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Risk factors for bloodstream infection in paediatric Haematopoietic stem cell transplantation: A systematic review and meta-analysis
Yang, M., Xin, L., Li, H., Lu, X., Pan, X., Lei, S., Li, Y., Zhu, L., Zhu, Q., Jiang, R., et al
The Journal of hospital infection. 2023
Abstract
BACKGROUND Haematopoietic stem cell transplantation (HSCT), a standard treatment for paediatric haematological diseases, is highly associated with bloodstream infections (BSIs), which may increase mortality. AIM: This study aimed to explore the risk factors for BSI in paediatric HSCT recipients. METHODS We searched three English databases and four Chinese databases from inception to March 17, 2022. Eligible studies included randomized controlled trials, cohort studies, and case-control studies that enrolled HSCT recipients aged ≤ 18 years and reported BSI risk factors. Two reviewers independently screened studies, extracted data, and assessed the risk of bias. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) we assessed certainty of body of evidence. FINDINGS Fourteen studies involving 4602 persons were included. The incidences of BSI and associated mortality in paediatric HSCT recipients were approximately 10%-50% and 5%-15%, respectively. Meta-analysis of all studies revealed that previous BSI before HSCT (relative effect [RE] 2.28, 95% confidence interval [CI] 1.19-4.34, moderate certainty) and receiving an umbilical cord blood transplant (RE 1.55, 95% CI 1.22-1.97, moderate certainty) were probably associated with an increased risk of BSI. Meta-analysis of studies with low risk of bias reassured that previous BSI before HSCT probably increased the risk of BSI (RE 2.28, 95% CI 1.19-4.34, moderate certainty), and revealed that steroid use (RE 2.72, 95% CI 1.31-5.64, moderate certainty) was likely a risk factor while autologous HSCT was probably a protective factor of BSI (RE 0.65, 95% CI 0.45-0.94, moderate certainty).
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Clinical outcome of infantile-onset inflammatory bowel disease in 102 patients with interleukin-10 signalling deficiency
Ye, Z., Qian, L., Hu, W., Miao, S., Wang, Y., Lu, J., Zhou, Y., Lu, X., Zhang, Y., Zheng, C., et al
Alimentary pharmacology & therapeutics. 2022
Abstract
BACKGROUND Infantile-onset inflammatory bowel disease can be caused by defects in interleukin-10 signalling. The natural history and clinical outcomes of allogeneic haematopoietic stem cell transplantation, medical treatment and surgery have not been thoroughly described. AIMS This study evaluates disease progression and clinical outcome in patients with interleukin-10 signalling deficiency. METHODS One hundred and nine patients with interleukin-10 signalling deficiency were retrospectively reviewed from a single tertiary centre. The Kaplan-Meier method was applied to calculate probabilities of survival and interval between transplant and stoma closure. RESULTS One hundred and nine patients were reviewed, and 102 patients were included in the survival analysis. One hundred and eight patients were identified with IL10RA mutations, and one patient harboured IL10RB mutation. Seventy-three patients received haematopoietic stem cell transplantation. The overall survival after transplantation was 64.2% (95% confidence interval, 52.8 to 75.6), and without transplantation, it was 47.5% (95% confidence interval, 14.8 to 80.2, P = 0.47). The median timeframe between transplant and stoma closure was 19.6 months. The probability of survival was significantly lower in patients with perforation (P < 0.001), ileus (P = 0.038) and without thalidomide treatment (P < 0.001) among patients who did not receive haematopoietic stem cell transplantation. The survival probability was not associated with timeframe between transplant and onset, graft source and genotypes. CONCLUSIONS The survival probability was not significantly different between patients with transplantation and the non-transplanted patients.
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Outcomes after late bone marrow and very early central nervous system relapse of childhood B-Acute lymphoblastic leukemia: a report from the Children's Oncology Group phase III study AALL0433
Lew, G., Chen, Y., Lu, X., Rheingold, S. R., Whitlock, J. A., Devidas, M., Hastings, C. A., Winick, N. J., Carroll, W. L., Wood, B. L., et al
Haematologica. 2020
Abstract
Outcomes after relapse of childhood B-acute lymphoblastic leukemia (B-ALL) are poor, and optimal therapy is unclear. Children's Oncology Group study AALL0433 evaluated a new platform for relapsed ALL. Between March 2007 and October 2013 AALL0433 enrolled 275 participants with late bone marrow or very early isolated central nervous system (iCNS) relapse of childhood B-ALL. Patients were randomized to receive standard versus intensive vincristine dosing; this randomization closed due to excess peripheral neuropathy in 2010. Patients with matched sibling donors received allogeneic hematopoietic cell transplantation (HCT) after the first three blocks of therapy. The prognostic value of minimal residual disease (MRD) was also evaluated in this study. The 3-year event free and overall survival (EFS/OS) for the 271 eligible patients were 63.6% +/- 3.0% and 72.3% +/- 2.8% respectively. MRD at the end of Induction-1 was highly predictive of outcome, with 3-year EFS/OS of 84.9 +/- 4.0% and 93.8 +/- 2.7% for patients with MRD <0.1%, vs. 53.7 +/- 7.8% and 60.6 +/- 7.8% for patients with MRD ≥0.1% (p<0.0001). Patients who received HCT vs. chemotherapy alone had an improved 3-year disease-free survival (77.5 +/- 6.2% vs. 66.9 +/- 4.5%, p=0.03) but not OS (81.5 +/- 5.8% for HCT vs. 85.8 +/- 3.4% for chemotherapy, p=0.46). Patients with early iCNS relapse fared poorly, with a 3-year EFS/OS of 41.4% +/- 9.2% and 51.7% +/- 9.3%, respectively. Infectious toxicities of the chemotherapy platform were significant. The AALL0433 chemotherapy platform is efficacious for late bone marrow relapse of B-ALL, but with significant toxicities. The MRD threshold of 0.1% at the end of Induction-1 was highly predictive of outcome. The optimal role for HCT for this patient population remains uncertain. This trial is registered at clinicaltrials.gov (NCT# 00381680).
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Higher Reported Lung Dose Received during Total Body Irradiation for Allogeneic Hematopoietic Stem Cell Transplantation in Children with Acute Lymphoblastic Leukemia is Associated with Inferior Survival: A Report from the Children's Oncology Group
Esiashvili, N., Lu, X., Ulin, K., Laurie, F., Kessel, S., Kalapurakal, J. A., Merchant, T. E., Followill, D. S., Sathiaseelan, V., Schmitter, M. K., et al
International journal of radiation oncology, biology, physics. 2019
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Abstract
PURPOSE To examine the relationship between lung radiation dose and survival outcomes in children undergoing total body irradiation (TBI)-based hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia (ALL) on Children's Oncology Group (COG) trial. PATIENTS AND METHODS TBI (1200 or 1320 cGy given twice daily in 6 or 8 fractions) was used as part of 3 HSCT preparative regimens; allowing institutional flexibility regarding TBI techniques, including lung shielding. Lung doses as reported by each participating institution were calculated for different patient setups, with and without shielding, with a variety of dose calculation techniques. The association between lung dose and transplant-related mortality (TRM), relapse-free (RFS) and overall-survival (OS) was examined using Cox proportional hazard regression model controlling for the following variables: TBI dose rate, TBI fields, patient position during TBI, donor type, and pre-HSCT minimal residual disease (MRD) level. RESULTS From a total of 143 eligible patients127 had lung doses available for this analysis. The TBI techniques were heterogeneous. The mean lung dose was reported as 904.5cGy (SD +/-232.3). Patients treated with lateral fields were more likely to receive lung doses ≥800cGy (p<0.001). Lung dose ≥800cGy influence on TRM was not significant (HR 1.78; p=0.21). On univariate analysis, lung dose ≥800cGy was associated with inferior RFS (HR 1.76; p=0.04) and OS (HR 1.85; p=0.03); in the multivariate analysis, OS maintained statistical significance (HR 1.85; p=0.04). CONCLUSION The variability in TBI techniques result in an uncertainty with reported lung doses. Lateral fields were associated with higher lung dose, hence better be avoided. Patients treated with lung dose <800 cGy in this study had better outcome. This approach is currently been investigated in COG AALL1331 study. Additionally, the Imaging and Radiation Oncology Core (IROC) Group is evaluating effects of TBI techniques on lung doses using a phantom.
PICO Summary
Population
Children with acute lymphoblastic leukaemia undergoing allogeneic stem cell transplantation (n=143)
Intervention
TBI (1200 or 1320 cGy given twice daily in 6 or 8 fractions), given with or without shielding, using heterogeneous TBI techniques.
Comparison
Lung doses as reported by each participating institution were calculated for different patient setups.
Outcome
The mean lung dose was reported as 904.5cGy. Patients treated with lateral fields were more likely to receive lung doses >/=800cGy. Lung dose >/=800cGy influence on TRM was not significant. On univariate analysis, lung dose >/=800cGy was associated with inferior RFS and OS; in the multivariate analysis, OS maintained statistical significance. The variability in TBI techniques resulted in an uncertainty with reported lung doses. Patients treated with lung dose <800 cGy had better outcome.