To the Editor:
Although chemotherapy-induced oral mucositis (COM) is a common complication of cancer treatment, occurring in approximately 52%–80% of children receiving cytotoxic drugs,
1
, 2
it is often overlooked and not sufficiently studied. Treatment regimen, type of cancer, age, and oral care measures are the most important factors related to COM development in cancer patients.Clinical symptoms range from soreness and mild mucosal erythema to widespread ulceration. The latter is associated with severe pain, fungal and bacterial infections, fever, and decreased dietary intake leading to dehydration and poor nutritional status, resulting in decreased quality of life. As a result, cancer treatment may be compromised and necessitate dose intensity modulation, treatment breaks, or discontinuation.
3
Currently, neither standard therapy nor evidence-based guidelines for prevention and treatment of severe refractory mucositis in pediatric cancer patients are available. Some recommendations do opt for preventive measures and treatment protocols, among which are mouth care, oral cryotherapy, oral glutamine, oral sucralfate suspension, chlorhexidine or benzydamine mouthwash, supersaturated calcium phosphate mouth rinses, antibiotic and antifungal therapy, tailored pain therapy, and nutritional support.
4
It also has been suggested that recombinant human keratinocyte growth factor 1 (palifermin) has an important role in COM treatment as it stimulates proliferation and modifies differentiation in epithelial cells. Furthermore, some experience from different randomized, placebo-controlled trials showed a hypothetical role for low-level infrared laser therapy in addition to oral care. The Multinational Association of Supportive Care in Cancer and the International Society of Oral Oncology systematic reviews also support these management interventions5
, 6
, 7
in specific subsets of cancer patients. Although these strategies seem to contribute to the healing process, they have limited clinical application, and there are limited therapeutic options available in case these strategies fail.In situ application of heterologous platelet gel-released supernatant seems to be effective in refractory treatment-related mucositis in adult cancer patients.
8
, 9
Our experience may be the first reported evidence in the management of pediatric refractory COM resulting from solid tumor chemotherapy.Case
In February 2013, we admitted a five-year-old patient with Stage IV ocular rhabdomyosarcoma, in active treatment with chemotherapy, to home care at the Medical Oncology Division of the University Hospital of Siena. Because the patient lived 200 miles away from Siena, she was followed by the Home Care Unit for early integration of supportive care.
On day 10 of the second course of chemotherapy, the patient experienced Grade 4 ulcerative (1.5–2 cm) COM with severe pain (Numerical Rating Scale [NRS] score 10, G3) and fever (38.5°C). The patient was not able to eat, drink, or swallow, and the Lansky play-performance status was 40 (meaning the patient was “mostly in bed and participates in quiet activities”). Complete blood count revealed G4 neutropenia, G4 leukopenia, G3 anemia, and G3 thrombocytopenia (according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03).
We started a supportive treatment protocol with intravenous (IV) ceftazidime 150 mg/kg/day, IV fluconazole 5 mL three times/day, IV morphine 15 mg/day, and chlorhexidine oral rinses. We also started parenteral nutrition. After three days, and in spite of treatment, no overall improvement was observed.
Considering the persistence of G4 mucositis with severe pain (NRS score 10, G3), the complete inability to tolerate oral intake, and the related life-threatening possible consequences, after a thorough discussion with specialists in the Transfusion Medicine Division, we started a three-times-daily oral application of platelet gel-released supernatant.
The platelet suspension gel was prepared as follows: platelet-rich plasma (3Å∼106 μL) was prepared from buffy coat derived from a blood donor. The platelet-rich plasma was exposed to 40 Gy of radiation and, in a sterile room, was coagulated by activation with calcium gluconate (1:10). Supernatant, rich in platelet growth factors, was collected and stored at −18°C (65°F) for a maximum of 30 days.
10
Before use, each single aliquot was mixed (1:1, total volume 20 mL) with miconazole 2% oral gel, which was the pharmacological vehicle.After receiving written informed consent, we trained the patient's parents on how to apply the platelet gel-released supernatant three times a day, recommending that they make sure the patient kept the gel in her mouth as long as possible and did not swallow any food or liquids for the next hour.
After 12 hours, we observed a dramatic improvement in oral mucositis. Ulcers had become smaller and pink in color, with evidence of healing. The patient was able to eat bland creamy foods feeling less pain (NRS score 3). The IV morphine dose was reduced to 10 mg/day.
In the next 48 hours, there was a progressive healing of ulcers and an improvement in patient performance status. All medications were stopped, including IV morphine. The patient was fully able to eat, drink, and swallow. She continued with chemotherapy treatment, without any dose intensity modulation. There were no observed treatment-related side effects.
Comment
This may be the first experience of platelet gel-released supernatant application for treatment-resistant COM among the pediatric population. In addition, this may be the first evidence among pediatric cancer patients for whom treatment is provided on a home care basis.
We observed a dramatic resolution of oral mucositis after only 12 hours, with a prompt improvement of pain and oral intake. Rapid resolution of oral mucositis is important, especially among the pediatric population.
Based on our experience and on the limited evidence reported in the literature,
8
, 9
topical application of platelet gel-released supernatant seems to allow for prompt healing of oral mucositis, helping in symptom control and maintaining the scheduled treatment program.One potential limitation of our report is that we did not analyze overall costs of platelet supernatant gel preparation and administration. Also, we have no images related to the presented case as the particular situation did not allow us to take any photos.
Our experience with this pediatric patient should be considered preliminary. Further studies are needed and recommended.
References
- Incidence and risk factors of oral mucositis in paediatric and adolescent patients undergoing chemotherapy.Oral Oncol. 2011; 47: 153-162
- Oral manifestations of cancer treatment in children: a review of the literature.Clin J Oncol Nurs. 2010; 14: 481-490
- Determinants of severe oral mucositis in paediatric cancer patients: a prospective study.Int J Paediatr Dent. 2011; 21: 210-216
- Prevention of oral mucositis in children receiving cancer therapy: a systematic review and evidence-based analysis.Oral Oncol. 2013; 49: 102-107
- Systematic review of oral cryotherapy for management of oral mucositis caused by cancer therapy.Support Care Cancer. 2013; 21: 327-332
- Systematic review of cytokines and growth factors for the management of oral mucositis in cancer patient.Support Care Cancer. 2013; 21: 343-355
- Systematic review of laser and other light therapy for the management of oral mucositis in cancer patients.Support Care Cancer. 2013; 21: 333-341
- An in situ gelling buccal spray containing platelet lysate for the treatment of oral mucositis.Curr Drug Discov Technol. 2011; 8: 277-285
- Topical application of platelet supernatant gel in the management of radiotherapy-induced mucositis: a case report.Blood Transfus. 2014; 12: 107-110
- The effects of platelet gel-released supernatant on human fibroblasts.Wound Repair Regen. 2013; 21: 300-308
Article info
Publication history
Published online: August 14, 2014
Identification
Copyright
© 2014 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc.
