Risk factors for hemorrhagic cystitis in children undergoing hematopoietic stem cell transplantation: a systematic review and meta-analysis.

BACKGROUND: The risk factors for hemorrhagic cystitis (HC) in children undergoing hematopoietic stem cell transplantation (HSCT) are unclear. Therefore, we conducted this systematic review and meta-analysis to investigate the risk factors for HC in children undergoing HSCT. METHODS: We performed this meta-analysis by retrieving studies from PubMed, EMBASE, and the Cochrane Library up to October 10, 2023, and analyzing those that met the inclusion criteria. I2 statistics were used to evaluate heterogeneity. RESULTS: Twelve studies, including 2,764 patients, were analyzed. Male sex (odds ratio [OR] = 1.52; 95% confidence interval [CI], 1.16-2.00; p = 0.003, I2 = 0%), allogeneic donor (OR = 5.28; 95% CI, 2.60-10.74; p < 0.00001, I2 = 0%), human leukocyte antigen (HLA) mismatched donor (OR = 1.86; 95% CI, 1.00-3.44; p = 0.05, I2 = 31%), unrelated donor (OR = 1.58; 95% CI, 1.10-2.28; p = 0.01, I2 = 1%), myeloablative conditioning (MAC) (OR = 3.17; 95% CI, 1.26-7.97; p = 0.01, I2 = 0%), busulfan (OR = 2.18; 95% CI, 1.33-3.58; p = 0.002, I2 = 0%) or anti-thymoglobulin (OR = 1.65; 95% CI, 1.07-2.54; p = 0.02, I2 = 16%) use, and cytomegalovirus (CMV) reactivation (OR = 2.64; 95% CI, 1.44-4.82; p = 0.002, I2 = 0%) were risk factors for HC in children undergoing HSCT. CONCLUSIONS: Male sex, allogeneic donor, HLA-mismatched, unrelated donor, MAC, use of busulfan or anti-thymoglobulin, and CMV reactivation are risk factors for HC in children undergoing HSCT.

Echinicola rosea sp. nov., a marine bacterium isolated from surface seawater.

A novel Gram-stain-negative, rod-shaped, gliding, halotolerant, aerobic, light-pink-pigmented bacterium, strain JL3085T, was isolated from surface water of the South China Sea (16° 49' 4″ N 112° 20' 24″ E; temperature: 28.3 °C, salinity: 34.5%). The major respiratory quinone was menaquinone 7 (MK-7). The polar lipids of strain JL3085T comprised phosphatidylethanolamine, four unidentified phospholipids and three unidentified lipids. The major fatty acids were iso-C15 : 0, summed feature 3 (comprising iso-C15 : 0 2-OH and/or C16 : 1ω7c), iso-C17 : 0 3-OH, iso-C17 : 1ω9c, C17 : 1ω6c, anteiso-C15 : 0 and C16 : 1ω5c. The DNA G+C content of strain JL3085T was 43.8 mol%. 16S rRNA gene sequence analysis indicated that strain JL3085T was affiliated with the genus Echinicola, a member of the phylum Bacteroidetes, and was related most closely to Echinicola vietnamensis KMM 6221T (96.8 % similarity). DNA-DNA relatedness between strain JL3085T and E. vietnamensis KMM 6221T was 27.5 %. Based on the evidence presented here, strain JL3085T is regarded as representing a novel species of the genus Echinicola, for which the name Echinicola rosea sp. nov. is proposed. The type strain is JL3085T (=NBRC 111782T=CGMCC 1.15407T).

Early Post-Transplant Serum Ferritin Levels as Predictive Biomarkers for Severe Acute Graft-Versus-Host Disease in Pediatric Umbilical Cord Blood Transplantation for Acute Leukemia.

BACKGROUND Allogeneic hematopoietic stem cell transplantation (allo-HSCT) using umbilical cord blood is a valuable therapy option for patients with acute leukemia (AL). Acute graft-versus-host disease (aGVHD) remains the most frequently encountered complication. This study investigated risk factors for aGVHD and assessed whether post-transplant serum ferritin (SF) within 2 weeks is a potential biomarker for aGVHD in pediatric patients with AL undergoing umbilical cord blood transplantation (UCBT). MATERIAL AND METHODS We conducted a retrospective cohort study of 71 patients with AL who underwent UCBT at the Children's Hospital of Soochow University between 2017 and 2022. We evaluated several factors related to aGVHD. Univariate and multivariate analyses were performed using the proportional subdistribution hazard regression model of Fine and Gray. Analyses of overall survival (OS) were performed using the Kaplan-Meier method, and differences were compared using log-rank tests. RESULTS Of the 71 patients, 23 (32.4%) experienced grade II-IV aGVHD, of whom 18 (25.4%) developed grade III-IV aGVHD. Patients with grade II-IV and III-IV aGVHD had worse 5-year OS (69.4±10%, p=0.01; and 60.6±11.6, P=0.007, respectively). Conditioning intensity was a risk factor for grade III-IV aGVHD (HR: 0.34, 95% CI: 0.13-0.89, P=0.027). An SF level >1650 ng/mL within 2 weeks post-transplant was associated with an increased risk of severe aGVHD (HR: 3.61, 95% CI: 1.09-11.97, P=0.036). CONCLUSIONS Post-transplant SF within 2 weeks was a potential biomarker for developing severe aGVHD. Higher levels of post-transplant SF are associated with a higher incidence of grade II-IV aGVHD and grade III-IV aGVHD.

Combination of trimethoprim-sulfamethoxazole and mesenchymal stem cell therapy to treat toxoplasmic encephalitis after hematopoietic stem cell transplantation: A case report.

Toxoplasmosis, caused by the parasite Toxoplasma gondii, is a life-threatening infection that may occur following hematopoietic stem cell transplantation (HSCT). Toxoplasmic encephalitis (TE) is one of the most severe manifestations of this infection and often results in unsatisfactory therapeutic outcomes, especially regarding neurological damage. Recent studies have demonstrated that human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) can significantly aid in neural repair and remodeling. Furthermore, hUC-MSCs have been shown to reduce the risk of graft-versus-host disease (GVHD) associated with the reduction or discontinuation of immunosuppressive therapy. In this case report, we present a pediatric patient who developed TE as a complication of haploidentical HSCT. The patient received a combined treatment regimen of standard anti-Toxoplasma therapy and adjunctive hUC-MSC therapy. The outcomes were satisfactory. The patient regained consciousness, maintained a stable body temperature, and regained the ability to perform daily activities independently. Additionally, next-generation sequencing revealed a decrease in Toxoplasma DNA sequences in the blood and cerebrospinal fluid to undetectable levels. This case report underscores the potential of hUC-MSCs as a promising therapeutic modality for TE.

The efficacy and safety of third-party umbilical blood/umbilical cord mesenchymal stem cell assisted related haploid hematopoietic stem cell transplantation in pediatric patients with acute leukemia: an observational study.

Background: There is limited data on third-party umbilical cord blood (UCB) or mesenchymal stem cell (MSC) transplantation-assisted haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in pediatric patients. Objective: To evaluate the efficacy and safety of UCB and MSC transplantation-assisted haplo-HSCT in pediatric patients with acute leukemia (AL). Design: Observational study. Methods: Clinical data of 152 children with AL undergoing haplo-HSCT at the Children's Hospital of Soochow University between January 2020 and June 2022 were collected. The patients were divided into the haplo-HSCT + UCB group (n = 76), haplo-HSCT + MSC group (n = 31), and haplo-HSCT group (n = 45). Hematopoietic reconstruction time, complications within 30 days after transplantation, and survival and recurrence at 3 years after transplantation were compared among the groups. Results: Multivariate analysis revealed that haplo-HSCT with MSC and human leukocyte antigen (HLA) matching ⩾6/10 were independent factors reducing engraftment syndrome (ES) incidence. There were no significant differences among the groups in the hematopoietic reconstruction time or incidence of complications within 30 days after transplantation (p > 0.05). Overall survival, relapse-free survival, cumulative incidence of relapse, cumulative incidence of hematological relapse, and 3-year transplant-related mortality were not significantly different (p > 0.05). The incidence of adverse reactions in the haplo-HSCT + UCB group was 97.3% within 4 h after UCB infusion, with a particularly high occurrence rate of 94.7% for hypertension. No transfusion-related adverse reactions occurred after the transfusion of umbilical cord MSC in the haplo-HSCT + MSC group. Conclusion: MSC-assisted haplo-HSCT can reduce ES incidence after transplantation in pediatric patients with AL. UCB infusion is associated with a high incidence of reversible hypertension. However, no adverse reactions were observed in umbilical cord MSC transfusion.

Anagrelide and idarubicin combination induces GSDME-mediated pyroptosis as a potential therapy for high-PDE3A acute myeloid leukemia.

Acute myeloid leukemia (AML) is an invasive hematopoietic malignancy requiring novel treatment strategies. In this study, we identified phosphodiesterase 3 A (PDE3A) as a potential new target for drug repositioning in AML. PDE3A was preferentially overexpressed in AML cells than in normal cells, and high expression of PDE3A was correlated with lower event-free survival (EFS) in de novo AML patients. The PDE3A inhibitor anagrelide (ANA) profoundly suppresses the proliferation of high PDE3A-expressing AML cells while exhibiting minimal impact on those with low PDE3A expression. Moreover, synergistic effect of ANA with other chemotherapeutic drugs in high PDE3A expression AML cells was observed. The ANA-idarubicin (IDA) combination showed the most remarkable synergistic effect among all ANA-chemotherapeutic drugs commonly used in AML cell line models. Mechanistically, the synergy between ANA and IDA inhibited the survival of PDE3Ahigh AML cell lines through pyroptosis. This mechanism was initiated by GSDME cleavage triggered by caspase-3 activation. In vivo combination treatment of leukemic animals with high PDE3A expression significantly reduced leukemia burden and prolonged survival time compared with single-drug and vehicle control treatments. Our findings suggest that combined ANA and IDA treatment is an innovative and promising therapeutic strategy for AML patients with high PDE3A expression.