Abstract

Pathogen reduction (PR) technologies for blood components have been established to reduce the residual risk of known and emerging infectious agents. THERAFLEX UVPlatelets, a novel UVC light-based PR technology for platelet concentrates, works without photoactive substances. This randomized, controlled, double-blind, multicenter, noninferiority trial was designed to compare the efficacy and safety of UVC-treated platelets to that of untreated platelets in thrombocytopenic patients with hematologic-oncologic diseases. Primary objective was to determine non-inferiority of UVC-treated platelets, assessed by the 1-hour corrected count increment (CCI) in up to eight per-protocol platelet transfusion episodes. Analysis of the 171 eligible patients showed that the defined non-inferiority margin of 30% of UVC-treated platelets was narrowly missed as the mean differences in 1-hour CCI between standard platelets versus UVC-treated platelets for intention-to-treat and perprotocol analyses were 18.2% (95% confidence interval [CI]: 6.4%; 30.1) and 18.7% (95% CI: 6.3%; 31.1%), respectively. In comparison to the control, the UVC group had a 19.2% lower mean 24-hour CCI and was treated with an about 25% higher number of platelet units, but the average number of days to next platelet transfusion did not differ significantly between both treatment groups. The frequency of low-grade adverse events was slightly higher in the UVC group and the frequencies of refractoriness to platelet transfusion, platelet alloimmunization, severe bleeding events, and red blood cell transfusions were comparable between groups. Our study suggests that transfusion of pathogen-reduced platelets produced with the UVC technology is safe but non-inferiority was not demonstrated. (The German Clinical Trials Register number: DRKS00011156).

Abstract

BACKGROUND Polypectomy is a widely used and effective procedure to treat precancerous polyps. Delayed post-polypectomy bleeding (DPPB), a common complication of polypectomy, may diminish the utility of this procedure. Previous data on the efficacy of hemoclips has been conflicting, therefore we aimed to collectively evaluate and analyze the data to reach a definitive conclusion on the efficacy of using hemoclips to prevent incidences of DPPB in patients with large polyps (≥10 mm). METHODS We identified a total of 261 studies based on our previously defined search strategy. After screening, we included 6 randomized controlled trials. A meta-analysis was performed comparing the use of prophylactic application of hemoclips to a standard group without prophylactic clip placement for large polyps. RESULTS We found a statistically significant reduction in the incidence of DPPB when using hemoclips for large polyps. The overall incidence of DPPB was lower in the hemoclip group compared to the standard group for all large polyps ≥10 mm (relative risk 0.51, 95% confidence interval 0.35-0.75; P=0.01; I (2)=0%). CONCLUSIONS The use of hemoclips in achieving hemostasis for large polyps has a beneficial effect and appears to prevent DPPB. This reinforces the routine clinical practice of using hemoclips in polypectomy procedures.

Abstract

BACKGROUND Gastrointestinal bleeding is the most common clinical manifestation of gastrointestinal stromal tumor. It is of great significance to the prognosis of patients. But the results are controversial. The purpose of this study was to evaluate the relationship between gastrointestinal bleeding and clinical prognosis in patients with GIST. METHODS A systematic literature search was performed in Pumbed, Cochrane Library, EMBASE, ClinicalTrials.gov, CNKI, VIP and wanfang databases with the pattern of unlimited languages. 12 studies with 2781 individuals were included in the final analysis. The overall survival (OS), recurrence-free survival/disease-free survival (RFS/DFS) and related factors affecting bleeding in patients with gastrointestinal stromal tumor (GIST) were extracted. Hazard ratio (HR) and 95% confidence interval (CI) were used for in the meta-analysis. RESULTS A total of 12 articles were included in the study, including 2781 patients with GIST, including 845 patients with gastrointestinal bleeding. The OS of GIST patients with gastrointestinal bleeding was significantly worse (HR = 2.54, 95% CI = 1.13-5.73, P = 0.025). But there was no significant difference in RFS between gastrointestinal bleeding patients and non-bleeding patients (HR = 1.35, 95% CI = 0.70-2.61, P = 0.371). Further analysis of the related factors of GI bleeding in GIST patients was observed, besides the aging factor (HR = 1.02, 95% CI = 0.69-1.50, P = 0.929), Small intestinal stromal tumor (HR = 0.56, 95% CI = 0.41-0.76, P < 0.001), tumor diameter ≥ 5 cm (HR = 2.09, 95% CI = 1.20-3.63, P = 0.009), Mitotic index ≥ 5/50 HPF (HR = 1.66, 95% CI = 1.11-2.49, P = 0.014) and tumor rupture (HR = 2.04, 95% CI = 1.0-3.82, P = 0.026) all increased the risk of GI bleeding in patients with GIST. CONCLUSIONS The OS of GIST patients with GI bleeding was worse than non-GI bleeding, but had no significant effect on RFS. Nevertheless the aging factor, the location of GIST in the small intestine, tumor diameter ≥ 5 cm, Mitotic index ≥ 5/50 HPF and tumor rupture all increased the risk of GI bleeding in patients with GIST.

Abstract

BACKGROUND Despite common use in clinical practice, the impact of blood transfusions on prognosis among patients with lung cancer remains unclear. The purpose of the current study is to perform an updated systematic review and meta-analysis to evaluate the influence of blood transfusions on survival outcomes of lung cancer patients. METHODS We searched PubMed, Embase, Cochrane Library, and Ovid MEDLINE for publications illustrating the association between blood transfusions and prognosis among people with lung cancer from inception to November 2019. Overall survival (OS) and disease-free survival (DFS) were the outcomes of interest. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were computed using the random-effects model. Study heterogeneity was evaluated with the I(2) test. Publication bias was explored via funnel plot and trim-and-fill analyses. RESULTS We included 23 cohort studies with 12,175 patients (3,027 cases and 9,148 controls) for meta-analysis. Among these records, 22 studies investigated the effect of perioperative transfusions, while one examined that of transfusions during chemotherapy. Two studies suggested the possible dose-dependent effect in accordance with the number of transfused units. In pooled analyses, blood transfusions deleteriously influenced both OS (HR=1.35, 95% CI: 1.14-1.61, P<0.001, I(2)=0%) and DFS (HR=1.46, 95% CI: 1.15-1.86, P=0.001, I(2)=0%) of people with lung cancer. No evidence of significant publication bias was detected in funnel plot and trim-and-fill analyses (OS: HR=1.26, 95% CI: 1.07-1.49, P=0.006; DFS: HR=1.35, 95% CI: 1.08-1.69, P=0.008). CONCLUSIONS Blood transfusions were associated with decreased survival of patients with lung cancer.

Abstract

BACKGROUND To evaluate the efficacy and safety of recombinant human serum albumin /granulocyte colony-stimulating factor (rHSA/G-CSF) in breast cancer following receipt of cytotoxic agents. METHODS The phase 1b trial assessed the pharmacokinetics, pharmacodynamics, and safety of dose-escalation, ranging from rHSA/G-CSF 1800 μg, 2100 μg, and 2400 μg. Randomized controlled phase 2b trial was further conducted to ensure the comparative efficacy and safety of rHSA/G-CSF 2400 μg and rhG-CSF 5 μg/kg. In multicenter, randomized, open-label, parallel, phase 2 study, participants treated with anthracycline-containing chemotherapy were assigned in a ratio 1:1:1 to receive double delivery of rHSA/G-CSF 1200 μg, 1500 μg, and continuous rhG-CSF 5 μg/kg. RESULTS Between December 16, 2014, to July 23, 2018, a total of 320 patients were enrolled, including 25 individuals in phase 1b trial, 80 patients in phase 2b trial, and 215 participants in phase 2 study. The mean duration of agranulocytosis during the first chemotherapeutic intermission was observed as 1.14 ± 1.35 days in rHSA/G-CSF 1500 μg, which was comparable with that of 1.07 ± 0.97 days obtained in rhG-CSF control (P = 0.71). Safety profiles were assessed to be acceptable ranging from rHSA/G-CSF 1800 μg to 2400 μg, while the double delivery of HSA/G-CSF 2400 μg failed to meet the noninferiority in comparison with rhG-CSF. CONCLUSION The prospective randomized controlled trials demonstrated that rHSA/G-CSF was efficacious and well-tolerated with an approachable frequency and expense of application for prophylactic management of agranulocytosis. The double delivery of rHSA/G-CSF 1500 μg in comparisons with paralleling G-CSF preparations is warranted in the phase 3 trial. TRIAL REGISTRATION ClinicalTrials.gov identifiers: NCT02465801 (11/17/2014), NCT03246009 (08/08/2017), NCT03251768 (08/07/2017).

Abstract

More than 40 tyrosine kinase inhibitors (TKIs) have received hematological or oncological indications over the past 20 years, following the approval of imatinib, and many others are currently being tested in clinical and preclinical level. Beyond their common toxicities, no certain agent from this large class of molecularly targeted therapies was strongly associated with "off-target" impairment of neuromuscular transmission, and although myasthenia gravis (MG) is a well-characterized autoimmune disorder, only few sporadic events proven by serologically detected causative autoantibodies and/or by positive electrophysiological tests are reported in the literature. Herein, we present the first case of anti-MUSK (+) MG in a woman with metastatic BRAF-mutant melanoma after long-term treatment with dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor). Triggered by this report, a systematic literature review was conducted, summarizing all other cancer cases that developed MG, after exposure to any type of targeted agent and regardless of the underlying malignancy. All available data on the clinical diagnosis, the potential of administered TKIs to induce a seropositive myasthenic syndrome, the immune and non-immune-mediated pathogenesis of postsynaptic damage, and the challenging management of this neuromuscular toxicity were collected and discussed. In the presented case, MG was confirmed by both autoantibodies and nerve-conduction tests, while its reactivation after TKIs rechallenge supports a more than coincidental association. The following review identified 12 cancer cases with TKI-related MG in six case reports and one case series. In most of them, the myasthenia diagnosis was challenging, since the clinical symptomatology of fatigable weakness was not corroborating with consistent laboratory and electrophysiological findings. In fact, anti-AchR titers were positive in five and anti-MuSK only in the abovementioned individual. The symptomatology corresponded to TKI discontinuation and standard treatment with pyridostigmine and prednisolone; intravenous immunoglobulin was added only in three, and two required mechanical ventilation. In an era where TKIs will be prescribed more frequently for various malignancies, even in combinations with immune-checkpoint inhibitors, this report synthesizes their risk for neuromuscular complications and increases the clinicians' awareness in order to extend the on-treatment and overall survival of TKI-treated cancer patients.

Abstract

BACKGROUND The high proportion of blood transfusions before and during surgery carries unnecessary risk and results in poor prognosis in colorectal cancer patients. Different pharmacological interventions (i.e., iron supplement or recombinant erythropoietin) to reduce blood transfusion rates have shown inconclusive results. METHODS This network meta-analysis (NMA) consisted of randomized controlled trials (RCTs) comparing the efficacy of different pharmacologic interventions (i.e., iron supplementation or recombinant erythropoietin) to reduce the blood transfusion rate. NMA statistics were conducted using the frequentist model. Results: Seven RCTs (688 participants) were included in this study. The NMA demonstrated that the combination of high-dose recombinant human erythropoietin and oral iron supplements was associated with the least probability of receiving a blood transfusion [odds ratio = 0.24, 95% confidence intervals (95% CIs): 0.08 to 0.73] and best reduced the amount of blood transfused if blood transfusion was necessary (mean difference = -2.62 U, 95% CI: -3.55 to -1.70 U) when compared to the placebo/control group. None of the investigated interventions were associated with any significantly different dropout rate compared to the placebo/control group. CONCLUSIONS The combination of high-dose recombinant human erythropoietin and oral iron supplements might be considered as a choice for reducing the rate of blood transfusion in patients with colorectal cancer. However, future large-scale RCT with long-term follow-up should be warranted to approve the long-term safety.

Abstract

BACKGROUND Chemotherapy plus granulocyte colony-stimulating factor (GCSF) regimen is one of the available approaches to mobilize peripheral blood progenitor cells (PBPCs). It causes thrombocytopenia and delays leukapheresis. This study aimed to evaluate the role of recombinant human thrombopoietin (rhTPO) before mobilization chemotherapy in facilitating leukapheresis in patients with lymphoma. METHODS In this randomized open-label phase 2 trial, patients were randomly assigned in a 1:2 ratio to receive mobilization with rhTPO plus GCSF in combination with chemotherapy (the rhTPO plus GCSF arm) or GCSF alone in combination with chemotherapy (the GCSF alone arm). The recovery of neutrophils and platelets and the amount of platelet transfusion were monitored. RESULTS Thirty patients were enrolled in this study between March 2016 and August 2018. Patients in the rhTPO plus GCSF arm (n = 10) had similar platelet nadir after mobilization chemotherapy (P=0.878) and similar amount of platelet transfusion (median 0 vs. 1 unit, P=0.735) when compared with the GCSF alone arm (n = 20). On the day of leukapheresis, the median platelet count was 86 × 10(9)/L (range 18-219) among patients who received rhTPO and 73 × 10(9)/L (range 42-197) among those who received GCSF alone (P=0.982). After the use of rhTPO, the incidence of platelet count <75 × 10(9)/L on the day of leukapheresis did not decrease significantly (30.0% vs. 50.0%, P=0.297). Platelet recovery after PBPC transfusion was more rapid in the rhTPO plus GCSF arm (median 8.0 days [95% confidence interval 2.9-13.1] to platelets ≥50 × 10(9)/L vs. 11.0 days [95% confidence interval 8.6-13.4], P=0.011). The estimated total cost of the mobilization and reconstitution phases per patient was similar between the two treatmtent groups (P=0.362 and P=0.067, respectively). CONCLUSIONS Our findings indicate that there was no significant clinical benefit of rhTPO use in facilitating mobilization of progenitor cells, but it may promote platelet recovery in the reconstitution phase after high-dose therapy. TRIAL REGISTRATION This trial has been registered in Clinicaltrials.gov as NCT03014102.

Abstract

INTRODUCTION AND IMPORTANCE Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by increased platelet count and a high risk of bleeding or thrombotic events due to platelet dysfunction. Patients with ET are treated according to their risk of complications with cytoreductive or anti-aggregant treatment. Neither guidelines for oncologic patients nor perioperative management of patients with ET have been determined. CASE PRESENTATION A 41-year-old female patient with ET who had alternating constipation and diarrhea was referred after a screening colonoscopy diagnosing a locally advanced rectosigmoid junction colon adenocarcinoma with liver metastases. Systemic preoperative chemotherapy was indicated. The patient underwent laparoscopic low anterior resection plus volume-preserving right lobectomy of the liver. Postoperative bleeding of the internal iliac artery (IIA) associated with hematoma at the lower pelvic cavity was diagnosed and treated by interventional radiology; the patient was discharged without other complications 16 days after surgery. CLINICAL DISCUSSION ET has been related to the development of hematologic complications or second non-hematologic malignancies. A systematic review was conducted to seek guidance for the management of such patients in the perioperative period. Special perioperative care must be taken, and complications management should avoid further hemorrhages or cloth formation. CONCLUSION Under oncologic and hematological guidance, minimally invasive surgery and non-invasive management of complications are advised in the lack of published perioperative management guidelines of ET patients with colorectal cancer.

Abstract

Background: Nanoparticle albumin-bound paclitaxel (nab-PTX) has exhibited clinical efficacy in breast cancer treatment, but toxicities can be yielded more at the same time. We did this meta-analysis aiming to unambiguously compare nab-PTX with conventional solvent-based paclitaxel (sb-PTX) in breast cancer patients of all stages. Method: Pubmed, Embase and Cochrane Library were searched for head-to-head randomized controlled trials of nab-PTX and sb-PTX in breast cancer. Risk ratio (RR) with 95% confidence interval was used for dichotomous variables while Hazard ratio (HR) was used for time-to-event outcomes. Results: Our review finally included 9 studies with 3508 patients. Nab-PTX showed a benefit on objective response rate (ORR) (RR=1.22 [1.04-1.43], P=0.01) as well as non-inferiority compared with sb-PTX in disease control rate (DCR) (RR=1.01 [0.98-1.04], P=0.44), overall survival (OS) (HR=0.99 [0.93-1.05], P=0.81) and disease free survival/progression free survival (DFS/PFS) (HR=0.92 [0.81-1.05], P=0.21). However, when it comes to toxicities (fatigue, nausea or vomiting, peripheral sensory neuropathy and adverse event related discontinuation), results favored sb-PTX (RR=2.89 [1.07-7.8], 3.15 [1.78-5.59], 2.11 [1.32-3.37], 2.02 [1.61-2.53]; P<0.05). Patients with metastatic tumors or undergoing conventional schedule responses better to nab-PTX than the compared groups (RR of ORR in metastatic vs early or locally advanced patients: 1.46 [1.09-1.96] vs 1.01 [0.94-1.08]; conventional vs dose dense group: 1.59 [1.23-2.06] vs 1.01 [0.91-1.12]). Conclusions: Nab-PTX can improve ORR compared with paclitaxel and should be given priority to when aiming to reduce tumor load in breast cancer. Sb-PTX of dose dense schedule is recommended when toxicity of nab-PTX is hard to bear for breast cancer patients.