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Although daily higher urinary sodium (Na) and potassium (K) excretion ratio is associated with the risk of cardiovascular disease in the general population, a low Na/K ratio is associated with renal dysfunction in critically ill patients. Thus, we retrospectively analyzed the impact of daily urinary Na and K excretion and their ratio on non-relapse mortality (NRM) and overall mortality in 172 adult single-unit cord blood transplantation (CBT) patients treated at our institution between 2007 and 2020. Multivariate analysis showed that a low urinary Na/K ratio at both 14 days (hazard ratio [HR], 4.82; 95% confidence interval [CI], 1.81–12.83; P = 0.001) and 28 days (HR, 4.47; 95% CI 1.32–15.12; P = 0.015) was significantly associated with higher NRM. Furthermore, a low urinary Na/K ratio at 28 days was significantly associated with higher overall mortality (HR, 2.38; 95% CI 1.15–4.91; P = 0.018). Patients with a low urinary Na/K ratio had decreased urine volume, more weight gain, experienced more grade III–IV acute graft-versus-host disease, and required corticosteroids by 28 days after CBT. These findings indicate that a low urinary Na/K ratio early after single-unit CBT is associated with poor NRM and survival in adults. [ABSTRACT FROM AUTHOR]

Keywords: busulfan; cord blood transplantation; cyclophosphamide; fludarabine; hematopoietic cell transplantation; myeloablative conditioning EN busulfan cord blood transplantation cyclophosphamide fludarabine hematopoietic cell transplantation myeloablative conditioning 374 376 3 08/05/21 20210901 NES 210901 ACKNOWLEDGEMENTS The authors thank all of the physicians and staff at the hospital and the cord blood banks in Japan for their help in this study. This retrospective study included 31 adult patients who underwent unrelated single-unit CBT (SCBT) following a radiation-free myeloablative conditioning regimen, consisting of fludarabine added to full-dose busulfan and cyclophosphamide for the treatment of hematological malignancies at our hospital between 2002 and 2020. Radiation-free myeloablative conditioning consisting of fludarabine added to full-dose busulfan and cyclophosphamide in single-unit cord blood transplantation for adults. [Extracted from the article]

Interleukin-2 (IL-2) is one of the most important cytokines that regulate the activation and proliferation of T cells and natural killer cells. The production of IL-2 may be affected by polymorphisms in the promoter region of the IL-2 gene (rs2069762). In allogeneic hematopoietic cell transplantation (HCT) from adult donors, rs2069762 has been associated with the incidence of acute and chronic graft-versus-host disease (GVHD). However, the impacts of IL-2 polymorphism on cord blood transplantation (CBT) outcomes remain unclear. The objective of this study was to assess the impact of IL-2 polymorphism rs2069762 on transplant outcomes, such as hematopoietic recovery, GVHD, overall survival, relapse, and non-relapse mortality (NRM) after CBT. We conducted a retrospective analysis of data from adult patients who underwent single-unit CBT at our institution from November 2005 to March 2023 for whom DNA samples from recipients and donors were available. IL-2 genotyping was performed using real-time polymerase chain reaction with the TaqMan® SNP genotyping assay for rs2069762. A total of 143 recipient and donor pairs were included in this study. The proportion of recipient IL-2 polymorphism rs2069762 was 48 % (n = 69) for AA, 42 % (n = 60) for CA, and 10 % (n = 14) for CC. The proportion of donor IL-2 polymorphism rs2069762 was 43 % (n = 61) for AA, 48 % (n = 69) for CA, and 9 % (n = 13) for CC. In the multivariate analysis, the use of an rs2069762 CA + CC donor was associated with lower neutrophil recovery compared to an rs2069762 AA donor (hazard ratio [HR], 0.66; 95 % confidence interval [CI], 0.50–0.88; P = 0.004). Furthermore, recipients of rs2069762 CA + CC were associated with higher NRM compared to recipients of rs2069762 AA (HR, 2.32; 95 % CI, 1.01–5.34; P = 0.047). Serum IL-2 levels at 8 weeks were significantly higher in rs2069762 CA + CC recipients compared to those with rs2069762 AA recipients (P = 0.014). Our data showed that donor IL-2 polymorphism affects neutrophil recovery and recipient IL-2 polymorphism affects NRM in adults undergoing single-unit CBT. The polymorphism of IL-2 rs2069762 in recipients and donors might be associated with the clinical outcomes of single-unit CBT. [ABSTRACT FROM AUTHOR]

Comparative studies between total body irradiation (TBI)-based and busulfan-based myeloablative conditioning (MAC) regimens for cord blood transplantation (CBT) have been limited. We retrospectively analyzed the results of single-unit CBT in 333 adult patients who received either TBI-based (n = 258) or busulfan-based (n = 75) MAC regimens at our institute. After adjusting for significant variables in the univariate analysis, there were no significant differences in neutrophil recovery (hazard ratio (HR), 0.88; p =.460), grade III–IV acute graft-versus-host disease (GVHD) (HR: 1.40, p =.410), extensive chronic GVHD (HR: 0.73, p =.380), relapse (HR: 0.61, p =.270), non-relapse mortality (HR: 1.38, p =.420), overall survival (HR: 1.18, p =.637), or event-free survival (HR: 1.08, p =.773), although platelet recovery was lower with marginal significance for the busulfan-based regimen (HR: 0.67, p =.068). In subgroup analysis, TBI-based regimens were superior to busulfan-based regimens in terms of survival for acute lymphoblastic leukemia, but not for myeloid malignancies. Further investigation is warranted even for CBT. [ABSTRACT FROM AUTHOR]

Introduction: After the first appearance of peripheral blood neutrophils, recipients from adult donor sources have a rapid increase in neutrophil recovery, whereas cord blood transplantation (CBT) recipients have a slow increase. However, the momentum of neutrophil recovery after CBT varies widely among individuals, but optimal methods to evaluate the momentum of neutrophil recovery and their clinical impacts are yet to be clarified. Methods: We retrospectively examined the prognostic effect of the momentum of neutrophil recovery in the last 7 days until neutrophil engraftment, which was calculated by an exponential growth model, after single CBT following myeloablative conditioning for 207 adults. Results: Among patients who achieved each hematopoietic lineage recovery by day 100, the momentum of neutrophil recovery, which was represented as a growth constant, was associated with the day of neutrophil engraftment (P <.0001), red blood cell engraftment (P <.0001), and platelet engraftment (P <.0001) using the Spearman's rank correlation coefficient test. More importantly, overall survival was superior with a higher growth constant compared with a lower growth constant (P <.001). In the multivariate analysis, a higher growth constant showed a lower overall mortality compared with a lower growth constant (hazard ratio: 0.48, P =.014). Conclusion: Our data demonstrated that the momentum of neutrophil recovery during the last 7 days before neutrophil engraftment, which was measured using an exponential growth model, was associated not only with hematopoietic recovery but also with a better prognosis after single CBT. [ABSTRACT FROM AUTHOR]

Introduction: The appearance of erythroblasts (EBLs) in peripheral blood occurs in a variety of serious conditions and has been associated with mortality in critically ill patients. However, the incidence, risk factor, and outcomes of EBLs after cord blood transplantation (CBT) remain unclear. Methods: We have investigated the impact of EBLs on transplant outcomes on 225 adult patients who underwent single‐unit CBT at our single institute. Results: The cumulative incidences of EBL ≥200 × 106/L and EBL ≥1000 × 106/L at 60 days after CBT were 17% and 4%, respectively, detected after a median of 35 days and 36.5 days. Multivariate analysis using erythroblastosis as time‐dependent covariates demonstrated the significant association of EBL ≥1000 × 106/L, but not EBL ≥200 × 106/L, with the development of grade III‐IV acute graft‐versus‐host disease (GVHD, hazard ratio [HR]: 18.56; P <.001), higher nonrelapse mortality (HR: 13.38; P <.001), and overall mortality (HR: 4.97; P =.001). Conclusion: These data suggested that higher levels of EBLs were recognized as a significant risk factor for severe acute GVHD and mortality after single‐unit CBT. Higher levels of EBLs may serve as a surrogate marker for poor single CBT outcomes. [ABSTRACT FROM AUTHOR]

This document discusses the prevalence and risk factors of polypharmacy among disease-free survivors of adults after allogeneic hematopoietic cell transplantation (HCT). The study found that 29% of adult survivors of allogeneic HCT were in a polypharmacy situation, with factors such as age over 55 years, duration from HCT exceeding 8 years, and the presence of chronic graft-versus-host disease (GVHD) being associated with polypharmacy. The study emphasizes the importance of monitoring and managing polypharmacy in allogeneic post-transplant survivors, particularly in elderly patients and those with chronic GVHD. Another article by a group of authors explores the topic of genetic mutations in cancer cells, highlighting the significance of understanding these mutations for targeted cancer therapies. The article discusses the challenges in identifying and analyzing these mutations and the potential benefits of advanced technologies in this field. It provides a comprehensive overview of current research and advancements in the study of genetic mutations in cancer. [Extracted from the article]

Therefore, some patients require the discontinuation of CSP due to various toxicities including neurotoxicity, nephrotoxicity, and fluid retention early after CBT. Among the 175 patients, CSP was discontinued and switched to corticosteroids in 27 patients with a median of 15 days (range, 0-30) within the first 30 days of CBT. [Extracted from the article]

Given that all six patients developed thyrotoxicosis with no apparent antecedent infection, immune-mediated reactions might be associated with thyrotoxicosis after CBT. A retrospective study by EUROCORD showed that autoimmune diseases occurred after CBT in approximately 5% of patients, and the most common autoimmune disease was cytopenia followed by autoimmune diseases of the thyroid [[10]]. Dear Editor, Thyroid dysfunction is a common endocrine complication after allogeneic hematopoietic cell transplantation (HCT). [Extracted from the article]

An intensified myeloablative conditioning regimen, involving the addition of granulocyte colony-stimulating factor (G-CSF)-combined high-dose cytarabine (12 g/m2) to standard total body irradiation and cyclophosphamide, has been performed for adult patients with myeloid malignancies in single-unit cord blood transplantation (CBT) since 1998 in our institute. We update the results of CBT, as the first allogeneic hematopoietic cell transplantation after this conditioning regimen, in 169 patients with a median long-term follow-up of 10.4 years. The median age was 43 years (range, 16 to 59 years). Ninety-four patients (56%) were in non-remission at the time of CBT, and 124 patients (73%) were acute myeloid leukemia. The median cryopreserved cord blood total nucleated cell dose and CD34+ cell dose was 2.40 × 107/kg and 0.93 × 105/kg, respectively. The cumulative incidence of neutrophil recovery at 42 days was 94.4% (95% confidence interval [CI]: 88.6–97.3%). Among the whole cohort, 105 patients were still alive at the end of the study period. The cumulative incidences of relapse and non-relapse mortality at 10 years were 26.0% (95% CI: 19.5–33.0%) and 16.9% (95% CI: 11.4–23.4%), respectively. There was an overall survival probability of 62.5% (95% CI: 54.3–69.7%) at 10 years. Higher disease risk index alone significantly affected higher overall mortality (hazard ratio 2.21, P = 0.003) in multivariate analysis. These outcomes demonstrate that G-CSF-combined myeloablative conditioning could have favorable long-term remission rates for adult patients with myeloid malignancies undergoing single-unit CBT. [ABSTRACT FROM AUTHOR]