and 10 post-transplant.

The second chapter of the dissertation involved a cross-sectional study carried out between 2006 and 2014, where 120 patients undergoing the first allogeneic HSCT at the Hospital de Clínicas da Unicamp/Hemocentro were evaluated. Five out of a total of eight clinical hyposalivation criteria were validated, which enabled the development of a Scoring System for Dry Mouth (SPBS), based on the following criteria: 1) high adherence of the wooden spatula to the buccal mucosa; 2) absence of sublingual lake; 3) thick and viscous saliva; 4) absence of salivary secretion after milking the protid duct; 5) patient's impression of the sensation of dry mouth.

For the authors, SPBS proved to be a reliable tool for diagnosing hyposalivation in the studied population.

For Vinicius and Maria Elvira, the great difference of this second study is the fact that it proposes a tool capable of diagnosing the condition of hyposalivation through clinical parameters that are easy to apply by the nursing and medical team, who are in constant contact with patients, which are not for the exclusive use of the dental surgeon.

RESULTS

The characterization of dry mouth can determine two types of actions. The most immediate is the introduction of palliative measures that contribute to better lubrication of the mouth and patient comfort, with a temporary effect. The other involves placing patients diagnosed with hyposalivation in a specific protocol, with the aim of minimizing the adverse effects arising from the lack of saliva. It considers, for example, the control of periodontal infections and tooth decay, and mainly oral health education through improvements in oral hygiene, which can be accompanied by the prescription of fluoride-based mouthwashes in greater intensity and/or frequency.

As at Hemocentro these patients are systematically monitored after bone marrow transplantation, the guidelines set out in the protocol are reviewed and reinforced, when necessary. The concern is always to minimize, over time, the inevitable adverse effects on the mouth of individuals undergoing HSCT, contributing to the maintenance of oral health and greater patient comfort. However, more than that, the study allows oral complications arising from allogeneic HSCT to be better understood and measured, enabling their more appropriate management.

The advisor considers that two major lessons can be learned from the study. That salivary changes occur at a very early stage of the transplant, in the first few days after its completion, and that the salivary pattern will probably remain altered, even after the patient has recovered. For this reason, salivary changes in the context of HSCT need to be better studied and understood for better patient care.

The second is that the proposed test can be used as an effective tool to characterize and diagnose hyposalivation in the studied population, enabling prompt adoption of the necessary measures.

MULTIDISCIPLINARY

Professor Elvira highlights the importance of the knowledge acquired by the dental surgeon when working in a multidisciplinary oncohematology team. “We must be grateful for the learning opportunity provided by working with a multidisciplinary team like ours, which allows for frank dialogue, in addition to the patience and generosity of patients during consultations. It’s an experience that you don’t have in undergraduate courses.”

Vinicius' commitment and trajectory are also worth highlighting. In 2011, he enrolled in the then newly created Integrated Multiprofessional Residency in Health course, offered by the Professor Edgard Santos University Hospital, at the Federal University of Bahia, when he had just completed his degree. Once selected, he completed the two-year course, which aimed to train a professional capable of working in a hospital, within a multi-professional environment, a possibility that rarely occurs during an undergraduate degree in dentistry. “At the hospital I had contact with the ICU routine, with the wards in the transplant and cardiology areas, facing situations that I learned to deal with. I fell in love with the work and was particularly interested in caring for patients with oncohematological diseases,” he says.

After finishing his residency, he applied for a place on the postgraduate course in stomatopathology, at master's level, offered by FOP/Unicamp, fulfilling his dream of doing a postgraduate course at Unicamp, considering it an enriching experience. Given his interest in working in the field of hematology, he was referred to the University's HC Blood Center to be guided by Maria Elvira. Enthusiastic, he states: “The experience proved to be wonderful and within the expectations of what I intended and wanted. Here there is a range of patients with profiles that I intended to study, ranging from hereditary or acquired coagulopathies, through those with oncohematological diseases, to bone marrow transplantation. Furthermore, I counted on the experienced and dedicated guidance of Professor Elvira.”

Publication

Dissertation: “The influence of allogeneic hematopoietic stem cell transplantation on salivary flow”

Author: Vinicius Rabelo Torregrossa

counselor: Maria Elvira Pizzigatti Correa

Units: Faculty of Dentistry of Piracicaba (FOP) and Faculty of Medical Sciences (FCM)