-
Biology of Blood and Marrow... Apr 2016Oral mucositis (OM) is a debilitating early adverse effect of allogeneic hematopoietic stem cell transplantation (HSCT). The intensity of the conditioning regimen... (Review)
Review
Oral mucositis (OM) is a debilitating early adverse effect of allogeneic hematopoietic stem cell transplantation (HSCT). The intensity of the conditioning regimen correlates with the incidence and severity of OM, but no studies have analyzed this relationship among various conditioning regimens. We performed a systematic review on the incidence and outcomes of OM in allogeneic HSCT patients and analyzed this association. A comprehensive search of several databases (Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Cochrane CRCT, Cochrane DSR, Scopus) from 1990 to 2014 for studies of OM in allogeneic HSCT patients was conducted. Professional societies' meeting abstracts were also searched. Grade of OM was analyzed based on the World Health Organization (WHO) or National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events scales. Severe mucositis was defined as either grades 2 to 4 or grades 3 and 4, depending on the studies' definition of severity. Cohorts were analyzed based on regimen intensity; ie, reduced-intensity conditioning (RIC) (including nonmyeloablative) and myeloablative (MA). Random effect (RE) and standard logistic models weighted by the number of patients in each cohort were used for comparisons. A total of 624 studies were generated from the search. Of the 395 patients in 8 eligible MA regimen studies, 73.2% experienced any OM, whereas in 245 patients in the 6 eligible RIC regimen studies, 86.5% experienced any OM (chi-square P < .0001; RE, P = .05). Severe (grades 2 to 4) OM occurred among 79.7% of the WHO/NCI-graded MA patients and 71.5% of RIC patients (chi-square, P = .0421; RE, P < .01). In comparing graft-versus-host disease (GVHD) prophylaxis, only 55.4% of patients receiving nonmethotrexate regimens experienced OM; this was lower (chi-square, P < .0001; RE, P = .06) than that found among patients who received methotrexate (83.4%), either standard or reduced dose. Besides NCI and WHO grading scales, other scales included in the studies were Oral Mucositis Index, the Southwest Oncology Group Criteria, and Eastern Cooperative Oncology Group scale. To our knowledge, this is the first analysis on OM in allogeneic HSCT patients with respect to conditioning regimens, and we observed that RIC regimens led to a high incidence of OM similar to that of MA regimens. Clinical trials on treatment of OM are lacking, emphasizing the essential need for prospective studies in this arena. A significant variance in the criteria for grading OM underscores the importance of establishing a standard grading system for OM measurement in future allogeneic HSCT clinical trials.
Topics: Busulfan; Cyclophosphamide; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Methotrexate; Mouth Mucosa; Myeloablative Agonists; Severity of Illness Index; Stomatitis; Transplantation Conditioning; Transplantation, Homologous; Vidarabine
PubMed: 26409924
DOI: 10.1016/j.bbmt.2015.09.014 -
Hematology/oncology and Stem Cell... 2011Cyclophosphamide plus total body irradiation (CYTBI) and oral busulfan plus cyclophosphamide (BUCY) are commonly used conditioning regimens prior to allogeneic... (Comparative Study)
Comparative Study Meta-Analysis Review
Cyclophosphamide plus total body irradiation compared with busulfan plus cyclophosphamide as a conditioning regimen prior to hematopoietic stem cell transplantation in patients with leukemia: a systematic review and meta-analysis.
BACKGROUND AND OBJECTIVES
Cyclophosphamide plus total body irradiation (CYTBI) and oral busulfan plus cyclophosphamide (BUCY) are commonly used conditioning regimens prior to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with leukemia. However, there is conflicting data on the superiority of one regimen over the other. Our aim was to critically appraise and synthesize available evidence regarding the efficacy and safety of CYTBI compared to BUCY as a conditioning regimen.
DESIGN AND SETTING
Systematic review and meta-analysis of randomized, controlled trials (RCTs) comparing BUCY with CYTBI.
METHODS
We did a systematic search of the indexed medical literature using appropriate keywords to identify potentially relevant articles. The primary outcome of interest was efficacy measured by overall survival (OS) and disease-free survival (DFS). Acute and late toxicity were secondary endpoints. Meta-analysis was attempted only on RCTs. A relative risk or risk ratio (RR) and 95% confidence interval (CI) was calculated for each outcome in the meta-analysis.
RESULTS
Fifteen non-randomized comparative studies involving 6280 patients were included in a narrative review without attempting a pooled analysis, in view of the potential for significant bias. Outcome data from seven RCTs involving 730 patients randomly assigned to either CYTBI or BUCY was pooled using meta-analytic methods. CYTBI was associated with a modest but non-significant reduction in all cause mortality (RR=0.82, 95%CI: 0.64-1.05; P=.12) and relapse of leukemia (RR=0.89, 95%CI: 0.72-1.10; P=.28). Transplant-related mortality (TRM) was significantly lesser with CYTBI compared to oral BUCY (RR-0.53, 95%CI: 0.31-0.90; P=.02). The cumulative incidence of major complications was not significantly different between the two regimens, but specific complications varied according to the conditioning regimen. TBI-based regimens were associated with more severe late effects on growth and development in children.
CONCLUSION
This analysis represents the largest comparative analyses of CYTBI with BUCY as a conditioning regimen prior to HSCT in the indexed medical literature. Conditioning regimen and disease (type and setting) can significantly affect outcomes. TRM is significantly lesser with CYTBI, but this does not translate into a significant survival benefit. There remain valid concerns regarding the late effects of TBI, particularly in children. Although not overly superior, the weight of evidence favors CYTBI over BUCY as a first choice-conditioning regimen in patients with leukemia.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Cyclophosphamide; Databases as Topic; Disease-Free Survival; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Leukemia; Randomized Controlled Trials as Topic; Registries; Transplantation Conditioning; Treatment Outcome; Whole-Body Irradiation
PubMed: 21460603
DOI: 10.5144/1658-3876.2011.17 -
The Cochrane Database of Systematic... 2000Currently hydergine is used almost exclusively for treating patients with either dementia, or 'age-related' cognitive symptoms. Since the early eighties there have been... (Review)
Review
BACKGROUND
Currently hydergine is used almost exclusively for treating patients with either dementia, or 'age-related' cognitive symptoms. Since the early eighties there have been over a dozen more clinical trials, yet hydergine's efficacy remains uncertain. Although previous reviews offer generally favorable support for hydergine's efficacy, they were, however, limited by a bias with respect to the particular clinical studies chosen (eg, the inclusion of case reports, and uncontrolled trials), and by authors' impressionistic assessments of results. Not surprisingly, there has been a lack of consensus among reviewers with regard to the efficacy of hydergine. In 1994, a meta-analysis was published by the present reviewers who reported that overall, hydergine was more effective than placebo. However they also observed that the statistical evidence for efficacy in 'possible or probable Alzheimer's disease' patients was so modest that one additional statistically non-significant trial would have reduced the results to non significance.
OBJECTIVES
Because of uncertainty surrounding the efficacy of hydergine, the goals of this overview were to assess its overall effect in patients with possible dementia, and to investigate potential moderators of an effect.
SEARCH STRATEGY
The Cochrane Dementia Group Register of Clinical Trials was searched using the terms 'hydergine', 'ergoloids,' 'ergoloid mesylates,' 'dihydroergocristine,' 'dihydroergocryptine,' 'dihydroergotoxine,' and 'dihydroergocornine. MEDLINE, EMBASE, and two proprietary databases were searched also. Published reviews were inspected for further sources.
SELECTION CRITERIA
Trials to be included must be randomized, double-blind, parallel-group, and unconfounded comparisons of hydergine with placebo for a treatment duration of greater than 1 week in subjects with dementia or symptoms consistent with dementia.
DATA COLLECTION AND ANALYSIS
Data were extracted independently by the reviewers, pooled where appropriate and possible, and the pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Where possible, intention-to-treat data were used. Outcomes of interest included clinical global impressions of change and comprehensive rating scales. Potential moderating variables of a treatment effect included: inpatient/outpatient status, trial duration, age, sex, medication dose, publication year, and diagnostic grouping.
MAIN RESULTS
There were a total of nineteen trials that met inclusion criteria and that had data sufficient for analysis. Thirteen trials reported sufficient information to use a global rating of improvement and nine trials provided information on a comprehensive rating scale. Three trials provided both outcome measures. It was not possible to use many of the published results in a combined analysis owing to the lack of sufficient data to perform statistical analyses. For the twelve trials that used global ratings, there was a significant effect favoring hydergine (OR 3.78, 95%CI, 2.72-5.27). For the nine trials that used comprehensive ratings, there was a significant mean difference favoring hydergine (WMD 0.96, 95%CI, 0. 54-1.37). Hydergine was well tolerated in these trials, with 78% of randomized subjects available for data analyses. Greater effect sizes on global ratings were associated with younger age, and possibly higher dose, although most of the subgroup analyses were statistically insignificant.
REVIEWER'S CONCLUSIONS
As in an earlier systematic review, we found hydergine to show significant treatment effects when assessed by either global ratings or comprehensive rating scales (based here on a smaller set of trials than in the earlier published systematic review because trials were required to have data that could conform with MetaView, the Cochrane Collaboration statistics software). The small number of trials available for analysis, however, limited the ability of subgroup analyses to identify statistically significant modera
Topics: Aged; Alzheimer Disease; Dementia; Ergoloid Mesylates; Humans; Nootropic Agents
PubMed: 10796534
DOI: 10.1002/14651858.CD000359