Blinatumomab Therapy Is Associated with Favorable Outcomes after Allogeneic Hematopoietic Cell Transplantation in Pediatric Patients with B Cell Acute Lymphoblastic Leukemia.

Blinatumomab, a bispecific T cell engager that binds CD19 in leukemic cells and CD3 in cytotoxic T cells and leads to leukemic blast lysis, is often used in pediatric patients with relapsed/refractory (R/R) B cell acute lymphoblastic leukemia (B-ALL) prior to allogeneic hematopoietic cell transplantation (allo-HCT). Concerns about the potential risk of blinatumomab-related immune-mediated toxicities after allo-HCT have not been adequately addressed. These include graft-versus-host disease (GVHD), delayed engraftment, and graft failure or rejection. Pediatric-specific data reporting post-HCT outcomes of patients treated with blinatumomab are scarce and limited to small cohorts. We sought to investigate the clinical outcomes of pediatric patients with R/R B-ALL who received blinatumomab therapy pre-HCT, focusing on overall survival (OS), leukemia-free survival (LFS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM), as well as the incidence of immune-mediated post-HCT complications including GVHD, delayed neutrophil or platelet engraftment, graft failure, and graft rejection. We also investigated blinatumomab's effects on B cell reconstitution based on achievement of i.v. immunoglobulin (IVIG) independence post-HCT. This single-center, retrospective study included patients with B-ALL receiving blinatumomab therapy before undergoing allo-HCT, with transplantation performed between 2016 and 2021 at our institution. Patients receiving blinatumomab for relapse after allo-HCT were excluded. Patients receiving chemotherapy alone before allo-HCT during the same period composed the control group. Seventy-two patients were included, 31 of whom received blinatumomab before allo-HCT. Survival estimates were obtained using the Kaplan-Meier method, and the log-rank test was used to analyze differences between groups. Categorical variables were compared between groups using the chi-square test or Fisher exact test, and continuous variables were compared using the Wilcoxon rank-sum test. Cumulative incidences were estimated using the competing risks method, and Gray's test was used to analyze differences between groups. A Cox proportional hazards regression model was used for univariate and multivariable analyses for OS. Landmark analysis was performed at the set time points of 30 days and 100 days post-allo-HCT. Most patients in the study cohort had high-risk relapsed B-ALL. Blinatumomab therapy induced minimal residual disease (MRD)-negative remissions in all patients, whereas 5 patients (12.2%) receiving chemotherapy alone had persistent MRD pre-allo-HCT. Time from the start of therapy to the date of allo-HCT was shorter for patients who received blinatumomab compared with those who received chemotherapy (P < .0001). Blinatumomab therapy was associated with greater LFS compared to chemotherapy alone (P = .049), but when limited to 1 year, LFS was not significantly different from control (P = .066). There appeared to be higher OS, lower CIR, and lower NRM in patients receiving blinatumomab compared to the control group; however, the differences were not significant. None of the variables assessed in multivariable analysis was associated with differences in OS. When compared to the controls, blinatumomab therapy did not result in a higher incidence of acute or chronic GVHD, delayed neutrophil or platelet engraftment, or graft failure or rejection. The time to IVIG infusion independence post-allo-HCT was similar in the 2 groups. This study supports the use of blinatumomab salvage therapy for R/R B-ALL before allo-HCT given its efficacy in inducing MRD-negative remissions and optimizing LFS, as well as its lack of association with an increased incidence of post-allo-HCT adverse immune-mediated toxicities. Larger, prospective studies are needed to confirm these findings and to investigate blinatumomab's effects in long-term post-allo-HCT events.

Hematopoietic stem cell transplantation for B-thalassemia major with alemtuzumab.

While matched related donor (MRD) allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option for transfusion-dependent beta-thalassemia (TDT), the use of alternative sources has increased, resulting in the exploration of novel transplant-conditioning regimens to reduce the contribution of graft-versus-host disease (GVHD) and graft failure (GF) to transplant-related morbidity and mortality. Alemtuzumab is a CD52 monoclonal antibody that has been successfully incorporated into myeloablative conditioning regimens for other hematologic conditions, yet there have been limited studies regarding the use of alemtuzumab in HSCT for TDT. The purpose of this study was to evaluate engraftment, incidence of GVHD, and transplant related morbidity and mortality in patients with TDT who received alemtuzumab in addition to standard busulfan-based conditioning. The primary endpoint was severe GVHD-free, event-free survival (GEFS). Our cohort included 24 patients with a median age of 6.8 years (range 1.5-14.9). Eleven patients received a 10/10 MRD HSCT, eleven 10/10 unrelated donor (UD), and two mismatched UD. All patients achieved primary engraftment. For all patients, 5-year GEFS was 77.4% and 5-year overall survival (OS) was 91%. The 5-year cumulative incidence of GF (attributed to poor graft function) without loss of donor chimerism was 13.8% (95% CI: 4.5, 35.3). We report low rates of significant acute GVHD grade II-IV (12.5%) and chronic GVHD (4.4%). Younger age and MRD were associated with significantly improved GEFS, OS and EFS. Our results show that the use of alemtuzumab promotes stable engraftment, may reduce rates of severe GVHD, and results in acceptable GEFS, OS, and EFS.

Cord blood transplantation for nonmalignant disorders: early functional immunity and high survival.

There is no consensus on the best donor for children with nonmalignant disorders and immune deficiencies in the absence of a matched related donor (MRD). We evaluated the 2-year overall survival (OS) after umbilical cord blood transplantation (UCBT) in patients with nonmalignant disorders from 2009 to 2020 enrolled in a prospective clinical trial using either 5/6 or 6/6 UCB as the cell source. Patients receive a fully ablative busulfan, cyclophosphamide, and fludarabine without serotherapy. Fifty-five children were enrolled, median age 5 months (range, 1-111 months); primary immune deficiency (45), metabolic (5), hemophagocytic lymphohistiocytosis (1), and hematologic disorders (4). Twenty-six patients had persistent infections before transplant. Nineteen of them (34%) were 6/6 matched, and 36 (66%) were 5/6 human leukocyte antigen-matched. The OS at 2 years was 91% (95% cumulative incidence, 79-96), with a median follow-up of 4.3 years. The median time to neutrophil and platelet recovery were 17 days (range, 5-39 days) and 37 days (range, 20-92 days), respectively. All but one evaluable patient achieved full donor chimerism. The cumulative incidence of acute GVHD grades 2-4 on day 100 was 16% (n = 9). All patients with viral infections at the time of transplant cleared the infection at a median time of 54 days (range, 44-91 days). All evaluable patients underwent correction of their immune or metabolic defects. We conclude that in the absence of MRD, UCBT following myeloablative conditioning without serotherapy is an excellent curative option in young children with nonmalignant disorders. This trial has been registered at www.clinicaltrials.gov as NCT00950846.

Chlorhexidine gluconate (CHG) foam improves adherence, satisfaction, and maintains central line associated infection rates compared to CHG wipes in pediatric hematology-oncology and bone marrow transplant patients.

CHG-based hygiene methods are often a component of daily hygiene bundles to prevent central line-associated blood stream infections (CLABSIs) in pediatric hematology-oncology patients; however, adherence with 2% CHG wipes was inconsistent within our institution, risking infection for immunocompromised patients. A new 4% CHG foam method offers an alternative and is applied while bathing, as opposed to wipes used 1 h after bathing. An initial cohort of 24 high-risk oncology and bone marrow transplant (BMT) patients agreed to use 4% CHG foam in place of wipes, and then answered surveys to describe their experiences. Ninety-two percent preferred foam over wipes and were more likely to use the foam moving forward. CHG foam was then made available as an option to all patients in need of central line care upon admission to the hospital. Hygiene bundles in the electronic medical record were reviewed to measure baseline adherence rates. Random audits by nursing administration prospectively assessed CHG adherence. CLABSI data were collected prospectively with routine quality metric reports. Results were analyzed using run charts and u-charts, respectively. Hematology-Oncology unit adherence rates remained at a higher rate of adherence, and BMT unit adherence rates increased from an average of 55%-81.6% (p < 0.001). Primary CLABSIs remained rare events (average <1/1000 CVL days). On cost analysis, utilizing CHG foam results in an annual savings estimate of $40,000 for a 24-bed unit. In conclusion, 4% CHG foam provides a cost-effective and patient-preferred option for daily hygiene that maintains CLABSI preventative efforts.

A Novel Oncodental Collaborative Team: Integrating Expertise for Central Line-Associated Bloodstream Infection Prevention in Pediatric Oncology Patients.

PURPOSE: Pediatric oncology and bone marrow transplant patients are at high risk of infection, and limitations to dental expertise among medical providers render patients vulnerable to central line-associated bloodstream infections from oral pathogens. Traditionally, oral health maintenance relied on patients and bedside nurses; however, routine methods are often suboptimal to prevent central line-associated bloodstream infection in high-risk patients. Limited overlap of medical and dental expertise, and limited dental resources in typical oncology units, prevent optimal oral care for children with cancer, requiring novel solutions to better integrate specialties. METHODS: Here, we outline the creation of a novel Pediatric oncodental team to address oral-systemic infection prevention strategies for high-risk patients. RESULTS: Our oncology and dental teams created a systematic approach for increasing oral surveillance and treatment in select high-risk patients. Supervised pediatric dental residents participated in scheduled oncology rounds, and a permanent oral health educator with a background in dental hygiene was also hired as a dedicated dental professional within our oncology department. CONCLUSION: Our pediatric oncodental team aims to sustain optimal oral complication prevention strategies to reduce the risk of infection, provide education on the significance of the oral-systemic link in cancer care, and improve access and continuity of care.

Efficacy and safety of mesh closure in preventing wound failure following emergency laparotomy: a systematic review and meta-analysis.

AIMS: To evaluate comparative outcomes of emergency laparotomy closure with and without prophylactic mesh. METHODS: A systematic review was performed via literature databases: PubMed, Cochrane Library, Science Direct, and Google Scholar. Studies were examined for eligibility and included if they compared prophylactic mesh closure to the conventional laparotomy closure following emergency abdominal surgery. Both acute wound failure and incisional hernia (IH) occurence were our primary outcomes. Secondary outcomes included surgical site infection (SSI), seroma/hematoma formation, Clavien-Dindo complications (score ≥ 3), total operative time, and length of hospital stay (LOS). RESULTS: Two randomised controlled trials (RCTs) and four comparative studies with a total of 817 patients met the inclusion criteria. Overall acute wound failure and incisional hernia rate was significantly lower in the mesh group compared to non-mesh group (odd ratio (OR) 0.23, p = 0.002) and (OR 0.21, p = 0.00001), respectively. There was no significant difference between the two groups regarding the following outcomes: total operative time (mean difference (MD) 21.44, p = 0.15), SSI (OR 1.47, p = 0.06), seroma/haematoma formation (OR 2.74, p = 0.07), grade ≥ 3 Clavien-Dindo complications (OR 2.39, p = 0.28), and LOS (MD 0.26, p = 0.84). CONCLUSION: The current evidence for the use of prophylactic mesh in emergency laparotomy is diverse and obscure. Although the data trends towards a reduction in the incidence of IH, a reliable conclusion requires further high-quality RCTs to fully assess the efficacy and safety of mesh use in an emergency setting.

Delayed Adult Gastric Perforation Following Insertion of a Feeding Nasogastric Tube.

Although complications of a nasogastric tube (NGT) are identified and managed in daily clinical practice, gastric perforation following NGT insertion is a serious and rarely reported condition in adults. We present a case of a 71-year-old male who was brought to the hospital after having a cardiac arrest. Following stabilisation and receiving an emergency percutaneous coronary intervention (PCI), he was admitted to the intensive care unit (ICU), where he required NGT for feeding purposes. A few days later, abdominal distension was noted, and chest imaging was requested mainly for worsening respiratory parameters. A computed tomography (CT) scan confirmed gastric perforation and a misplaced NGT. Being a high-risk patient and in the absence of peritonism and frank sepsis, conservative management was adopted and included proton pump inhibitors (PPI), total parenteral nutrition (TPN), stomach aspiration via a Ryle tube and consideration of imaging-guided drainage. No risk factor for gastric perforation was identified in this presented case. The stable course of follow-up suggested sealed perforation; however, he died due to an extensive intracardiac thrombus. Though this incidence did not contribute directly to the patient's death, it definitely added to the overall morbidity and negatively influenced the management of the other medical conditions. For complement, we also report a review of the ten similar cases in the literature, highlighting the associated risk factors, relevant clinical challenges, lines of management executed. The main aim of this case report is to enhance doctors' awareness of this serious complication, especially in patients with risk factors, and its diagnostic dilemmas. Early recognition and prompt intervention are recommended for a better outcome.

Meta-analysis of transanal total mesorectal excision versus laparoscopic total mesorectal excision in management of rectal cancer.

OBJECTIVES: To evaluate comparative outcomes of transanal total mesorectal excision (TaTME) and laparoscopic TME (LaTME) in patients with rectal cancer. METHODS: We systematically searched multiple databases and bibliographic reference lists. A combination of free text and controlled vocabulary search adapted to thesaurus headings, search operators, and limits were applied. Overall intraoperative complications, overall postoperative complications, anastomotic leak, surgical site infections (SSIs), completeness of mesorectal excision, R0 resection, distal (DRM) and circumferential resection margin (CRM), number of harvested lymph nodes, and procedure time were the evaluated outcome parameters. RESULTS: We identified 18 comparative studies reporting a total of 2048 patients evaluating outcomes of TaTME (n = 1000) and LaTME (n = 1048) in patients with rectal cancer. TaTME was associated with significantly higher number of R0 resection (OR 1.67, P = 0.01) and harvested lymph nodes (MD 1.08, P = 0.01), and lower rate of positive CRM (OR 0.67, P = 0.04) and conversion to an open procedure (OR 0.17, P < 0.00001) compared with LaTME. However, there was no significant difference in intraoperative complications (OR 1.18, P = 0.54), postoperative complications (OR 0.89, P = 0.24), anastomotic leak (OR 0.88, P = 0.42), SSIs (OR 0.64, P = 0.26), completeness of mesorectal excision (OR 1.43, P = 0.19), DRM (MD 1.87, P = 0.16), CRM (MD 0.36, P = 0.58), and procedure time (MD - 10.87, P = 0.18) between TaTME and LaTME. Moreover, for low rectal tumours, TaTME was associated with significantly lower rate of anastomotic leak and higher number of lymph nodes (MD 2.06, P = 0.002). CONCLUSIONS: Although the meta-analysis of best available evidence (level 2) demonstrated that TaTME may be associated with better short-term oncological outcomes and similar clinical outcomes compared with LaTME, the differences between the two groups were small questioning their clinical relevance. No solid conclusions can be made due to lack of high quality randomised studies.

Adolescent and Young Adult Oral Maxillofacial Tumors: A Single-Institution Case Series and Literature Review.

Adolescent and young adult (AYA) oral maxillofacial tumors are rare and account for ∼12% of all AYA cancers. Due to the low incidence of these malignancies, diagnostic considerations, therapeutic approaches, and factors affecting prognosis have been difficult to characterize. Given the anatomic structures located within the head and neck, patients are at risk for treatment-related morbidity that may adversely impact their quality of life. We present a single-institution case series of AYA patients with oral maxillofacial tumors treated at the University of Illinois at Chicago. A multidisciplinary treatment approach, including collaboration with the Oral Maxillofacial Surgery, Dentistry, and the Ear, Nose, and Throat teams along with the utilization of Children's Oncology Group treatment protocols, can serve as a model to address the challenges in the management of these complex cases.

The Impact of Multiple Risk Factors for Venous Thromboembolism and Its Implications for Management.

Venous thromboembolism (VTE) is a rare multifactorial disorder in childhood with an annual incidence of about 0.07 to 0.14 per 10 000 children. A 15-year-old female with a body mass index of 48 kg/m2 who endorsed oral contraceptive use presented with clinical findings consistent with deep venous thrombosis along with the presence of a pulmonary embolism. Further workup revealed that the patient was heterozygous for factor V Leiden and homozygous for prothrombin G20210A mutations. There are no current pediatric guidelines for the antithrombotic management of patients with multiple risk factors for VTE. Two such risk factors, obesity and the use of estrogen-containing hormone contraceptives, have been implicated in adult VTE cases but have not been clearly delineated in pediatric patients. The need for guidance regarding the VTE management of these patients has become more apparent given the increasing incidence of childhood obesity and the number of adolescents using oral contraceptives. Additionally, thrombophilia testing remains controversial though testing may be indicated in asymptomatic first-degree relatives and in families with antithrombin, protein C, or protein S deficiencies. Given the increased incidence of multiple risk factors for VTE, there is also a need to develop a comprehensive risk assessment tool for pediatric patients at high risk of VTE.

Pilot study of propranolol premedication to reduce FDG uptake in brown adipose tissue on PET scans of adolescent and young adult oncology patients.

OBJECTIVE: Physiologic uptake of 18F-fluorodeoxyglucose (FDG) in brown adipose tissue (adipose tissue) of cancer patients may confound interpretation of positron emission tomography (PET) scans. Uptake in adipose tissue occurs in up to half of pediatric oncology patients undergoing PET scans, and is especially common in adolescents. adipose tissue is innervated by the sympathetic nervous system, and beta blockers such as propranolol have shown efficacy in reducing adipose tissue uptake on PET scans done in older adult oncology patients. PARTICIPANTS: Because propranolol may cause hypoglycemia or other side effects in fasting patients, we prospectively assessed the safety of a single dose of 20 mg propranolol in adolescent and young adult oncology patients undergoing FDG-PET imaging. METHODS: Ten patients (median age 18 years, range 14-24) received propranolol premedication prior to FDG-PET. RESULTS: No adverse effects or clinically significant changes in serum glucose, heart rate, or blood pressure were observed. Five of the 10 patients had adipose tissue identified on previous PET scans. However, following propranolol administration only, one patient had persistent uptake in adipose tissue. CONCLUSIONS: Propranolol was convenient and safe in fasting adolescent and young adult oncology patients undergoing PET scans. Larger studies are warranted to better define the effectiveness of this approach.

Orthostatic hypotension: definition, diagnosis and management.

Orthostatic hypotension commonly affects elderly patients and those suffering from diabetes mellitus and Parkinson's disease. It is a cause of significant morbidity in the affected patients. The goal of this review is to outline the pathophysiology, evaluation, and management of the patients suffering from orthostatic hypotension.