Although unrelated-donor (URD) hematopoietic cell transplantation (HCT) is associated with many toxicities, a detailed analysis of adverse events, as defined by the Common Terminology Criteria for Adverse Events (CTCAE), has not previously been curated. This represents a major unmet need, especially as it relates to assessing the safety of novel agents. We analyzed a detailed AE database from the "ABA2" randomized, double-blind, placebo-controlled clinical trial of abatacept for acute graft-versus-host disease (AGVHD) prevention, for which the FDA mandated a detailed AE assessment through Day +180, and weekly neutrophil and platelet counts through Day +100. These were analyzed for their relationship to key transplant outcomes, with a major focus on the impact of AGVHD on the development/severity of AEs. A total of 2102 AEs and 1816 neutrophil/pla- telet counts were analyzed from 142 8/8-HLA-matched URD HCT recipients on ABA2 (placebo cohort, n = 69, abatacept cohort, n = 73). This analysis resulted in 2 major obser- vations. (1) Among graft source, conditioning intensity, age, and Grade 2 to 4 AGVHD, only AGVHD impacted Grade 3 to 5 AE acquisition after the first month post-transplant. (2) The development of Grade 3 to 4 AGVHD was associated with thrombocytopenia. We have created a detailed resource for the transplant community by which to contextualize clinical toxicities after transplant. It has identified AGVHD as a major driver of post-HCT Grade 3 to 5 AEs, and underscored a link between AGVHD and thrombocytopenia. This establishes a critical safety framework upon which the impact of novel post-transplant AGVHD therapeutics should be evaluated. This trial was registered at www.clinicaltrials. gov (#NCT01743131). (c) 2024 Published by Elsevier Inc. on behalf of The American Society for Transplantation and Cellular Therapy.

Chronic graft-versus-host-disease (cGVHD) is divided into two subtypes: classic (absence of acute GVHD features) and overlap cGVHD (‘ocGVHD’), in which both chronic and acute GVHD clinical features are present simultaneously. While worse outcomes with ocGVHD have been reported, there are few recent analyses. We performed a secondary analysis of data from the ABA2 trial (N = 185), in which detailed GVHD data were collected prospectively and systematically adjudicated. Analyses included cumulative incidence of classic versus ocGVHD, their specific organ manifestations, global disease severity scores, non-relapse mortality (NRM), disease-free survival (DFS) and overall survival (OS) in these two cGVHD subtypes. Of 92 patients who developed cGVHD, 35 were classified as ocGVHD. The 1-year cumulative incidence, organ involvement, and global severity of classic and ocGVHD were similar between ABA2 patients receiving CNI/MTX+placebo and CNI/MTX+abatacept; thus, cohorts were combined for ocGVHD evaluation. This analysis identified ocGVHD as having significantly higher severity at presentation and at maximum global severity compared to classic cGVHD. OS and DFS were significantly lower for ocGVHD versus classic cGVHD. OcGVHD is associated with increased cGVHD severity scores, and is associated with decreased OS and DFS compared to classic cGVHD, underscoring the high risks with this cGVHD subtype.

In the ABA2 study, the T-cell costimulation blockade agent, abatacept, was safe and effective in preventing acute graft-versus-host disease (aGVHD) after unrelated-donor hematopoietic cell transplant (HCT), leading to US Food and Drug Administration approval. Here, we performed a determination of abatacept pharmacokinetics (PK), which enabled an examination of how abatacept exposure-response relationships affected clinical outcomes. We performed a population PK analysis of IV abatacept using nonlinear mixed-effect modeling and assessed the association between abatacept exposure and key transplant outcomes. We tested the association between the trough after dose 1 (Ctrough_1) and grade (GR) 2 or 4 aGVHD (GR2-4 aGVHD) through day +100. An optimal Ctrough_1 threshold was identified via recursive partitioning and classification tree analysis. This demonstrated that abatacept PK was characterized by a 2-compartment model with first-order elimination. The ABA2 dosing regimen was based on previous work targeting a steady-state abatacept trough of 10 μg/mL. However, a higher Ctrough_1 (≥39 μg/mL, attained in ∼60% of patients on ABA2) was associated with a favorable GR2-4 aGVHD risk (hazard ratio, 0.35; 95% confidence interval, 0.19-0.65; P < .001), with a Ctrough_1 <39 μg/mL associated with GR2-4 aGVHD risk indistinguishable from placebo (P = .37). Importantly, no significant association was found between Ctrough_1 and key safety indicators, including relapse, and cytomegalovirus or Epstein-Barr virus viremia. These data demonstrate that a higher abatacept Ctrough_1 (≥39 μg/mL) was associated with a favorable GR2-4 aGVHD risk, without any observed exposure-toxicity relationships. This trial was registered at www.clinicaltrials.gov as #NCT01743131.

AbstractChronic active Epstein-Barr virus (EBV) disease (CAEBV) is characterized by high levels of EBV predominantly in T and/or natural killer cells with lymphoproliferation, organ failure due to infiltration of tissues with virus-infected cells, hemophagocytic lymphohistiocytosis, and/or lymphoma. The disease is more common in Asia than in the United States and Europe. Although allogeneic hematopoietic stem cell transplantation (HSCT) is considered the only curative therapy for CAEBV, its efficacy and the best treatment modality to reduce disease severity prior to HSCT is unknown. Here, we retrospectively assessed an international cohort of 57 patients outside of Asia. Treatment of the disease varied widely, although most patients ultimately proceeded to HSCT. Though patients undergoing HSCT had better survival than those who did not (55% vs 25%, P < .01), there was still a high rate of death in both groups. Mortality was largely not affected by age, ethnicity, cell-type involvement, or disease complications, but development of lymphoma showed a trend with increased mortality (56% vs 35%, P = .1). The overwhelming majority (75%) of patients who died after HSCT succumbed to relapsed disease. CAEBV remains challenging to treat when advanced disease is present. Outcomes would likely improve with better disease control strategies, earlier referral for HSCT, and close follow-up after HSCT including aggressive management of rising EBV DNA levels in the blood.

In the United Blacks and Hispanics are less likely than Whites to survive acute leukemias and other serious hematologic malignancies. 1-3 Allogeneic hematopoietic

Following hematopoietic stem cell transplant (HSCT), patients are at increased risk of vaccine-preventable diseases (VPDs) and experience worse outcomes of VPDs compared to immunocompetent patients. Therefore, patients are routinely vaccinated post-HSCT to restore VPD immunity. Published guidelines recommend revaccination based on time post-HSCT, although optimal revaccination timing and the value of using other clinical and laboratory variables to guide revaccination remain unclear. An institutional immune recovery-based protocol to guide timing of revaccination is used at Children's Hospital Colorado. This protocol incorporates time from transplant, time off immunosuppressive therapy and intravenous immunoglobulin replacement, absence of active graft-versus-host disease (GVHD), and minimum absolute CD4 count, absolute lymphocyte count (ALC), and immunoglobulin G (IgG) levels. The objective of this study is to evaluate the performance of this immune recovery-based revaccination protocol by determining rates of seroprotective vaccine responses achieved and describing demographic, clinical, and laboratory markers associated with protective antibody titers post-revaccination. Rates of seroprotection following revaccination were retrospectively determined for patients who received autologous or allogeneic HSCTs at Children's Hospital Colorado from 2007 to 2017. Percent seropositivity after revaccination was determined for ten VPDs: measles, mumps, rubella, varicella, tetanus, diphtheria, Haemophilus influenzae type B (Hib), poliovirus, hepatitis B virus (HBV), and Streptococcus pneumoniae. The impact of covariates, including post-HSCT vaccine timing, patient demographics, clinical features (diagnosis, donor and conditioning regimen data, GVHD, cytomegalovirus disease), and laboratory parameters (CD4 count, ALC, IgG level), on rates of seroprotection post-revaccination was determined using Wilcoxon rank sum, Fisher's exact, or chi-square tests, as appropriate. One hundred-twelve unique patients among 427 HSCT recipients had available data for both revaccination timing and vaccine titers. Among these, high rates of seroprotection were achieved after revaccination for rubella (100%), diphtheria (100%), tetanus (100%), and Hib (98%). More modest rates of seroprotection were achieved after revaccination with HBV (87%) and pneumococcal conjugate (85%) vaccines. Seroprotection was lower after revaccination with measles (76%), pneumococcal polysaccharide (72%), mumps (67%), and varicella (25%) vaccines. Greater rates of seroprotection were associated with younger age (hepatitis B vaccine, P = .04), lack of prior rituximab treatment (pneumococcal conjugate vaccine, P = .005), lack of total body irradiation (pneumococcal conjugate vaccine, P = .03), and receipt of a non-cord blood transplant (pneumococcal polysaccharide vaccine, P = .04). These results suggest that a revaccination protocol that incorporates both time post-HSCT and patient-specific indicators of immunologic recovery can achieve high rates of seroprotection against most VPDs. Seroprotection rates for HBV and PCV were notably among the highest reported in children post-HSCT, suggesting that an immune recovery-based protocol may improve seroprotection for some VPDs that frequently are associated with lower vaccine responses post-HSCT. Seroprotection rates for other VPDs remained suboptimal after revaccination. Therefore, evaluation of additional strategies, such as the use of novel markers of immune competence and new vaccines, to further optimize protection against VPDs in this population is warranted.

The timely identification of germline genetic causes of pediatric bone marrow failure (BMF) impacts medical screening practices, family counseling, therapeutic decision-making, and risk of progression to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). At diagnosis, treatment decisions need to be made quickly to mitigate risks associated with profound cytopenias. As genetic testing options are rapidly evolving, an efficient multi-disciplinary approach and algorithm, including early involvement of a genetics team, is needed to expedite diagnosis and therapeutic decision-making. This process aids in the identification of appropriate candidates for molecular genetic testing. We present our single center experience reviewing the implementation of genetic counseling and a diagnostic and therapeutic algorithm used to guide genetic evaluation of pediatric BMF. Disease-specific next-generation sequencing (NGS) panels were most often pursued in patients who presented with a clinical phenotype consistent with a known inherited BMF syndrome and when trying to reduce incidental or uninformative results. Broader BMF NGS panels were most often utilized when unable to narrow the suspected etiology to a single disorder. Whole exome sequencing helped with optimizing treatment decision-making in higher risk children with BMF who required expedited hematopoietic stem cell transplantation. The experience has led to improvements to our process for evaluating patients with BMF.

PURPOSE Severe (grade 3-4) acute graft-versus-host disease (AGVHD) is a major cause of death after unrelated-donor (URD) hematopoietic cell transplant (HCT), resulting in particularly high mortality after HLA-mismatched transplantation. There are no approved agents for AGVHD prevention, underscoring the critical unmet need for novel therapeutics. ABA2 was a phase II trial to rigorously assess safety, efficacy, and immunologic effects of adding T-cell costimulation blockade with abatacept to calcineurin inhibitor (CNI)/methotrexate (MTX)-based GVHD prophylaxis, to test whether abatacept could decrease AGVHD. METHODS ABA2 enrolled adults and children with hematologic malignancies under two strata: a randomized, double-blind, placebo-controlled stratum (8/8-HLA-matched URD), comparing CNI/MTX plus abatacept with CNI/MTX plus placebo, and a single-arm stratum (7/8-HLA-mismatched URD) comparing CNI/MTX plus abatacept versus CNI/MTX CIBMTR controls. The primary end point was day +100 grade 3-4 AGVHD, with day +180 severe-AGVHD-free-survival (SGFS) a key secondary end point. Sample sizes were calculated using a higher type-1 error (0.2) as recommended for phase II trials, and were based on predicting that abatacept would reduce grade 3-4 AGVHD from 20% to 10% (8/8s) and 30% to 10% (7/8s). ABA2 enrolled 142 recipients (8/8s, median follow-up = 716 days) and 43 recipients (7/8s, median follow-up = 708 days). RESULTS In 8/8s, grade 3-4 AGVHD was 6.8% (abatacept) versus 14.8% (placebo) ( P = .13, hazard ratio = 0.45). SGFS was 93.2% (CNI/MTX plus abatacept) versus 82% (CNI/MTX plus placebo, P = .05). In the smaller 7/8 cohort, grade 3-4 AGVHD was 2.3% (CNI/MTX plus abatacept, intention-to-treat population), which compared favorably with a nonrandomized matched cohort of CNI/MTX (30.2%, P < .001), and the SGFS was better (97.7% v 58.7%, P < .001). Immunologic analysis revealed control of T-cell activation in abatacept-treated patients. CONCLUSION Adding abatacept to URD HCT was safe, reduced AGVHD, and improved SGFS. These results suggest that abatacept may substantially improve AGVHD-related transplant outcomes, with a particularly beneficial impact on HLA-mismatched HCT.

INTRODUCTION:131 I-meta-iodobenzylguanidine (131 I-MIBG) is effective in relapsed neuroblastoma. The Children's Oncology Group (COG) conducted a pilot study (NCT01175356) to assess tolerability and feasibility of induction chemotherapy followed by 131 I- MIBG therapy and myeloablative busulfan/melphalan (Bu/Mel) in patients with newly diagnosed high-risk neuroblastoma. METHODS:Patients with MIBG-avid high-risk neuroblastoma were eligible. After the first two patients to receive protocol therapy developed severe sinusoidal obstruction syndrome (SOS), the trial was re-designed to include an 131 I-MIBG dose escalation (12, 15, and 18 mCi/kg), with a required 10-week gap before Bu/Mel administration. Patients who completed induction chemotherapy were evaluable for assessment of 131 I-MIBG feasibility; those who completed 131 I-MIBG therapy were evaluable for assessment of 131 I-MIBG + Bu/Mel feasibility. RESULTS:Fifty-nine of 68 patients (86.8%) who completed induction chemotherapy received 131 I-MIBG. Thirty-seven of 45 patients (82.2%) evaluable for 131 I-MIBG + Bu/Mel received this combination. Among those who received 131 I-MIBG after revision of the study design, one patient per dose level developed severe SOS. Rates of moderate to severe SOS at 12, 15, and 18 mCi/kg were 33.3%, 23.5%, and 25.0%, respectively. There was one toxic death. The 131 I-MIBG and 131 I-MIBG+Bu/Mel feasibility rates at the 15 mCi/kg dose level designated for further study were 96.7% (95% CI: 83.3%-99.4%) and 81.0% (95% CI: 60.0%-92.3%). CONCLUSION:This pilot trial demonstrated feasibility and tolerability of administering 131 I-MIBG followed by myeloablative therapy with Bu/Mel to newly diagnosed children with high-risk neuroblastoma in a cooperative group setting, laying the groundwork for a cooperative randomized trial (NCT03126916) testing the addition of 131 I-MIBG during induction therapy.

BACKGROUND:Adenovirus (AdV) is increasingly recognized as a threat to successful outcomes after allogeneic hematopoietic cell transplantation (allo-HCT). Guidelines have been developed to inform AdV screening and treatment practices, but the extent to which they are followed in clinical practice in the United States is still unknown. The incidence of AdV in the United States is also not well documented. The main objectives of the AdVance US study were thus to characterize current AdV screening and treatment practices in the United States and to estimate the incidence of AdV infection in allo-HCT recipients across multiple pediatric and adult transplant centers.METHODS:Fifteen pediatric centers and 6 adult centers completed a practice patterns survey, and 15 pediatric centers and four adult centers completed an incidence survey.RESULTS:The practice patterns survey results confirm that pediatric transplant centers are more likely than adult centers to routinely screen for AdV, and are also more likely to have a preemptive AdV treatment approach compared to adult centers. Perceived risk of AdV infection is a determining factor for whether routine screening and preemptive treatment are implemented. Most pediatric centers screen higher-risk patients for AdV weekly, in blood, and have a preemptive AdV treatment approach. The incidence survey results show that from 2015 to 2017, a total of 1230 patients underwent an allo-HCT at the 15 pediatric transplant centers, and 1815 patients underwent an allo-HCT at the 4 adult transplant centers. The incidences of AdV infection, AdV viremia, and AdV viremia ≥ 1000 copies/mL within 6 months after the first allo-HCT were 23%, 16%, and 9%, respectively, for patients at pediatric centers, and 5%, 3%, and 2%, respectively, for patients at adult centers.CONCLUSIONS:These findings provide a more recent estimate of the incidence of AdV infection in the United States, as well as a multicenter view of practice patterns around AdV infection screening and intervention criteria, in pediatric and adult allo-HCT recipients.

Background: Pediatric patients undergoing hematopoietic stem cell transplantation (HSCT) may be at risk for malglycemia and adverse outcomes, including infection, prolonged hospital stays, organ dysfunction, graft-versus-host-disease, delayed hematopoietic recovery, and increased mortality. Continuous glucose monitoring (CGM) may aid in describing and treating malglycemia in this population. However, no studies have demonstrated safety, tolerability, or accuracy of CGM in this uniquely immunocompromised population. Materials and Methods: A prospective observational study was conducted, using the Abbott Freestyle Libre Pro, in patients aged 2-30 undergoing HSCT at Children's Hospital Colorado to evaluate continuous glycemia in this population. CGM occurred up to 7 days before and 60 days after HSCT, during hospitalization only. In a secondary analysis of this data, blood glucoses collected during routine HSCT care were compared with CGM values to evaluate accuracy. Adverse events and patient refusal to wear CGM device were monitored to assess safety and tolerability. Results: Participants (n = 29; median age 13.1 years, [interquartile range] [4.7, 16.6] years) wore 84 sensors for an average of 25 [21.5, 30.0] days per participant. Paired serum-sensor values (n = 893) demonstrated a mean absolute relative difference of 20% ± 14% with Clarke Error Grid analysis showing 99% of pairs in the clinically acceptable Zones (A+B). There were four episodes of self-limited bleeding (4.8% of sensors); no other adverse events occurred. Six patients (20.7%) refused subsequent CGM placements. Conclusions: CGM use appears safe and feasible although with suboptimal accuracy in the hospitalized pediatric HSCT population. Few adverse events occurred, all of which were low grade.

Autoimmune cytopenias (AICs) are rare, but serious complications of allogeneic hematopoietic cell transplantation (allo‐HSCT).

Introduction Autoimmune cytopenia (AIC) is a rare, but serious complication of allogeneic hematopoietic cell transplantation (HCT), and treatment for post-HCT AIC can have severe short- and long-term consequences. We sought to identify AIC risk factors and evaluate treatment-related late effects, in order to better guide management. Methods We performed a retrospective case-control study of pediatric patients who underwent HCT at Children's Hospital Colorado from June 2005 to March 2019. We compared clinical and transplant-related characteristics, chimerism, immune reconstitution, outcomes and late effects between patients who developed AICs (n=20) and a control group (n=40) matched by primary disease category and donor source. Results The incidence of AIC was 5.6% amongst all patients who received allogeneic HCT in the study timeframe (n=354). Of these, 75% had non-malignant disease (n=15). Thirteen developed autoimmune hemolytic anemia (65%), 5 had immune thrombocytopenia (25%), 1 had Evans syndrome (5%) and 1 had autoimmune neutropenia (5%). Median time to AIC was 219 days (range 97-1205 days). There was no difference between AIC patients and controls in gender, age at HCT, conditioning regimen, serotherapy, total body irradiation (TBI), GVHD prophylaxis, chronic GVHD, or time to neutrophil and platelet recovery. Compared to controls, more AIC patients had ABO mismatch (50% vs. 40%, p=0.07), and a higher proportion of grade I-II acute GVHD (93.9% vs. 50%, p=0.06), but was not statistically significant. Seventeen patients (85%), had >95% donor chimerism immediately prior to development of AIC. Fifteen patients (75%) received steroids as part of first-line therapy for AIC and 17 patients (85%) received rituximab as part of all therapy. Eleven patients (64.7%) received rituximab as part of first-line therapy. Only 25% of patients (n=5) responded to initial therapy. Median time to resolution of AIC was 12.0 months (range 10 days to 90 months). Strikingly, 12 patients (70.6%) are still receiving intravenous immune globulin (IVIG) replacement for hypogammaglobulinemia at least 1-year after HCT at a median time of 597.5 days (range 83-3715 days) from last rituximab dose. Iron overload was more prevalent in AIC patients compared to controls (n=8 vs n=1, p=0.0004, median of 2.3 years after HCT). The overall survival (OS) of the AIC cohort was similar to the control group (85% vs 82.5%). No patients in the AIC cohort died from AIC-related complications. In the AIC cohort, 2 patients died from sepsis and 1 patient died from relapsed disease. Conclusions In this case-control study of pediatric HCT patients, AIC was not associated with mixed chimerism or GVHD. The majority of AIC cases did not respond to first-line therapy and required multiple treatment modalities to achieve a complete response. Late effects from AIC-directed therapies include prolonged hypogammaglobulinemia and iron overload.

Background: Among pediatric hematopoietic stem cell transplant (HSCT) recipients, abnormal glycemic control is shown to be associated with increased risk of transplant-related mortality, death from any cause, risk of infection, increased hospitalized, and intensive care days. Independent effects of higher glycemic variability, a component of glycemic control, have not been described. This study aimed to characterize risk factors for, and consequences of, higher glycemic variability in HSCT patients. Procedure: Medical records for a cohort of 344 patients, age 0-30 years, who underwent first HSCT from 2007 to 2016 at Children's Hospital Colorado were retrospectively reviewed. Glucose coefficients of variation (CV) were analyzed for HSCT days -14 to 0 and 0-30, and patients were assessed for potential risk factors and outcomes. Results: Roughly one-third of patients had pre-HSCT and day 0-30 glucose CV above the reported healthy adult range. Independent of HSCT type, doubling of pre-HSCT glucose CV was associated with a 4.91-fold (95% confidence interval [CI], 1.40-17.24) increased hazard of infection, as well as increased risk for intensive care hospitalization for allogenicHSCT patients. Multivariable analysis demonstrated that allogeneicHSCT patients had a 1.40- and 1.38-fold (95% CI, 0.98-1.99 and 1.00-1.91) increased hazard of death for every doubling of pre-HSCT and day 0-30 glucose CV, respectively. Conclusions: Just as with higher mean glucose, higher glycemic variability in the pediatric HSCT population is independently associated with significantly increased morbidity. Additional research is required to evaluate the utility of glucose control to mitigate these relationships and improve HSCT outcomes.

Background Myeloablative (MAC) or reduced toxicity conditioning (RTC) followed by UCBT in children with malignant and non-malignant diseases is safe and effective (Geyer/Cairo, BJH 2011). However, concentration of CD34+ HPCs in UCB is low, leading to delayed hematopoietic reconstitution and high incidence of engraftment failure (Satwani/Cairo, BBMT 2013). HPDSCs are rich in HPCs, low in HLA Class I/II expression and T-cells, and have regenerative, anti-inflammatory, and immunosuppressive properties (Liao/Cairo, Stem Cells Translational Medicine 2018). Objective To determine the safety and efficacy of HPDSC with UCBT in children with malignant and non-malignant diseases. Design/Method 4-6/6 HLA matched UCB with TNC ≥ 5 × 107/kg (4/6 HLA match) or ≥ 3.5 × 107/kg (5-6/6 HLA match) were included. Patients received MAC or RTC followed by UCB plus HPDSC infusion. GVHD prophylaxis consisted of tacrolimus and mycophenolate mofetil as previously described  (Bhatia/Cairo, BBMT 2009). Results To date, 28 patients ≤18 years were enrolled, 15 males and 13 females. Mean age in years ± SD was 6.8±5.5. There were 12 patients with non-malignant disease including ALD (2), CAT (1), CGD (1), SCID (2), dyskeratosis congenita (1), congenital neutropenia (1), SAA (2), LCH (1), and SDS (1) and 16 patients with malignant disease including pre B-cell ALL- CR1 (4), pre B-cell ALL - CR2 (4), T-cell ALL – CR1 (1), AML-CR1 (4), JMML-CR1 (1), TLL - CR1 (1), and BL - CR2 (1). Mean UCB TNC±SD and CD34±SD infused were 7.7 × 107±5.0/kg and 0.48 × 106±0.59/kg, respectively. There were no SAEs associated with HPDSC infusions. Four patients were removed prior to day 180 due to progressive disease (1) and engraftment failure necessitating alternative treatment (3). Probability of neutrophil engraftment was 89.2%, median day 22 (13-53). Of neutrophil engrafted evaluable patients (n=22), the probability of platelet engraftment by day 100 was 90.9%, median day 42 (20-98). Of neutrophil engrafted, evaluable patients at day 30, 60, 100 and 180, mean whole blood UCB chimerism was 92, 99, 96 and 99%, respectively. Average whole blood HPDSC chimerism was <1% at day 30 and not detected beyond day 60. The probability of grade 2-4 aGVHD at day 100 was 17.3% (CI95: 0.9-51.9). Of patients without grade 2-4 aGVHD, normalization of CD3+, CD19+, and CD56+ cells occurred by day 100, and CD8+ and CD4+ cells by day 270. The probability of OS at 1 year was 78.0% (CI95: 55.0-90.2). Deaths occurred due to systemic adenovirus (3), RSV (1) and relapse (1). Conclusions These results suggest that UCBT with HPDSC is safe and well tolerated, has a lower than expected probability of Grade 2-4 aGVHD, and results in robust immune reconstitution. A larger cohort and longer follow-up is required to determine the clinical significance of these findings.

Malglycemia (hypoglycemia, hyperglycemia, and/or glycemic variability) in adult hematopoietic stem cell transplant (HSCT) recipients is associated with increased infection, graft-versus-host disease, organ dysfunction, delayed engraftment, and mortality. Malglycemia has not been studied in pediatric HSCT recipients. This study aimed to characterize the incidence and consequences of malglycemia in this population. Medical records for a cohort of 344 patients, age 0 to 30 years, who underwent first HSCT from 2007 to 2016 at Children's Hospital Colorado were retrospectively reviewed. Glucose data were analyzed in intervals and assessed for potential risk factors and associated outcomes. Malglycemia occurred in 43.9% of patients. Patients with a day 0 to 100 mean glucose of 100 to 124 mg/dL had a 1.76-fold (95% confidence interval [CI], 1.10-2.82; P = .02) increased risk of death and patients with a day 0 to 100 mean glucose ≥ 125 mg/dL had a 7.06-fold (95% CI, 3.84-12.99; P < .0001) increased risk of death compared with patients with a day 0 to 100 mean glucose < 100 mg/dL. For each 10 mg/dL increase in pre-HSCT glucose, there was a 1.11-fold (95% CI, 1.04-1.18; P = .0013) increased risk of post-HSCT infection. These adverse impacts of malglycemia occurred independent of transplant type, graft-versus-host disease, and steroid therapy. Malglycemia in the pediatric HSCT population is independently associated with significantly increased risk of morbidity and mortality. Further research is required to evaluate the utility of glucose control to mitigate these relationships and improve HSCT outcomes. This trial was registered at www.clinicaltrials.gov as #NCT03482154.

When hematopoietic stem cell transplant (HSCT) is necessary for children with acute myeloid leukemia (AML), there remains debate about the best stem cell source. Post-HSCT relapse is a common cause of mortality, and complications such as chronic graft versus host disease (cGVHD) are debilitating and life-threatening. To compare post-HSCT outcomes of different donor sources, we retrospectively analyzed consecutive transplants performed in several international centers from 2005 to 2015. A total of 317 patients were studied: 19% matched sibling donor (MSD), 23% matched unrelated donor (MUD), 39% umbilical cord blood (UCB), and 19% double UCB (dUCB) recipients. The median age at transplant was 10 years (range, 0.42-21 years), and median follow-up was 4.74 years (range, 4.02-5.39 years). Comparisons were made while controlling for patient, transplant, and disease characteristics. There were no differences in relapse, leukemia-free survival, or nonrelapse mortality. dUCB recipients had inferior survival compared with matched sibling recipients, but all other comparisons showed similar overall survival. Despite the majority of UCB transplants being HLA mismatched, the rates of cGVHD were low, especially compared with the well-matched MUD recipients (hazard ratio, 0.3; 95% confidence interval, 0.14-0.67; P = .02). The composite measure of cGVHD and leukemia-free survival (cGVHD-LFS), which represents both the quality of life and risk for mortality, was significantly better in the UCB compared with the MUD recipients (HR, 0.56; 95% confidence interval, 0.34-1; P = .03). In summary, the use of UCB is an excellent donor choice for pediatric patients with AML when a matched sibling cannot be identified.