Oral Adverse Event and the Risk Factor in Patients with Hematologic Malignancy Receiving Chemotherapy: A Retrospective Cohort Study in Japan

Statements of the problem

Patients with hematologic malignancy requiring chemotherapy are susceptible to infection due to myelosuppression. It has been reported that dental focal infection such as severe periodontitis can cause systemic morbidity and adverse impact on the chemotherapy schedule. At the 97^th annual meeting of AAOMS, we reported the clinical importance to eliminate a potential dental focal infection before the first cycle of chemotherapy. Then, we found that 12.0% patients had oral adverse events (e.g., aggravation of periodontitis, oral mucositis, and perioperative surgical site infection [SSI]) after the chemotherapy. However, there is no literature for the risk factors of oral adverse events in patients with hematologic malignancy among a large-scale population in Japan. This study aimed to explore the oral adverse events and the risk factors in patients with hematologic malignancy in larger sample size.

Patients and methods

We conducted a retrospective cohort study using the medical records from the Department of Oral and Maxillofacial Surgery, Center Hospital, National Center for Global Health and Medicine (NCGM) in Japan. We selected patients with hematologic malignancies (multiple myeloma, malignant lymphoma, leukemia, and myelodysplastic syndrome) who received their first cycle of chemotherapy at the Division of Hematology, Department of Internal Medicine, NCGM from January 2011 to December 2015. All patients were required to have an oral health care and dental treatments including a tooth extraction. We excluded patients who had already received chemotherapy, a bisphosphonate, or a RANK ligand inhibitor (e.g., denosumab) before the study period. We obtained clinical data included charts, panoramic radiographs, and result of blood tests to evaluate the health status before and after chemotherapy. We observed each patient from the start of the first cycle antineoplastic chemotherapy to just before the start of the second cycle.

Results

A total of 365 patients with hematologic malignancy visited the NCGM during the study period. After exclusion, we identified 186 patients (108 men [58.1%], 78 women [41.9%]) with a median of 66.0 (range, 16 to 93) years at first visit. Of these, 23 patients (12.4%) experienced oral adverse events after chemotherapy. The most frequent adverse event was the aggravation of marginal periodontitis on an unrelated to the surgical site (n = 10; 43.5%) followed by oral mucositis (n=7; 30.4%) and dry mouth (n=3; 13.0%). Three of 67 dental extraction cases (4.5%) had a SSI or a dry socket. Among the 23 patients with oral adverse events, 15 patients (65.2%) with under 100/ƒÊL neutrophil count during the follow-up duration tended to cause more severe oral symptoms and accompanied by systemic morbidity such as a sepsis (n=3; 13.0%).

Conclusions

In the present study, nearly half of the patients with oral adverse events had an aggravation of marginal periodontitis. Because the inflammatory findings associated with chemotherapy may lead to sepsis in the patients with a decreased neutrophil count in particular, medical and dental specialists should pay close attention to oral health status in patients with hematologic malignancy. Further, statistical analysis is required to investigate the various potential risk factors.

References

1)       Tsuji K, Shibuya Y, Akashi M et al (2015) Prospective study of dental intervention for hematopoietic malignancy. J Dent Res 94: 289-296. doi: 10.1177/0022034514561768

2)       Safdar A, Armstrong D (2011) Infections in patients with hematologic neoplasms and hematopoietic stem cell transplantation: neutropenia, humoral, and splenic defects. Clin Infect Dis 53: 798-806. doi: 10.1093/cid/cir492