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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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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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3.
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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4.
Comparable Efficacy of Submucosal Platelet-Rich Plasma and Combined Platelet-Rich Plasma Noncrosslinked Hyaluronic Acid Injections in Vulvovaginal Atrophy: A Cancer Survivorship Issue
Omar, S. S., Elmulla, K. F., AboKhadr, N. A., Badway, A. A., Ramadan, E. N., Hassouna, A. M., Heikal, L. A., Arafat, W. O.
Journal of women's health (2002). 2023
Abstract
Background: Cancer survivors are often reluctant to discuss sexual complaints with their oncologists and treatment is frequently unsatisfactory due to paucity of controlled studies and inapplicability of vaginal estrogen. We aimed to evaluate efficacy and tolerability of platelet-rich plasma (PRP) injections alone or in combination with noncrosslinked hyaluronic acid compared with standard therapy with topical hyaluronic acid gel in the management of cancer therapy-induced or aggravated vulvovaginal atrophy. Materials and Methods: This prospective, parallel-group comparative study was conducted on 45 female patients with a history of cancer and complaining of symptoms of vulvovaginal atrophy either induced or aggravated by cancer treatment. Patients were randomly divided into three groups (A, B, and C). Group A patients received two submucosal vaginal PRP injections, group B patients received two similar injections of PRP combined with noncrosslinked hyaluronic acid, and group C received a topical vaginal hyaluronic acid gel applied three times weekly for 2 months. Main outcome measures were vulvovaginal atrophy symptom severity and vaginal health index (VHI) scores before treatment (v0), 1 month from baseline (v1), 2 months from baseline (v2), and 3 months after the last visit (v3). Results: Both groups A and B showed greater improvement of frequency of intercourse avoidance than group C. Group A showed greater improvement of dyspareunia than group C. Groups A and B demonstrated greater improvement of vaginal pH, fluid volume, and total VHI scores than group C. Short-term topical hyaluronic acid (HA) was not associated with any significant improvement of vaginal elasticity. Group B showed greater improvement of vaginal dryness and moisture scores than group C. Reported adverse events were injection-related pain in all patients of groups A and B and vaginal spotting in groups A and B. Conclusion: Both PRP and PRP-HA have comparable efficacy and patient-reported treatment satisfaction. PRP injections were better tolerated by patients than PRP-HA. Clinical trial registration number: NCT05782920.
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5.
A randomized controlled trial to explore the safety and efficacy of irradiated buffy-coat granulocytes in pediatric patients with febrile neutropenia
Ramachandran, M., Gupta, A. K., Meena, J. P., Upadhyay, A. D., Coshic, P., Lodha, R., Seth, R.
American journal of blood research. 2023;13(5):152-161
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Editor's Choice
Abstract
BACKGROUND Transfusion of granulocytes obtained by apheresis is beneficial in febrile neutropenia (FN) but expensive and time-consuming. Buffy-coat-derived granulocytes could be an alternative. We studied the efficacy and safety of the administration of irradiated buffy-coat-derived granulocytes along with the standard of care in pediatric high-risk (HR) FN. METHODS Sixty children ≤18 years with malignancy and chemotherapy-induced HR FN were randomized to either the granulocyte transfusion (GT) arm which received irradiated buffy-coat derived granulocyte transfusion along with the standard treatment or the standard treatment (ST) arm. RESULTS Baseline characteristics, day-to-defervescence, antibiotic duration, hospital stay, and mortality were comparable between the groups. A significant difference was seen in days to achieve absolute neutrophil count (ANC) >500/mm(3) in the 2 groups: 4.5 days (3-6.5) in the GT arm v/s 8 days (4-11) in the ST arm (P=0.01). CONCLUSION Buffy-coat-derived granulocyte transfusion was safe and led to early hematological recovery but was not associated with survival benefits. Future studies with earlier initiation in the intended dose could be undertaken to generate more evidence.
PICO Summary
Population
Children with malignancy and chemotherapy-induced high-risk febrile neutropenia (n= 60).
Intervention
Irradiated buffy-coat derived granulocyte transfusion along with the standard treatment (GT arm, n= 30).
Comparison
Standard treatment, including: antimicrobials, blood component support, and G-CSF as per the protocol (ST arm, n= 30).
Outcome
Baseline characteristics, day-to-defervescence, antibiotic duration, hospital stay, and mortality were comparable between the groups. A significant difference was seen in days to achieve absolute neutrophil count >500/mm(3) in the 2 groups: 4.5 days (3, 6.5) in the GT arm versus 8 days (4, 11) in the ST arm.
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6.
Ferric carboxymaltose infusion versus oral iron supplementation for preoperative iron deficiency anaemia in patients with colorectal cancer (FIT): a multicentre, open-label, randomised, controlled trial
Talboom K, Borstlap WAA, Roodbeen SX, Bruns ERJ, Buskens CJ, Hompes R, Tytgat Kmaj, Tuynman JB, Consten ECJ, Heuff G, et al
The Lancet. Haematology. 2023
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Editor's Choice
Abstract
BACKGROUND A third of patients with colorectal cancer who are eligible for surgery in high-income countries have concomitant anaemia associated with adverse outcomes. We aimed to compare the efficacy of preoperative intravenous and oral iron supplementation in patients with colorectal cancer and iron deficiency anaemia. METHODS In the FIT multicentre, open-label, randomised, controlled trial, adult patients (aged 18 years or older) with M0 stage colorectal cancer scheduled for elective curative resection and iron deficiency anaemia (defined as haemoglobin level of less than 7·5 mmol/L (12 g/dL) for women and less than 8 mmol/L (13 g/dL) for men, and a transferrin saturation of less than 20%) were randomly assigned to either 1-2 g of ferric carboxymaltose intravenously or three tablets of 200 mg of oral ferrous fumarate daily. The primary endpoint was the proportion of patients with normalised haemoglobin levels before surgery (≥12 g/dL for women and ≥13 g/dL for men). An intention-to-treat analysis was done for the primary analysis. Safety was analysed in all patients who received treatment. The trial was registered at ClincalTrials.gov, NCT02243735, and has completed recruitment. FINDINGS Between Oct 31, 2014, and Feb 23, 2021, 202 patients were included and assigned to intravenous (n=96) or oral (n=106) iron treatment. Treatment began a median of 14 days (IQR 11-22) before surgery for intravenous iron and 19 days (IQR 13-27) for oral iron. Normalisation of haemoglobin at day of admission was reached in 14 (17%) of 84 patients treated intravenously and 15 (16%) of 97 patients treated orally (relative risk [RR] 1·08 [95% CI 0·55-2·10]; p=0·83), but the proportion of patients with normalised haemoglobin significantly increased for the intravenous treatment group at later timepoints (49 [60%] of 82 vs 18 [21%] of 88 at 30 days; RR 2·92 [95% CI 1·87-4·58]; p<0·0001). The most prevalent treatment-related adverse event was discoloured faeces (grade 1) after oral iron treatment (14 [13%] of 105), and no treatment-related serious adverse events or deaths were observed in either group. No differences in other safety outcomes were seen, and the most common serious adverse events were anastomotic leakage (11 [5%] of 202), aspiration pneumonia (5 [2%] of 202), and intra-abdominal abscess (5 [2%] 202). INTERPRETATION Normalisation of haemoglobin before surgery was infrequent with both treatment regimens, but significantly improved at all other timepoints following intravenous iron treatment. Restoration of iron stores was feasible only with intravenous iron. In selected patients, surgery might be delayed to augment the effect of intravenous iron on haemoglobin normalisation. FUNDING Vifor Pharma.
PICO Summary
Population
Patients with colorectal cancer and iron deficiency anaemia scheduled for elective curative resection; enrolled in the FIT trial in the Netherlands and Italy (n= 202).
Intervention
Intravenous ferric carboxymaltose (n= 96).
Comparison
Oral ferrous fumarate (n= 106).
Outcome
Treatment began a median of 14 days (IQR 11-22) before surgery for intravenous iron and 19 days (IQR 13-27) for oral iron. Normalisation of haemoglobin at day of admission was reached in 14 (17%) of 84 patients treated intravenously and 15 (16%) of 97 patients treated orally (relative risk [RR] 1.08, 95% CI [0.55, 2.10]), but the proportion of patients with normalised haemoglobin significantly increased for the intravenous treatment group at later timepoints (49 [60%] of 82 vs. 18 [21%] of 88 at 30 days; RR 2.92, 95% CI [1.87, 4.58]).
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Oxidized Regenerated Cellulose Versus Calcium Alginate in Controlling Bleeding From Malignant Wounds: A Randomized Controlled Trial
Firmino F, Villela-Castro D, Santos Vlcg
Cancer nursing. 2023
Abstract
BACKGROUND There is no consensus on the best intervention for topical management of bleeding in malignant wounds. Although surgical hemostatic dressings are recommended, the use of calcium alginate (CA) is frequent among practitioners. OBJECTIVE The aim of this study was to evaluate the hemostatic efficacy of oxidized regenerated cellulose (ORC) and CA dressing in the management of bleeding from malignant wounds resulting from breast cancer. METHODS This was a randomized open clinical trial. The outcomes measured were total time to hemostasis and the number of hemostatic products used. RESULTS Sixty-one patients were potentially eligible for the study, 1 did not consent, and 32 were assessed to be ineligible, resulting in a sample of 28 who were randomized to 2 study groups. Total time to hemostasis was 93.8 seconds in the ORC group, with an average of 30.1 seconds (95% confidence interval, 18.6-189 seconds), and 67 seconds in the CA group, with an average of 30.4 seconds (confidence interval, 21.7 seconds to imprecise upper limit). The main difference was 26.8 seconds. Kaplan-Meier log-rank test, and Cox model showed no statistical significance (P = 0.894). A total of 18 hemostatic products were used in the CA group and 34 in the ORC group. No adverse effects were identified. CONCLUSIONS Although no significant differences were identified in terms of time, more hemostatic products were used in the ORC group, highlighting the effectiveness of CA. IMPLICATIONS FOR PRACTICE Calcium alginate may be the first choice in the management of bleeding in malignant wounds, favoring nursing in the most immediate hemostatic actions.
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Endoscopic variceal ligation versus propranolol for the primary prevention of oesophageal variceal bleeding in patients with hepatocellular carcinoma: an open-label, two-centre, randomised controlled trial
Yang, T. C., Chen, W. C., Hou, M. C., Chen, P. H., Lee, P. C., Chang, C. Y., Lu, H. S., Chen, Y. J., Hsu, S. J., Huang, H. C., et al
Gut. 2023
Abstract
OBJECTIVE This randomised trial aimed to address whether endoscopic variceal ligation (EVL) or propranolol (PPL) is more effective at preventing initial oesophageal variceal bleeding (EVB) in patients with hepatocellular carcinoma (HCC). DESIGN Patients with HCC and medium-to-large oesophageal varices (EVs) but without previous EVB were randomised to receive EVL (every 3-4 weeks until variceal eradication) or PPL (up to 320 mg daily) at a 1:1 ratio. Long-term follow-up data on EVB, other upper gastrointestinal bleeding (UGIB), non-bleeding liver decompensation, overall survival (OS) and adverse events (AEs) were analysed using competing risk regression. RESULTS Between June 2011 and April 2021, 144 patients were randomised to receive EVL (n=72) or PPL (n=72). In the EVL group, 7 patients experienced EVB, and 30 died; in the PPL group, 19 patients had EVB, and 40 died. The EVL group had a lower cumulative incidence of EVB (Gray's test, p=0.009) than its counterpart, with no mortality difference (Gray's test, p=0.085). For patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B, EVL was better than PPL in reducing EVB (p<0.001) and mortality (p=0.003). For patients beyond BCLC stage B, between-group outcomes were similar. Other UGIB, non-bleeding liver decompensation and AEs did not differ between groups. A competing risk regression model confirmed the prognostic value of EVL. CONCLUSION EVL is superior to PPL in preventing initial EVB in patients with HCC. The benefits of EVL on EVB and OS may be limited to patients with BCLC stage A/B and not to those with BCLC stage C/D. TRIAL REGISTRATION NUMBER NCT01970748.
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9.
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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10.
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.