OM is one of the most common complications of HSCT. However, to the best of our knowledge, the incidence and severity of OM among patients with PTCy-based allogeneic HSCT have been unclear to date.[19]
In our cohort of 140 cases who received transplants with PTCy treatment, the incidences of any OM (82.9%) and severe OM (28.6%) were comparable to those in previous reports, in cases using a traditional transplant regimen other than PTCy (47.2–100% and 2.5–60.9%, respectively).[1, 20–25, 19, 26] PTCy-based prophylaxis was reported to show a better safety profile compared with ATG and was associated with reduced severity of mucositis.[27] In our study, more severe OM was observed in patients after an intensive conditioning regimen (MAC) compared with that after a less intensive regimen (RIC). In a recent study using RIC and PTCy, severe OM was observed at a similar frequency (15%) in patients with leukemia or myelodysplastic syndrome.[28] Using the PTCy platform, OM typically began about 1 week after completing the conditioning regimen and lasted for 6–10 days. An early onset of OM would suggest a greater possibility of subsequent severe OM. This information is important for a nursing team to establish a personalized protocol for an oral care regimen.
Because severe OM requires special medical attention such as parenteral nutrition, infection prophylaxis, and fluid replacement, we focused on the risk factors associated with severe OM (above grade 3 according to the WHO criteria) as opposed to cases of mild or moderate OM. MAC was associated with increased risk of severe OM in our cohort, based on both univariate and multivariate analyses. This result was in line with those of previous studies.[19, 29–31] However, the incidence of severe OM in this study was lower than that in previous reports.[1] This might be reflective of the relatively younger patients, more frequent use of fludarabine-based reduced toxicity conditioning regimens,[19] and the standardized and intensified oral care protocol. Notably, mismatched donors and lack of ATG in the GVHD prophylaxis regimen were significantly related to severe OM in multivariate analysis. The underlying reason for these protective effects is currently unclear. Therefore, studies on whether and how the immune status plays a role in the mechanism of early OM post-transplant are warranted.
In line with previous studies, severe OM was not associated with higher incidence of aGVHD and cGVHD. We also did not observe a detrimental influence of severe OM on engraftment of neutrophils and platelets. Although the occurrence of severe OM did not lead to significantly worse overall survival, the clinical implications of severe OM should not be ignored. Indeed, OM has been reported to be the single most debilitating complication of a transplant, causing severe pain, affecting oral function, increasing the risk for bleeding and systemic infection, and having the potential to compromise the upper airway. References are needed to support this statement. Accordingly, oral care was intensively implemented from the beginning of HSCT according to our institutional protocol, including prevention and symptomatic management of OM.
There are several limitations to this study. First, although OM was graded according to the WHO scale, the full picture of oral changes such as the number, location, and stage of the lesions was not systematically recorded and analyzed. Including the specific symptoms and findings from the oral examination may offer a better definition of the mucositis burden and phenotype. Second, although OM was prospectively documented daily following the local protocol, this was not a prospectively designed study. Therefore, the grading of OM would have likely differed according to the individual primary nurses. Finally, this was a single-cohort study, which might have limited the power to detect meaningful associations.
In summary, OM remains a high-burden complication among allogeneic-HSCT recipients receiving PTCy treatment. However, the incidence of severe OM does not appear to be increased on this platform. Patients who receive MAC and cells from a mismatched donor are at greater risk for developing severe OM. ATG included in the GVHD prophylaxis may reduce the risk of severe OM via an as-yet unknown mechanism. The occurrence of severe OM did not lead to a worse transplant outcome if intensified oral care was adopted. Understanding the pathophysiology of OM development could facilitate the development of novel strategies to manage oral complications in allogeneic-HSCT recipients.