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The Cochrane Database of Systematic... Mar 2016People with haematological disorders are frequently at risk of severe or life-threatening bleeding as a result of thrombocytopenia (reduced platelet count). This is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
People with haematological disorders are frequently at risk of severe or life-threatening bleeding as a result of thrombocytopenia (reduced platelet count). This is despite the routine use of prophylactic platelet transfusions to prevent bleeding once the platelet count falls below a certain threshold. Platelet transfusions are not without risk and adverse events may be life-threatening. A possible adjunct to prophylactic platelet transfusions is the use of antifibrinolytics, specifically the lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid (EACA). This is an update of a Cochrane review first published in 2013.
OBJECTIVES
To determine the efficacy and safety of antifibrinolytics (lysine analogues) in preventing bleeding in people with haematological disorders.
SEARCH METHODS
We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (The Cochrane Library 2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 07 March 2016.
SELECTION CRITERIA
We included RCTs involving participants with haematological disorders, who would routinely require prophylactic platelet transfusions to prevent bleeding. We only included trials involving the use of the lysine analogues TXA and EACA.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened all electronically-derived citations and abstracts of papers, identified by the review search strategy, for relevancy. Two review authors independently assessed the full text of all potentially relevant trials for eligibility, completed the data extraction and assessed the studies for risk of bias using The Cochrane Collaboration's 'Risk of bias' tool. We requested missing data from one author but the data were no longer available. The outcomes are reported narratively: we performed no meta-analyses because of the heterogeneity of the available data.
MAIN RESULTS
We identified three new studies in this update of the review. In total seven studies were eligible for inclusion, three were ongoing RCTs and four were completed studies. The four completed studies were included in the original review and the three ongoing studies were included in this update. We did not identify any RCTs that compared TXA with EACA.Of the four completed studies, one cross-over TXA study (eight participants) was excluded from the outcome analysis because it had very flawed study methodology. Data from the other three studies were all at unclear risk of bias due to lack of reporting of study methodology.Three studies (two TXA (12 to 56 participants), one EACA (18 participants) reported in four articles (published 1983 to 1995) were included in the narrative review. All three studies compared the drug with placebo. All three studies included adults with acute leukaemia receiving chemotherapy. One study (12 participants) only included participants with acute promyelocytic leukaemia. None of the studies included children. One of the three studies reported funding sources and this study was funded by a charity.We are uncertain whether antifibrinolytics reduce the risk of bleeding (three studies; 86 participants; very low-quality evidence). Only one study reported the number of bleeding events per participant and there was no difference in the number of bleeding events seen during induction or consolidation chemotherapy between TXA and placebo (induction; 38 participants; mean difference (MD) 1.70 bleeding events, 95% confidence interval (CI) -0.37 to 3.77: consolidation; 18 participants; MD -1.50 bleeding events, 95% CI -3.25 to 0.25; very low-quality evidence). The two other studies suggested bleeding was reduced in the antifibrinolytic study arm, but this was statistically significant in only one of these two studies.Two studies reported thromboembolism and no events occurred (68 participants, very low-quality evidence).All three studies reported a reduction in platelet transfusion usage (three studies, 86 participants; very low-quality evidence), but this was reported in different ways and no meta-analysis could be performed. No trials reported the number of platelet transfusions per participant. Only one study reported the number of platelet components per participant and there was a reduction in the number of platelet components per participant during consolidation chemotherapy but not during induction chemotherapy (consolidation; 18 participants; MD -5.60 platelet units, 95% CI -9.02 to -2.18: induction; 38 participants, MD -1.00 platelet units, 95% CI -9.11 to 7.11; very low-quality evidence).Only one study reported adverse events of TXA as an outcome measure and none occurred. One study stated side effects of EACA were minimal but no further information was provided (two studies, 74 participants, very low-quality evidence).None of the studies reported on the following pre-specified outcomes: overall mortality, adverse events of transfusion, disseminated intravascular coagulation (DIC) or quality of life (QoL).
AUTHORS' CONCLUSIONS
Our results indicate that the evidence available for the use of antifibrinolytics in haematology patients is very limited. The trials were too small to assess whether or not antifibrinolytics decrease bleeding. No trials reported the number of platelet transfusions per participant. The trials were too small to assess whether or not antifibrinolytics increased the risk of thromboembolic events or other adverse events. There are three ongoing RCTs (1276 participants) due to be completed in 2017 and 2020.
Topics: Aminocaproic Acid; Antifibrinolytic Agents; Erythrocyte Transfusion; Hematologic Diseases; Hemorrhage; Humans; Lysine; Platelet Transfusion; Thrombocytopenia; Thromboembolism; Tranexamic Acid
PubMed: 26978005
DOI: 10.1002/14651858.CD009733.pub3 -
Leukemia & Lymphoma 2016The outcomes of acute promyelocytic leukemia (APL) in pregnancy are largely unknown. The MEDLINE database was systematically searched to obtain 43 articles with 71... (Meta-Analysis)
Meta-Analysis
The outcomes of acute promyelocytic leukemia (APL) in pregnancy are largely unknown. The MEDLINE database was systematically searched to obtain 43 articles with 71 patients with new-onset APL during pregnancy. Induction therapy included various regimens of all-trans retinoic acid (ATRA), cytarabine, and anthracycline and resulted in a complete remission rate of 93%. Obstetric and fetal complications included pre-term deliveries (46%), spontaneous/therapeutic abortion/intrauterine death (33.3%) and other neonatal complications (25.9%). Mothers diagnosed in the first trimester were more likely to experience obstetric (p < 0.01) and fetal (p < 0.01) complications. To our knowledge, this is the largest systematic review of APL in pregnancy. The vast majority of APL patients in pregnancy may achieve remission with initial induction therapy. APL or its therapy in pregnancy, however, is associated with a high risk of fetal and obstetrical complications. The results of our study may help in patient counseling and informed decision-making.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Consolidation Chemotherapy; Female; Humans; Leukemia, Promyelocytic, Acute; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Remission Induction; Treatment Outcome; Tretinoin; Young Adult
PubMed: 26110880
DOI: 10.3109/10428194.2015.1065977 -
The Cochrane Database of Systematic... Jun 2015Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by systemic intravascular activation of coagulation, leading to deposition of fibrin... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by systemic intravascular activation of coagulation, leading to deposition of fibrin in the bloodstream. It may occur in patients with acute and chronic leukemia and is particularly associated with acute promyelocytic leukemia (a subtype of acute myeloid leukemia).
OBJECTIVES
To assess the clinical benefits and harms of any pharmacological intervention for treating DIC in patients with acute or chronic leukemia.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2015, Issue 05), MEDLINE (1946 to 7 May 2015), LILACS (1982 to 7 May 2015) and African Index Medicus (7 May 2015). There was no language restrictions. We sought additional randomized controlled trials (RCTs) from the World Health Organization International Clinical Trials Registry Platform and the reference lists of primary studies identified.
SELECTION CRITERIA
RCTs assessing the clinical benefits and harms of interventions for treating DIC in patients with acute and chronic leukemia.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed trial selection, 'Risk of bias' assessment and data extraction. Primary outcomes were overall mortality, in-hospital mortality from any cause (15-day and 30-day) and adverse events.
MAIN RESULTS
In this Cochrane Review update we did not include any new RCT compared with the first review version. Accordingly, four RCTs (388 participants) met the inclusion criteria. These trials evaluated the human activated protein C, recombinant human soluble thrombomodulin, tranexamic acid and dermatan sulphate. Included trials reported data on mortality and bleeding. The studies were conducted in Japan, Italy and the Netherlands. We classified the included trials as: 1) including patients with or without leukemia which did not report data for the leukemia subgroup (366 participants); and 2) only including patients with leukemia (22 participants). Overall, the risk of bias of the included trials was high, since the trial authors did not provide a detailed description about trial design and execution.According to the GRADE recommendations, we judged the overall quality of the body of evidence for all prefixed outcomes as 'very low', due to methodological limitations and very small sample size.One trial, including 10 participants with leukemia and comparing dermatan sulphate with heparin, reported no deaths during trial treatment.In terms of bleeding data, we were unable to pool results from two studies that were only conducted with leukemia patients due to the inconsistency in the measurement and reporting of this outcome. One trial, including 12 participants with leukemia, found very low quality evidence that tranexamic acid can reduce the cumulative hemorrhagic score in participants compared with those assigned to placebo (P = 0.0015, very low quality evidence). On the contrary, there is no evidence that dermatan sulphate compared with placebo reduces new events of hemorrhagic diathesis (1/5 (20%) versus 2/5 (40%); RR 0.50; 95% CI 0.06 to 3.91; P = 0.51, very low quality evidence).No thromboembolic complications were reported in either trial that included patients with leukemia only (very low quality evidence). The safety profile was inconclusive.The included trials did not assess overall mortality, resolution of respiratory failure, renal failure or shock.
AUTHORS' CONCLUSIONS
Due to a lack of new RCTs, our conclusions in this Cochrane Review update are the same as the previous review version. We included four RCTs which reported mortality and bleeding data. It is not possible to determine whether human activated protein C, recombinant human soluble thrombomodulin, tranexamic acid and dermatan sulphate are effective or harmful for patients presenting with DIC related to acute or chronic leukemia. The quality of the evidence was low to very low. Therefore, prescription of these interventions for treating DIC in patients with acute and chronic leukemia can neither be supported nor rejected, unless new evidence from a large high-quality trial alters this conclusion.
Topics: Acute Disease; Anticoagulants; Chronic Disease; Dermatan Sulfate; Disseminated Intravascular Coagulation; Humans; Leukemia; Protein C; Randomized Controlled Trials as Topic; Thrombomodulin; Tranexamic Acid
PubMed: 26107113
DOI: 10.1002/14651858.CD008562.pub3 -
OncoTargets and Therapy 2014Multiple myeloma (MM) is a clonal malignancy characterized by the proliferation of malignant plasma cells in the bone marrow and the production of monoclonal... (Review)
Review
Multiple myeloma (MM) is a clonal malignancy characterized by the proliferation of malignant plasma cells in the bone marrow and the production of monoclonal immunoglobulin. Although some newly approved drugs (thalidomide, lenalidomide, and bortezomib) demonstrate significant benefit for MM patients with improved survival, all MM patients still relapse. Arsenic trioxide (ATO) is the most active single agent in acute promyelocytic leukemia, the antitumor activity of which is partly dependent on the production of reactive oxygen species. Due to its multifaceted effects observed on MM cell lines and primary myeloma cells, Phase I/II trials have been conducted in heavily pretreated patients with relapsed or refractory MM. Therapy regimens varied dramatically as to the dosage of ATO and monotherapy versus combination therapy with other agents available for the treatment of MM. Although ATO-based combination treatment was well tolerated by most patients, most trials found that ATO has limited effects on MM patients. However, since small numbers of patients were randomized to different treatment arms, trials have not been statistically powered to determine the differences in progression-free survival and overall survival among the experimental arms. Therefore, large Phase III studies of ATO-based randomized controlled trials will be needed to establish whether ATO has any potential beneficial effects in the clinical setting.
PubMed: 25246802
DOI: 10.2147/OTT.S67165