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The reactivation of BK polyomavirus (BKPyV) during severe immunosuppression plays a crucial role in two significant syndromes observed in transplant recipients: BK polyomavirus-associated nephropathy (BKPyVAN) in kidney transplant patients and BK polyomavirus-associated hemorrhagic cystitis (BKPyV-HC) in hematopoietic cell transplant (HCT) recipients. This review aims to summarize the current understanding and lingering ambiguity by looking at three primary questions: (1) In cases with BKPyV-related illnesses in transplant patients, which diagnostic methods have the best track record of accuracy and success? (2) Which therapy approaches have the best track records of safety and efficacy in real-world clinical settings? (3) What can immunological research teach us about the development of future tailored treatments? Diagnosis involves the patient’s appearance, ruling out other potential causes, and employing quantitative PCR to identify active viral replication in urine or plasma. BKPyV-HC can vary from self-limited hematuria to potentially fatal bleeding, while BKPyVAN may lead to loss and dysfunction of the allograft. Reducing immunosuppression remains the key aspect of treatment. However, the effectiveness of antivirals (such cidofovir and leflunomide) is not always the same, and supporting measures depend on the syndrome. Researchers are looking into new immunotherapies, such as virus-specific cytotoxic T cells. Due to the intricate viro-immunopathology and lack of defined treatment regimens, future initiatives should focus on prospective studies to establish validated thresholds, enhance management algorithms, and integrate immune surveillance into individualized therapy.

Transfusion-dependent thalassemia (TDT) is an inherited disorder characterized by absent or defective production of α- or β-hemoglobin chains. If untreated, the disease invariably culminates in death in early infancy due to cardiac failure or overwhelming infection. Although there is clear evidence of good health-related quality of life and return to normal life style, the choice to undergo hematopoietic stem cell transplantation (HSCT) remains a challenge because of the potential risk of transplant-related mortality (TRM) in TDT. Successful hematopoietic stem cell transplantation may cure the hematological manifestations of TDT, but introduces risks of TRM and morbidity. The low incidence of graft-versus-host disease (GVHD) provides the major rationale for pursuing unrelated cord blood transplantation (CBT). Considerable evidence suggests a lower rate of recurrence after CBT than after transplantation from adult donors. As the TRM, overall survival, and thalassemia-free survival for CBT improve, the utility of this stem cell source will expand to indications that have hitherto rarely used unrelated CBT. This paper summarizes the current progress in understanding the advances in unrelated CBT for thalassemia. Although as yet only in a limited number of patients, the results of unrelated CBT for thalassemia are encouraging.

Richter transformation (RT) affects 2–10% of chronic lymphocytic leukemia (CLL) patients, evolving into an aggressive lymphoma—most often diffuse large B-cell lymphoma—with poor prognosis, especially when clonally related to CLL. Key risk factors include unmutated IGHV, TP53 and NOTCH1 mutations, stereotyped B-cell receptors, and complex cytogenetics. This review summarizes RT biology, clinical predictors, and treatment outcomes. Traditional chemoimmunotherapy (e.g., R-CHOP) yields complete response rates around 20–30% and median overall survival of 6–12 months; intensified regimens (R-EPOCH, hyper-CVAD) offer only modest gains. Allogeneic hematopoietic stem cell transplantation is potentially curative but limited to fit patients due to high treatment-related mortality. Emerging therapies now include Bruton’s tyrosine kinase and BCL-2 inhibitors, which achieve partial responses but short progression-free survival. CD19-directed chimeric antigen receptor T-cell therapies produce overall response rates of 60–65%, though relapses remain frequent. Bispecific antibodies (e.g., CD3×CD20 agents epcoritamab and mosunetuzumab) show promising activity and tolerable toxicity in relapsed/refractory RT. Ongoing trials are exploring combinations with checkpoint inhibitors, triplet regimens, and novel targets such as ROR1, CD47, and CDK9. Continued research into optimized induction, consolidation, and innovative immunotherapies is essential to improve outcomes in this biologically distinct, high-risk CLL-related lymphoma.

Background: Similar in histological characteristics and clinical manifestations, bronchiolitis obliterans syndrome (BOS) can develop following lung transplantation (LTx) or hematopoietic cell transplantation (HCT). In contrast to lung transplantation, where BOS is restricted to the lung allograft, HCT-related systemic graft-versus-host disease (GVHD) is the root cause of BOS. Because lung function declines following HCT, diagnosis becomes more difficult. Given the lack of proven effective medicines, treatment is based on empirical evidence. Methods: Cross-disciplinary learning is crucial, and novel therapies are under investigation to improve survival and avoid LTx. Recent advances have focused on updating the understanding of the etiology, clinical features, and pathobiology of BOS. It emphasizes the significance of learning from experts in other transplant modalities, promoting cross-disciplinary knowledge. Results: Our treatment algorithms are derived from extensive research and expert clinical input. It is important to ensure that immunosuppression is optimized and that any other conditions or contributing factors are addressed, if possible. Clear treatment algorithms are provided for each condition, drawing from the published literature and consensus clinical opinion. There are several novel therapies currently being investigated, such as aerosolized liposomal cyclosporine, Janus kinase inhibitors, antifibrotic therapies, and B-cell-directed therapies. Conclusions: We urgently need innovative treatments that can greatly increase survival rates and eliminate the need for LTx or re-transplantation.

Background High-dose methotrexate (HD-MTX) is a cornerstone of pediatric acute lymphoblastic leukemia (ALL) treatment but poses a risk for delayed clearance and associated toxicities. While hydration is standard to enhance methotrexate (MTX) excretion, the relationship between urine output (UO) and time to MTX clearance remains underexplored. Methods We conducted a retrospective study of pediatric ALL patients treated with HD-MTX at Chang Gung Memorial Hospital between August 2023 and February 2025. Patients were stratified into higher (H-UO) and lower urine output (L-UO) groups using a 5.0 mL/kg/hr cutoff. Clinical outcomes including time to MTX normalization, delayed MTX clearance, hospitalization duration, and use of adjunctive diuretics were analyzed. Results Thirty-nine patients were included. The H-UO group showed significantly faster MTX clearance (2.0 vs. 4.0 days, P  = 0.0035), lower incidence of delayed clearance (18.2% vs. 70.6%, P  = 0.0025), and shorter hospital stays (5.0 vs. 7.0 days, P  = 0.019). Diuretic use was higher in the L-UO group, primarily as a reactive measure. No significant difference in MTX-related major toxicities was observed. Conclusions Higher UO is associated with more efficient time to MTX clearance and shorter hospitalization in pediatric ALL patients receiving HD-MTX. Prospective studies are warranted to optimize supportive care protocols.

Cord blood transplantation (CBT) provides a treatment scheme for hematologic diseases and leukemia in both children and adults. However, adverse reactions and transplantation-related death may still occur in patients receiving CBT even when donor and recipient have fully matched HLA in high-resolution HLA typing analysis. Single nucleotide polymorphisms (SNPs) of HLA-related and unrelated genes are known to associate with disease status of patients with unrelated stem cell transplantation. In this study, the genomic regions ranging from 500 base pairs upstream to 500 base pairs downstream of the eight SNPs that were reported as transplantation determinants by Petersdorf et al. were analyzed to evaluate whether genetic variants were associated with the survival status of patients, and the risk for severe (grades 3–4) graft-versus-host disease (GVHD) or cytomegalovirus (CMV) infection/reactivation. The analyses were performed in the mode of recipient genotype, donor genotype, and recipient-donor mismatching, respectively. By analysis of sixty-five patients and their HLA-matched unrelated donors, we found that five SNPs were associated with patient survival which included the recipient genotype with SNPs of rs107822 in the RING1 gene, and rs2070120, rs17220087 and rs17213693 in the HLA-DOB gene; and the recipient-donor mismatching with SNPs of rs9282369 in HLA-DOA gene, and rs2070120, rs17220087 and rs17213693 in the HLA-DOB gene. Five SNPs were associated with the risk for severe GVHD which included the donor genotype with SNPs of rs213210 and rs2523675; the recipient genotype with SNPs of rs9281491 in the HCP5 gene; and the recipient-donor mismatching with SNPs of rs209130 in the TRIM27 gene, and rs986522 in the COL11A2 gene. Six SNPs were related to the risk for CMV infection/reactivation which included the donor genotype with SNPs of rs435766, rs380924, and rs2523957; and the recipient-donor mismatching with SNPs of rs2070120, rs17220087, and rs17213693 in the HLA-DOB gene; and rs435766 and rs380924 in the MICD gene. This study provides the basis for larger analyses and if the results are confirmed, a way of selecting better unrelated CBT candidate donors.

The knowledge surrounding the application of immune checkpoint inhibitors (ICIs) in the treatment of pediatric cancers is continuously expanding and evolving. These therapies work by enhancing the body’s natural immune response against tumors, which may have been suppressed by certain pathways. The effectiveness of ICIs in treating adult cancers has been widely acknowledged. However, the results of early phase I/II clinical trials that exclusively targeted the use of ICIs for treating different pediatric cancers have been underwhelming. The response rates to ICIs have generally been modest, except for cases of pediatric classic Hodgkin lymphoma. There seems to be a notable disparity in the immunogenicity of childhood cancers compared to adult cancers, potentially accounting for this phenomenon. On average, childhood cancers tend to have significantly fewer neoantigens. In recent times, there has been a renewed sense of optimism regarding the potential benefits of ICI therapies for specific groups of children with cancer. In initial research, individuals diagnosed with pediatric hypermutated and SMARCB1-deficient cancers have shown remarkable positive outcomes when treated with ICI therapies. This is likely due to the underlying biological factors that promote the expression of neoantigens and inflammation within the tumor. Ongoing trials are diligently assessing the effectiveness of ICIs for pediatric cancer patients in these specific subsets. This review aimed to analyze the safety and effectiveness of ICIs in pediatric patients with different types of highly advanced malignancies.

This systematic review discusses the use of prophylaxis to prevent cytomegalovirus (CMV) infection in recipients who have undergone hematopoietic cell transplantation. It highlights the need for new approaches to control and prevent CMV infection. The approval of the anti-CMV drug letermovir has made antiviral prophylaxis more popular. CMV-specific T cell-mediated immunity tests are effective in identifying patients who have undergone immune reconstitution and predicting disease progression. Maribavir (MBV) has been approved for the treatment of post-transplant CMV infection/disease in adolescents. Adoptive T-cell therapy and the PepVax CMV vaccine show promise in tackling refractory and resistant CMV. However, the effectiveness of PepVax in reducing CMV viremia/disease was not demonstrated in a phase II trial. Cell-mediated immunity assays are valuable for personalized management plans, but more interventional studies are needed. MBV and adoptive T-cell therapy are promising treatments, and trials for CMV vaccines are ongoing.

Background. In unresectable hepatoblastoma (HB), particularly “pre-treatment extent of tumor” (PRETEXT) IV tumors or those with positive annotation factors, standard management consists of intensive chemotherapy followed by surgical resection or orthotopic liver transplantation (OLT). Radiotherapy has traditionally been avoided because of the liver’s radiosensitivity and the risk of radiation-induced liver disease. Proton beam therapy (PBT), owing to its dosimetric advantage and ability to spare uninvolved liver parenchyma, may represent a potential local control strategy in selected pediatric patients for whom curative surgery or OLT is not feasible. Case Presentation. We describe five pediatric patients with advanced hepatoblastoma treated with proton beam therapy at our institution between February 2022 and January 2024. The cohort included three girls and two boys, with a median age of 3.0 years (interquartile range [IQR], 1.6–4.0) and a median alpha-fetoprotein level of 435,453 ng/mL (IQR: 7,668–1,276,681) at diagnosis. All patients were initially considered inoperable because of extensive hepatic involvement, inadequate future liver remnant, or multifocal disease, and OLT was not feasible owing to donor limitations or medical comorbidities. All received neoadjuvant chemotherapy using SIOPEL-based regimens, achieving partial tumor response. Tumors ranged from 5 to 12 cm and involved central hepatic segments, the portal region, or both lobes. PBT was delivered at a total dose of 50 GyE in 10–25 fractions as definitive or consolidative therapy, followed by surgical resection in three patients. Two patients additionally received targeted therapy and immunotherapy. At last follow-up, four patients were alive with no evidence of disease, while one patient died from tumor progression. Conclusions. These cases suggest that proton beam therapy may serve as a feasible liver-sparing local treatment option for selected pediatric patients with unresectable or residual hepatoblastoma when surgery or OLT is not possible. While limited by availability and cost, PBT may facilitate multimodal therapy and preserve future treatment options.

Purpose We examined the association between health-related quality of life (HRQoL) of pediatric patients during hospitalization for allogeneic hematopoietic cell transplantation (HCT) and length of hospital stay, and 1-year survival. Methods Primary family caregivers were proxy-assessors for the Pediatric Quality of Life (PedsQL) Stem Cell Transplant Module at three time points: 5-days pre-HCT (T0); 14-days post-HCT (engraftment, T1); and 1-week before hospital discharge (T2). Cox regression analyses determined predictors of the overall 1-year survival after allogeneic HCT. Results Thirty-nine eligible caregivers completed all assessments. The mean age of the pediatric patients was 9.07 years (SD = 5.2). PedsQL Stem Cell Transplant Module scores decreased from 71.33 (SD = 13.26) at T0 to 55.41(SD = 13.05) at T1 ( p  < 0.001) and increased to 68.46 (SD = 13.97) at T2 ( p  < 0.001). There was no significant difference between scores at T0 and T2. Longer length of hospital stay was associated with children who were younger and had greater relative changes in scores on the caregiver-proxy PedsQL Stem Cell Transplant Module from T0 to T1. PedsQL Stem Cell Transplant Module scores ≥ 58.07 at T2 were associated with higher 1-year survival rates (Hazard Ratio = 0.12, 95% Confidence Interval = 0.02–0.78; p  = 0.03). Conclusion Our findings suggest that assessment of HRQoL during early HCT can add prognostic value beyond demographic and HCT factors. Understanding the HRQoL status during hospitalization for HCT could help identify pediatric patients with low prospects of 1-year survival in order to provide support interventions to improve HRQoL and survival rates.