***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: Severe oral mucositis is a major cause of morbidity following  allogeneic hematopoietic stem cell transplantation ( AHSCT ) . Cryotherapy , that is , the application of ice chips on the mucosa of the oral cavity during the administration of antineoplastic agents , may reduce the incidence and severity of chemotherapy-related oral mucositis . In this multicenter r and omized study , we addressed whether cryotherapy during MTX administration is effective in the prevention of severe oral mucositis in patients undergoing myeloablative AHSCT . One hundred and thirty patients undergoing myeloablative AHSCT and MTX-containing GVHD prophylaxis were enrolled and r and omized to receive or not receive cryotherapy during MTX administration . The incidence of severe ( grade 3–4 ) oral mucositis , the primary end point of the study , was comparable in patients receiving or not cryotherapy . Moreover , no difference was observed in the incidence of oral mucositis grade 2–4 and the duration of oral mucositis grade 3–4 or 2–4 , or in the kinetics of mucositis over time . In univariate and multivariate analysis , severe oral mucositis correlated with TBI in the conditioning regimen and lack of folinic acid rescue following MTX administration . Thus , cryotherapy during MTX administration does not reduce severe oral mucositis in patients undergoing myeloablative allogeneic HSCT . Future studies will assess cryotherapy before allogeneic HSCT Purpose : Edatrexate ( 10-Edam ) is a methotrexate analog with improved intracellular transport , polyglutamation , and antitumor activity compared to the parent compound . Edatrexate shows schedule-dependent synergism with platinum compounds in pre clinical studies . We performed a phase I trial to determine toxicities and establish the maximum tolerated dose ( MTD ) of edatrexate in combination with carboplatin . Based on the short initial plasma half-life of edatrexate , prophylactic ice chip cryotherapy was used to reduce the severity of mucositis . Patients and methods : Forty-six chemotherapy-naive patients with advanced solid tumors were treated .  Edatrexate was given weekly for 5 doses ( 50 % on day 8) , and then every other week , followed by carboplatin at a fixed dose of 350 mg/m2 on day 1 and then every 4 weeks for 8 cycles . Edatrexate dose was increased at increments of 10 mg/m2/dose level beginning at 60 mg/m2/week ( range 60–120 mg/m2 ) . Results : All patients were assessable for toxicity and response analysis . The median number of cycles administered per patients was 4 . This combination chemotherapy regimen was well tolerated . Using ice chip cryotherapy , no grade IV mucositis was observed . Grade III mucositis occurred in only 7/46 pts and was not dose-related . Protocol -defined dose-limiting toxicity occurred at a edatrexate dose level of 120 mg/m2 , yielding an MTD of 110 mg/m2 . Responding tumor types included non-small cell and small lung cancer , head and neck cancer , and bladder cancer . Conclusions : 1 ) This phase I study demonstrated the safety and tolerability of this edatrexate and carboplatin combination . 2 ) Dose-limiting mucositis did not occur allowing escalation of edatrexate dose above levels previously achieved with this edatrexate dose schedule . This was most likely a result of prophylactic ice chip cryotherapy . 3 ) An edatrexate dose of 110 mg/m2 with ice chip cryotherapy is recommended for Phase II trials of this combination AIM AND OBJECTIVE To investigate if oral cryotherapy during myeloablative therapy may influence frequency and severity of mucositis , nutritional status and infection rate after  bone marrow transplantation .  BACKGROUND Patients treated with intensive myeloablative treatment before bone marrow transplantation  are all at risk to develop mucositis . Oral mucositis causes severe pain and oral dysfunction , which can contribute to local and systemic infections and bleeding ; it may even interrupt cancer therapy . Oral mucositis also decreases the oral food intake , which increases the risk for malnutrition and infection . Reduced food intake , loss of fat and muscles , alterations in energy and substrate metabolism leads to malnutrition . DESIGN A r and omised controlled trial with a r and om assignment to experimental or control group . METHOD A stratified r and omisation was used with regard to the type of transplantation . Mucositis was measured on WHO mucositis scale . Number of days of total parenteral nutrition , infection rate , weight , albumin levels and days at hospital was compared . RESULTS There were significantly fewer patients in the experimental group with  mucositis grade 3 - 4 than in the control group and significantly lower number of days in the hospital ( allogeneic patients ) . Less total parenteral nutrition was needed in the experimental group in both setting s , and the S-albumin level was significantly better preserved . No significant difference could be found with regard to infection rate . CONCLUSION Oral cryotherapy reduced mucositis , number of hospital days , the need for total parenteral nutrition and result ed in a better nutritional status . RELEVANCE TO CLINICAL PRACTICE Nurses caring for patients treated with myeloablative therapy  should place high priority to prevent oral mucositis and hereby reduce its side effects AIMS AND OBJECTIVES The study aim ed to compare the use of plain ice , flavoured ice and st and ard care , to evaluate the effect on mucositis and to determine patients ' perceptions of the two forms of oral cryotherapy . BACKGROUND Despite evidence that oral cryotherapy is useful in preventing mucositis in patients receiving 5-fluorouracil  , concerns have been expressed about its clinical utility , due to potential side effects and negative perceptions . DESIGN A r and omized , controlled , crossover trial was conducted in the outpatient chemotherapy department of an acute care teaching hospital in Perth , Western Australia . Patients were r and omized to receive each of three interventions across three cycles of chemotherapy : st and ard care alone ; st and ard care plus plain ice ; and st and ard care plus flavoured ice . METHODS Oral mucositis was assessed by nurses prior to each of the three chemotherapy cycles and 15 days after each intervention . Two assessment tools were used , the Oral Assessment Guide , and the Western Consortium Cancer Nursing Research Scale . Participants completed a question naire to determine their comfort and satisfaction with oral cryotherapy , as well as factors affecting compliance . RESULTS Findings from 67 patients revealed that when participants used st and ard care alone , they were significantly more likely to experience symptoms of mucositis than when they used either plain or flavoured ice . Odds ratios were at least threefold higher for st and ard care alone , varying according to the instrument used . The two main concerns reported were the taste of flavoured ice and the time required to complete the cryotherapy interventions . Side effects such as nausea , sensitivity and headache were reported more frequently for flavoured ice ( n = 11 ) compared with plain ice ( n = 5 ) and st and ard care ( n = 1 ) . CONCLUSIONS Both forms of oral cryotherapy were effective in reducing the severity of oral mucositis after chemotherapy and were more effective than st and ard care alone . Flavoured ice was associated with the highest frequency of side effects . RELEVANCE TO CLINICAL PRACTICE The benefits of cryotherapy appear to outweigh the problems in this sample of patients . The intervention should be tailored to individual patients , based on preferences for plain versus flavoured ice and small chips vs. larger blocks . Unsweetened frozen fruit juices should be evaluated . Time constraints could be addressed by providing transportable containers of ice Recently , a r and omised study demonstrated the utility of oral cooling ( cryotherapy ) in the prevention of 5-fluorouracil (5FU)-induced stomatitis . In order to verify these results a confirmatory study , using identical treatment regimen , was initiated . 84 patients treated with a 5-FU-containing regimen were r and omised to a  control arm or to receive oral cryotherapy . End point evaluation was obtained by a global assessment of the physician 's judgement and patients ' description of mucositis severity grade d 0 - 4 . Mucositis was significantly reduced by cryotherapy considering both the first cycle of therapy ( the mean toxicity score for cryotherapy was 0.59 and it was 1.1 for the control group , P < or = 0.05 ) and all the chemotherapeutic courses ( the mean toxicity score for cryotherapy was 0.36 when it was 0.69 for the control group , P < or = 0.05 ) . In conclusion , the present study confirms that cryotherapy can decrease 5FU-induced stomatitis and should be recommended for patients receiving bolus 5FU-containing regimens Mucositis is a significant dose-limiting toxicity associated with fluorouracil ( 5FU ) , particularly when it is combined with leucovorin . We hypothesized that oral cryotherapy would cause local vasoconstriction and would temporarily decrease blood flow to the oral mucous membranes . If cryotherapy were used during the time of peak serum 5FU levels , then the oral mucous membranes would have less exposure to 5FU and thus develop less mucositis . To test this hypothesis , 95 patients scheduled to receive their first cycle of 5FU plus leucovorin  were r and omized to have oral cryotherapy at the time of chemotherapy administration or to serve as a control group . Subsequent mucositis was significantly reduced in the group assigned to receive cryotherapy as judged by the attending physicians ( P = .0002 ) and by the patients themselves ( P = .0001 ) . We now routinely recommend this cryotherapy procedure for our patients receiving daily bolus 5FU plus leucovorin Stomatitis is a common adverse effect of intravenously infused 5-fluorouracil ( 5FU ) . Although there are encouraging studies about the preventive role of oral cryotherapy in stomatitis induced by intravenous administration of 5FU , this simple and cost-effective method is not part of clinical practice . This prospect i ve r and omized study investigates whether oral cryotherapy alleviates  5FU-induced stomatitis .  Thirty six patients , included in the cryotherapy group , were instructed to hold ice cubes in their oral cavity , shortly before , during and shortly after the infusion of 5FU . Both mean physician and patient- grade d stomatitis of our cryotherapy group were compared with those of a control group ( 40 patients ) and were found significantly reduced for all three chemotherapy cycles . The percentage of patients who were free from oral toxicity was significantly higher in the cryotherapy group in all three chemotherapy cycles , as judged both by patients and physicians . The results of this study encourage the use of cryotherapy in patients receiving 5FU in alleviating stomatitis by using a side-effect-free , easy to perform and inexpensive measure , which does not interfere with the efficacy of antineoplastic agents Mucosal toxicity is an incapacitating complication of intensive chemo-radiotherapy for children with malignant disorders , and is physically and psychologically distressful . It is therefore important to minimize mucosal toxicity in those patients . In this report , the effects of the combined prophylaxis of oral cooling ( cryotherapy ) and administration of propantheline , an anticholinergic drug , were studied in patients ( aged 2 - 16 year ) with acute leukemias or solid tumors , who underwent myeloablative chemo-radiotherapy and autologous peripheral blood stem cell rescue from 1993 to 1997 . Patients were pretreated with the combined prophylaxis ( n = 12 ) or single prophylaxis ( n = 5 ) , or left untreated ( n = 7 ) . The combined prophylaxis significantly reduced the severe mucositis ( combined , 8.3 % ; single , 20.0 % ; and untreated , 42.9 % ) and severe diarrhea ( combined , 16.7 % ; single , 60.0 % ; and untreated , 57.1 % ) . Moreover , the combined prophylaxis tended to shorten the periods of febrile episodes defined as temperature > 38 degrees C ( combined , 3.8 days ; single , 4.6 days ; and untreated , 5.6 days ) . Therefore , the combination of propantheline and oral cryotherapy may be feasible and effective for reduction of mucosal toxicity in patients with malignancy who undergo high-dose chemotherapy Background . The authors previously reported that 30 minutes of oral cryotherapy  inhibits 5‐fluorouracil (5‐FU)‐induced stomatitis . The current trial was design ed to determine whether a longer duration of cryotherapy would provide additional protection Introduction Mucositis is a major complication in myeloablative therapy , which often necessitates advanced pharmacological pain treatment , including i.v . opioids . Attempts to prevent oral mucositis have included oral cryotherapy , which has been shown to reduce mucositis , but there is a lack of knowledge concerning the effect of oral cryotherapy on opioid use by reducing the mucositis for patients treated with myeloablative therapy before bone marrow transplantation ( BMT ) . Aim The aim of the present study was to evaluate if oral cryotherapy could delay or alleviate the development of mucositis and thereby reduce the number of days with i.v . opioids among patients who receive 
    Output:
    
The recommendation for the use of oral cryotherapy to prevent oral mucositis in patients receiving bolus fluorouracil ( 5-FU ) was maintained , in agreement with the 2007 guidelines .
Conclusions The evidence continues to support the use of oral cryotherapy for prevention of oral mucositis in patients receiving bolus 5-FU chemotherapy or high-dose melphalan .
This intervention is consistent with the MASCC/ISOO guidelines published in 2007 .