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

Abstract

Summary. 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±cyclo-phosphamide (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.

The Prospective Oral Mucositis Audit: relationship of severe oral mucositis with clinical and medical resource use outcomes in patients receiving high-dose melphalan or BEAM-conditioning chemotherapy and autologous SCT

“…This supports previous observations that healing of OM coincides with neutrophil recovery. [20][21][22][23] Although some investigators have failed to find a link between OM and neutropenia, 5,24 Rapoport et al 25 noted that duration of neutropenia was a risk factor for OM and the severity of OM has been linked to the degree of neutropenia. 26 Oral neutrophil kinetic studies (using mouth rinses) in patients recovering from profound neutropenia have demonstrated that neutrophils are present in the tissues before peripheral neutrophil counts recover, 21,27,28 consistent with their important role in mucosal defence and repair.…”

Reliability and validity of a patient self-administered daily questionnaire to assess impact of oral mucositis (OM) on pain and daily functioning in patients undergoing autologous hematopoietic stem cell transplantation (HSCT)

“…1 Almost all patients experience some degree of OM after myeloablative therapy and BMT and approximately 75% have oral ulcers within 3-5 days after BMT. [2][3][4] OM is a result of a complex cascade of physiological events. 5 Damage from radiotherapy and chemotherapy to the rapidly dividing tissues that comprise the mucosal epithelium of the mouth and throat is followed by upregulation of transcription factors and proinflammatory cytokines in the submucosa, in turn leading to oral ulceration.…”

Mouth-washings with recombinant human granulocyte–macrophage colony stimulating factor (rhGM-CSF) do not improve grade III–IV oropharyngeal mucositis (OM) in patients with hematological malignancies undergoing stem cell transplantation. Results of a randomized double-blind placebo-controlled study

“…1 It causes significant discomfort and stress in transplanted patients, worsens night sleep quality and deteriorates oral intake. It may lead to the need for a wide variety of analgesics, including opioids, and to the use of total parenteral nutrition.…”

“…On the other hand, other authors have shown an increase in the incidence of OM with the systemic use of these cytokines. 1,10 Growth factors have also been used topically for prevention or treatment of OM. Although one randomized study which included non-Hodgkin's lymphoma (NHL) patients treated with high-dose methotrexate showed a small reduction in the severity of OM using topically applied G-CSF, 11 in their recent study, van der Lelie and coworkers found no significant difference in OM with respect to a placebo group when using a solution of 300 g rhGM-CSF in a 2% methylcellulose gel from day ϩ1 to neutrophil recovery in patients undergoing stem cell transplantation.…”

“…1 Mucosal damage is a multistep process involving the release of inflammatory cytokines and DNA damage leading to a breakdown of mucosal barriers and an increased risk of infections. 2 It not only causes pain and makes oral food intake difficult but also produces sleep disorders.…”