Respiratory Failure in Cancer Patients: Non-Infectious Complications of Antineoplastic Agents for Solid Tumors

2528 Background: Chimeric antigen receptor (CAR) T cell therapy has made significant progress in the treatment of blood cancers such as leukemia, lymphoma, and myeloma. However, the therapy faces many challenges in treating solid tumors. These challenges include physical barriers, tumor microenvironment immunosuppression, tumor heterogeneity, target specificity, and limited expansion in vivo. Methods: We designed a CAR lentivirus vector that consisted of a humanized CD19-specific single-chain variable fragment (scFv), a 4-1BB costimulatory domain, and a CD3ζ signaling domain.The lentivirus was produced by transfecting HEK-293T cells with CAR lentiviral vectors and viral packaging plasmids. Patient’s CD3 T cells was cultured in X-VIVO medium containing 125U/mL 1interleukin-2 (IL-2), and transduced with CAR lentivirus at certain MOI 24h after stimulated by anti-CD3/CD28 magnetic beads. Transduction efficiency was evaluated at 7 to 9 days after CAR lentivirus transduction, and quality controls for fungi, bacteria, mycoplasma, chlamydia, and endotoxin were performed. After infusion, serial peripheral blood samples were collected, and the expansion and the cytokine release of CART cells were detected by FACS and QPCR,respectively. The evaluation of response level for patients were performed at month 1,month 3,and month 6 by PET/CT. Results: We engineered CoupledCAR T cells with lentiviral vectors encoding an anti-GCC (guanylate cyclase 2C) CAR molecule. To verify the safety and efficacy of CoupledCAR-T cells for treating solid tumors, we conducted several clinical trials for different solid tumors, including seven patients with colorectal cancer. These seven patients failed multiple rounds of chemotherapy and radiotherapy. In the clinical trial, the metastatic colorectal cancer patients were infused with autologous anti-GCC CoupledCAR-T cells range from 4.9×105/kg to 2.9×106/kg. We observed that CoupledCAR-T cells expanded significantly in the patients and infiltrated tumor tissue sites, demonstrating enhanced anti-tumor activities. PET/CT showed significant tumor shrinkage and SUV max declined, and the ongoing responses were monitored. Patient 3 achieved complete response and the best overall response rate (ORR, include complete remission, complete metabolic response, and partial response.) was 57.1% (4/7), complete remission (CR) rate was 14.3% (1/7). Conclusions: In conclusion, the clinical data demonstrated that CoupledCAR-T cells effectively expanded, infiltrated tumor tissue sites, and kill tumor cells in patients with colorectal cancer. We used immunotherapy to achieve complete remission in patients with advanced colorectal cancer for the first time. We are recruiting more colorectal cancer patients to further test the safety and efficacy of anti-GCC CoupledCAR T cells. Since our CoupledCAR technology is a platform technology, we are expanding it to treat other solid tumors using different target tumor markers.

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P012: Mortality rate of cancer patients by type presenting to the intensive care unit with sepsis.

CJEM ◽

10.1017/cem.2019.203 ◽

2019 ◽

Vol 21 (S1) ◽

pp. S67

Author(s):

S. Beckett ◽

E. Karreman ◽

R. Hughes

Keyword(s):

Logistic Regression ◽

Intensive Care ◽

Mortality Rate ◽

Cancer Patients ◽

Solid Tumors ◽

Predictive Factors ◽

Poor Prognosis ◽

Solid Tumours ◽

Icu Mortality ◽

Icu Admission

Introduction: Sepsis in cancer patients is associated with higher mortality rates than non-cancer patients. As a whole, hematological or solid tumor cancers have not demonstrated a prognostic link to sepsis survival rates in intensive care units (ICU), however poor-prognosis solid tumours (less than 25% 5-year survival) have not been investigated. This study examined ICU mortality rate and its predictive factors of patients with sepsis and poor-prognosis solid tumors in comparison to patients with higher prognosis solid tumours. Methods: A 6-year retrospective chart review of 79 patients with sepsis and solid tumour cancers and/or metastatic cancers admitted to the ICU was conducted. Information regarding mortality rate within 14 days, length of ICU stay, incidence of intubation, and other primary reasons for ICU admission was collected. Data was analysed using logistic regression. Results: Logistic regression results showed intubation as the only significant factor contributing to patient mortality (p < .001), with the odds of mortality being 12.3 times higher for intubated than non-intubated patients. Five-year cancer survival rate was the second best predictor (p = .082), while age, sex, and metastasis were also not significant predictive factors for survival. Intubated patients with poor prognosis cancers had the lowest survival chance as further indicated by the 16 patients who met this criterion, of which 14 died within two weeks of ICU admission. Conclusion: The fact that poor prognosis cancers in sepsis were not significantly predictive of ICU mortality supports current literature regarding solid tumors in general, while intubation being a significant predictor for mortality in patients with sepsis and cancer regardless of type builds on previous research. A limitation of this study is the relative low number of included cases with poor-prognosis cancer types. Further evaluation is needed to understand the implications of our results for end-of-life care and ICU admission for patients with these characteristics.

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A study on cancer pain and sleep parameters of cancer patıents: Hydromorphone Hydrochloride

Journal of Human Sciences ◽

10.14687/jhs.v14i4.4443 ◽

2017 ◽

Vol 14 (4) ◽

pp. 4149

Author(s):

Hayriye Baltaoğlu Alp

Keyword(s):

Respiratory Failure ◽

Side Effects ◽

Cancer Pain ◽

Sleep Disorder ◽

Cancer Patients ◽

Shortness Of Breath ◽

Sleep Parameters

The ratio of painless sleep was 80% in our study.26 (52%) of the patients showed no side effects, while 10 (20%) had nausea and 6 (12%) had constipation. 8 (16%) of the patients were found to have other side effects. The frequency of those side effects was nausea, constipation, dizziness, vomiting, respiratory failure and diarrhea respectively.[table 4]Hydromorphone hydrochloride helped to eliminate sleep disorder, shortness of breath and snoring and relatively improved amount of sleep and adequacy of sleep. It was found that 90% of our patients were able to fall asleep in 1-5 minutes; however 82% did not have enough amount of sleep. 78% of patients had no feeling of dizziness during the day; 82% did not have shortness of breath; 80% reported that they slept without pain, while 41% reported that they did not sleep at all.

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INFECTIOUS COMPLICATIONS CAUSED BY NON-SPOREFORMING ANAEROBIC BACTERIA IN CANCER PATIENTS. RELEVANCE OF THE PROBLEM

Siberian Journal of Oncology ◽

10.21294/1814-4861-2020-19-4-146-151 ◽

2020 ◽

Vol 19 (4) ◽

pp. 146-151

Author(s):

I. V. Tereshchenko ◽

Z. V. Grigoryevskaya ◽

I. N. Petukhova ◽

N. S. Bagirova ◽

V. D. Vinnikova ◽

...

Keyword(s):

Cancer Patients ◽

Anaerobic Bacteria ◽

Infectious Complications

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The Optimal Time of Applying Enteral Immunonutrition in Esophageal Cancer Patients Receiving Esophagectomy: A Network Meta-Analysis of Randomized Clinical Trials

10.21203/rs.3.rs-235527/v1 ◽

2021 ◽

Author(s):

Xu Tian ◽

Yan-Fei Jin ◽

Zhao-Li Zhang ◽

Hui Chen ◽

Wei-Qing Chen ◽

...

Keyword(s):

Esophageal Cancer ◽

Cancer Patients ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Infectious Complications ◽

Cochrane Library ◽

Optimal Time ◽

Registration Number ◽

Meta Analyses ◽

The Impact

Abstract Background: Enteral immunonutrition (EIN) has been extensively applied in cancer patients, however its role in esophageal cancer (EC) patients receiving esophagectomy remains unclear. We performed this network meta-analysis to investigate the impact of EIN on patients undergoing surgery for EC and further determine the optimal time of applying EIN.Methods: We searched PubMed, EMBASE, Cochrane library, and China National Knowledgement Infrastructure (CNKI) to identify eligible studies. Categorical data was expressed as the odds ratio with 95% confidence interval (CI), and continuous data was expressed as mean difference (MD) with 95% CI. Pair-wise and network meta-analysis was performed to evaluate the impact of EIN on clinical outcomes using RevMan 5.3 and ADDIS V.1.16.8 softwares. The surface under the cumulative ranking curve (SUCRA) was calculated to rank all nutritional regimes.Results: Total 14 studies involving 1071 patients were included. Pair-wise meta-analysis indicated no difference between EIN regardless of the application time and standard EN (SEN), however subgroup analyses found that postoperative EIN was associated with decreased incidence of total infectious complications (OR=0.47; 95%CI=0.26 to 0.84; p=0.01) and pneumonia (OR=0.47; 95%CI=0.25 to 0.90; p=0.02) and shortened LOH (MD=-1.01; 95%CI=-1.44 to -0.57; p<0.001) compared to SEN, which were all supported by network meta-analyses. Ranking probability analysis further indicated that postoperative EIN has the highest probability of being the optimal option in terms of these three outcomes.Conclusions: Postoperative EIN should be preferentially utilized in EC patients undergoing esophagectomy because it has optimal potential of decreasing the risk of total infectious complications and pneumonia and shortening LOH.OSF registration number: 10.17605/OSF.IO/KJ9UY.

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Acute Non-Infectious Complications of Pediatric Hematopoietic Stem Cell Transplantation: An in-Hospital Nationwide Study in the United States from 2001-2019

Blood ◽

10.1182/blood-2020-139715 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 32-32

Author(s):

Maria Alejandra Pereda ◽

Sindhoosha Malay ◽

Jignesh Dalal

Keyword(s):

Mechanical Ventilation ◽

Logistic Regression ◽

Stem Cell ◽

Respiratory Failure ◽

Hematopoietic Stem Cell Transplantation ◽

Infectious Complications ◽

P Value ◽

Early Complications ◽

Hematopoietic Stem ◽

Icu Admission

Introduction Hematopoietic stem cell transplantation (HSCT) is an effective treatment for malignant and non-malignant disorders and may be the only curative option for some diseases. Although overall outcomes of HSCT in pediatrics have improved HSCT is still associated with high morbidity and mortality. Toxicity following HSCT can virtually affect any organ and occur at different steps in the process. Early complications are to occur in the first 100 days post transplant. In this study we aimed to describe the frequency of early complications following HSCT and possible risk factors associated with increased ICU care and mortality. Methods With IRB approval, the Pediatric Health Information Systems (PHIS) database was queried to analyze information of all HSCT performed admitted between January 2001 and December 2019. The PHIS database is a comprehensive pediatric database that includes inpatient encounters for more than 52 children's hospitals. We extracted relevant ICD-9 and 10 diagnoses, procedure codes, and medications for each patient related to toxicities as outlined by the NCI. For Sinusoidal obstructive syndrome, graft failure and posterior reversible encephalopathy syndrome only ICD 10 code were reported. Clinical characteristics, demographics, procedures and medication of patients were presented using frequency and percentages for categorical variables with a Chi-square p-value (comparisons by ICU admission and Mortality). Univariate and multivariate logistic regression was performed with 'discharge mortality' and 'ICU admission' as primary outcomes. P-value of less than 0.05 or absence of 1 in the 95% confidence intervals was considered statistically significant. All statistical analyses were performed using SAS software, version 9.4 (SAS Institute, Cary, NC) and R software, version 4.0.0. Results A total of 13,538 patients met primary inclusion criteria of HSCT. Of these 6,938 transplants (51.2%) were performed to treat a malignant condition. 95.4% of these transplants were allogeneic and most of them performed within 2011 to 2019 (63.4%). Adolescents and Young adults accounted for 18.3% of patients and 8% of all HSCT patients passed away. The most common conditioning regimen reported was Busulfan and Cyclophosphamide (21.04%) and the most used GVHD prophylaxis was Methotrexate and Tacrolimus (21.1%). Common complications reported were acute kidney injury (14%), respiratory failure (12.8%) and acute GVHD (10%). From the patients that developed respiratory failure 90.5% were in the ICU, 80.9% required Mechanical ventilation and 49.6% died. 239 patients developed sinusoidal obstructive syndrome with 67.4% requiring ICU and 20.5% mortality. Defibrotide was used in 60.3% of these patients. Table 1 and 2 describe our findings and statistically significant results for ICU admission and discharge mortality. Logistic regression and multivariate analysis showed increased ICU admission and discharge mortality in AYA patients (OR 1.36, CI 1.20-1.53, p<.0001 and OR 1.29, CI 1.03-1.64, p<0.03, respectively). From 2009 to 2019 there is an increased OR for ICU admission post HSCT but significant decreased in discharge mortality. Mechanical ventilation was the strongest predictor for ICU admission and discharge mortality (OR 44.81, CI = 37.19-53.99, p<.0001 and OR 31.23, CI = 23.57 - 41.38, p<.0001, respectively), followed by dialysis (OR 5.74, CI = 3.98-8.27, p<.0001 and OR 5.82, CI = 4.62-7.32, p<.0001). Patients diagnosed with sinusoidal obstructive syndrome had 3.2 times OR for ICU (CI = 2.29-4.57, p<.0001) but decreased OR for mortality (OR 0.62, CI 0.39-0.98, p=0.038). SCID and Mucopolysaccharidosis patients had increased OR for ICU admission but not for discharge mortality. Conclusion To our knowledge this is the largest multicenter database analysis describing acute non-infectious complications of pediatric HSCT. Survival of HSCT patients that developed SOS have improved since 2016 which may be reflecting the introduction of Defibrotide. Mechanical ventilation was the strongest predictor for mortality with almost 30 times increased in odds ratio. Mucopolysaccharidosis and SCID showed increased need for ICU care but decreased mortality suggesting improvement in intensive care unit management. Prospective studies are needed to better describe outcomes of HSCT patients as well as areas of possible improvement to increase overall survival. Disclosures No relevant conflicts of interest to declare.

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