Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study
Bone marrow transplantation. 2020
Although most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapy-based conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2-18 years after MAC for first allo-HSCT of bone marrow (BM) or peripheral blood stem cells (PBSC) from matched-related (MRD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to control pretreatment imbalances of the observed variables. 3.054 patients were analyzed. CR1 (1.498): median follow-up (FU) after FTBI (1.285) and CC (213) was 6.8 and 6.1 years. Survivals were not significantly different. CR2 (1.556): median FU after FTBI (1.345) and CC (211) was 6.2 years. Outcomes after FTBI were superior as compared with CC with regard to overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and nonrelapse mortality (NRM). However, we must emphasize the preliminary character of the results of this retrospective "real-world-practice" study. These findings will be prospectively assessed in the ALL SCTped 2012 FORUM trial.
Phenotypes and Baseline Risk Factors of Acute Kidney Injury in Children After Allogeneic Hematopoietic Stem Cell Transplantation
Frontiers in pediatrics. 2020;8:499
Background: Acute kidney injury (AKI) is a frequent and widely recognized complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Despite relatively high prevalence, AKI after allo-HSCT and its risk factors in children remain obscure. The aim of this study was to describe the prevalence and course of AKI during the first 100 days after allo-HSCT in children and to investigate its associations with baseline characteristics. Methods: Retrospective single-center chart review of all patients under 18 who underwent allo-HSCT during 2011-2017 was performed. AKI was defined using the pediatric RIFLE criteria and only the patients with pRIFLE stage I (eGFR decrease by 50% or more) or higher were considered for the analysis. Recurrent AKI and acute kidney disease (AKD) were defined according to the Acute Disease Quality Initiative consensus. Demographic, clinical, and procedure-related characteristics were recorded at the day of HSCT. Results: Fifty-one patients (68.6% boys) with a median age of 9 years (range: 0.25-17) were included. During a median follow-up of 82 (IQR, 60-98) days, 27 (52.9%) patients experienced a total of 39 AKI episodes, translating into one AKI episode per 100 patient days. Multiple AKIs occurred in 11 (21.6%) patients and 18 (35.3%) progressed to AKD. Four patients died, all with ongoing or previous AKI. Patients with AKD were, on average, older (10 vs. 6 years; p = 0.03) and had higher baseline body mass index (BMI) [standard deviation score (SDS) 0.83 vs. 0.04, p = 0.05], whereas patients with recurrent AKI had higher baseline estimated glomerular filtration rate (eGFR) (244.1 vs. 193.9 ml/min/1.73 m(2), p = 0.02). In the adjusted Cox models (HR; 95% CI), older age (1.10; 1.01-1.20) was associated with higher risk of overall AKI and higher eGFR (1.02; 1.01-1.04) was associated with higher risk of recurrent AKI, while older age (1.17; 1.04-1.31), higher eGFR (HR 1.01; 1.0-1.02), and higher BMI SDS (1.66; 1.01-2.72) were associated with higher risk of AKD. Conclusions: AKI is a frequent early complication of allo-HSCT in children, and approximately one fifth experience AKI recurrence and one third develop AKD. Older age, higher BMI, and higher eGFR at the day of transplant may have an effect on the risk of AKI development and its course.
Low burden of minimal residual disease prior to transplantation in children with very high risk acute lymphoblastic leukaemia: The NOPHO ALL2008 experience
British journal of haematology. 2019
The population-based Nordic/Baltic acute lymphoblastic leukaemia (ALL) Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol combined minimal residual disease (MRD)-driven treatment stratification with very intense first line chemotherapy for patients with high risk ALL. Patients with MRD ≥5% at end of induction or ≥10(-3) at end of consolidation or following two high risk blocks were eligible for haematopoietic cell transplantation (HCT) in first remission. After at least three high risk blocks a total of 71 children received HCT, of which 46 had MRD ≥5% at end of induction. Ten patients stratified to HCT were not transplanted; 12 received HCT without protocol indication. Among 69 patients with evaluable pre-HCT MRD results, 22 were MRD-positive, one with MRD ≥10(-3) . After a median follow-up of 5.5 years, the cumulative incidence of relapse was 23.5% (95% confidence interval [CI]: 10.5-47.7) for MRD-positive versus 5.1% (95% CI: 1.3-19.2), P = 0.02) for MRD-negative patients. MRD was the only variable significantly associated with relapse (hazard ratio 9.1, 95% CI: 1.6-51.0, P = 0.012). Non-relapse mortality did not differ between the two groups, resulting in disease-free survival of 85.6% (95% CI: 75.4-97.2) and 67.4% (95% CI: 50.2-90.5), respectively. In conclusion, NOPHO block treatment efficiently reduced residual leukaemia which, combined with modern transplant procedures, provided high survival rates, also among pre-HCT MRD-positive patients.
Antimicrobial resistance in Gram-negative rods causing bacteremia in hematopoietic stem cell transplant patients: intercontinental prospective study of Infectious Diseases Working Party of the European Bone Marrow Transplantation group
Clinical Infectious Diseases. 2017
Background: This intercontinental study aimed to study Gram-negative rods (GNR) resistance in hematopoietic stem cell transplantation (HSCT). Methods: GNR bacteremias occurring during six months post-HSCT (February/2014-May/2015) were prospectively collected, and analysed for rates and risk factors for resistance to fluoroquinolones, non-carbapenem anti-Pseudomonas beta-lactams (non-carbapenems), carbapenems and multidrug-resistance (MDR). Results: Sixty-five HSCT centers from 25 countries (Europe, Australia, Asia) reported data on 655 GNR episodes/704 pathogens in 591 patients (Enterobacteriaceae, 73%; non-fermentatives, 24% and 3% others). Half GNR were fluoroquinolone- and non-carbapenems-resistant; 18.5% carbapenem-resistant; 35.2% MDR. The total resistance rates were higher in allo-HSCT vs. auto-HSCT patients (p<0.001); but similar in community-acquired infections. Non-carbapenems-resistance and MDR were higher in auto-HSCT patients in centers providing vs. non-providing fluoroquinolone prophylaxis (p<0.01). Resistance rates were higher in southeast vs. north-west Europe; similar in children and adults; excluding higher fluoroquinolone- and beta-lactam beta-lactamase inhibitors-resistance rates in allo-HSCT adults. Non-Klebsiella Enterobacteriaceae were rarely carbapenem-resistant. Multivariable analysis revealed resistance risk factors in allo-HSCT patients: fluoroquinolone-resistance: adult, prolonged neutropenia, breakthrough on fluoroquinolones; non-carbapenems-resistance: hospital-acquired infection, breakthrough on non-carbapenems or other antibiotics (excluding fluoroquinolones, non-carbapenems, carbapenems), donor type; carbapenem-resistance: breakthrough on carbapenem, longer hospitalization, intensive care unit, previous other antibiotic therapy; MDR: longer hospitalization, breakthrough on beta-lactam beta-lactamase inhibitors and carbapenems. Inappropriate empirical therapy and mortality were significantly more common in infections caused by resistant bacteria. Conclusion: Our data question the recommendation for fluoroquinolone prophylaxis and call for reassessment of local empirical antibiotic protocols. Knowledge of pathogen-specific resistances enable early appropriate empirical therapy. Monitoring of resistance is crucial.