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

Abstract

Four hundred and twenty-nine patients received myeloablative chemotherapy for solid and haematological malignancies in a bone marrow transplantation unit. Regimens appropriate to the tumour type were administered and haemopoietic reconstitution was achieved with peripheral blood progenitor cells (PBPC; n = 275), autologous bone marrow (auto-BMT; n = 69) or allogeneic bone marrow (allo-BMT; n = 85). World Health Organization (WHO) oral mucositis scores were collected prospectively from the start of chemotherapy (d 1) until d 28 or discharge. Oral mucositis (OM) was experienced by 425 (99%) patients and in 289 (67.4%) this was grade III or IV. Strong opiate analgesia was prescribed for a median of 6 d to 47% of patients. Univariate analysis suggested that the area under the OM curve (AUC; sum of daily mucositis grades, d 1-28) was associated with the myeloablative regimen, haemopoietic progenitor source (PBPC > allo-BMT > auto-BMT), use of myeloid growth factors and age. Multivariate analysis showed that the only independent risk factor 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 irradiation (TBI) (34), cyclophosphamide-carmustine (BCNU) (20) and cyclophosphamide-etoposide-carmustine (CVB) (19). HDM regimens resulted in the highest mean peak OM (3.6), followed by busulphan regimens (2.6), cyclophosphamide/TBI (2.3) and cyclophosphamide-carmustine and CVB (1.4). Busulphan produced significantly delayed OM (median 3 d; P < 0.00005). There was a linear association 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), implying that haematological and mucosal toxicity are not associated. The cytotoxic regimen is the most significant determinant of OM. Studies investigating agents to ameliorate mucosal toxicity should be stratified according to cytotoxic regimen.