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Health Technology Assessment... Dec 2010Acute leukaemia is a group of rapidly progressing cancers of bone marrow and blood classified as either acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia... (Review)
Review
BACKGROUND
Acute leukaemia is a group of rapidly progressing cancers of bone marrow and blood classified as either acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL). Haemopoietic stem cell transplantation (SCT) has developed as an adjunct to or replacement for conventional chemotherapy with the aim of improving survival and quality of life.
OBJECTIVES
A systematic overview of the best available evidence on the clinical effectiveness and cost-effectiveness of SCT in the treatment of acute leukaemia.
DATA SOURCES
Clinical effectiveness: electronic databases, including MEDLINE, EMBASE and the Cochrane Library, were searched from inception to December 2008 to identify published systematic reviews and meta-analyses. Cochrane CENTRAL, MEDLINE, EMBASE and Science Citation Index (SCI) were searched from 1997 to March 2009 to identify primary studies. Cost-effectiveness: MEDLINE, EMBASE, Database of Abstracts of Reviews of Effects (DARE) and NHS Economic Evaluation Database (NHS EED) were searched from inception to January 2009.
STUDY SELECTION
Potentially relevant papers were retrieved and independently checked against predefined criteria by two reviewers (one in the case of the cost-effectiveness review).
STUDY APPRAISAL
Included reviews and meta-analyses were critically appraised and data extracted and narratively presented. Included randomised controlled trials (RCTs) and donor versus no donor (DvND) studies were mapped to the evidence covered in existing systematic reviews and meta-analyses according to a framework of 12 decision problems (DPs): DP1 related to SCT in adults with AML in first complete remission (CR1); DP2 to adults with AML in second or subsequent remission or with refractory disease (CR2+); DP3 to children with AML in CR1; DP4 to children with AML in CR2+; DP5 to adults with ALL in CR1; DP6 to adults with ALL in CR2+; DP7 to children with ALL in CR1; DP8 to children with ALL in CR2+; DP9 to comparison of different sources of stem cells in transplantation; DP10 to different conditioning regimens; DP11 to the use of purging in autologous SCT; and DP12 to the use of T-cell depletion in allogeneic SCT.
RESULTS
Fifteen systematic reviews/meta-analyses met the inclusion criteria for the review of clinical effectiveness, thirteen of which were published from 2004 onwards. Taking into account the timing of their publications, most reviews appeared to have omitted an appreciable proportion of potentially available evidence. The best available evidence for effectiveness of allogeneic SCT using stem cells from matched sibling donors came from DvND studies: there was sufficient evidence to support the use of allogeneic SCT in DP1 (except in good-risk patients), DP3 (role of risk stratification unclear) and DP5 (role of risk stratification unclear). There was conflicting evidence in DP7 and a paucity of evidence from DvND studies for all decision problems concerning patient groups in CR2+. The best available evidence for effectiveness of autologous SCT came from RCTs: overall, evidence suggested that autologous SCT was either similar to or less effective than chemotherapy. There was a paucity of evidence from published reviews of RCTs for DPs 9-12. Nineteen studies met the inclusion criteria in the cost-effectiveness review, most reporting only cost information and only one incorporating an economic model. Although there is a wealth of information on costs and some information on cost-effectiveness of allogeneic SCT in adults with AML (DPs 1 and 2), there is very limited evidence on relative costs and cost-effectiveness for other DPs.
LIMITATIONS
Time and resources did not permit critical appraisal of the primary studies on which the reviews/meta-analyses reviewed were based; there were substantial differences in methodologies, and consequently quantitative synthesis of data was neither planned in the protocol nor carried out; some of the studies were quite old and might not reflect current practice; and a number of the studies might not be applicable to the UK.
CONCLUSIONS
Bearing in mind the limitations, existing evidence suggests that sibling donor allogeneic SCT may be more effective than chemotherapy in adult AML (except in good-risk patients) in CR1, childhood AML in CR1 and adult ALL in CR1, and that autologous SCT is equal to or less effective than chemotherapy. No firm conclusions could be drawn regarding the cost-effectiveness of SCT in the UK NHS owing to the limitations given above. Future research should include the impact of the treatments on patients' quality of life as well as information on health service use and costs associated with SCT from the perspective of the UK NHS.
Topics: Adult; Child; Cost-Benefit Analysis; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 21138675
DOI: 10.3310/hta14540 -
JAMA Jun 2009The optimal treatment of acute myeloid leukemia (AML) in first complete remission (CR1) is uncertain. Current consensus, based on cytogenetic risk, recommends... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
The optimal treatment of acute myeloid leukemia (AML) in first complete remission (CR1) is uncertain. Current consensus, based on cytogenetic risk, recommends myeloablative allogeneic stem cell transplantation (SCT) for poor-risk but not for good-risk AML. Allogeneic SCT, autologous transplantation, and consolidation chemotherapy are considered of equivalent benefit for intermediate-risk AML.
OBJECTIVE
To quantify relapse-free survival (RFS) and overall survival benefit of allogeneic SCT for AML in CR1 overall and also for good-, intermediate-, and poor-risk AML.
METHODS
Systematic review and meta-analysis of prospective trials evaluating allogeneic SCT vs nonallogeneic SCT therapies for AML in CR1. The search used the combined search terms allogeneic; acut* and leukem*/leukaem*/leucem*/leucaem*/aml; myelo* or nonlympho* in the PubMed, Embase, and Cochrane Registry of Controlled Trials databases in March 2009. The search identified 1712 articles.
STUDY SELECTION
Prospective trials assigning adult patients with AML in CR1 to undergo allogeneic SCT vs nonallogeneic SCT treatment(s) based on donor availability and trials reporting RFS and/or overall survival outcomes on an intention-to-treat, donor vs no-donor basis were identified.
DATA EXTRACTION
Two reviewers independently extracted study characteristics, interventions, and outcomes. Hazard ratios (HRs) with 95% confidence intervals (CIs) were determined.
DATA SYNTHESIS
Overall, 24 trials and 6007 patients were analyzed (5951 patients in RFS analyses and 5606 patients in overall survival analyses); 3638 patients were analyzed by cytogenetic risk (547, 2499, and 592 with good-, intermediate-, and poor-risk AML, respectively). Interstudy heterogeneity was not significant. Fixed-effects meta-analysis was performed. Compared with nonallogeneic SCT, the HR of relapse or death with allogeneic SCT for AML in CR1 was 0.80 (95% CI, 0.74-0.86). Significant RFS benefit of allogeneic SCT was documented for poor-risk (HR, 0.69; 95% CI, 0.57-0.84) and intermediate-risk AML (HR, 0.76; 95% CI, 0.68-0.85) but not for good-risk AML (HR, 1.06; 95% CI, 0.80-1.42). The HR of death with allogeneic SCT for AML in CR1 was 0.90 (95% CI, 0.82-0.97). Significant overall survival benefit with allogeneic SCT was documented for poor-risk (HR, 0.73; 95% CI, 0.59-0.90) and intermediate-risk AML (HR, 0.83; 95% CI, 0.74-0.93) but not for good-risk AML (HR, 1.07; 95% CI, 0.83-1.38).
CONCLUSION
Compared with nonallogeneic SCT therapies, allogeneic SCT has significant RFS and overall survival benefit for intermediate- and poor-risk AML but not for good-risk AML in first complete remission.
Topics: Antineoplastic Agents; Clinical Trials as Topic; Humans; Leukemia, Myeloid, Acute; Remission Induction; Risk Assessment; Stem Cell Transplantation; Survival Analysis; Transplantation, Homologous
PubMed: 19509382
DOI: 10.1001/jama.2009.813 -
The Cochrane Database of Systematic... Jan 2009Febrile neutropenia (FN) and other infectious complications are some of the most serious treatment-related toxicities of chemotherapy for cancer, with a mortality rate... (Review)
Review
BACKGROUND
Febrile neutropenia (FN) and other infectious complications are some of the most serious treatment-related toxicities of chemotherapy for cancer, with a mortality rate of 2% to 21%. The two main types of prophylactic regimens are granulocyte (G-CSF) or granulocyte-macrophage colony stimulating factors (GM-CSF); and antibiotics, frequently quinolones or cotrimoxazole. Important current guidelines recommend the use of colony stimulating factors when the risk of febrile neutropenia is above 20% but they do not mention the use of antibiotics. However, both regimens have been shown to reduce the incidence of infections. Since no systematic review has compared the two regimens, a systematic review was undertaken.
OBJECTIVES
To compare the effectiveness of G-CSF or GM-CSF with antibiotics in cancer patients receiving myeloablative chemotherapy with respect to preventing fever, febrile neutropenia, infection, infection-related mortality, early mortality and improving quality of life.
SEARCH STRATEGY
We searched The Cochrane Library, MEDLINE, EMBASE, databases of ongoing trials, and conference proceedings of the American Society of Clinical Oncology and the American Society of Hematology (1980 to 2007). We planned to include both full-text and abstract publications.
SELECTION CRITERIA
Randomised controlled trials comparing prophylaxis with G-CSF or GM-CSF versus antibiotics in cancer patients of all ages receiving chemotherapy or bone marrow or stem cell transplantation were included for review. Both study arms had to receive identical chemotherapy regimes and other supportive care.
DATA COLLECTION AND ANALYSIS
Trial eligibility and quality assessment, data extraction and analysis were done in duplicate. Authors were contacted to obtain missing data.
MAIN RESULTS
We included two eligible randomised controlled trials with 195 patients. Due to differences in the outcomes reported, the trials could not be pooled for meta-analysis. Both trials showed non-significant results favouring antibiotics for the prevention of fever or hospitalisation for febrile neutropenia.
AUTHORS' CONCLUSIONS
There is no evidence for or against antibiotics compared to G(M)-CSFs for the prevention of infections in cancer patients.
Topics: Antibiotic Prophylaxis; Antineoplastic Combined Chemotherapy Protocols; Fever; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Infection Control; Neoplasms; Neutropenia; Randomized Controlled Trials as Topic
PubMed: 19160320
DOI: 10.1002/14651858.CD007107.pub2 -
Biology of Blood and Marrow... Feb 2007Myeloablative high-dose therapy and single autologous stem cell transplantation (HDT) is frequently performed early in the course of multiple myeloma, supported by some... (Meta-Analysis)
Meta-Analysis Review
High-dose therapy with single autologous transplantation versus chemotherapy for newly diagnosed multiple myeloma: A systematic review and meta-analysis of randomized controlled trials.
Myeloablative high-dose therapy and single autologous stem cell transplantation (HDT) is frequently performed early in the course of multiple myeloma, supported by some randomized controlled trials (RCTs) indicating overall survival (OS) and progression-free survival (PFS) benefit compared with nonmyeloablative standard-dose therapy (SDT). Other RCTs, however, suggest variable benefit. We therefore undertook a systematic review and meta-analysis of all RCTs evaluating upfront HDT versus SDT in myeloma. The primary objective was to quantify OS benefit with HDT, with PFS benefit a secondary objective. Anticipating heterogeneity, sensitivity and subgroup analyses were undertaken to assess robustness of results. Assessment of harms (treatment-related mortality) was also undertaken. We searched the PubMed, Embase, and Cochrane Collection of Controlled Trials databases using the terms myeloma combined with autologous or transplant or myeloablative or stem cell. In total, 3407 articles were accessed, and 10 RCTs prospectively comparing upfront HDT with SDT, with > or =2-year follow-up, and reporting OS benefit on an intent-to-treat basis were identified. Two reviewers independently extracted study characteristics, interventions, and outcomes. Hazard ratios (with 95% confidence interval) were determined. Nine studies comprising 2411 patients were fully analyzed. Significant heterogeneity was present. The combined hazard of death with HDT was 0.92 (95% confidence interval, 0.74-1.13). The combined hazard of progression with HDT was 0.75 (95% confidence interval, 0.59-0.96). The totality of the randomized data indicates PFS benefit but not OS benefit for HDT with single autologous transplantation performed early in multiple myeloma. Sensitivity and subgroup analyses supported the findings and indicated that, contrary to current reimbursement criteria, PFS benefit with upfront HDT is not restricted to chemoresponsive myeloma. However, the overall risk of developing treatment-related mortality with HDT was increased significantly (odds ratio, 3.01; 95% confidence interval, 1.64-5.50). Hence, evaluating alternative therapeutic options upfront may also be reasonable.
Topics: Dose-Response Relationship, Radiation; Hematopoietic Stem Cell Transplantation; Humans; Multiple Myeloma; Myeloablative Agonists; Odds Ratio; Randomized Controlled Trials as Topic; Survival Analysis; Transplantation Conditioning; Transplantation, Autologous
PubMed: 17241924
DOI: 10.1016/j.bbmt.2006.09.010