Abstract Background Cerebral sinus venous thrombosis (CSVT) is a rare but serious complication of childhood acute lymphoblastic leukemia (ALL) therapy. No available consensus exists regarding its risk factors and appropriate management due to the rarity of cases. Procedures Out of 209 ALL patients aged 1–21 years treated at the Children's Cancer Center of Lebanon between May 2002 and May 2015, 13 developed CSVT during therapy. Patient characteristics, clinical management, and outcomes were studied. Results The incidence of CSVT was 6.2% (95% confidence interval [CI]: 3.4–10.4). Using univariate analysis, increased risk of CSVT was observed with age >10 years (odds ratio [OR]: 3.56, 95% CI: 1.13–11.2), T‐cell immunophenotype (OR: 4.14, 95% CI: 1.16–14.7), and intermediate/high risk disease (OR: 3.4, 95% CI: 1.03–11.7). The only statistically significant risk factor by multivariate analysis was the treatment as per the intermediate‐/high‐risk protocol (HR: 15.6, 95% CI: 1.43–171.3). Most cases (77%) occurred in the postinduction phases of treatment while receiving a combination of asparaginase and dexamethasone rather than prednisone. Treatment with low molecular weight heparin (LMWH) for a minimum of 3 months and until significant radiological improvement is observed resulted in 100% survival rate. All but one patient had complete neurological recovery. Conclusions CSVT is an important complication of childhood ALL therapy. Postinduction combined asparaginase and dexamethasone intensive treatment for intermediate‐/high‐risk patients was the most important risk factor. Treatment with LMWH for a minimum of 3 months, and until asparginase therapy is over, with major radiological improvement seems to be effective and feasible.
Introduction: High rates of patients require readmission to the hospital within 6 months of hematopoietic stem cell transplantation (HSCT). We investigated the relationship between readmission rates and outcomes after HSCT in children, adolescents, and young adults (CAYA). Materials and Methods: A retrospective analysis of patients (26 years or younger) treated with HSCT was conducted. Results: A chart review of 435 CAYA who underwent HSCT from 2008 to 2015 revealed that 171 patients (39%) had at least 1 hospital readmission within 180 days of transplant; 87% received allogeneic and 13% received autologous HSCT. A total of 312 readmission events were reported. The median follow-up time was 31 months. Documented infection (n=99) and graft-versus-host disease complications (n=60) were the most common causes. Higher than 2 readmission rates were associated with lower overall survival (OS) ( P =0.001) and disease-free survival ( P <0.001) in patients who received allogeneic HSCT. These findings were not found in the autologous HSCT. In a multivariate analysis of those who received allogeneic HSCT, prior treatment with ≥2 chemotherapy regimens ( P =0.03) was independent predictor of lower OS. There were also trends noted toward lower OS for patients with documented infections at index admission or subsequent readmissions ( P =0.09). Conclusions: More than 2 hospital readmissions within 6 months of allogeneic HSCT in CAYA, who are either heavily pretreated or had documented infections at index admission or subsequent readmissions adversely affected the outcomes.
Background : Inadequate numbers of trained healthcare providers (HCPs), contribute to poor pediatric oncology (PO) outcomes, particularly in low- and lower middle–income countries (L/LMICs). An understanding of the characteristics of the workforce challenges are vital for addressing these problems. Methods : The Pediatric Oncology East and Mediterranean (POEM) Group surveyed PO centers in countries of the North Africa, Middle East, Central Asia and Indian subcontinent on infrastructure and workforce capacity, service availability, and training opportunities for HCPs. Participating centers were categorized by the World Bank income levels for their countries and correlated with services, workload and staffing characteristics, and training needs. Results : Fifty of 82 member-centers (61%) from 21 countries responded to the survey. 299 pediatric oncologists and 1,176 nurses treated 12,496 new PO patients/year, with a 1,451 beds utilization. The majority (71%) of new cases occurred in L/LMICs. The availability of HCPs correlated with country income level, as did pediatric subspecialty access, while availability of support services was unrelated. Twenty-five centers in 11 countries offered PO fellowship training for physicians, whereas 13 PO nurse training centers in 9 countries had the capacity to train 273 nurses annually. The survey respondents indicated that, among their existing workforce, an average of 3·5 physicians and 14 nurses per institution would benefit from additional PO training opportunities. Conclusions : The participating centers exhibited intra-regional heterogeneity in financial resources, infrastructure, workload, workforce, and medical services. Our findings provide insight into the disparities and regional resources available to POEM, which can be mobilized to rectify specific deficiencies. This article is protected by copyright. All rights reserved
Abstract Desmoplastic small round cell tumor (DSRCT) is a rare mesenchymal tumor that typically presents with multiple abdominal masses. Initial treatment is multimodal in nature. Patients with relapsed DSRCT have a poor prognosis, and there are no standard therapies. We report our experience with five patients treated with vinorelbine, cyclophosphamide, and temsirolimus (VCT). Median number of VCT courses delivered was 7 (range 4–14 courses), and partial response was observed in all patients. Median time to progression or relapse was 8.5 months (range 7–16 months). Neutropenia and mucositis were most common toxicities (n = 4 each).
Hematopoietic stem cell transplantation (HSCT) provides potential curative treatment for various benign and malignant conditions. However, there is a high rate of patients requiring readmission to the hospital within six months of transplantation. There is only limited literature evaluating risk factors and causes of readmission of children, adolescents and young adults (AYA) who underwent HSCT.
In HLA-matched T-cell depleted (TCD) HCT, recipients lacking class I ligands for donor inhibitory KIR have lower relapse and higher survival. The "missing ligand" effect on clinical outcome is likely due to temporary licensing post-transplant of the normally hyporesponsive NK cells expressing KIR for non-self HLA ligands. Because the KIR-expressing NK repertoire following HCT can be affected by T-cells in the allograft, we examined NK functional reconstitution in recipients of unmodified HCT. We assessed NK function in 10 patients following unmodified stem cell transplantation from an HLA-identical sibling or HLA-compatible unrelated donor. All patients received a myeloablative regimen and post-HSCT immunosuppression. Peripheral blood mononuclear cell (PBMC) samples were collected from donors and from recipients pre-transplant and at days 30, 60 and 200 post-transplant. Using multiparameter flow cytometric analysis, we evaluated intracellular IFN-γ production among inhibitory KIR-expressing NK subsets following activation with the class I-deficient 721.221 target cell line or with 721.221 transfectants expressing the KIR ligands HLA -Cw3, -Cw4, or -Bw4. Unlicensed NK cells expressing inhibitory KIR for non-self HLA were hyporesponsive in normal donors. In comparison, the same NK subsets in patients early post-HCT (days 15-60) demonstrated robust IFN-γ production to target cells lacking cognate class I ligand (p<0.001). As for TCD HCT, the temporary licensing effect of nonself-specific NK cells following T-replete HCT lasted for approximately 100 days, after which NK cells expressing KIR for non-self HLA returned to a hyporesponsive state. NK cells expressing inhibitory KIR for self-HLA remained unchanged in their responsiveness pre- and post-HCT. These findings contrasted with our previous results in recipients of T-cell depleted grafts where both licensed and unlicensed NK cells demonstrated increased functional activity early post SCT. KIR expression was generally delayed following T-replete HCT, with KIR2DL1 particularly lagging in expression beyond 100 days post-HCT. These results demonstrate that T-cells in the HCT allograft do not interfere with the temporary licensing effects on NK cells expressing inhibitory KIR for non-self HLA, which mediate NK alloreactivity in HLA-matched HCT.
Cerebral sinus venous thrombosis (CSVT) is one of the many side effects encountered during acute lymphoblastic leukemia (ALL) therapy. Due to the rarity of cases, lack of data, and consensus management, no recommendations exist to target the population at risk.This is a retrospective chart review of 229 consecutive patients diagnosed with ALL with an age range of 1-21 years, treated at the Children's Cancer Center of Lebanon between October 2007 and February 2018.The incidence of CSVT was 10.5%. Using univariate analysis, increased risk of CSVT was observed with male gender, age >10 years, T-cell immunophenotype, intermediate/high-risk disease, maximum triglyceride (TG) level of >615 mg/dl, presence of mediastinal mass, and larger body surface area (BSA). With multivariate analysis, the only statistically significant risk factors were maximum TG level, BSA, presence of mediastinal mass, and risk stratification (intermediate/high risk).Our study was able to unveil TG level of >615 mg/dl, mediastinal mass, and a larger BSA as novel risk factors that have not been previously discussed in the literature.
