Abstract: We identified 16 eligible trials. Four trials are ongoing and two have been completed but the results have not yet been published (trial completion dates: April 2012 to February 2017). Therefore, the review included 10 trials in eight references with 554 participants. Six trials (336 participants) only included participants with acute myeloid leukaemia undergoing intensive chemotherapy, two trials (38 participants) included participants with lymphoma undergoing intensive chemotherapy and two trials (180 participants) reported participants undergoing allogeneic stem cell transplantation. Men and women were equally well represented in the trials. The age range of participants included in the trials was from 16 years to 81 years. All trials took place in high-income countries. The manufacturers of the agent sponsored eight trials that were under investigation, and two trials did not report their source of funding. No trials assessed artificial platelet substitutes, fibrinogen concentrate, recombinant activated factor VII or desmopressin. Nine trials compared a TPO mimetic to placebo or standard care; seven of these used pegylated recombinant human megakaryocyte growth and differentiation factor (PEG-rHuMGDF) and two used recombinant human thrombopoietin (rhTPO). One trial compared platelet-poor plasma to platelet transfusion. We considered that all the trials included in this review were at high risk of bias and meta-analysis was not possible in seven trials due to problems with the way data were reported. We are very uncertain whether TPO mimetics reduce the number of participants with any bleeding episode (odds ratio (OR) 0.40, 95% confidence interval (CI) 0.10 to 1.62, one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce the risk of a life-threatening bleed after 30 days (OR 1.46, 95% CI 0.06 to 33.14, three trials, 209 participants, very low quality evidence); or after 90 days (OR 1.00, 95% CI 0.06 to 16.37, one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce platelet transfusion requirements after 30 days (mean difference -3.00 units, 95% CI -5.39 to -0.61, one trial, 120 participants, very low quality evidence). No deaths occurred in either group after 30 days (one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce all-cause mortality at 90 days (OR 1.00, 95% CI 0.24 to 4.20, one trial, 120 participants, very low quality evidence). No thromboembolic events occurred for participants treated with TPO mimetics or control at 30 days (two trials, 209 participants, very low quality evidence). We found no trials that looked at: number of days on which bleeding occurred, time from randomisation to first bleed or quality of life. One trial with 18 participants compared platelet-poor plasma transfusion with platelet transfusion. We are very uncertain whether platelet-poor plasma reduces the number of participants with any bleeding episode (OR 16.00, 95% CI 1.32 to 194.62, one trial, 18 participants, very low quality evidence). We are very uncertain whether platelet-poor plasma reduces the number of participants with severe or life-threatening bleeding (OR 4.00, 95% CI 0.56 to 28.40, one trial, 18 participants, very low quality evidence). We found no trials that looked at: number of days on which bleeding occurred, time from randomisation to first bleed, number of platelet transfusions, all-cause mortality, thromboembolic events or quality of life. There is insufficient evidence to determine if platelet-poor plasma or TPO mimetics reduce bleeding for participants with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation. To detect a decrease in the proportion of participants with clinically significant bleeding from 12 in 100 to 6 in 100 would require a trial containing at least 708 participants (80% power, 5% significance). The six ongoing trials will provide additional information about the TPO mimetic comparison (424 participants) but this will still be underpowered to demonstrate this level of reduction in bleeding. None of the included or ongoing trials include children. There are no completed or ongoing trials assessing artificial platelet substitutes, fibrinogen concentrate, recombinant activated factor VII or desmopressin in people undergoing intensive chemotherapy or stem cell transplantation for haematological malignancies.

Plain-language summary: The evidence is current to May 2016. We identified 16 clinical trials: 10 completed trials and six ongoing trials. We included the 10 completed trials in this review. Six trials included adults with acute myeloid leukaemia undergoing intensive chemotherapy, two trials included adults with lymphoma undergoing intensive chemotherapy and two trials included adults undergoing allogeneic stem cell transplantation. The age range of participants was between 16 and 81 years. Men and women were equally well represented. All trials took place in high-income countries. The manufacturer of the agent that was under investigation sponsored eight trials, and two trials did not report their source of funding. We identified nine trials (536 participants) assessing thrombopoietin mimetics and one trial (18 participants) assessing platelet-poor plasma. These trials were conducted between 1974 and 2015. No trial assessed artificial platelets, fibrinogen concentrate, recombinant activated factor VII or desmopressin). For adults treated with thrombopoietin mimetics, we are very uncertain whether there is a difference in the number of participants with: any bleeding, risk of life-threatening bleeding, number of platelet transfusions, overall risk of death or thromboembolic events because the quality of the evidence was very low. We found no trials of thrombopoietin mimetics that looked at: the number of days on which bleeding occurred, time from start of trial to first bleed or quality of life. For adults treated with platelet-poor plasma, we are very uncertain whether there is a difference in the number of participants with: any bleeding or risk of life-threatening bleeding. We found no trials that looked at: the number of days on which bleeding occurred, time from start of trial to first bleeding episode, number of platelet transfusions, overall risk of death, thromboembolic events or quality of life. The quality of the evidence was very low, making it difficult to draw conclusions or make recommendations regarding the usefulness and safety of thrombopoietin mimetics or platelet-poor plasma. There was no trial evidence for artificial platelets, fibrinogen concentrate, recombinant activated factor VII or desmopressin.