Prospective evaluation of oral mucositis in patients receiving myeloablative conditioning regimens and haemopoietic progenitor rescue

Four hundred and twenty-nine patients received myeloablative chemotherapy f or solid and haematological malignancies in a bone marrow transplantation u nit. Regimens appropriate to the tumour type were administered and haemopoi etic reconstitution was achieved with peripheral blood progenitor cells (PB PC: n = 275), autologous bone marrow (auto-BMT; n = 69) or allogeneic bone marrow (allo-BMT: n = 85). World Health Organization (WHO) oral mucositis s cores were collected prospectively from the start of chemotherapy (d 1) unt il d 28 or discharge. Oral mucositis (OM) was experienced by 425 (99%) pati ents and in 289 (67.4%) this was grade III or IV. Strong opiate analgesia w as prescribed for a median of 6 d to 47% of patients. Univariate analysis s uggested that the area under the OM curve (AUC; sum of daily mucositis grad es, d 1-28) was associated with the myeoloablative regimen, haemopoietic pr ogenitor source (PBPC > allo-BMT > auto-BMT), use of myeloid growth factors and age, Multivariate analysis showed that the only independent risk facto r for mucositis was the conditioning regimen (P < 0.00005). The mean OM AUC for high-dose melphalan (HDM) regimens (52 grade-days) exceeded busulphan (41), busulphan-cyclophosphamide (35), cyclophosphamide-total body irradiat ion (TBI) (34), cyclophoswphamide-carmustine (BCNU) (20) and cyclophosphami de-etoposide-carmustine (CVB) (19). HDM regimens resulted in the highest me an peak OM (3.6), followed by busulphan regimens (26), cyclophosphamide/TBI (2.3) and cyclophosphamide-carmustine and CVB (1.4). Busulphan produced si gnificantly delayed OM (median 3 d; P < 0.00005). There was a linear associ ation between the area under the OM curve for each treatment group and the time to reach grade 3 OM (P < 0.00005), but no association with the time to reach grade 4 neutropenia (P = 0.24) or thrombocytopenia (P = 0.73), imply ing that haematological and mucosal toxicity are not associated. The cytoto xic regimen is the most significant determinant of OM. Studies investigatin g agents to ameliorate mucosal toxicity should be stratified according to c ytotoxic regimen.