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1.
The Pitfalls of Global Hemostasis Assays in Myeloproliferative Neoplasms and Future Challenges
Tiu A, Chiasakul T, Kessler CM
Seminars in thrombosis and hemostasis. 2023
Abstract
Venous and arterial thromboembolism are major complications of myeloproliferative neoplasms (MPNs), comprising polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Global hemostasis assays, including thrombin generation assay (TGA), rotational thromboelastometry (ROTEM), and thromboelastography (TEG), have been proposed as biomarkers to assess the hypercoagulability and thrombotic risk stratification in MPNs. We performed a systematic literature review on the parameters of TGA, ROTEM, and TEG and their association with thrombotic events and treatment strategies in MPNs. Thirty-two studies (all cross-sectional) were included, which collectively enrolled 1,062 controls and 1,608 MPN patients. Among the 13 studies that reported arterial or venous thrombosis, the overall thrombosis rate was 13.8% with 6 splanchnic thromboses reported. Out of the 27 TGA studies, there was substantial heterogeneity in plasma preparation and trigger reagents employed in laboratory assays. There was a trend toward increased peak height among all MPN cohorts versus controls and higher endogenous thrombin potential (ETP) between ET patients versus controls. There was an overall trend toward lower ETP between PV and PMF patients versus. controls. There were no substantial differences in ETP between JAK2-positive versus JAK2-negative MPNs, prior history versus negative history of thrombotic events, and among different treatment strategies. Of the three ROTEM studies, there was a trend toward higher maximum clot firmness and shorter clot formation times for all MPNs versus controls. The three TEG studies had mixed results. We conclude that the ability of parameters from global hemostasis assays to predict for hypercoagulability events in MPN patients is inconsistent and inconclusive. Further prospective longitudinal studies are needed to validate these biomarker tools so that thrombotic potential could be utilized as a primary endpoint of such studies.
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2.
Access and use of immunoglobulins in secondary supportive cancer care: A systematic literature review
Counihan, M., Cervenakova, L., Misztela, D., Van Baelen, M., Naughton, B. D.
The journal of medicine access. 2023;7:27550834231197315
Abstract
BACKGROUND Immunoglobulin replacement therapy (IgRT) benefits patients with primary immuno deficiency (PID) originating from the innate or polygenic defects in the immune system. However, evidence supporting their therapeutic role is not as explicit in secondary immuno deficiency (SID) resulting from the treatment of haematological malignancies. OBJECTIVES This study aimed to (1) create a dataset of relevant research papers, which explore the use of IgRT in SID for analysis, (2) assess the risk of bias within this dataset and (3) study the characteristics of these papers. DESIGN This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. In addition to the risk of bias, the study characteristics explored in this article included study design, study geographical location and year of publication. DATA SOURCES AND METHODS To identify studies relevant to the research question, EMBASE and PubMed databases were searched. The Population, Intervention, Comparison and Outcome (PICO) framework was used to assess study quality. Risk of bias and quality of studies were assessed in accordance with the study design. As one model was not appropriate to assess bias in all articles, several tools were used. RESULTS A total of 43 studies were identified from the literature search as relevant to the research objective. The most common study design was a retrospective case-control cohort study (n = 16/43), and randomised trials were among the least commonly used approaches (n = 1). Research in this area is occurring around the globe including the United States (n = 7), Italy (n = 7), China, India, Japan and throughout Europe. The annual number of papers in this area has varied from 2012 (n = 1) to 2021 (n = 7). The studies in this article demonstrated a varied risk of bias, with 9 of the 20 cohort studies scoring less than 5 out of 9 stars. CONCLUSIONS Randomised controlled trials are less frequently used to assess access and use of immunoglobulins. More commonly, a retrospective case-control cohort study was used which correlates with the higher risk of bias seen in the studies in this article. Most of the research concerning immunoglobulin use and access occurs in higher-income countries.
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3.
Efficacy and safety of thrombopoietin receptor agonists in solid tumors with chemotherapy-induced thrombocytopenia: a meta-analysis
Chen, W., Liu, Y., Li, L., Zeng, X.
BMC pharmacology & toxicology. 2023;24(1):71
Abstract
OBJECTIVE To evaluate the efficacy and safety of thrombopoietin receptor agonists (TPO-RAs) in solid tumors with chemotherapy-induced thrombocytopenia (CIT). METHODS We conducted a comprehensive search of PubMed, FMRS, Cochrane Library, Web of Science, EMBASE, and ClinicalTrials.gov for randomized controlled trials (RCTs) reporting the efficacy and safety of TPO-RAs in solid tumors with CIT. The search was limited to articles published before April 30, 2022. Primary outcomes included chemotherapy dose reduction or delays, platelet transfusion, the incidence of grade 3 or 4 thrombocytopenia, and bleeding events. Secondary outcomes encompassed the incidence of platelet count > 400 × 10(9)/L, adverse events (AEs), serious AEs, thrombosis, and mortality. RESULTS Our analysis encompassed six studies: five rigorous RCTs and one unique study comparing romiplostim to an observation group, involving a total of 489 patients. For primary outcomes, TPO-RAs significantly reduced the incidence of grade 3 or 4 thrombocytopenia (RR = 0.69, 95% CI: 0.52-0.91). After applying the Bonferroni correction for multiple comparisons, the significance of the reduction in grade 3 or 4 thrombocytopenia incidence persisted (P = 0.008). TPO-RAs showed no significant impact on chemotherapy dose reduction or delays (RR = 0.81, 95% CI: 0.65-1.01), platelet transfusion (RR = 1.04, 95% CI: 0.48-2.27), or bleeding events (RR = 0.50, 95% CI: 0.23-1.10). In terms of safety, there were no significant difference in the incidence of any AEs (RR = 0.98, 95% CI:0.92-1.04), serious AEs (RR = 0.79, 95% CI:0.45-1.40), thrombotic events (RR = 1.20, 95% CI:0.51-2.84) and mortality (RR = 1.15, 95% CI:0.55-2.41). CONCLUSIONS This meta-analysis suggests that TPO-RAs are generally well-tolerated. However, their efficacy in solid tumors with CIT appears limited, as they only demonstrate a reduction in the incidence of grade 3 or 4 thrombocytopenia.
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4.
The efficacy and safety of Trilaciclib in preventing chemotherapy-induced myelosuppression: a systematic review and meta-analysis of randomized controlled trials
Qiu, J., Sheng, D., Lin, F., Jiang, P., Shi, N.
Frontiers in pharmacology. 2023;14:1157251
Abstract
Background: This study aims to assess the clinical efficacy and safety of Trilaciclib in preventing chemotherapy-induced myelosuppression in adult patients through meta-analysis. Methods: The PubMed, Embase, Cochrane Library, Clinical Trials, EU Clinical Trials Register, and International Clinical Trials Registry Platform were searched up to 25 October 2022. Only randomized controlled trials (RCTs) comparing the clinical outcomes of Trilaciclib and Trilaciclib plus chemotherapy for treating malignant cancers in adult patients were included. The primary outcome included the incidence of SN, FN, the DSN, and administration of ESAs, G-CSFs, and RBC or platelet transfusions, while the secondary outcomes included the risk of adverse events (AEs) and severe adverse events (SAEs). Results: In total, four randomized controlled trials (RCTs) involving 345 patients with SCLC or breast cancer were included in this meta-analysis. Results showed that administration of Trilaciclib significantly reduced the occurrence of SN (19.3% vs. 42.2%, OR = 0.31), FN (3.22% vs. 6.72%, OR = 0.47), anemia (20.5% vs. 38.2%, OR = 0.38) and shortened the DSN during treatment. The proportion of patients receiving therapeutic use of ESAs (4.03% vs. 11.8%, OR = 0.31), G-CSF (37.0% vs. 53.5%, OR = 0.52), RBC transfusions (19.8% vs. 29.9%, OR = 0.56) was also statistically lower in the experimental group than in the control group. Meanwhile, the ORR, overall survival, and progress-free survival of the two groups were identical, and no negative impact of Trilaciclib on the clinical outcomes of chemotherapy treatments was found. Other chemotherapy-induced adverse events (AEs) and severe adverse events (SAEs) like diarrhea, fatigue, nausea, and vomiting were identical regardless of Trilaciclib usage. Conclusion: Trilaciclib demonstrated its efficacy in reducing the occurrence of chemotherapy-induced myelosuppression and utilization of supportive care interventions without undermining the clinical benefits of chemotherapy regimens during treatment with an acceptable safety profile.
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5.
Does perioperative allogeneic blood transfusion worsen the prognosis of patients with hepatocellular carcinoma? A meta-analysis of propensity score-matched studies
Hu, L., Li, Z., Qiao, Y., Wang, A.
Frontiers in oncology. 2023;13:1230882
Abstract
BACKGROUND Allogeneic blood transfusion is required in a part of liver resection. The effect of allogeneic blood transfusion on the prognosis of patients with hepatocellular carcinoma (HCC) remains controversial. To investigate whether perioperative allogeneic blood transfusion (PBT) affects the long-term prognosis of patients with HCC, we conducted a meta-analysis that included only propensity score-matched (PSM) studies. METHODS The Cochrane Library, Embase, PubMed, and Web of Science databases were systematically searched to identify PSM studies that compared the long-term outcomes of allogeneic blood transfusion in resected HCC patients. Overall survival (OS) and recurrence-free survival (RFS) rates were calculated. RESULTS This meta-analysis included 9 PSM studies with 12 datasets involving 2476 patients. Lower OS and RFS in HCC patients receiving allogeneic blood transfusion were observed than those in patients not receiving blood transfusion (OS: hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.10-1.64; p < 0.01; RFS: HR, 1.29; 95% CI, 1.07-1.56; p < 0.01). Subgroup analysis revealed that among patients with BCLC A HCC, those receiving allogeneic blood transfusion had lower OS and RFS (OS: HR, 2.27; 95% CI, 1.61-3.21; RFS: HR, 2.11; 95% CI, 1.30-3.41). OS and RFS were similar in both groups of patients with BCLC B and C HCC. CONCLUSION The receipt of perioperative allogeneic blood transfusion is associated with a decrease in OS and RFS. These results seem to be reliable for patients in BCLC stage A. But more high-quality research is needed to confirm this conclusion.
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6.
Prostate Artery Embolization in the Treatment of Massive Intractable Bleeding from Prostatic Neoplasms: A Case Report and Systematic Review
Moramarco, L., Grande, A. M., Vertemati, M., Aseni, P.
Journal of clinical medicine. 2023;13(1)
Abstract
Lower urinary tract symptoms (LUTS) and hematuria are common symptoms in men with neoplasms, mainly affecting the elderly population. Prostatic arterial embolization (PAE) is a minimally invasive procedure that has shown promising results in managing LUTS and massive intractable prostatic hematuria in patients with benign prostatic hyperplasia (BPH) and prostate cancer (PCa). A few studies, however, have provided valuable insights into the durability and efficacy of PAE focusing on the long-term effectiveness, quality of life, and cancer-specific control of hemostasis and urinary symptoms. As a result of concomitant cardiovascular conditions, these patients often take anticoagulants or antithrombotics, which can worsen their hematuria and clinical status. Transurethral resection of the prostate (TURP) is considered a very high-risk procedure, even without massive bleeding, and requires discontinuation of vitamin K antagonists and antiplatelet therapies. Such patients usually have their surgery postponed, and PAE should be considered a safe alternative treatment. We aimed to report a narrative review from 1976 to June 2023 of the current state of PAE for massive and intractable hematuria, highlighting recent developments in this technique, including prospective cohort studies, and focusing on long-term outcome, safety, and complication management of patients with prostatic neoplasms who develop significant hemorrhagic symptoms. Additionally, we present a case report and a simple algorithm for treating intractable bleeding in a 92-year-old man with PCa and massive hematuria.
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7.
Intravenous Iron Therapy to Treat Anemia in Oncology: A Mapping Review of Randomized Controlled Trials
Lim, J., Auerbach, M., MacLean, B., Al-Sharea, A., Richards, T.
Current oncology (Toronto, Ont.). 2023;30(9):7836-7851
Abstract
Anemia is a common problem when patients present with cancer, and it can worsen during treatment. Anemia can directly impact the cognitive and physical quality of life and may impair fitness for oncological therapy. The most common cause of anemia is iron deficiency. Newer intravenous (IV) iron formulations offer a safe and rapidly effective treatment option. We performed a systematic mapping review of randomized controlled trials (RCTs) evaluating intravenous iron therapy in patients with cancer and anemia and their outcomes. A total of 23 RCTs were identified. The median number of patients enrolled was 104 (IQR: 60-134). A total of 5 were focused on surgical outcomes (4 preoperative, 1 postoperative), and 15 were in adjuvant therapies for a variety of tumor types (breast, colorectal, lung, gynecological, myeloid, and lymphomas), 10 of which were in combination with erythropoietin-stimulating agents (ESAs) therapy, 2 in radiotherapy, and 1 in palliative care. Overall, the studies reported that the use of IV iron increased hemoglobin concentration and decreased transfusion rates during different cancer treatment regimes. IV iron can be administered safely throughout the cancer treatment pathway from primary surgery to the palliative setting. More studies are needed to demonstrate net clinical outcomes.
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8.
Efficacy and safety of gastroscopic hemostasis in the treatment of acute gastric hemorrhage: A meta-analysis
Pan, H. Y., Wang, X. W., He, Q. X., Lu, Y. D., Zhang, W. Y., Jin, J. W., Lin, B.
World journal of gastrointestinal oncology. 2023;15(11):1988-1997
Abstract
BACKGROUND Gastric cancer (GC) is a malignant tumor with a high incidence and mortality rate worldwide for which acute bleeding is a common clinical complication. Gastroscopic hemostasis is an important method for treating acute bleeding in GC; however, its efficacy and safety remain controversial. AIM: To systematically analyze the efficacy and safety of gastroscopic hemostasis for the treatment of acute gastric hemorrhage. METHODS The PUBMED, Web of Science, Wiley Library, EMBASE, Wanfang, CNKI, and VIP databases were searched for studies related to gastroscopic hemostatic treatment for acute GC published through February 20, 2023. The literature was screened according to the inclusion and exclusion criteria, data were extracted, and literature quality was evaluated. The meta-analysis was performed using RevMan software (version 5.3), while Begg's test for publication bias was performed using Stata 13.0 software. RESULTS Six randomized controlled trials and two retrospective analyses were retrieved. Five studies had a low, two had an uncertain, and one had a high risk of bias. Compared with the control group, the hemostatic rate of gastroscopic hemostasis was increased [relative risk (RR) = 1.24; 95% confidence interval (CI): 1.08 to 1.43; P = 0.003]; the rate of rebleeding (RR = 0.27; 95%CI: 0.09 to 0.80; P = 0.02), rate of surgery transfer (RR = 0.16; 95%CI: 0.06 to 0.43; P = 0.0003), serum C-reactive protein level [mean difference (MD) = -5.16; 95%CI: -6.11 to 4.21; P < 0.00001], interleukin-6 level (MD = -6.37; 95%CI: -10.33 to -2.42; P = 0.002), and tumor necrosis factor-α level (MD = -2.29; 95%CI: -4.06 to -0.52; P = 0.01) were decreased; and the quality of life improvement rate was increased (RR = 1.95; 95%C I= 1.41-2.71; P < 0.0001). Begg's test revealed no significant publication bias. CONCLUSION The efficacy and safety of endoscopic hemostasis were higher than those of the control group, suggesting that it is an effective treatment for acute GC hemorrhage.
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9.
Intravenous iron versus oral iron versus no iron with or without erythropoiesis- stimulating agents (ESA) for cancer patients with anaemia: a systematic review and network meta-analysis
Adams, A., Scheckel, B., Habsaoui, A., Haque, M., Kuhr, K., Monsef, I., Bohlius, J., Skoetz, N.
The Cochrane Database of Systematic Reviews. 2022;6(6):Cd012633
Abstract
BACKGROUND Anaemia is common among cancer patients and they may require red blood cell transfusions. Erythropoiesis-stimulating agents (ESAs) and iron might help in reducing the need for red blood cell transfusions. However, it remains unclear whether the combination of both drugs is preferable compared to using one drug. OBJECTIVES To systematically review the effect of intravenous iron, oral iron or no iron in combination with or without ESAs to prevent or alleviate anaemia in cancer patients and to generate treatment rankings using network meta-analyses (NMAs). SEARCH METHODS We identified studies by searching bibliographic databases (CENTRAL, MEDLINE, Embase; until June 2021). We also searched various registries, conference proceedings and reference lists of identified trials. SELECTION CRITERIA We included randomised controlled trials comparing intravenous, oral or no iron, with or without ESAs for the prevention or alleviation of anaemia resulting from chemotherapy, radiotherapy, combination therapy or the underlying malignancy in cancer patients. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data and assessed risk of bias. Outcomes were on-study mortality, number of patients receiving red blood cell transfusions, number of red blood cell units, haematological response, overall mortality and adverse events. We conducted NMAs and generated treatment rankings. We assessed the certainty of the evidence using GRADE. MAIN RESULTS Ninety-six trials (25,157 participants) fulfilled our inclusion criteria; 62 trials (24,603 participants) could be considered in the NMA (12 different treatment options). Here we present the comparisons of ESA with or without iron and iron alone versus no treatment. Further results and subgroup analyses are described in the full text. On-study mortality We estimated that 92 of 1000 participants without treatment for anaemia died up to 30 days after the active study period. Evidence from NMA (55 trials; 15,074 participants) suggests that treatment with ESA and intravenous iron (12 of 1000; risk ratio (RR) 0.13, 95% confidence interval (CI) 0.01 to 2.29; low certainty) or oral iron (34 of 1000; RR 0.37, 95% CI 0.01 to 27.38; low certainty) may decrease or increase and ESA alone (103 of 1000; RR 1.12, 95% CI 0.92 to 1.35; moderate certainty) probably slightly increases on-study mortality. Additionally, treatment with intravenous iron alone (271 of 1000; RR 2.95, 95% CI 0.71 to 12.34; low certainty) may increase and oral iron alone (24 of 1000; RR 0.26, 95% CI 0.00 to 19.73; low certainty) may increase or decrease on-study mortality. Haematological response We estimated that 90 of 1000 participants without treatment for anaemia had a haematological response. Evidence from NMA (31 trials; 6985 participants) suggests that treatment with ESA and intravenous iron (604 of 1000; RR 6.71, 95% CI 4.93 to 9.14; moderate certainty), ESA and oral iron (527 of 1000; RR 5.85, 95% CI 4.06 to 8.42; moderate certainty), and ESA alone (467 of 1000; RR 5.19, 95% CI 4.02 to 6.71; moderate certainty) probably increases haematological response. Additionally, treatment with oral iron alone may increase haematological response (153 of 1000; RR 1.70, 95% CI 0.69 to 4.20; low certainty). Red blood cell transfusions We estimated that 360 of 1000 participants without treatment for anaemia needed at least one transfusion. Evidence from NMA (69 trials; 18,684 participants) suggests that treatment with ESA and intravenous iron (158 of 1000; RR 0.44, 95% CI 0.31 to 0.63; moderate certainty), ESA and oral iron (144 of 1000; RR 0.40, 95% CI 0.24 to 0.66; moderate certainty) and ESA alone (212 of 1000; RR 0.59, 95% CI 0.51 to 0.69; moderate certainty) probably decreases the need for transfusions. Additionally, treatment with intravenous iron alone (268 of 1000; RR 0.74, 95% CI 0.43 to 1.28; low certainty) and with oral iron alone (333 of 1000; RR 0.92, 95% CI 0.54 to 1.57; low certainty) may decrease or increase the need for transfusions. Overall mortality We estimated that 347 of 1000 participants without treatment for anaemia died overall. Low-certainty evidence from NMA (71 trials; 21,576 participants) suggests that treatment with ESA and intravenous iron (507 of 1000; RR 1.46, 95% CI 0.87 to 2.43) or oral iron (482 of 1000; RR 1.39, 95% CI 0.60 to 3.22) and intravenous iron alone (521 of 1000; RR 1.50, 95% CI 0.63 to 3.56) or oral iron alone (534 of 1000; RR 1.54, 95% CI 0.66 to 3.56) may decrease or increase overall mortality. Treatment with ESA alone may lead to little or no difference in overall mortality (357 of 1000; RR 1.03, 95% CI 0.97 to 1.10; low certainty). Thromboembolic events We estimated that 36 of 1000 participants without treatment for anaemia developed thromboembolic events. Evidence from NMA (50 trials; 15,408 participants) suggests that treatment with ESA and intravenous iron (66 of 1000; RR 1.82, 95% CI 0.98 to 3.41; moderate certainty) probably slightly increases and with ESA alone (66 of 1000; RR 1.82, 95% CI 1.34 to 2.47; high certainty) slightly increases the number of thromboembolic events. None of the trials reported results on the other comparisons. Thrombocytopenia or haemorrhage We estimated that 76 of 1000 participants without treatment for anaemia developed thrombocytopenia/haemorrhage. Evidence from NMA (13 trials, 2744 participants) suggests that treatment with ESA alone probably leads to little or no difference in thrombocytopenia/haemorrhage (76 of 1000; RR 1.00, 95% CI 0.67 to 1.48; moderate certainty). None of the trials reported results on other comparisons. Hypertension We estimated that 10 of 1000 participants without treatment for anaemia developed hypertension. Evidence from NMA (24 trials; 8383 participants) suggests that treatment with ESA alone probably increases the number of hypertensions (29 of 1000; RR 2.93, 95% CI 1.19 to 7.25; moderate certainty). None of the trials reported results on the other comparisons. AUTHORS' CONCLUSIONS When considering ESAs with iron as prevention for anaemia, one has to balance between efficacy and safety. Results suggest that treatment with ESA and iron probably decreases number of blood transfusions, but may increase mortality and the number of thromboembolic events. For most outcomes the different comparisons within the network were not fully connected, so ranking of all treatments together was not possible. More head-to-head comparisons including all evaluated treatment combinations are needed to fill the gaps and prove results of this review.
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10.
The addition of oral iron improves chemotherapy-induced anemia in patients receiving erythropoiesis-stimulating agents
Tan J, Du S, Zang X, Ding K, Ginzburg Y, Chen H
International journal of cancer. 2022
Abstract
Although many studies have shown that supplementation with iron and erythropoiesis-stimulating agents (ESA) is frequently used for managing chemotherapy-induced anemia (CIA), optimal combination therapy using these agents together to ameliorate anemia is not well characterized. To assess the effects of ESA combined with oral or intravenous (IV) iron on relieving CIA, PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI) were searched for articles. Data collected in the articles were meta-analyzed using RevMan 5.3 software with a random-effects model. Our comprehensive search yielded 1666 potentially relevant trials. A total of 41 trials randomizing 4200 patients with CIA fulfilled inclusion criteria, including 34 Chinese articles and 7 English articles. Meta-analysis showed that treatment with both ESA and iron more effectively improved CIA relative to iron supplementation alone, with increased hemoglobin, hematocrit, red blood cell count and haematopoietic response rate. Subgroup analyses revealed iron administration, both oral and IV iron, improved anemia in ESA-treated cancer patients with CIA. Our analysis demonstrates that iron supplementation combined with ESA more effectively ameliorates CIA relative to iron supplementation alone, without regard to whether IV or oral iron was used. Together, our findings may contribute to the clinical treatment of CIA using iron therapy with or without ESA. This article is protected by copyright. All rights reserved.