Platelet Derived Growth Factors in a Mucoadhesive Vehicle for Treatment of Patients with Oral Mucositis in Graft Versus Host Disease

Abstract

Oral Mucositis (OM) frequently occurs in patients (pts) who develop acute or chronic Graft versus Host Disease (GvHD) after an allogeneic stem cell transplant. Severity and extension of the disease vary, ranging from mild atrophy to severe ulceration.The consequences of OM often include pain, inadequate nutrition and potentially life-threatening infections. Conventional treatments (topical anaesthetics, oral hygiene, protective coative agents, analgesics) often fail in curing OM. Recently, platelet derived growth factors (PDGF), in liquid or gel form have shown efficacy in repairing different tissues (bone, cartilage, skin) damaged by trauma, vascular or metabolic dysfunction.Basing on these evidences, we decided to test PDGFs combined with a mucoadhesive, biocompatible vehicle for :safety and tolerability when applied on oral mucosa,efficacy in controlling the damaged mucosa of GvHD patients.Patients and Methods6 male pts were enrolled in the study. OM was assessed according to the WHO scale. Platelet lysate derived either from allogeneic platelet apheresis or autologous peripheral blood was added to a mucoadhesive biocompatible vehicle under sterile conditions and stored at 4°C for a maximum of 15 days. A sample for microbial and fungal detection was taken from each preparation. Platelet Lysate in mucoadhesive Vehicle (PLV) was applied on the oral mucosa 3 times/day for a maximum of 30 days. At the time of application there was no evidence of local infection. Use of analgesics, local infection and percentage of body weight increase (as index of trophism) were evaluated every 2 days. Pts characteristics after 30 days of treatment are shown in table 1. The response to treatment was defined as following:no response: no improvement or worsening of OM.25% response: reduction of extension in one oral lesion, slight reduction of pain, unchanged dosage of analgesic.50% response: reduction of extension in two or more lesions, important improvement of pain, nutrition with solid food, reduction of analgesic.100% response: disappearance of oral lesions and pain. No use of analgesics, normal nutrition.Results: Results are shown in table 2. No evidence of bacterial or fungal contamination in PLV emerged. No local infections during application were observed.ConclusionsOur preliminary experience demonstrate that oral application of PLV is safe, well tolerated and may be effective in treating OM (grade II–IV) in GvHD patients. Confirmation of our data in a larger randomized study could open a simple and economic possibility to cure lesions otherwise very difficult to treat.Table 1. Characteristics of pts treated with PLV.Pts n.AgeGvHDMucositis (grade)Plt lysate113Acute (grade III)IVallogeneic251chronic extensiveIIIautologous334Chronic extensiveIIIallogeneic433Chronic extensiveIIIautologous517Chronic extensiveIIIallogeneic645Chronic extensiveIIautologousTable 2. Results after 30 days of treatment of OM with PLV.Pts n.Weight (% increase)ResponseUse of analgesicsOral infection10aunchangedno210dnono37creductionno42bunchangedno510dnono63bunchangedno