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Clinical implications of augmented renal clearance after unrelated single cord blood transplantation in adults
Konuma, T., Takano, K., Monna-Oiwa, M., Isobe, M., Kato, S., Takahashi, S., Nannya, Y.
International journal of hematology. 2023
Abstract
Augmented renal clearance (ARC) is a phenomenon characterized by increased renal functionality, which can impact the pharmacokinetics and pharmacodynamics of antimicrobial drugs eliminated by the kidneys. It is a potential concern for infection treatment. Cord blood transplantation (CBT) is primarily impeded by delayed neutrophil recovery and immune reconstitution, thereby increasing susceptibility to infection. However, the clinical implications of ARC following CBT remain unexplored. We retrospectively assessed the influence of ARC on post-transplant outcomes at various time points in 194 adult recipients of single-unit unrelated CBT between 2007 and 2022 at our institution. ARC was observed in 52.9% of patients at 1 day, 39.8% at 15 days, and 26.5% at 29 days post-CBT. ARC was not significantly associated with bloodstream infection, acute graft-versus-host disease, or veno-occlusive disease/sinusoidal obstruction syndrome at any time point. ARC at 1 day, 15 days, and 29 days post-CBT was not significantly associated with overall survival, non-relapse mortality, or relapse rates. These findings suggest that ARC is common in adults during the early stages of CBT, but does not discernibly influence clinical outcomes or post-CBT complications.
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Incidence and risk factors of late-onset hemorrhagic cystitis after single umbilical cord blood transplantation with myeloablative conditioning regimen
Jiang, H., Geng, L., Wan, X., Song, K., Tong, J., Zhu, X., Tang, B., Yao, W., Zhang, X., Sun, G., et al
International journal of hematology. 2021
Abstract
OBJECTIVE To explore the incidence and risk factors of late-onset hemorrhagic cystitis (LOHC) in patients undergoing single umbilical cord blood transplantation for hematological malignancies. METHODS Clinical data from 234 patients who consecutively underwent single UCBT using a myeloablative conditioning regimen without antithymocyte globulin in our center were retrospectively analyzed. RESULTS In total, 64 (27.4%) patients developed LOHC with a median onset time of 40.5 (range 8-154) days, and 15 (6.4%) patients gradually developed grade III-IV LOHC. The incidence of LOHC was marginally higher in adults (31.0%) than in children (23.7%) (p?=?0.248). HLA matching?=?6/8 (HR?=?2.624, 95% CI 1.112-6.191, p?=?0.028) was an independent risk factor for LOHC. The overall survival of LOHC patients (59.8%, 95% CI 61.7-85.5%) was significantly lower than that of patients without LOHC (86.8%, 95% CI 79.6-91.6%) at 130 days post transplantation (p?=?0.036). CONCLUSION Patients with less well-matched grafts have a higher incidence of LOHC. Inherent deficiencies in immunity in the context of HLA disparity and more intense pharmacologic immunosuppression after severe acute graft-versus-host disease may contribute to viral activation. Prevention and treatment of LOHC have the potential to prolong long-term survival.
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Early-Phase Peripheral Blood Eosinophilia Predicts Lower Overall and Non-Relapse Mortality After Single-Unit Cord Blood Transplantation
Konuma, T., Monna-Oiwa, M., Kaito, Y., Isobe, M., Okabe, M., Kato, S., Takahashi, S., Tojo, A.
Transplantation and cellular therapy. 2021;27(4):336.e1-336.e9
Abstract
Peripheral blood eosinophilia has been associated with the development of graft-versus-host disease (GVHD) and survival after allogeneic hematopoietic cell transplantation (HCT). However, the impacts of eosinophilia on cord blood transplantation (CBT) outcomes remain unclear. The objective of this study was to examine the associations between eosinophilia and overall survival, relapse incidence, non-relapse mortality, and acute and chronic GVHD after single-unit CBT for adults. We retrospectively analyzed the data for 225 adult patients who received single-unit CBT at our institute between March 2004 and March 2020. The cumulative incidence of eosinophilia, defined as an absolute eosinophil count of =500 × 10(6)/L in peripheral blood, was 48.9% (95% confidence interval, 42.2% to 55.2%) at 60 days after CBT. Recipient cytomegalovirus seronegative status and higher cryopreserved cord blood CD34(+) cell dose were significantly associated with a higher incidence of eosinophilia after CBT. Among patients who achieved neutrophil recovery, neutrophil recovery was significantly earlier in patient with eosinophilia compared to those without eosinophilia (P = .016). Serum levels of interleukin-5 at 4 weeks were significantly higher in patients with eosinophilia compared with those without eosinophilia (P = .041). Multivariate analysis, in which the development of eosinophilia was treated as a time-dependent covariate, showed that eosinophilia was significantly associated with lower overall mortality (hazard ratio [HR], .58; P = .034) and non-relapse mortality (HR, .41; P = .029), but not relapse incidence or development of acute or chronic GVHD. Our data suggested that early-phase eosinophilia is a predictor of favorable outcomes in adult patients undergoing single-unit CBT.
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Hemophagocytic Lymphohistiocytosis and Graft Failure Following Unrelated Umbilical Cord Blood Transplantation in Children
Noguchi, M., Inagaki, J.
Journal of pediatric hematology/oncology. 2020
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Editor's Choice
Abstract
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 <1.0x10/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.
PICO Summary
Population
Paediatric patients who underwent umbilical cord blood transplantation (UCBT) (n=66)
Intervention
Identifying cases of haemophagocytic lymphohistiocytosis (HLH) following transplant
Comparison
None
Outcome
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% at day 60. In univariate analysis, the cumulative incidence of HLH was significantly higher in patients with infused CD34 cells <1.0x10/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.
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Readmissions after Umbilical Cord Blood Transplantation and Impact on Overall Survival
Crombie, J., Spring, L., Li, S., Soiffer, R. J., Antin, J. H., Alyea, E. P., 3rd, Glotzbecker, B.
Biology of Blood & Marrow Transplantation. 2017;23(1):113-118
Abstract
Patients treated with allogeneic hematopoietic stem cell transplantation (SCT) have high rates of readmission, but the incidence after umbilical cord blood transplantation (UCBT) is poorly described. The goal of this study was to identify the incidence and risk factors for readmission after UCBT and the impact of readmission on overall survival (OS). A retrospective review of patients receiving a UCBT at Dana-Farber/Brigham and Women's Hospital between January 1, 2004 and December 31, 2013 was performed. The readmission rates 30 days after discharge from the UCBT admission and at day +100 after the UCBT were examined. Reasons for readmission, as well as sociodemographic, disease-, and SCT-related variables were evaluated. Predictors of readmission and the impact of readmission on OS were identified using multivariate regression analysis. Of patients who received a UCBT, 42 of 126 patients (33.3%) were readmitted within 30 days of discharge and 57 of 123 patients (46.3%) were readmitted by day +100 after transplantation. The most common causes for readmission were infection (38.3%), fever without a source (14.8%), and graft-versus-host disease (8.6%). Infection during the index admission was the only significant risk factor for readmission at both time points in a univariate and multivariate regression analysis (OR, 11.66; 95% CI, 2.77 to 49.13; P<.01 and OR, 5.4; 96% CI, 1.87 to 15.58; P<.01). Prior radiation therapy was also associated with an increased risk of readmission at both time points in the multivariate regression model (OR, 20.6; 95% CI, 3.53 to 120.04; P<=.01 and OR, 5; 95% CI, 1.21 to 20.71; P=.03). The multivariate regression model also showed that black race and a median income of <60,000 in the patient's home zip code increased the risk of readmission by day +100 (OR, 30.17; 95% CI, 1.33 to 684.48; P=.03 and OR, 2.88; 95% CI, 1.04 to 7.8; P=.04, respectively). After adjusting for age, disease type, and the disease status at transplant, OS was reduced for the patients who were readmitted by day +100 (HR, 2.44; 95% CI, 1.46 to 4.06; P<.01). There was also a trend toward decreased survival in patients readmitted 30 days after discharge (HR, 1.58; 95% CI, .96 to 2.6; P=.07). Readmissions are common after UCBT. Infections and fever without a source are the most common causes of readmission. Being readmitted by day +100 resulted in a lower 5-year OS rate as compared with patients who were not readmitted. Prior radiation and infection during the transplant admission resulted in increased risk of readmission by 30 days and day +100. Similarly, race and socioeconomic status predicted readmission by day +100. Further understanding of the mechanisms leading to readmissions in these groups may allow for identification of interventions that could reduce readmissions and thus improve mortality. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.