Pediatric Allogeneic Hematopoietic Cell Transplantation Research Articles

Prognostic significance of early nk cell recovery in pediatric t-cell replete allogeneic hematopoietic stem cell transplantation.

Early immune reconstitution, particularly of natural killer (NK) cells with strong graft-versus-leukemia effects, is crucial for the prognosis of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective study examined 122 pediatric patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) who underwent T-cell replete allo-HSCT at the Children's Hospital of Soochow University from 2019 to 2021. Peripheral blood lymphocyte counts on days 30 and 60 post-transplant were analyzed, focusing on NK cell recovery and its impact on overall survival (OS), relapse-free survival (RFS), non-relapse mortality (NRM), relapse, graft-versus-host disease, and CMV reactivation. Patients were categorized into high and low NK cell groups by the median NK cell counts at day 30 (NK30) and day 60 (NK60) after HSCT. Patients with high NK30 and NK60 levels had significantly better 3-year OS rates compared to their respective low NK count groups (86.8% ± 4.7% versus 67.6% ± 7.0%, P = 0.046; 95.7% ± 3.0% versus 63.7% ± 8.7%, P < 0.001, respectively). NK60 was found to be an independent predictor for 3-year OS and RFS in multivariate analysis. Early NK reconstitution was also related to lower NRM rates. However, this correlation disappeared in patients with ALL and those undergoing haploidentical transplantation. In addition, A positive association between early T cell and NK cell reconstitution was found in our study. Higher NK cell counts on days 60 can predict superior OS, RFS and lower NRM in pediatric AML allo-HSCT patients.

Lineage-Specific Mixed Chimerism in Pediatric Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia

Hematopoietic Stem Cell Transplantation (HSCT) is considered a curative option for children with Acute Myeloid Leukemia (AML). Post-HSCT relapse in pediatric AML is associated with poor outcomes. Our ability to predict this event is limited.

Immunogenicity and Antibody Persistence of the Inactivated Quadrivalent Influenza Vaccine in Pediatric Patients Post-Chemotherapy or Allogeneic Hematopoietic Stem Cell Transplantation Versus Healthy Controls.

Pediatric patients who have undergone hematopoietic stem cell transplantation (HSCT) or chemotherapy are at increased risk for severe influenza complications, necessitating annual vaccination. This study evaluated the immunogenicity and antibody persistence of the 2021-2022 seasonal quadrivalent influenza vaccine in pediatric patients post-HSCT or chemotherapy, compared to healthy controls. A prospective cohort study included 80 pediatric participants divided into three groups: chemotherapy (n = 33), HSCT (n = 27), and healthy controls (n = 20). All participants were vaccinated with the 2021-2022 GC FLU Quadrivalent vaccine. Hemagglutination inhibition (HI) assays measured seroprotection rates (SPR), geometric mean titers (GMT), and seroconversion rates (SCR) for the four vaccine antigens (A/H1N1, A/H3N2, B/Victoria, B/Yamagata) at one, three, and six months post-vaccination. At one month post-vaccination, all groups met the 70% SPR threshold for A/H1N1 and A/H3N2, but not for B/Victoria. For B/Yamagata, the SPR was low in the chemotherapy and HSCT groups (18.18% and 33.33%, respectively), compared to 80.00% in controls (p < 0.0001 and p = 0.0015). While A/H1N1 and A/H3N2 GMTs were protective in all groups, only controls achieved protective levels for B/Yamagata. Over time, the control group maintained >70% SPR for A/H1N1 up to six months, but the chemotherapy and HSCT groups declined by three and six months, respectively. For A/H3N2, the SPR in controls dropped below 70% at three months, while it remained above 70% in the chemotherapy and HSCT groups until three months. None of the groups achieved protective GMTs for B strains at three or six months. Pediatric patients post-HSCT or chemotherapy demonstrated a comparable immune response to healthy controls for A/H1N1 and A/H3N2, but the rapid decline in A/H1N1 antibody levels suggests the need for ongoing monitoring and adjusted vaccination schedules. The poor response to B antigens, particularly B/Yamagata, underscores the need for improved vaccination strategies in these vulnerable populations.

Impact of Body Mass Index on Outcomes in Pediatric Allogeneic Hematopoietic Stem Cell Transplantation Recipients: A Single-Center Retrospective Study.

Pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) face several risk factors influencing transplantation success, including nutritional status as measured by body mass index (BMI). This study analyzed BMI data collected from patients transplanted between 2003 and 2023, and aimed to evaluate whether deviations from normal BMI are associated with poorer clinical outcomes. BMI levels assessed before and after first-line treatment and pre-transplantation were analyzed retrospectively to determine a correlation with survival and post-transplant complications. Underweight patients had significantly lower 12- and 36-month overall survival rates compared to normal-weight and overweight patients (p = 1.22 × 10-8 and p = 8.88 × 10-8, respectively). Event-free survival was also lower for underweight patients at all time points. A higher pre-transplant BMI increases the risk of acute graft-versus-host disease (GVHD, p = 0.00068). Otherwise, pre-transplant BMI was not significantly correlated with early TRCs and cGVHD. As secondary objectives, this study identified differences in BMI across primary disease groups, with solid tumor patients having the highest BMI and myelodysplastic syndrome patients having the lowest. BMI cut-offs were identified to predict or protect against serious outcomes, including delayed engraftment, TRCs, and acute and chronic GVHD. This study highlights the importance of nutritional assessment and management in pediatric patients undergoing allo-HSCT to optimize post-transplant outcomes, as deviations from a normal BMI can significantly impact post-transplant health. These findings underscore the importance of integrating BMI assessment throughout the entire pre-HSCT therapeutic course to identify patients at higher risk for complications and to define more effective nutritional management strategies.

Viral epitope profiling of hematopoietic cell transplant recipients with respiratory syncytial virus upper respiratory tract and lower respiratory tract infections

Abstract Background The pre-fusion conformation of the F glycoprotein of respiratory syncytial virus (RSVpreF) has been the target of recent respiratory syncytial virus (RSV) therapies, including monoclonal antibodies for immunocompetent children and vaccines for the elderly. However, the utility of targeted therapies against RSVpreF is unknown in pediatric or adult hematopoietic cell transplant (HCT) recipients, and there are limited natural history studies characterizing humoral immune responses after RSV infection in HCT recipients. We utilized VirScan, a novel high-throughput profiling of antiviral antibody epitopes, to identify differences in global RSV-related epitope hits after an RSV infection. Methods We evaluated adult and pediatric allogeneic HCT recipients who acquired RSV from 12/2011 to 12/2019. Patients were categorized into 3 groups: upper respiratory tract infections (URTI) only, those who progressed from URTI to lower respiratory tract infections (progressors) and lower respiratory tract infections (LRTI) at diagnosis, and tested at baseline prior to infection (pre-RSV), at RSV URTI or LRTI diagnosis (RSV diagnosis), at LRTI progression (LRTI), 4-6 weeks after infection (Response 1) and &amp;gt;8 weeks after infection (Response 2), depending on sample availability. We interrogated the viral antibody repertoire using a serosurvey (VirScan) that detects immunoglobulin G responses to 206 viruses. VirScan metrics evaluated included: (1) number of RSV epitope hits, (2) log10 of the maximum RSV epitope binding signal (EBS), analogous to an antibody titer for each epitope, and (3) geometric mean of all RSV EBS. Kruskal-Wallis tests were used to compare groups for each VirScan metric at the different time points. Results A total of 129 samples from 39 patients were analyzed; 24 with URTI only, 8 progressors, and 7 with LRTI at diagnosis. At each time point, VirScan metrics were similar among the 3 patient groups (Table 1). Though patterns of VirScan metrics following RSV diagnosis varied by patient, most showed a modest increase in values (Figure 1). Conclusion In this preliminary study, we utilized the power of VirScan, a comprehensive serologic profiling tool of the entire human virome, to characterize RSV specific antibody changes after RSV infection in allogeneic HCT recipients. There were no differences in global RSV VirScan metrics between the 3 groups, suggesting that antibodies may not be the primary driver of viral infection attenuation in this population. Future analyses will focus on differences in individual epitope acquisition, including RSVpreF, between the 3 groups, and investigate possible interactions with humoral responses to other viruses. Figure 1. Longitudinal RSV VirScan metrics for each patient separated by 3 groups (top row: RSV URTI only; middle row: progressors from URTI to LRTI; bottom row: LRTI at diagnosis). Each line is an individual patient. The different panels show the changes in RSV related epitope hits (A), the log10 maximum epitope binding signal (EBS) among RSV epitopes (B), and the geometric mean of all the RSV related EBS (C). Open circles represent time points prior to RSV diagnosis, filled circles represent time points just prior to, on or after URTI, and asterisks represent time points just prior to, on, or after LRTI.

Dietary intake and risk of metabolic syndrome in long-term survivors of pediatric allogeneic hematopoietic stem cell transplantation

We explored the dietary intake and metabolic syndrome (MetS) in 85 survivors of pediatric stem cell transplantation (median age 30 years, median follow-up time 20 years). Overall, the distribution of fatty acid deviated from the recommendations with a higher intake of saturated fat and a lower intake of unsaturated fat but was comparable to that of the background population. The prevalence of MetS was 27%, corresponding to that of the elderly background population. We compared the intake of macronutrients between those with MetS and those without MetS and found that overall fat intake was higher in patients with MetS (36.7E% [range, 27.2–51.2E%] vs. 33,5E% (range, 23.4–45.1E%), P = 0.016). Within the subgroup of patients treated with total body irradiation (TBI), we found a higher fat intake in those with MetS (36.8E% (range, 27.2–51.2E%) versus 32.0E% (range, 24.6–42.1E%), P = 0.013). This was confirmed in a multivariate analysis adjusted for TBI, sex, and age at follow-up (OR 1.20 (1.06–1.39), P = 0.008). Our findings suggest that conditioning with the use of TBI may induce a state of hypersensitivity to the potentially harmful effects of fat in the diet and suggest that this risk of MetS after TBI treatment may be modifiable by dietary changes.

Cytomegalovirus viral load at initiation of pre-emptive antiviral therapy impacts cytomegalovirus dynamics in pediatric allogeneic hematopoietic cell transplantation recipients.

Cytomegalovirus (CMV) contributes to morbidity and mortality in allogeneic hematopoietic cell transplantation (allo-HCT) recipients. Pre-emptive antiviral therapy (PET) reduces the incidence of CMV end-organ disease (EOD), though relevant viral thresholds to initiate PET remain undefined. We evaluated the impact of viral loads (VLs) at PET initiation on virologic and clinical outcomes following pediatric allo-HCT. Single-center retrospective cohort analysis of children who underwent their first allo-HCT from January 2014 to December 2020. Weekly quantitative plasma CMV polymerase chain reaction was performed until Day +100 and PET was initiated once VL exceeded a pre-defined threshold per institutional guidelines. Patients were followed for 1-year post-HCT to evaluate virologic and clinical outcomes including end-organ disease (EOD), overall survival (OS), and non-relapse mortality (NRM). Among 146 allo-HCT recipients, CMV DNAemia occurred in 40 patients (27%) at a median of 15 days post-HCT (interquartile range 6-28.5). Ten percent (n = 4) had spontaneous resolution of DNAemia, while 90% (n = 36) required PET. PET initiated when CMV VL was ≥ 1000 IU/mL (n = 21) vs when VL < 1000 IU/mL (n = 15) resulted in higher peak CMV VL (12,670vs. 1284 IU/mL, p = 0.0001) and longer time to CMV DNAemia resolution (36vs. 24 days, p = 0.035). There were no differences in EOD, OS, or NRM at 12 months post-HCT based on VL at PET initiation. Initiating PET when CMV VL was ≥1000 IU/mL resulted in significantly higher peak VL and prolonged DNAemia, with no differences in EOD, OS, or NRM at 12 months post pediatric HCT.

High infection rates and risk‐adapted prevention strategies in contemporary pediatric allogeneic hematopoietic stem cell transplantation

AbstractWith recent changes in hematopoietic stem cell transplantation (HSCT) practices, such as the increasing use of alternative donors and ex vivo T‐cell depletion, how various risk factors interplay and affect the timeline of infections have not been well elucidated. We retrospectively reviewed the first 100 consecutive HSCT from April 2019 to October 2021 in the only pediatric HSCT center in Hong Kong. We found that the vast majority of the allogeneic transplant recipients (69/74, 93.2%) had infections after HSCT, amongst which bacterial, viral, and fungal infection rates were 35.1%, 90.5%, and 9.5%, respectively. In contrast, only 30.8% (8/26) of autologous transplant recipients had infections (rate of bacterial, viral, and fungal infection were 19.2%, 15.4%, and 3.8%, respectively). Human herpesvirus 6 (HHV‐6) and BK virus (BKV) typically occurred early after HSCT, adenovirus (ADV) and varicella zoster virus (VZV) thereafter, and cytomegalovirus (CMV) and Epstein–Barr virus (EBV) throughout the entire 2.5‐year observation period. Ex vivo T‐cell depletion was a general risk factor for viral infection with HHV‐6 (hazard ratio [HR] = 3.03), BKV (HR = 3.36), CMV (HR = 4.45), and EBV (HR = 7.15); all p &lt; 0.02. Cancer in second‐complete remission compared with first‐complete remission was a risk factor for bacterial infection (OR = 6.0, 95% CI = 1.12–32.2, and p = 0.037). Patients with gut graft‐versus‐host disease were at risk for fungal infections (OR = 12.3, 95% CI = 1.33–114.4, and p = 0.027). The infection‐related mortality rate was 10.0%, which occurred only in allogeneic HSCT patients with hematological malignancies receiving cord blood (n = 4) or haploidentical HSCT (n = 6). Collectively, our findings in pediatric patients after contemporary HSCT support both time‐dependent and risk‐adapted measures against infective complications to improve transplant outcome.

Prophylactic use of liposomal amphotericin B in children and adolescents undergoing allogeneic hematopoietic cell transplantation: A 10-years single center experience

BackgroundAzoles are recommended as antifungal prophylaxis in decreasing the incidence of invasive fungal disease (IFD) in high-risk patients in pediatric oncology, including patients receiving allogeneic hematopoietic cell transplantation (HCT). However, azole related toxicity, pharmacological interactions with immunosuppressive medication and conditioning regimen and growing incidence of azole resistance makes this antifungal agent not ideal in the transplant setting. This study reports on the contemporary incidence and outcome of IFD after allogeneic HCT in children with prophylactic liposomal amphotericin B (L-AMB). MethodsThis single-center retrospective study included all patients transplanted between 2012 and 2022. Primary endpoint was the incidence of IFD until hospital discharge post-transplant. Secondary aims were the incidence of IFD and survival 180 days after allogeneic HCT, the evaluation of toxicity of L-AMB and further risk factors for development of IFD during antifungal prophylaxis. Descriptive statistics were performed. Results161 pediatric patients received L-AMB. Incidence of breakthrough IFD post-transplant was 7.5 % (12/161). The 12 cases comprised of three invasive yeast infections (1.9 %), three probable (1.9 %) and six possible (3.7 %) mold infections. Adverse events were in 22.4 % of the patients, most of them mild and reversible. Discontinuation of L-AMB occurred in 2.5 % (4/161) of the patients due to severe hypersensitivity reactions. ConclusionsThe risk of breakthrough IFD in pediatric patients undergoing allogeneic HCT under L-AMB prophylaxis is comparable with the reported risk under first line recommendation drugs for antifungal prophylaxis. If no hypersensitivity reaction occurs, L-AMB is tolerated with manageable side effects. This antifungal agent should therefore be considered as an alternative option to azoles in pediatric allogeneic HCT recipients.

Effect of clofarabine and fludarabine exposure on outcome after pediatric allogeneic hematopoietic cell transplantation

Effect of clofarabine and fludarabine exposure on outcome after pediatric allogeneic hematopoietic cell transplantation

Pulmonary hypertension in the intensive care unit after pediatric allogeneic hematopoietic stem cell transplant: incidence, risk factors, and outcomes.

To determine the incidence, risk factors, and outcomes of pulmonary hypertension (PH) in the pediatric intensive care unit (PICU) after pediatric hematopoietic stem cell transplant (HCT). This was a retrospective study of pediatric patients who underwent allogeneic HCT between January 2008-December 2014 at a center contributing to the Center for International Blood and Marrow Transplant Research data registry. Incidence of PH was assessed from PICU diagnostic codes from records merged from the Virtual Pediatric Systems database. Regression and survival analyses identified factors associated with post-HCT PH. Additional post-HCT morbidities and survival after PH were also assessed. Among 6,995 HCT recipients, there were 29 cases of PH, a cumulative incidence of 0.42% (95% CI 0.27%-0.57%) at 60 months post-HCT. In the sub-cohort of 1,067 patients requiring intensive care after HCT, this accounted for a PH prevalence of 2.72% (95% CI 1.74-3.69%). There was an increased risk of developing PH associated with Black/African American race, metabolic disorders, partially HLA-matched or cord blood allografts, graft-versus-host prophylaxis regimen, and lower pre-HCT functional status. Patients who developed PH had significant PICU comorbidities including heart failure, pulmonary hemorrhage, respiratory failure, renal failure, and infections. Survival at 6 months after diagnosis of post-HCT PH was 51.7% (95% CI 32.5%-67.9%). PH is a rare but serious complication in the pediatric post-HCT population. A significant burden of additional comorbidities, procedural interventions, and risk of mortality is associated with its development. Close monitoring and prompt intervention for this severe complication are necessary in this vulnerable population.

Severe Impairment of T-cell Immunity and Pulmonary GvHD Are Major Risk Factors for Nontuberculous Mycobacterial Infection After Pediatric Allogeneic Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplant recipients are prone to infectious complications. Infections caused by nontuberculous mycobacteria have increased in adults but literature in children is scarce. We report 6 episodes of disseminated or pulmonary nontuberculous mycobacteria infection among 5 pediatric hematopoietic stem cell transplant recipients. All but one were caused by Mycobacterium avium complex. Four patients died, 2 related to nontuberculous mycobacteria infection.

The Impact of Pretransplant Respiratory Virus Detection on Posttransplant Outcomes in Children Undergoing Hematopoietic Cell Transplantation.

Pretransplant respiratory virus (RV) infections have been associated with negative transplant outcomes in adult hematopoietic cell transplantation (HCT) recipients. In the era of HCT delay because of high-risk RVs, we examined the impact of pretransplant RV detection on transplant outcomes in pediatric HCT recipients. This retrospective cohort study included pediatric myeloablative allogeneic HCT recipients from 2010 to 2019. All patients were screened for RV at least once within 90 days before HCT using reverse transcriptase polymerase chain reaction (PCR), regardless of symptoms. Posttransplant outcomes included days alive and out of hospital and progression to lower respiratory tract infection (LRTI). Among 310 patients, 134 had an RV detected in the 90 days before HCT. In univariable analysis, transplant factors including younger age, total body irradiation, umbilical cord blood transplantation, lymphocyte count <100/mm3, HCT comorbidity index score ≥3, and viral factors including symptomatic infection, human rhinovirus as a virus type, and symptomatic pretransplant upper respiratory tract infection were associated with fewer days alive and out of hospital. In multivariable analysis, transplant factors remained significant, but not viral factors. There was a higher incidence of progression to posttransplant LRTI with the same pretransplant RV if the last positive PCR before HCT was ≤30 days compared with >30 days (P = .007). In the setting of recommending HCT delay for high-risk RVs, symptomatic upper respiratory tract infection, including human rhinovirus infections, may lead to increased duration of hospitalization and early progression to LRTI when transplantation is performed within 30 days of the last positive PCR test.

Approach for defining human adenovirus infection and disease for central review adjudication in clinical studies.

Pediatric allogeneic hematopoietic cell transplant (allo-HCT) recipients are at risk for morbidity and mortality from human adenovirus (HAdV). HAdV can be detected in an asymptomatic state, referred to as infection or with signs or symptoms of illness, referred to as disease. Standardized case definitions are needed to distinguish infection from disease and allow for consistent reporting in both observational cohort studies and therapeutic clinical trials. A working group of experts in virology, transplant infectious disease, and HCT was assembled to develop HAdV infection and disease definitions with the degree of certainty (i.e., possible, probable, and proven). Definitions were further refined through an iterative process and independently applied by two central review committees (CRCs) to 20 pediatric allo-HCT recipients with at least one HAdV-positive PCR. Initial HAdV infection and disease definitions were developed and updated through an iterative process after reviewing clinical and virological details for 81 subjects with at least one positive HAdV PCR detected in a clinical specimen. Independent application of final definitions to 20 HAdV positive allo-HCT recipients by two CRCs yielded similar number of HAdV infection or disease events but with variation of degree of certainty for some events. Application of definitions by a CRC for a study of HAdV infection and disease is feasible and can provide consistency in the assignment of outcomes. Definitions need further refinement to improve reproducibility and to provide guidance on determining clinical improvement or worsening after initial diagnosis of HAdV infection or disease.

Treatment-Sensitive and Treatment-Dependent Chronic Graft-versus-Host Disease Yield Superior Failure-Free and Overall Survival Compared to Treatment-Resistant Chronic Graft-versus-Host Disease

Response to treatment of chronic graft-versus-host disease (cGVHD) may help predict prognosis and outcomes. We hypothesized that the response of cGVHD to treatment and the ability to taper immunosuppression define distinct treatment response categories that differ in terms of risk factors and prognosis. Our aim was to determine specific clinical characteristics and outcomes associated with 3 distinct cGVHD treatment response groups based on the response to and duration of immunosuppressive therapy (IST) as treatment-sensitive (TS), treatment-resistant (TR), and treatment-dependent (TD) cGVHD. This retrospective single-institution cohort study included 1142 consecutive adult and pediatric recipients of allogeneic hematopoietic cell transplantation (HCT) performed for malignant and nonmalignant disorders at the University of Minnesota between 2008 and 2016. All donor, graft, conditioning regimen, and GVHD prophylaxis strategies were included, but only patients who commenced systemic treatment within 30 days of cGVHD diagnosis were included. A total of 185 patients who developed cGVHD necessitating IST within 30 days of cGVHD diagnosis were included in this analysis. At 1 year after cGVHD onset, 13% of the patients were TS, 27% were TD, and 60% were TR (including 14% deceased), whereas at 2 years after cGVHD onset, 29% were TS, 5% were TD, and 66% were TR (including 22% deceased). In a landmark analysis starting at 1 year after cGVHD onset, 5-year failure-free survival (FFS) and overall survival (OS) were lowest in the TR group (FFS, 38%; OS, 70%), with comparable outcomes in the TD (74% and 82%, respectively) and TS (79% for both) groups. Compared to no cGVHD, TR cGVHD was associated with worse OS at 5 years after cGVHD (hazard ratio, 2.09 versus no cGVHD; 95% confidence interval, 1.3 to 3.3; P < .01). Our findings suggest that refining cGVHD classification into 3 treatment response states defines important predictors of early and late clinical outcomes and identifies patients needing more effective treatment.

Model-Based Dosing of Anti-Thymocyte Globulin in Pediatric Allogeneic Hematopoietic Cell Transplantation Improves Survival Chances: Updated Results from the Single Arm Phase II Parachute-Trial Combined with Real-World Data

Model-Based Dosing of Anti-Thymocyte Globulin in Pediatric Allogeneic Hematopoietic Cell Transplantation Improves Survival Chances: Updated Results from the Single Arm Phase II Parachute-Trial Combined with Real-World Data

Social determinants of health predict health outcomes following pediatric allogeneic hematopoietic stem cell transplant.

Pediatric hematopoietic stem cell transplantation (HCT) is an intensive medical procedure that places substantial financial and logistical burdens on families and is associated with significant health risks, such as graft-versus-host disease (GVHD), and infections. The influence of the social determinants of health (SDoH) on outcomes following pediatric HCT is understudied. This study aimed to examine whether SDoH predicts outcomes following pediatric HCT. Data were collected from 84 children who received HCT (Mage =5.8years, SD=3.7) and their primary caregiver. Detailed demographic information was collected from caregivers at baseline, and child health information was extracted from the electronic medical records. Multivariate logistic regression was used to examine the association between SDoH and health outcomes within a 24-month period following pediatric HCT. After controlling for malignancy as reason for transplant and donor type, lower family income predicted the incidence of chronic GVHD. Neighborhood deprivation, total family income, public health insurance, caregiver relationship status, caregiver educational attainment, and perceived family financial difficulties did not predict acute GVHD or the number of infections. Total family income is a simple family indicator of SDoH that predicts chronic GVHD after pediatric allogeneic HCT. These findings provide further support for the importance of screening of child and family SDoH risks to ensure that fundamental needs can be met to mitigate potential health disparities for up to 2years following pediatric HCT.

Disparities in Cytomegalovirus Infection Rates by Race and Ethnicity among Pediatric Allogeneic Hematopoietic Cell Transplantation Recipients at a Single Center

Previous literature has reported cytomegalovirus (CMV) infection rate disparities among racial/ethnic groups of hematopoietic cell transplantation (HCT) recipients. Because race and ethnicity categorizations are social constructs unlikely to affect biological systems, it is likely there are covariates on the pathway to CMV detection, known as mediators, that can explain the observed disparity. Recent developments in mediation analysis methods enable the analysis of time-to-event outcomes, allowing an investigation of these disparities to also consider the timing of CMV infection detection relative to HCT. This study aimed to explore whether racial and ethnic CMV infection disparities existed within a population of HCT recipients at our center, and whether clinical covariates explained any observed association. The study cohort included all recipients of allogeneic HCT performed at the Children's Hospital of Philadelphia between January 2004 and April 2017 who were CMV PCR-negative pretransplantation, had known donor/recipient CMV serology, and were under blood CMV PCR surveillance. Subjects were followed for 100 days post-HCT. Accelerated failure time models using subject's reported race/ethnicity, dichotomized into non-Hispanic White (NHW) and non-NHW, and exposure and time to CMV detection as outcomes examined whether selected clinical factors-donor/recipient CMV serostatus, recipient age, indication for HCT, hematopoietic cell source, match quality-mediated any identified exposure-outcome association. The analysis included 348 HCTs performed in 335 subjects, with 86 episodes (24.7%) in which CMV was detected via PCR analysis. The accelerated failure time model without mediators estimated that non-NHW subjects had fewer CMV-free survival days (time ratio, .21; 95% confidence interval, .10 to .44). Any hypothesized mediator mediated at most 5% of the total association between race/ethnicity and time to CMV detection. Non-NHW HCT recipients had fewer CMV-free survival days than NHW recipients; none of the clinical factors hypothesized to mediate this association accounted for a significant component of total association. Further research should focus on nonclinical factors influenced by systemic racism to better understand their effect on CMV infection among HCT recipients.

Intensive care risk and long-term outcomes in pediatric allogeneic hematopoietic cell transplant recipients

AbstractAllogeneic hematopoietic cell transplantation (HCT) can be complicated by life-threatening organ toxicity and infection necessitating intensive care. Epidemiologic data have been limited by single-center studies, poor database granularity, and a lack of long-term survivors. To identify contemporary trends in intensive care unit (ICU) use and long-term outcomes, we merged data from the Center for International Blood and Marrow Transplant Research and the Virtual Pediatric Systems databases. We identified 6995 pediatric patients with HCT aged ≤21 years who underwent first allogeneic HCT between 2008 and 2014 across 69 centers in the United States or Canada and followed patients until the year 2020. ICU admission was required for 1067 patients (8.3% by day +100, 12.8% by 1 year, and 15.3% by 5 years after HCT), and was linked to demographic background, pretransplant organ toxicity, allograft type and HLA-match, and the development of graft-versus-host disease or malignancy relapse. Survival to ICU discharge was 85.7%, but more than half of ICU survivors required ICU readmission, leading to 52.5% and 42.6% survival at 1- and 5-years post-ICU transfer, respectively. ICU survival was worse among patients with malignant disease, poor pretransplant organ function, and alloreactivity risk factors. Among 1-year HCT survivors, those who required ICU in the first year had 10% lower survival at 5 years and developed new dialysis-dependent renal failure at a greater rate (P<.001). Thus, although ICU management is common and survival to ICU discharge is high, ongoing complications necessitate recurrent ICU admission and lead to a poor 1-year outcome in select patients who are at high risk.

Stopping antibacterial prophylaxis in pediatric allogeneic hematopoietic cell transplantation: An internal audit.

Antibacterial prophylaxis in children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) is controversial and not recommended by international guidelines. We analyzed relevant posttransplant outcomes following discontinuation of antibacterial prophylaxis at a major European pediatric transplant center. The single-center retrospective audit included all pediatric allogeneic HCT patients (pts) transplanted between 2011 and 2020 before (≤2014) and after (≥2015) stopping routine antibacterial prophylaxis with penicillin, metronidazole, and ciprofloxacin upon start of the conditioning regimen. The primary endpoint was overall survival until the first hospital discharge. Secondary endpoints included the occurrence of fever; bacterial infections; and cumulative days with antibacterial agents until discharge. A total of 257 HCT procedures were performed in 249 pts (median age: 10 years, range, 0.2-22.5) for leukemia/lymphoma (n = 150) and nonmalignant disorders (n = 107). Of these, 104 procedures were performed before (cohort 1) and 153 after (cohort 2) stopping prophylaxis. Overall survival until discharge was 90.4% in cohort 1 and 96.1% in cohort 2 (p = .06). No differences were observed in the occurrence of fever (92.3vs. 94.1%; p = .57) and bacterial infections (34.6vs. 25.5%; p = .11). The median number of days on antibacterial agents was significantly lower in cohort 2 (39vs. 34; p = .002). Detection rates of resistant organisms were overall low. In this single-center audit, the stop of routine antibacterial prophylaxis had no effect on the occurrence of fever, bacterial infections, resistant organisms, and GVHD. Overall antibiotic use was significantly reduced, and survival was noninferior to the historical control cohort.