The impact of alternative donor types on viral infections in pediatric hematopoietic stem cell transplantation

Viral infections remain one of the most important complications following allogeneic HSCT. Few reports compare virus infection between different donor types in pediatric patients. We retrospectively analyzed viral infections and the outcome of one hundred and seventy‐one pediatric patients (median 7.38 years) who underwent allogeneic HSCT from matched related donor (MRD, n = 71), 10 of 10 HLA allele‐matched unrelated donors (MUD1; n = 29), 9 of 10 HLA allele‐matched unrelated donors (MUD2; n = 40), and haploidentical donors (n = 31). PCR screening for BK virus, adenovirus, Epstein‐Barr virus, parvovirus B19, human herpesvirus 6, and CMV were performed routinely weekly. Infections between 0‐30, 31‐100, and 101 days‐2 years were identified separately. BK virus and CMV reactivations were significantly low in MRD transplant patients (P = .046 and P < .0001, respectively), but incidences of all virus infections between MUD1, MUD2, and haplo‐HSCT were found statistically not different. The OS was found to be affected by having one or multiple virus infection (P = .04 and P = .0008). Despite antiviral prophylaxis and treatments, post‐transplant viral infections are associated with reduced overall survival. Haplo‐HSCT is comparable with MUD transplantation in the setting of viral infections. A larger study group and prospective studies are needed to confirm this observation.     

Pericardial effusion following hematopoietic stem cell transplantation in children: Incidence,risk factors,and outcomes

PCE is a complication of HSCT that has previously been described in small single‐center studies. This study aimed to assess the frequency of, risk factors for, and outcomes of children with a PCE following HSCT across a large multi‐center cohort. All patients ≤21 years undergoing first HSCT (1/2005‐9/2015) were identified from the Pediatric Health Information System. ICD‐9 codes were used to identify patients with a PCE during or following the transplant encounter. Multivariable modeling assessed risk factors for developing a PCE and assessed the impact of PCE on patient outcome. Of 10 455 included patients, 739 (7.1%) developed a PCE (median 69 days post‐HSCT, interquartile range 33‐165 days). PCE developed more commonly in allogeneic vs autologous HSCT recipients (9.1% vs 2.9%, P < .001). Among allogeneic HSCT recipients, independent risk factors for PCE included thrombotic microangiopathy (AHR 2.94, 95% CI 2.16‐4.00), heart failure (AHR 2.07, 95% CI 1.61‐2.66), PCE pre‐HSCT (AHR 1.92, 95% CI 1.19‐3.09), arrhythmia (AHR 1.76, 95% CI 1.44‐2.16), graft‐versus‐host disease (AHR 1.31, 95% CI 1.05‐1.62), female sex (AHR 1.28, 95% CI 1.07‐1.52), and malignancy (AHR 1.28, 95% CI 1.02‐1.60). Allogeneic HSCT patients with PCE demonstrated worse survival than those without PCE (5‐year survival 50.8% vs 76.9%, P < .001). PCE was independently associated with mortality (AHR 1.96, 95% CI 1.62‐2.37) following allogeneic HSCT and was not impacted by pericardial intervention. PCE occurs more commonly in patients following allogeneic (vs autologous) HSCT and is associated with inferior outcomes.     

Antithymocyte globulin in pediatric allogeneic hematopoietic stem cell transplantation: Infusion time and tolerability

Antithymocyte globulin is a major drug in transplantation. rATG has been successfully used to prevent graft‐versus‐host disease in allogeneic HSCT. However, its first infusion is associated with reactions ranging from simple fevers to distributive shocks and may interfere with the transplant conditioning. To evaluate the impact of rATG infusion rate on clinical tolerability, we conducted a retrospective study of all pediatric allogeneic HSCT patients who received rATG (Thymoglobulin®) as part of their conditioning at Lille University Hospital from 2003 to 2018. Until 2012, patients received rATG with a theoretical infusion time of 12 hours (12H group, n = 33). From 2012, they had a theoretical infusion time of 4 hours (4H group, n = 43). Patients from the 12H arm presented more ≥ grade 3 infusion‐related reactions at first dose (70% versus 44%, P = .027), had significantly higher fever (median of 39.6°C versus 39.2°C, P = .002), and needed a greater use of symptomatic treatments. However, they received a slightly higher first dose of rATG (median of 2.7 versus 2.3 mg/kg, P = .042). In view of these results, a rATG infusion time of 4 hours can be a relevant option for pediatric transplant centers to avoid interference with the conditioning regimen and facilitate medical surveillance.     

Transplant‐related mortality and survival in children with malignancies treated with allogeneic hematopoietic stem cell transplantation. A multicenter analysis

The aim of the study was to assess the risk of TRM in pediatric patients treated for malignant disorders with allogeneic HSCT, according to different risk factors. The treatment outcome was analyzed in 299 pediatric patients treated in pediatric transplant departments from 2006 to 2015. To compare the outcome, patients were analyzed all together and in groups according to the diagnosis, age at transplant, donor type, disease status, stem cell source, and pediatric TRM score. At the end of the observation time, 82 patients were alive, 82 died, of which 40 due to transplant‐related reasons. The most frequently observed causes of TRM were toxic complications effecting with organ failure (38%), followed by infections (26%), PTLD (14.3%), and GvHD (16.7%). There was no statistical difference in the incidence of TRM depending on stem cell source (P = .209) and primary diagnosis (P = .301). According to TRM score, TRM was significantly higher in high‐risk group (P = .006). High‐risk patients had lower survival comparing to low/intermediate group (P = .0001). OS did not differ between ALL, AML, and MDS/JMML groups. The study confirmed the utility of factors included in TRM score stratification in assessing the risk of transplant procedure in pediatric patients transplanted for malignancies.     

Comparison of survival outcome between donor types or stem cell sources for childhood acute myeloid leukemia after allogenic hematopoietic stem cell transplantation: A multicenter retrospective study of Study Alliance of Yeungnam Pediatric Hematology‐oncology

We compared transplant outcomes between donor types and stem cell sources for childhood acute myeloid leukemia (AML). The medical records of children with AML in the Yeungnam region of Korea from January 2000 to June 2017 were reviewed. In all, 76 children with AML (male‐to‐female ratio = 46:30) received allogenic hematopoietic stem cell transplantation (allo‐HSCT). In total, 29 patients received HSCT from either a matched‐related donor or a mismatched‐related donor, 32 patients received an unrelated donor, and 15 patients received umbilical cord blood. In term of stem cell sources, bone marrow was used in 15 patients and peripheral blood in 46 patients. For all HSCT cases, the 5‐year overall survival (OS) was 73.1% (95% CI: 62.7‐83.5) and the 5‐year event‐free survival (EFS) was 66.1% (95% CI: 54.5‐77.7). There was no statistical difference in 5‐year OS according to the donor types or stem cell sources (P = .869 and P = .911). There was no statistical difference in 5‐year EFS between donor types or stem cell sources (P = .526 and P = .478). For all HSCT cases, the 5‐year relapse rate was 16.1% (95% CI: 7.3‐24.9) and the 5‐year non‐relapse mortality (NRM) was 13.3% (95% CI: 5.1‐21.5). There was no statistical difference in the 5‐year relapse rate according to the donor types or stem cell sources (P = .971 and P = .965). There was no statistical difference in the 5‐year NRM between donor types or stem cell sources (P = .461 and P = .470).     

High incidence of BK virus‐associated hemorrhagic cystitis in children after second or third allogeneic hematopoietic stem cell transplantation

BKV‐HC is a serious complication of allogeneic HSCT. To characterize the incidence, risk factors, and clinical outcomes of post‐HSCT BKV‐HC, we retrospectively analyzed 112 patients who underwent one or more allogeneic HSCTs at our hospital between 2001 and 2017. Twenty underwent second or third HSCT thereafter. Ten patients developed BKV‐HC at a median of 30 days after HSCT. The 100‐day cumulative incidences of grade 0‐4 and grade 2‐4 BKV‐HC were 7.8% and 6.2%, respectively. HSCTs performed in 2011‐2017 associated with significantly higher 100‐day cumulative incidence of grade 2‐4 BKV‐HC (14.0%) than HSCTs performed in 2001‐2010 (1.3%, P = 0.004). On multivariate analysis, second or third HSCT was the only independent significant risk factor for development of grade 2‐4 BKV‐HC (P = 0.015). Serial PCR monitoring of urine and blood BKV load did not predict BKV‐HC. The recent increase in the incidence of BKV‐HC may reflect recent innovations in transplant technologies that facilitate second or third HSCT, which are known to cause prolonged immune deficiency. If safe and effective treatment or prophylaxis becomes available, it could be used to target the high‐risk patients for BKV‐HC.     

Control of graft‐versus‐host disease with rabbit anti‐thymocyte globulin,rituximab, and bortezomib in TCRαβ/CD19‐depleted graft transplantation for leukemia in children: a single‐center retrospective analysis of two GVHD‐prophylaxis regimens

Both acute GVHD and chronic GVHD remain the leading cause of morbidity and death after allogeneic HSCT. We conducted a retrospective analysis comparing two GVHD‐prophylaxis regimens: 35 patients received “Regimen 1” (horse ATG, tacrolimus, and methotrexate) and 46 “Regimen 2” (rabbit ATG, rituximab, and peritransplant bortezomib). All 81 patients with a median age of 9 (0.6‐23) years with ALL (n = 31) or AML (n = 50) in complete remission received TCRαβ/CD19‐depleted transplants between May 2012 and October 2016, from 40 HLA‐matched unrelated and 41 haploidentical donors. After a median follow‐up of 3.9 years, the CI of acute GVHD II‐IV was 15% (95% CI: 7‐30) in the “Regimen 2” group and 34% (95% CI: ?54) in the “Regimen 1” group, P = .05. “Regimen 2” was also more effective in the prevention of chronic GVHD; the CI at 1 year after HSCT was 7% (95% CI: 2‐19) vs 31% (95% CI: 19‐51), P = .005. The CI of relapse at 3 years adjusted for the GVHD‐prophylaxis regimen groups 31% (95% CI: 19‐51) for the “Regimen 1” vs 21% (95% CI: 11‐37) for the “Regimen 2”, P = .3. The retrospective observation suggests that the use of the rATG, rituximab, and bortezomib was associated with significantly lower rate of GVHD without the loss of anti‐leukemic activity.     

Quantiferon‐Cytomegalovirus assay: A potentially useful tool in the evaluation of CMV‐specific CD8+ T‐cell reconstitution in pediatric hematopoietic stem cell transplant patients

Pediatric HSCT recipients are at high risk for CMV reactivation due to their immature immune system and therapy following transplantation. Reconstitution of CMV‐specific T‐cell immunity is associated with control and protection against CMV. The clinical utility of monitoring CMV‐specific CMI to predict CMV viremia in pediatric HSCT patients using the Quantiferon‐CMV (QIAGEN^®) test was investigated prospectively. Thirty‐seven pediatric allogeneic HSCT recipients were enrolled from 3/2010‐6/2012. CMV viremia was detected via weekly real‐time PCR. The Quantiferon‐CMV test was conducted pretransplant, early after transplantation, 30, 90 , 180 , 270, and 360 days post‐transplantation. The incidence of CMV viremia was 51% (19/37) with half of the episodes within ≤30 days post‐transplant. Fifteen patients showed CMV‐specific immunity (average of 82 days). The cumulative incidence of CMV reactivation in patients who developed CMV‐specific immunity was lower than those who did not (15% vs 53%; P = .023). The ROC statistical analysis showed that the AUC was 0.725 in predicting viremia, for Quantiferon‐CMV test. In this cohort, the Quantiferon‐CMV assay was a valuable method for identifying pediatric HSCT patients at high risk for CMV viremia, suggesting potential clinical utility to individualize patient's management post‐transplant.     

Safety of hematopoietic cell infusion in children with malignant and non‐malignant diseases

HPC infusions have been associated with a variety of adverse events related to either patient or HPC product‐related factors. Studies documenting infusion‐related AEs in children are limited. We reviewed HPC infusion records in 354 children. Infusion‐related adverse events were classified as follows: grade 0—absent, grade I—mild, grade II—moderate, grade III—severe, grade IV—life‐threatening, and grade V—death. The percentage of patients with grade 0, I, and II‐IV AEs was as follows: 0 = 67%, I = 23.4%, and II‐V = 9.6% (one patient had fatal anaphylactic reaction to dimethyl sulfoxide). The incidence of grade II‐IV hypertension was 7.1%. There was a higher incidence of AEs with infusion of allogeneic bone marrow versus allogeneic PBSCs (47.4% vs 25.3%, P = .001). Cryopreserved products had a lower incidence of infusion‐associated AEs compared with fresh HPC products (24% vs 39.4%, P = .003). Allogeneic HPC infusion volume (>100 mL) was a significant risk factor for infusion‐associated AEs (P < .001). Patients >10 years who received autologous HPC infusions had higher risk of AEs when compared to patients <10 years (P = .01). Our study demonstrated that despite a high incidence of infusion‐associated hypertension, HPC infusion is relatively safe in children. Investigating strategies to optimize management of hypertension in the setting of HPC infusion is warranted.     

Hematopoietic stem cell transplantation without in vivo T‐cell depletion for pediatric aplastic anemia: A single‐center experience

For young patients, HLA‐MRD HSCT is the first‐line treatment of SAA. However, due to China's birth control policy, few patients could find suitable sibling donors and HLA‐MUD. More and more transplantation centers have used Haplo‐D as the donor source for young adult and pediatric patients. However, studies with larger amount of pediatric patients are rare. We retrospectively analyzed the data of children with AA who were treated with allogeneic HSCT and compared the therapeutic efficacy of Haplo‐HSCT and MRD/MUD group. A total of 62 patients were enrolled. Implantation was successfully performed in 58 patients. There was no significant difference in the time for reconstruction of hematopoietic function between patients in the two groups. Thirty‐two had grade I‐IV aGVHD with incidence of 51.61%. The incidence of aGVHD was 79.41% for patients in the Haplo‐HSCT, significantly higher than that of 17.86% for patients in the MRD/MUD group (P < .01). However, the incidence of cGVHD was not significantly different between patients in the two groups (26.47% vs 10.71%, P = .09), the incidence of CMV infection was 28.57% and 52.94% for patients in the MRD/MUD and Haplo group, respectively, showing no significant difference (P = .053). The incidence of EBV infection was 47.06% for patients in the Haplo group and 28.57% for patients in the MRD/MUD group, showing no significant difference (P = .11). However, the 3‐ and 5‐year cumulative OS and FFS rates showed statistically significant difference in the two groups, P = .012 and .045, respectively. Compared to Haplo‐HSCT, MRD/MUD is more economic. In this study, we achieved good Haplo transplantation results. The incidences of cGVHD and CMV/EBV were not significantly different between Haplo group and MRD/MUD group. Although OS and FFS of the Haplo group were not as good as those of the MRD/MUD group, it is still acceptable as an alternative treatment under emergency.     

Lymphocyte subset at time of Epstein‐Barr viremia post‐allogeneic hematopoietic stem cell transplantation in children may predict development of post‐transplant lymphoproliferative disease: CD8:CD20 ratio as a sensitive predictor

EBV–associated PTLD following allogeneic HSCT is a serious complication associated with significant mortality. In this retrospective study, we evaluated whether lymphocyte subset numbers and CD8:CD20 ratio at time of EBV viremia in children undergoing allogeneic HSCT could predict development of PTLD. Absolute lymphocyte count, lymphocyte subsets, and CD8:CD20 ratio at the time of EBV viremia were analyzed. Patients who were treated preemptively with rituximab for high blood EBV viral load were excluded. Out of 266 patients transplanted during the study period, 26 patients were included in the analysis. Patients were divided into two cohorts; cohort 1 included patients with EBV‐associated PTLD (n = 5; four with proven, one with probable PTLD). Cohort 2 included patients with EBV viremia without PTLD (n = 21). Lymphocyte recovery was slower in the PTLD group. CD8:CD20 ratio was significantly lower in the PTLD group (median 0.15) compared to the non‐PTLD group (median 2.4, P = .012). Using the ROC curve and 1 as the cutoff value, CD8:CD20 ratios were analyzed. In the PTLD group, 4/5 patients (80%) had a ratio <1 whereas in the non‐PTLD group, all 21 patients had a ratio >1. Sensitivity and specificity were 80% and 100%, respectively. Negative and PPVs were 95% and 100%, respectively. Profoundly low T‐cell count and CD8:CD20 ratio may be used to predict development of PTLD in the context of EBV viremia in children post‐allogeneic HSCT. Further studies are needed to validate this finding.     

Educational and learning morbidity in pediatric heart transplant recipients: A pediatric heart transplant society study

Educational development is an important component of quality of life for children with heart transplant. Aims include determining prevalence of and risk factors for modified education placement in a large representative sample of pediatric heart transplant recipients. Participants included 1495 patients (age 6‐18 years) from the PHTS database. Data on education placement and clinical predictors were collected at listing and at 1 and 3 years post‐transplant. At listing, 88% of patients were in typical education placement, while 12% were in modified education. Males (P = .02), those with CHD (P < .0001), those with non‐private insurance (P < .0001), and those with longer hospital stay (P = .001) were more likely to be in a modified education placement at time of listing. Age, race, listing status, mechanical support, and waitlist time were not significantly associated with placement. The prevalence of typical education placement was similar (87% at 1‐year and 86% at 3‐year) post‐transplant. Predictors of modified education placement at 3‐year follow‐up included placement at listing (OR = 12.9 [95% CI 7.6‐21.9], P < .0001), non‐private insurance (OR = 2.0 [95% CI 1.3‐3.2], P = .001), CHD (OR = 1.8 [95% CI 1.1‐2.7, P = .01), history of post‐transplant infection (OR = 1.9 [95% CI 1.2‐2.9, P = .007), and number of post‐transplant infections (OR = 1.3 [95% CI 1.1‐1.5, P = .002). Among pediatric heart transplant recipients, males, those with non‐private insurance, those with CHD, and those who experience post‐transplant infections are at greatest risk for modified academic placement, which persists for several years post‐transplant and deserves targeted intervention.     

Is there an optimal organ acceptance rate for pediatric heart transplantation: “A sweet spot”?

Despite a limited supply of donors, potential donor hearts are often declined for subjective concerns regarding organ quality. This analysis will investigate the relationship between donor heart AR and patient outcome at pediatric transplant centers. The UNOS database was used to identify all match runs for pediatric candidates (age < 18 years) from 2008 through March 2015 in which a heart offer was ultimately placed. Centers which received ≥10 offers/y were included (10 634 offers, 38 centers). Transplant centers were stratified based on their AR: low (<20%, n = 13), medium (20%‐40%, n = 16), or high (>40%, n = 9). Low AR centers experienced worse negative WL outcome compared with medium (P = .022) and high (P = .004) AR centers. Low AR centers had similar post‐transplant graft survival to medium (P = .311) or high (P = .393) AR centers; however, medium AR centers had better post‐transplant graft survival than high AR centers (P = .037). E‐F survival from listing regardless of transplant was worse for low AR centers compared with medium (P < .001) or high (P = .001) AR centers. Low AR centers experience worse WL outcomes without improvement in post‐transplant outcomes. High AR centers experience higher post‐transplant graft failure than medium AR centers. AR of 20%‐40% appears to have optimal WL and post‐transplant outcomes.     

Clinical and histopathologic features of antibody‐mediated rejection among pediatric renal transplant recipients with preformed vs de novo donor‐specific antibodies

Preformed and de novo donor specific antibodies (pDSA and dnDSA) are risk factors for ABMR. This study compares the effects of pDSA vs dnDSA in pediatric kidney transplant recipients. Sixteen pediatric patients with biopsy‐proven ABMR were evaluated. Strong DSA (MFI >10 000) was recorded at transplant, rejection, and follow‐up. DSAs with the highest MFI were termed iDSAs. Allograft biopsies were scored according to Banff 2013 criteria. Seven of 16 (44%) patients had pDSA at transplant; 9 (56%) developed dnDSA. Patients with pDSA developed ABMR earlier (median = 63 vs 1344 days, P = .017), while patients with dnDSA were more likely to have strong Class II iDSA (100% vs 28%, P = .009). Viral infection or non‐adherence was more common in patients developing dnDSA (88.8% vs 28.6%, P < .01). Pathology in those with pDSAs demonstrated worse transplant glomerulitis (g score 1.57 ± 0.98 vs 0.56 ± 0.73, P = .031); however, those with dnDSAs exhibited higher C4d+ ABMR (P = .013). Patients developing dnDSAs showed ABMR later post‐transplant with predominance of HLA‐Class II iDSAs. Inadequate immunosuppression likely contributes to dnDSA formation. Patients with no DSA who have unprotocolized decreases in immunosuppression should be screened for dnDSA as it could lead to early intervention and potentially better outcomes.     

The incidence of autoimmune hemolytic anemia in pediatric hematopoietic stem cell recipients post‐first and post‐second hematopoietic stem cell transplant

The reported incidence of post‐allogeneic HSCT AIHA was between 4.4% and 6% following a single transplant. Cord blood transplantation, T‐cell depletion, and chronic GvHD are significantly associated with post‐transplant AIHA. During an 11‐yr period, data for 500 pediatric HSCT recipients were eligible for evaluation of the incidence of AIHA post‐first and post‐second transplants. Demographic, transplant, and post‐transplant‐related variables were analyzed. Twelve of 500 (2.4%) recipients at a median of 273 days and seven of 72 (9.7%) recipients at a median of 157 days developed AIHA post‐first and post‐second HSCT, respectively. Post‐first HSCT, none of the MRD recipients developed AIHA (0/175 MRD vs. 12/325 other donors, p = 0.04). Four of 12 required a second HSCT to control the AIHA. After the second HSCT, MUD was significantly associated with the development of AIHA. No other variables were associated with the post‐second transplant AIHA. The incidence of AIHA post‐first and post‐second HSCT was less than the reported. The increased incidence of AIHA among recipients of second HSCT is most likely due to the profound immune dysregulation. A much larger, prospective study would be needed to evaluate the incidence, complications, and management of post‐transplant AIHA.     

Is ABO mismatch another risk factor for allogeneic hematopoietic stem cell transplantation in pediatric thalassemic patients?

The ABO incompatibility between donor and recipient is not considered a barrier to successful allogeneic HSCT. Nevertheless, conflicting data still exist about the influence of ABO incompatibility on transplant outcome in pediatric patients with thalassemia. Fifty‐one children with beta‐thalassemia major who underwent allogeneic HSCT were enrolled this study. Twenty‐three of them (45%) received an ABO‐incompatible transplant [minor ABO mismatch: six (26%), major ABO mismatch: fourteen (61%), and bidirectional mismatch: three (13%)]. In this study, ABO incompatibility did not significantly impair GVHD, VOD, neutrophil and platelet engraftment, TRM, OS and TFS. Particularly in major and bidirectional ABO‐mismatched patients, a delayed erythroid recovery was recorded as compared to the group receiving an ABO‐compatible graft (median time, 31 and 38 days vs. 19.5 days; p: 0.02 and p: 0.03). Median time to red cell transfusion independence was significantly longer in major ABO‐incompatible patients (median time, 87 days vs. 32 days; p: 0.001). Therefore, whenever feasible, major ABO‐mismatched donors should be avoided in HSCT recipients, to prevent delayed erythroid recovery with prolonged RBC transfusion needs and impaired quality of life.     

Detection of graft fibrosis by vibration‐controlled transient elastography in pediatric liver transplant recipients

Pediatric liver transplant recipients are at risk of developing graft fibrosis which can affect patient survival. VCTE is a non‐invasive tool that measures LSM and has been shown to correlate with hepatic fibrosis. The aim of this study was to therefore evaluate the ability of LSM to predict fibrosis in pediatric liver transplant recipients with different graft types. We performed a cross‐sectional study evaluating LSM of 28 pediatric liver transplant recipients who underwent a total of 20 liver biopsies within 1 month of LSM. LSM was compared to liver histology as well as graft type: WL or PL. The median LSM of all post‐transplant patients was 5.6 kPa (range = 2.7‐18.3). There was a statistically significant correlation between LSM and METAVIR fibrosis score (P = .001) and LAF score (P < .001). There was no difference in LSM between graft type (P = .088). The AUROC curve for LSM predicting any significant fibrosis (F ≥ 2) was 0.863. A cutoff value of 7.25 had a sensitivity of 71%, specificity of 100%, NPV of 87%, and PPV of 100% for significant fibrosis. LSM by VCTE is feasible in pediatric liver transplant recipients regardless of graft type. We found a significant correlation between LSM and hepatic fibrosis and established a cutoff value that may help determine which patients warrant further evaluation for graft fibrosis.     

Generalized and specific anxiety in adolescents following heart transplant

Mental health concerns are associated with worse outcomes after adult heart transplant. Illness‐specific anxiety is associated with worsened psychological well‐being after other solid organ transplants but has never been characterized after pediatric heart transplant. This single‐center cross‐sectional study aimed to evaluate illness‐specific and generalized anxiety after heart transplantation in adolescents. A novel 12‐item PHTF, GAD‐7, and the PedsQL were administered. Univariate associations of demographics, clinical features, and medication adherence as measured by immunosuppression standard deviation with the PHTF and GAD‐7 scores were evaluated. Internal consistency and validity of the PHTF were examined. In total, 30 patients participated. The most common illness‐specific fears were retransplantation, rejection, and more generally post‐transplant complications. The PHTF had good internal consistency (Cronbach α = .88). Construct validity was demonstrated between PHTF and GAD‐7 (r = .62) and PedsQL (r = ?.54 to ?.62). 23% endorsed moderate to severe generalized anxiety symptoms. More severe symptoms were associated with older age at survey (P = .03), older age at listing (P = .01) and having post‐transplant complications (P = .004). Patients with moderate or severe symptoms were more likely to report late immunosuppression doses (P = .004). Illness‐specific and generalized anxiety may be prevalent after pediatric heart transplant. Screening for anxiety in adolescents post‐transplant may identify those at risk for adverse outcomes including non‐adherence. The PHTF is a brief, valid, and reliable instrument identifying illness‐specific anxiety in this population.