Cord Blood Transplantation In Children Research Articles

Safety and feasibility of umbilical cord blood transplantation in children with neuronal ceroid lipofuscinosis: a retrospective study.

Ceroid lipofuscinosis neuronal (CLN) encompasses rare inherited neurodegenerative disorders that present in childhood with clinical features including epilepsy, psychomotor delay, progressive vision loss, and premature death. Published experience utilizing umbilical cord blood transplant (UCBT) for these disorders is limited. This retrospective analysis includes patients with CLN (2, 3, and 5) who underwent UCBT from 2012 to 2020. All subjects (n = 8) received standard-of-care myeloablative conditioning. Four also enrolled in clinical trial NCT02254863 and received intrathecal DUOC-01 cells posttransplant. Median age at UCBT was 5.9 years. All subjects achieved neutrophil engraftment with >95% donor chimerism at a median of 28.5 days. Sinusoidal obstructive syndrome was not observed. Severe acute graft-versus-host disease occurred in 12.5%. Other complications included autoimmune hemolytic anemia (25%) and viral reactivation/infection (62.5%). No transplant-related mortality was observed. Two CLN2 patients died, 1 from progressive disease and 1 from unknown cause at days +362 and +937, respectively. With median follow-up of 8 years, overall survival at 100 days and 24 months was 100% and 88%, respectively. Three of 4 CLN3 subjects stabilized Hamburg motor and language scores. While UCBT appears safe and feasible in these patients, given the variable expression and natural history, extended follow-up and further studies are needed to elucidate the potential impact of UCBT on clinical outcomes.

Graft-versus-host disease is associated with skewed γδ T-cell clonality after umbilical cord blood transplantation in children with nonmalignant diseases

Background aimsThe γδ T-cells (GDT) are a subpopulation of lymphocytes expressing a distinct T-cell receptor coded by the TRG and TRD genes. GDTs may have immunoregulatory function after stem cell transplantation (SCT), but the relationship between GDT clonality and acute graft-versus-host disease (aGVHD) is not known. MethodsWe prospectively studied spectratype complex complexity of TCR Vγ (γ) and TCR Vδ (δ) pre-SCT and at approximately day 100 and day 180 post-SCT in a cohort of immunocompetent children receiving allogeneic umbilical cord blood SCT for nonmalignant diseases, with identical reduced-intensity conditioning and aGVHD prophylaxis. ResultsWe studied 13 children undergoing SCT at a median age of 0.9 years (total range 0.4–16.6). In those with grade 0–1 aGVHD (N = 10), the spectratype complexity of most γ and δ genes was not significantly different from baseline at day 100 or day 180 post-SCT, and there was balanced expression of genes at the γ and δ loci. In those with grade 3 aGVHD (N = 3), spectratype complexity was significantly below baseline at day 100 and day 180, and there was relative overexpression of δ2. CD3+ cell counts were also lower in participants with grade 3 aGVHD. ConclusionsRecovery of a polyclonal GDT repertoire is an early part of immunological recovery after SCT. γ and δ gene expression is balanced in young children before and after SCT. Severe aGVHD is associated with GDT oligoclonality post-SCT and with skewed expression of δ2, which has not been previously reported. This association may reflect aGVHD therapy or aGVHD-associated immune dysregulation. Further studies of GDT clonality during the early post-SCT period may establish whether abnormal GDT spectratype precedes the clinical manifestations of aGVHD.

Nomogram for Predicting Early Mortality after Umbilical Cord Blood Transplantation in Children with Inborn Errors of Immunity

PurposePediatric patients with inborn errors of immunity (IEI) undergoing umbilical cord blood transplantation (UCBT) are at risk of early mortality. Our aim was to develop and validate a prediction model for early mortality after UCBT in pediatric IEI patients based on pretransplant factors.MethodsData from 230 pediatric IEI patients who received their first UCBT between 2014 and 2021 at a single center were analyzed retrospectively. Data from 2014–2019 and 2020–2021 were used as training and validation sets, respectively. The primary outcome of interest was early mortality. Machine learning algorithms were used to identify risk factors associated with early mortality and to build predictive models. The model with the best performance was visualized using a nomogram. Discriminative ability was measured using the area under the curve (AUC) and decision curve analysis.ResultsFifty days was determined as the cutoff for distinguishing early mortality in pediatric IEI patients undergoing UCBT. Of the 230 patients, 43 (18.7%) suffered early mortality. Multivariate logistic regression with pretransplant albumin, CD4 (absolute count), elevated C-reactive protein, and medical history of sepsis showed good discriminant AUC values of 0.7385 (95% CI, 0.5824–0.8945) and 0.827 (95% CI, 0.7409–0.9132) in predicting early mortality in the validation and training sets, respectively. The sensitivity and specificity were 0.5385 and 0.8154 for validation and 0.7667 and 0.7705 for training, respectively. The final model yielded net benefits across a reasonable range of risk thresholds.ConclusionThe developed nomogram can predict early mortality in pediatric IEI patients undergoing UCBT.

Unrelated umbilical cord blood transplantation for children with hereditary leukodystrophy: A retrospective study.

ObjectiveTo analyze the efficiency of unrelated umbilical cord blood transplantation (UCBT) in the treatment of hereditary leukodystrophy following busulfan- and cyclophosphamide-based myeloablative chemotherapy.MethodsA retrospective study was performed in patients with hereditary leukodystrophy who underwent UCBT after myeloablative chemotherapy between April 2015 and March 2020.ResultsThe study cohort included 12 pediatric patients (ten males), nine with cerebral adrenoleukodystrophy (ALD) and three with juvenile globoid cell leukodystrophy (GLD). All received HLA-matched or partially mismatched unrelated UCBT. There were no cases of graft rejection. Median neutrophil engraftment time was 20 days [12–33 days] and median platelet engraftment time was 29 days [14–65 days]. Median follow-up was 36 months [1–86 months], and the overall survival rate for patients with cerebral ALD and juvenile GLD after UCBT was 77.8% (7/9) and 100% (3/3), respectively. In patients with ALD, although lipid profiles (serum very-long-chain fatty acid) were improved post-UCBT, six patients demonstrated worse neurologic function score and performance status post-UCBT, and six patients had higher Loes scores at last follow-up compared with baseline. In patients with juvenile GLD, all patients showed stable neurologic function score and performance status despite the Loes score of one patient increased slightly after transplantation.ConclusionIn patients with cerebral ALD, patients with no or mild neurological symptoms can benefit from UCBT, while UCBT cannot reverse advanced disease. In patients with juvenile GLD, UCBT is safe and contributes to stabilize neurological function.

Abstract 15 Safety of DUOC-01, Intrathecal Cord Blood-Derived Cellular Therapy, as an Adjunct to Allogeneic Cord Blood Transplantation in Children with Inherited Metabolic Diseases

IntroductionUnrelated donor umbilical cord blood transplantation (CBT) improves function and extends life in children with certain inherited metabolic diseases (IMDs); however, progressive neurologic decline often occurs during the few months post-CBT prior to donor engraftment in the brain, causing residual, irreversible impairments. We previously described donor engraftment in the brain after CBT and developed DUOC-01, a monocyte-derived CB cell product, to attempt to accelerate donor cell delivery to the brain.ObjectiveThe objective of this study was to determine manufacturing feasibility and safety of intrathecal DUOC-01 in a phase I study in children with IMDs undergoing CBT after myeloablative cytoreduction (busulfan/cyclophosphamide/anti-thymocyte globulin).MethodsDUOC-01 was manufactured in adherent cell culture in a GMP lab over 21 days with a target dose of ≤100 × 105 cells. When cell dose permitted, 80% of the CB unit was used for transplant and 20% of the same unit was used to manufacture DUOC-01. Otherwise, DUOC-01 was manufactured from a unique CB unit. On day ≥+28 post-CBT, if there was evidence of hematopoietic engraftment without severe graft versus host disease or morbidity, DUOC-01 cells were harvested and administered intrathecally. Safety was monitored via neurologic exams, neuroimaging, and CSF studies.ResultsForty patients (aged 0-15 years) underwent CBT, 37 engrafted with donor cells. Median infused total nucleated cell count was 6.5 × 107/kg (range 2.9-33.1 × 107/kg); median time to neutrophil engraftment was 20 days (range 13-46 days). Ten patients did not receive DUOC-01 cells for the following reasons: engraftment failure (3), transplant-related morbidity (4), and low manufacturing yield (3). Thirty patients received 0.2-100 × 105 DUOC-01 cells intrathecally for a median of 31 days (range 27-77 days) post-CBT (19 with the same CB donor and 11 with a unique CB donor). Two patients developed transient fever and hypotension hours after unique-donor DUOC-01, consistent with an inflammatory response. Hydrocortisone (HC) was added to the final formulation, and post-validation, seven additional patients received unique-donor DUOC-01+HC without incident. No other DUOC-01-related serious adverse events occurred.DiscussionDUOC-01 is a CB-derived product intended to accelerate donor cell delivery to the brain of children with IMDs undergoing CBT. Intrathecal DUOC-01 administration is well-tolerated post-CBT from the same donor and, with the addition of HC, also from a unique donor. Escalating DUOC doses are being tested for safety and exploration of potential efficacy in a phase Ia trial of adults with multiple sclerosis.

Unrelated Cord Blood Transplantation in Children, Adolescents, and Young Adults with Acute Leukemia or Myelodysplastic Syndrome: A Retrospective Comparative Study from the French Society for Bone Marrow Transplantation and Cellular Therapy Between Real-World Data and Previously Reported Results of a Randomized Clinical Trial

We previously reported results of a French randomized clinical trial (RCT) comparing the risk of transplantation failure (including transplant-related mortality [TRM], engraftment failure, and autologous recovery) in single and double unrelated cord blood (UCB) transplantation in children and young adults with hematologic malignancies. We concluded that single-UCB transplantation with an adequate cell dose is the standard of care, leading to a 70% two-year overall survival (OS). It remains unclear, however, whether RCT participants have better outcomes than comparable patients not treated in the setting of a clinical trial. We compared the characteristics and outcomes of RCT participants (n=137) to a Francophone population-based registry of patients (real-world [RW] group) fulfilling the eligibility criteria used in our RCT and transplanted with 1 or 2 UCB units after a myeloablative conditioning (MAC) regimen between March 2015 (end of inclusion in the RCT) and February 2019 (n=141). The primary endpoint was the 2-year cumulative incidence (CI) of transplantation strategy failure as defined in our RCT. The 2 groups were comparable in terms of age, disease distribution, hematologic status at transplantation, follow-up, and HLA compatibility. Patients in the RW group were more likely to be transplanted with a single-unit UCB (87.9% versus 49.6%, P< .001) and to receive a radiation-free regimen (39.0% versus 60.6%, P< .001). The 2-year CI of transplantation strategy failure, TRM, and the 2-year probability of OS were similar between the 2 groups, although the relapse risk was higher in the RW group (31.2% ± 7.7% versus 20.4% ± 6.8%, P= .01), resulting in a significantly lower disease-free survival (DFS) (59.2% ± 8.4% versus 69.3% ± 8.0%, P= .047). This difference remained statistically significant only in the group of patients with acute lymphoid leukemia (ALL) who did not receive the conditioning regimen recommended by the RCT (fludarabine 75 mg/m2, total body irradiation 12 Gy, cyclophosphamide 120 mg/kg). The results of our RCT appear to be reproducible in real-world conditions, provided that the same cord blood selection criteria and conditioning regimen are used.

Radiation-sparing reduced-intensity unrelated umbilical cord blood transplantation for rare hematological disorders in children.

Graft failure is a major pitfall of unrelated umbilical cord blood transplantation (CBT) in children with rare hematological disorders other than acute leukemia, such as acquired and inherited bone marrow failure, myelodysplastic syndrome, juvenile myelomonocytic leukemia, and chronic myeloid leukemia. We developed a less-toxic conditioning regimen for CBT that achieves a higher rate of complete donor chimerism, and retrospectively compared it against two other conditioning regimens for CBT performed at our single institution. The engraftment rate with complete donor chimerism was 100% and 5-year event-free survival (5y-EFS) was 90.9% in patients using our latest regimen (n = 11) of reduced-intensity conditioning (RIC) containing fludarabine (Flu) 180mg/m2, melphalan (MEL) 210mg/m2, and low-dose rabbit anti-thymocyte globulin (LD-rATG) 2.5mg/kg without irradiation (regimen C). Outcomes were better than in patients (n = 10) treated with previous regimens involving irradiation (5y-EFS 30.0%, p = 0.004): regimen A, consisting of myeloablative conditioning containing cyclophosphamide (CY) and total body irradiation (TBI) with 8-12Gy, or regimen B, consisting of RIC with Flu, CY, horse ATG, and thoracoabdominal irradiation (TAI) with 6Gy. In conclusion, Flu/MEL/LD-rATG (regimen C) without TBI/TAI may be preferable as RIC for unrelated CBT in children with rare hematological disorders.

Review of Unrelated Donor Cord Blood Transplantation in Children over the Past 3 Decades

Review of Unrelated Donor Cord Blood Transplantation in Children over the Past 3 Decades

Clinical Significance of Natural Killer Cell-Mediated Alloreactivity in Unrelated Cord Blood Transplantation for Children with Acute Leukemia: A Japanese National Registry Study

Introduction: Natural killer (NK) cells are important components of graft-versus-leukemia alloreactivity after allogeneic hematopoietic cell transplantation (HCT) for leukemia, due to the inhibitory killer-cell immunoglobulin-like receptors (KIRs). Only NK cells expressing inhibitory KIRs to self human leukocyte antigen (HLA) can become licensed and more responsive to activating stimuli. However, NK cells with inhibitory KIRs for non-self HLA are proposed to exhibit transient alloreactivity after early allogeneic HCT. The inhibitory KIR2DL group of receptors interacts with HLA-C, which comprises two mutually exclusive groups: HLA-C1 (Asn80) and HLA-C2 (Lys80). KIR2DL1 receptor, which shows the most powerful inhibitory effect and is very frequently expressed in the Japanese population, recognizes the HLA-C2 group. Therefore, we studied combinations of donor and recipient HLA-C groups in children with acute leukemia who underwent unrelated cord blood transplantation (CBT) to clarify the impact of KIR2DL1 mediated-NK alloreactivity on clinical outcomes.Methods: The current study was approved by the institutional review board of Japanese Red Cross Nagoya First Hospital in Nagoya, Japan. A total of 662 children aged 15 years or younger at the time of CBT with acute myeloid leukemia (AML, n = 261) or acute lymphoblastic leukemia (ALL, n = 401) who underwent first unrelated CBT between 1998 and 2015 in Japan were retrospectively analyzed based on the data from the Japanese Data Center for Hematopoietic Cell Transplantation. Patient characteristics are summarized in Table. We compared engraftment rate, cumulative incidence of relapse (CIR), transplantation-related mortality (TRM), leukemia-free survival (LFS), and grade II-IV acute graft-versus-host disease (g2-4 aGVHD) in association with KIR2DL-1 mediated-NK alloreactivity.Results: Patients were divided into three groups according to the donor and recipient HLA-C status; licensedgroup (n = 92) with C1/C2 or C2/C2 donor and C1/C1 recipient, transientlyalloreactivegroup (n = 443) with C1/C1 donor and C1/C1 recipient, and nonreactive group (n = 127) with any donor and C1/C2 or C2/C2 recipients. Median follow-up of survivors was 45 months after CBT. There was no difference in engraftment rates at 50 days after CBT among the three groups, which was 91% for all groups (P= 0.83). The CIR/TRM/LFS at 3 years were 43%/7%/51% for the nonreactive group, 38%/12%/50% for the transiently alloreactive group, and 47%/10%/43% for the licensed group, respectively (P= 0.23, 0.29, and 0.50, respectively). The incidence rates of g2-4 aGVHD were 34%, 41%, and 47% for the nonreactive, transiently alloreactive, and licensed groups, respectively (P= 0.10). The CIR for transiently alloreactive group tended to be lower than those for the others, whereas the TRM for transiently alloreactive group was higher than those for the others; however, there was no difference in LFS among the three groups. Narrowing the cases to the HLA-C mismatch setting, the tendency of lower CIR and higher TRM for transiently alloreactive group became stronger. The CIR/TRM/LFS at 3 years in the HLA-C mismatch setting were 49%/6%/45% for the nonreactive group (n = 83), 36%/16%/48% for the transiently alloreactive group (n = 206), and 48%/11%/41% for the licensed group (n = 87), respectively (P= 0.09, 0.09, and 0.73, respectively, shown in Figure). The trend of lower CIR and higher TRM for the transiently alloreactive group remained unchanged for both AML and ALL patients.Conclusions: There was a significant association between transient KIR2DL1-mediated NK alloreactivity and reduced CIR after HLA mismatch CBT for childhood acute leukemia, which suggests improved LFS with efforts to reduce TRM. Further large studies are warranted. [Display omitted] DisclosuresAtsuta:Otsuka Pharmaceutical Co., Ltd.: Honoraria.

Conditioning with 10 Gy Total Body Irradiation, Cyclophosphamide, and Fludarabine without ATG Is Associated with Improved Outcome of Cord Blood Transplantation in Children with Acute Leukemia.

BackgroundThe optimal conditioning regimen in cord blood transplantation (CBT) needs to be determined. This study aimed to identify the impact of conditioning regimen on the outcome of CBT in children with acute leukemia.MethodsMedical records of patients with acute leukemia who received CBT were retrospectively reviewed.ResultsA total of 71 patients were allocated into 2 groups; patients who received total body irradiation 10 Gy, cyclophosphamide 120 mg/kg, and fludarabine 75 mg/m2 were named as TCF group (n = 18), while the non-TCF group (n = 53) included patients conditioned with regimens other than the TCF regimen. All patients in the TCF group were successfully engrafted, while 22.6% in the non-TCF group (n = 12) failed to achieve donor-origin hematopoiesis (P = 0.028). The incidence of cytomegalovirus diseases was 5.6% in the TCF group and 30.2% in the non-TCF group (P = 0.029). The 5-year overall survival rates of the TCF and non-TCF groups were 77.8% and 44.2%, respectively (P = 0.017).ConclusionPatients conditioned with the TCF regimen achieved better engraftment and survival rates, less suffering from cytomegalovirus disease. Our data suggest that the TCF regimen is a preferred option for CBT in children with acute leukemia.

Factors Associated With Outcome After Cord Blood Transplantation in Children With Acute Leukemia

AbstractWe have analyzed factors influencing the outcome of 102 children with acute leukemia given a cord blood transplantation (CBT) and reported to the Eurocord Registry. Seventy patients with acute lymphoblastic and 32 with acute myeloid leukemia were given either a related (n = 42) or an unrelated (n = 60) CBT. Children given CBT during first or second complete remission were considered as belonging to the good-risk group (n = 66), whereas those who received a transplant in a more advanced stage of disease were assigned to the poor-risk group (n = 36). In the related group (RCBT), 12 of 42 patients received transplantation from an HLA-disparate donor, whereas in the unrelated group (UCBT) 54 of 60 received an HLA mismatched CBT. Kaplan-Meier estimates for neutrophil recovery at day 60 were 84% ± 7% in RCBT and 79 ± 6% in UCBT (P = .16). In multivariate analysis, the most important factor influencing neutrophil engraftment in UCBT was a nucleated cell dose infused greater than 3.7 × 107/kg (P = .05, relative risk [RR] of 1.85, 95% confidence interval [CI]: 0.98-3.4). The incidence of grade II through IV acute graft-versus-host disease was 41% ± 8% in the RCBT group and 37% ± 6% in the UCBT group (P = .59). Kaplan-Meier estimates of 2-year event-free survival (EFS) after RCBT or UCBT were 39% ± 8% and 30% ± 7%, respectively (P = .19). In multivariate analysis, the most important factor influencing EFS was disease status at time of transplantation: good-risk patients had a 2-year EFS of 49% ± 7% as compared to 8% ± 5% in patients with more advanced disease (P = .0003, RR: 0.40, 95% CI: 0.24 to 0.65). This was a consequence of both an increased 1-year transplant related mortality and a higher 2-year relapse rate in the poor-risk group (65% ± 9% and 77% ± 14%, respectively), as compared with good risk patients (34% ± 6% and 31% ± 9%, respectively). These data confirm that allogeneic CBT from either a related or an unrelated donor is a feasible procedure able to cure a significant proportion of children with acute leukemia, especially if transplanted in a favorable phase of disease.

Hemophagocytic Lymphohistiocytosis and Graft Failure Following Unrelated Umbilical Cord Blood Transplantation in Children.

Hemophagocytic lymphohistiocytosis (HLH) following hematopoietic stem cell transplantation is closely correlated with graft failure and poor prognosis. Because of its rarity, the incidence, risk factors, and optimal treatment strategy are unclear. We analyzed data from cases of HLH following umbilical cord blood transplantation (UCBT) performed for pediatric patients at our center. Among 66 UCBT recipients, 5 developed HLH and imminent graft failure. The median time of diagnosis of HLH was 22 (range, 19 to 30) days after UCBT, and the cumulative incidence of HLH was 7.6% (95% confidence interval, 2.8-15.7) at day 60. In univariate analysis, the cumulative incidence of HLH was significantly higher in patients with infused CD34 cells <1.0×10/kg than in patients with higher CD34 cells. Patients with preengraftment infection showed a trend toward higher incidence of HLH compared with patients without any infection. All 5 patients with HLH received corticosteroids and low-dose etoposide (VP-16), with or without high-dose intravenous immunoglobulin. Following these treatments, successful engraftment was observed in 2 patients. Corticosteroids and low-dose VP-16 may be worthy of a trial before attempting salvage hematopoietic stem cell transplantation. Further analyses are required to identify risk factors and to develop methods for prophylaxis, diagnosis, and treatment of HLH.

Rapid reconstitution of regulatory T-cell subsets is associated with reduced rates of acute graft-versus-host disease and absence of viremia after cord blood transplantation in children with reduced-intensity conditioning using alemtuzumab

Forkhead box P3 (FOXP3)+ regulatory T cell (Treg) reconstitution after unrelated donor umbilical cord blood transplantation in chemotherapy-naïve children is incompletely characterized. We studied 21 children with nonmalignant diseases receiving an identical alemtuzumab-containing regimen. We hypothesized that Treg recovery may be perturbed in patients not only by acute graft-versus-host disease (aGVHD) but also by viremia. Tregs and their memory and naïve subsets were serially monitored for proliferation and apoptosis along with conventional T cells (Tcon). A “reconstitution index” (RI) was calculated relative to pretransplantation values for each parameter. At 3 months post-UCBT, the RI of Tregs was faster compared with other immune components tested and was most rapid in patients free of aGVHD and viremia. There were significantly fewer Tregs in patients experiencing grade I–II aGVHD and/or viremia, leading to an imbalance between Tregs-Tcon ratios. Central and effector memory Tregs were most affected at this time point when they dominated in the circulation. Impaired Treg proliferation without increased apoptosis accounted for the reduced Treg-Tcon ratio. In patients affected with grade II aGVHD and viremia, the overall reduction in circulating Treg pool were associated with a more oligoclonal T-cell receptor β repertoire. Taken together, aGVHD and viremia can lead to defective Treg expansion homeostasis.

Successful umbilical cord blood transplantation in children with leukocyte adhesion deficiency type I.

This study aims to investigate the efficacy and safety of umbilical cord blood transplantation (UCBT) without serotherapy for treating children with leukocyte adhesion deficiency type I (LAD-I). Clinical characteristics and data of five children with LAD-I who underwent UCBT at our hospital between September 2016 and September 2018 were retrospectively analyzed. Five (two boys and three girls) patients with LAD-I were included. The median age at UCBT was 9 months (range, 8 to 32 months). The same myeloablative conditioning regimen was administered for each patient and included busulfan, fludarabine, and cyclophosphamide. HLA matching of patients and umbilical cord blood was 8/10 to 10/10. The median dose of total nucleated cells (TNC) infused was 10.2×107/kg (range, 4.5×107 to 20.6×107/kg) and the median dose of CD34+ cells was 3.2×105/kg (range, 1.9×105 to 5.7×105/kg). The median time of neutrophil engraftment was 20 days (range, 13 to 28 days). The median time of platelet engraftment was 36 days (range, 32 to 56 days). All patients received complete donor chimerism (CDC). Four of the five patients developed grade II-IV acute graft-versus-host disease (GvHD). The median follow-up time after transplantation was 19 months (range, 8 to 38 months). Four of the patients survived and achieved complete clinical remission. The other patient died of bronchiolitis obliterans 8 months after UCBT. UCBT is an effective treatment method for LAD-I patients. Also, severe LAD-I patients should undergo stem cell transplantation as early as possible.

Outcomes of Umbilical Cord Blood Transplantation in Children with Batten Disease

Introduction Neuronal ceroid lipofuscinoses (NCL, Batten Disease) are a class of lysosomal storage diseases caused by mutations in ceroid lipofuscinoses (CLN) genes. Neurological deterioration is influenced by the CLN subtype, but death typically occurs in childhood. Symptoms include visual impairment, behavioral changes, loss of motor and/or cognitive skills, and seizures. Umbilical cord blood transplant (UCBT) is effective in treating many lysosomal storage disorders but there is very limited experience in BD. Methods We retrospectively studied 6 patients (pt) with BD receiving UCBT between the ages of 4 months and 8.6 years at our center. All received myeloablative conditioning with busulfan, cyclophosphamide and ATG. Cyclosporine and mycophenolate were given for prophylaxis of GVHD. Pts 5 and 6 were concomitantly enrolled on clinical trial (NCT02254863) and also received intra-thecal injection of DUOC-01 cells after hematologic engraftment. Selected patient and donor characteristics are shown in Table 1: Results Patients received UCB grafts matching at 4/6-6/6 loci with a median pre-cryo cell dose of 7.2 (range, 5.1-35.1) x107 cells/kg. All pts engrafted neutrophil and platelets in a median of 25 (range, 12-34) and 39 days (range, 32-105), respectively. Four patients developed Grade 2-4 acute GvHD and 2 developed extensive chronic GvHD. Pt 1, the only patient transplanted after severe neurologic decline with advanced disease, died from progressive BD and aseptic shock 12 months post-UCBT. All others are alive at a median of 3.8 years (range, 0.5-5.5). Pt 2 has normal motor function, is nonverbal and was diagnosed with autism 2 years post UCBT. Her brain MRI is normal to date. Pt 3 is blind, has had occasional seizures, requires educational support and has no MRI evidence of BD. Pts 4 and 5 have age appropriate neurocognition, no seizures, and receive only visual support in school. Both have normal MRIs. It is too early to assess neurologic outcomes in Pt 6 (7 months post-UCBT). Conclusion UCBT is feasible in children with BD. At a median follow up of 3.8 years (range, 0.5-5.5), 5/6 patients are alive and 4/5 are neuro-cognitively stable and one developed new onset seizures post-transplant. All 5 surviving pts have no MRI evidence of disease. With the inherent variability of the different forms of BD, additional pts and continued follow-up is needed to fully understand the effect of UCBT on the natural history of BD.

Current status of umbilical cord blood transplantation in children

The first umbilical cord blood (UCB) transplantation was performed 30years ago. UCB transplantation (UCBT) is now widely used in children with malignant and non-malignant disorders who lack a matched family donor. UCBT affords a lower incidence of graft-versus-host disease compared to alternative stem cell sources, but also presents a slower immune recovery and a high risk of infections if serotherapy is not omitted or targeted within the conditioning regimen. The selection of UCB units with high cell content and good human leucocyte antigen match is essential to improve the outcome. Techniques, such as double UCBT, ex vivo stem cell expansion and intra-bone injection of UCB, have improved cord blood engraftment, but clinical benefit remains to be demonstrated. Cell therapies derived from UCB are under evaluation as potential novel strategies to reduce relapse and viral infections following transplantation. In recent years, improvements within haploidentical transplantation have reduced the overall use of UCBT as an alternative stem cell source; however, each may have its relative merits and disadvantages and tailored use of these alternative stem cell sources may be the optimal approach.

Pediatric posttransplantation food allergy experience at a large US tertiary care center

The first case of new-onset food allergy after transplantation was reported in 1997. 1 Legendre C. Caillat-Zucman S. Samuel D. et al. Transfer of symptomatic peanut allergy to the recipient of a combined liver-and-kidney transplant. N Engl J Med. 1997; 337: 822-824 Crossref PubMed Scopus (133) Google Scholar , 2 Hosakoppal S.S. Bryce P.J. Transplant-acquired food allergy: current perspectives. J Asthma Allergy. 2017; 10: 307-315 Crossref PubMed Scopus (16) Google Scholar Although posttransplantation food allergy (PTFA) is most common after liver transplantation, with a prevalence ranging from 5.6% to 38%, new-onset food allergy has also been described after bone marrow transplantation (BMT). 2 Hosakoppal S.S. Bryce P.J. Transplant-acquired food allergy: current perspectives. J Asthma Allergy. 2017; 10: 307-315 Crossref PubMed Scopus (16) Google Scholar , 3 Needham J.M. Nicholas S.K. Davis C.M. Food allergies developing after solid organ transplant. Pediatr Transplant. 2015; 19: 827-835 Crossref PubMed Scopus (22) Google Scholar , 4 Hernandez-Ojeda A. Rojas N. Barriga F. Wietstruck M.A. Morales P.S. Borzutzky A. Incidence and risk factors of food allergy after umbilical cord blood transplantation in children. J Allergy Clin Immunol Pract. 2017; 5: 1789-1791 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar Tacrolimus, a medication used less frequently in BMT compared with solid organ transplantation, has been identified as a potentially modifiable risk factor for PTFA. 2 Hosakoppal S.S. Bryce P.J. Transplant-acquired food allergy: current perspectives. J Asthma Allergy. 2017; 10: 307-315 Crossref PubMed Scopus (16) Google Scholar Tacrolimus creates an immunologic imbalance that favors a TH2 response and increases intestinal permeability, which may increase allergen exposure via the gut. 2 Hosakoppal S.S. Bryce P.J. Transplant-acquired food allergy: current perspectives. J Asthma Allergy. 2017; 10: 307-315 Crossref PubMed Scopus (16) Google Scholar , 3 Needham J.M. Nicholas S.K. Davis C.M. Food allergies developing after solid organ transplant. Pediatr Transplant. 2015; 19: 827-835 Crossref PubMed Scopus (22) Google Scholar Most studies evaluating the prevalence of PTFA and risk factors have included small patient populations, and none compare risks of PTFA after solid organ transplantation vs BMT. 5 De Bruyne R. Dullaers M. Van Biervliet S. et al. Post-transplant food allergy in children is associated with liver and not with renal transplantation: a monocentric comparative study. Eur J Pediatr. 2013; 172: 1069-1075 Crossref PubMed Scopus (35) Google Scholar , 6 Marcus N. Amir A.Z. Grunebaum E. et al. De novo allergy and immune-mediated disorders following solid-organ transplantation-prevalence, natural history, and risk factors. J Pediatr. 2018; 196: 154-160.e152 Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar , 7 Ozbek O.Y. Ozcay F. Avci Z. Haberal A. Haberal M. Food allergy after liver transplantation in children: a prospective study. Pediatr Allergy Immunol. 2009; 20: 741-747 Crossref PubMed Scopus (54) Google Scholar We sought to compare the association between tacrolimus exposure and PTFA in BMT and solid organ transplantation recipients in a large cohort from a pediatric tertiary care center.

Outcomes of Umbilical Cord Blood Transplantation in Children with Batten Disease

Introduction Neuronal ceroid lipofuscinoses (NCL, Batten Disease) are a class of lysosomal storage diseases caused by mutations in ceroid lipofuscinoses (CLN) genes. Neurological deterioration is influenced by the CLN subtype, but death typically occurs in childhood. Symptoms include visual impairment, behavioral changes, loss of motor and/or cognitive skills, and seizures. Umbilical cord blood transplant (UCBT) is effective in treating many lysosomal storage disorders but there is very limited experience in BD. Methods We retrospectively studied 6 patients (pt) with BD receiving UCBT between the ages of 4 months and 8.6 years at our center. All received myeloablative conditioning with busulfan, cyclophosphamide and ATG. Cyclosporine and mycophenolate were given for prophylaxis of GVHD. Pts 5 and 6 were concomitantly enrolled on clinical trial (NCT02254863) and also received intra-thecal injection of DUOC-01 cells after hematologic engraftment. Selected patient and donor characteristics are shown in Table 1: Results Patients received UCB grafts matching at 4/6-6/6 loci with a median pre-cryo cell dose of 7.2 (range, 5.1-35.1) x107 cells/kg. All pts engrafted neutrophil and platelets in a median of 25 (range, 12-34) and 39 days (range, 32-105), respectively. Four patients developed Grade 2-4 acute GvHD and 2 developed extensive chronic GvHD. Pt 1, the only patient transplanted after severe neurologic decline with advanced disease, died from progressive BD and aseptic shock 12 months post-UCBT. All others are alive at a median of 3.8 years (range, 0.5-5.5). Pt 2 has normal motor function, is nonverbal and was diagnosed with autism 2 years post UCBT. Her brain MRI is normal to date. Pt 3 is blind, has had occasional seizures, requires educational support and has no MRI evidence of BD. Pts 4 and 5 have age appropriate neurocognition, no seizures, and receive only visual support in school. Both have normal MRIs. It is too early to assess neurologic outcomes in Pt 6 (7 months post-UCBT). Conclusion UCBT is feasible in children with BD. At a median follow up of 3.8 years (range, 0.5-5.5), 5/6 patients are alive and 4/5 are neuro-cognitively stable and one developed new onset seizures post-transplant. All 5 surviving pts have no MRI evidence of disease. With the inherent variability of the different forms of BD, additional pts and continued follow-up is needed to fully understand the effect of UCBT on the natural history of BD.

Autologous cord blood transplantation in children with acquired severe aplastic anemia.

To investigate the efficacy of ACBT for acquired SAA in children. Four patients including three girls and one boy were diagnosed with acquired SAA. Their ages were 5, 3, 1, and 3years, respectively. Patients received an immunoablative preparative regimen using low-dose antithymocyte globulin, cyclophosphamide, and fludarabine. The unrelated human umbilical cord MSC were infused before the autologous cord blood was transfused on day 0. The first and second patients were not treated with immunosuppressive agents after transplantation. The third and the fourth patients received cyclosporine A for half a year after transplantation followed by a 6-month taper. Initial hematopoietic reconstitution was seen in all the four patients. There was no association between engraftment time and the number of total cells and CD34+ cells. Relapse was seen in the first case about half a year after the transplantation. The other three patients with durable hematopoietic reconstitution are with good quality of life. No GVHD was observed. Three of four patients maintained prolonged hematopoiesis following an immunosuppressive-based preparative regimen and infusion of autologous cord blood cells. It is recommended that cyclosporine be maintained for 6months after transplantation. ACBT could be considered for acquired SAA if available.

Reduction of Graft Rejection By Fludarabine Combined Busulfan, Cyclophosphamide and Antithymocyte Globulin Conditioning in Cord Blood Transplantation for Children with Wiskott-Aldrich Syndrome

Background and Objectives: Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency with microthrombocytopenia. Hematopoietic stem cell transplantation is a curative treatment for WAS. Unrelated cord blood transplantation (UCBT) become a more successive alternative donor transplantation for WAS with the improvement of high resolution HLA-typing method. However, graft rejection is the primary cause for mortality of WAS after UCBT. We hypothesized that the addition of fludarabine to a myeloablative conditioning regimen with antithymocyte globulin (ATG) would support engraftment for these children.Methods: Seventeen Children with WAS underwent UBCT matched 6-10/10 at higher resolution (HLA-A, -B, -C, -DRB1and DQB1) in our center between 2013 and 2018. The conditioning regimen consisted of fludarabine 160 mg/m2 , busulfan (BU)12.8 mg/kg, cyclophosphamide (CY)120 mg/kg, ATG 7.5 mg/kg, and cyclosporine and mycophenolate for GVHD prophylaxis. Median follow-up time is 2.5 years (range, 0.2 to 3.5 years).Results: All children had sustained donor cell engraftment and are stable engraftment. Twelve (71%) patients had cytomegalovirus (CMV) antigenemia and no one developed into CMV disease. Six (35%) children underwent acute Graft-versus-host disease (GVHD) (grade II-IV) and four (24%) children developed into chronic GVHD (cGVHD). Among these cases, only one child with HLA matched 6/10 died of kidney failure because of cGVHD. He experienced aGVHD with skin bullosa. Sixteen (94%) children are survival.Conclusion: Conditioning regimen consisted of Fludarabine combined BUCY and ATG was able to reduce graft rejection in the WAS children after UCBT without increasing infection related mortality. Future efforts will focus on further reducing rates of acute GVHD and extensive cGVHD. DisclosuresNo relevant conflicts of interest to declare.