melphalan and Mouth-Diseases

Oral mucositis is a side effect of chemotherapy, head and neck radiotherapy, and targeted therapy, affecting over 75% of high risk patients. Ulceration can lead to severe pain and difficulty eating and drinking, which may necessitate opioid analgesics, hospitalisation and nasogastric or intravenous nutrition. These complications may lead to interruptions or alterations to cancer therapy, which may reduce survival. There is also a risk of death from sepsis if pathogens enter the ulcers of immunocompromised patients. Ulcerative oral mucositis can be costly to healthcare systems, yet there are few preventive interventions proven to be beneficial. Oral cryotherapy is a low-cost, simple intervention which is unlikely to cause side-effects. It has shown promise in clinical trials and warrants an up-to-date Cochrane review to assess and summarise the international evidence.. To assess the effects of oral cryotherapy for preventing oral mucositis in patients with cancer who are receiving treatment.. We searched the following databases: the Cochrane Oral Health Group Trials Register (to 17 June 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 5), MEDLINE via Ovid (1946 to 17 June 2015), EMBASE via Ovid (1980 to 17 June 2015), CANCERLIT via PubMed (1950 to 17 June 2015) and CINAHL via EBSCO (1937 to 17 June 2015). We searched the US National Institutes of Health Trials Registry, and the WHO Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching databases.. We included parallel-design randomised controlled trials (RCTs) assessing the effects of oral cryotherapy in patients with cancer receiving treatment. We used outcomes from a published core outcome set registered on the COMET website.. Two review authors independently screened the results of electronic searches, extracted data and assessed risk of bias. We contacted study authors for information where feasible. For dichotomous outcomes, we reported risk ratios (RR) and 95% confidence intervals (CI). For continuous outcomes, we reported mean differences (MD) and 95% CIs. We pooled similar studies in random-effects meta-analyses. We reported adverse effects in a narrative format.. We included 14 RCTs analysing 1280 participants. The vast majority of participants did not receive radiotherapy to the head and neck, so this review primarily assesses prevention of chemotherapy-induced oral mucositis. All studies were at high risk of bias. The following results are for the main comparison: oral cryotherapy versus control (standard care or no treatment). Adults receiving fluorouracil-based (5FU) chemotherapy for solid cancersOral cryotherapy probably reduces oral mucositis of any severity (RR 0.61, 95% CI 0.52 to 0.72, 5 studies, 444 analysed, moderate quality evidence). In a population where 728 per 1000 would develop oral mucositis, oral cryotherapy would reduce this to 444 (95% CI 379 to 524). The number needed to treat to benefit one additional person (NNTB), i.e. to prevent them from developing oral mucositis, is 4 people (95% CI 3 to 5).The results were similar for moderate to severe oral mucositis (RR 0.52, 95% CI 0.41 to 0.65, 5 studies, 444 analysed, moderate quality evidence). NNTB 4 (95% CI 4 to 6).Severe oral mucositis is probably reduced (RR 0.40, 95% CI 0.27 to 0.61, 5 studies, 444 analysed, moderate quality evidence). Where 300 per 1000 would develop severe oral mucositis, oral cryotherapy would reduce this to 120 (95% CI 81 to 183), NNTB 6 (95% CI 5 to 9). Adults receiving high-dose melphalan-based chemotherapy before haematopoietic stem cell transplantation (HSCT)Oral cryotherapy may reduce oral mucositis of any severity (RR 0.59, 95% CI 0.35 to 1.01, 5 studies, 270 analysed, low quality evidence). Where 824 per 1000 would develop oral mucositis, oral cryotherapy would reduce this to 486 (95% CI reduced to 289 to increased to 833). The NNTB is 3, although the uncertainty surrounding the effect estimate means that the 95% CI ranges from 2 NNTB, to 111 NNTH (number needed to treat in order to harm one additional person, i.e. for one additional person to develop oral mucositis).The results were similar for moderate to severe oral mucositis (RR 0.43, 95% CI 0.17 to 1.09, 5 studies, 270 analysed, low quality evidence). NNTB 3 (95% CI 2 NNTB to 17 NNTH).Severe oral mucositis is probably reduced (RR 0.38, 95% CI 0.20 to 0.72, 5 studies, 270 analysed, moderate quality evidence). Where 427 per 1000 would develop severe oral mucositis, oral cryotherapy would reduce this to 162 (95% CI 85 to 308), NNTB 4 (95% CI 3 to 9).Oral cryotherapy was shown to be safe, with very low rates of minor adverse effects, such as headaches, chills, nu. We are confident that oral cryotherapy leads to large reductions in oral mucositis of all severities in adults receiving 5FU for solid cancers. We are less confident in the ability of oral cryotherapy to reduce oral mucositis in adults receiving high-dose melphalan before HSCT. Evidence suggests that it does reduce oral mucositis in these adults, but we are less certain about the size of the reduction, which could be large or small. However, we are confident that there is an appreciable reduction in severe oral mucositis in these adults.This Cochrane review includes some very recent and currently unpublished data, and strengthens international guideline statements for adults receiving the above cancer treatments.

Topics: Adult; Antineoplastic Agents; Cryotherapy; Fluorouracil; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Mouth Diseases; Myeloablative Agonists; Neoplasms; Pain; Randomized Controlled Trials as Topic; Stomatitis

Oral graft-versus-host disease (GVHD) is a significant complication after allogeneic stem cell transplantation (SCT) and there is no consistent information about its characteristics in patients after reduced-intensity conditioning regimen FLU/MEL (fludarabine 120 mg/m² and melphalan 140 mg/m²).. This was a single-centre prospective observational study of patients after allogeneic SCT with FLU/MEL conditioning performed during the period 1/2005-12/2007. Characteristics of oral GVHD were observed in 71 patients. The observation was discontinued due to death, donor lymphocyte infusion (DLI) or new chemotherapy administration.. In 10/2010, the median duration of the observation of the cohort of the patients was 13 (0.2-69) months, and 42 (35-69) months in the still-ongoing 20/71 (28%) patients. Oral acute GVHD had sporadic 7% incidence, whereas oral chronic GVHD was observed in 33% of patients and persisted with median duration of 188 (11-665) days. Clinical and histopathological features were similar in both acute and chronic oral GVHD and included mucosal lichenoid changes, erythema, ulcerations and pseudomembranes, satellite necrosis, apoptotic bodies and lichenoid interface inflammation.. It is necessary to consider complex clinical symptomatology and pathological correlations when classifying the oral GVHD, because local oral symptoms and histopathological features in both acute and chronic oral GVHD forms can be similar. Even though the oral chronic GVHD was mild in the majority of patients, it can be considered as clinically significant due to its incidence, duration and symptomatology. The FLU/MEL conditioning regimen should not be considered as low-risk protocol in this context.

Topics: Acute Disease; Adult; Aged; Chronic Disease; Female; Graft vs Host Disease; Humans; Male; Melphalan; Middle Aged; Mouth Diseases; Stem Cell Transplantation; Transplantation Conditioning; Transplantation, Homologous; Vidarabine; Young Adult

Four patients with multiple myeloma refractory to conventional chemotherapy received high-dose melphalan. All experienced multiple oral complications. Extensive neutropenic ulceration and orofacial herpes simplex virus infection caused considerable morbidity in three patients during prolonged periods of neutropenia.

Topics: Adult; Female; Herpes Simplex; Humans; Male; Melphalan; Middle Aged; Mouth Diseases; Multiple Myeloma; Neutropenia; Opportunistic Infections; Stomatitis, Herpetic; Ulcer