Search Results (175)

Background/Objectives: Pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT) is complicated by iron overload and hypomagnesemia, both contributing to immune dysfunction and post-transplant morbidity. The combined impact of these metabolic disturbances on pediatric allo-HSCT outcomes remains unexplored. This study aims to determine whether hypomagnesemia can serve as a prognostic biomarker for delayed immune reconstitution and explores its interplay with iron overload in predicting post-transplant complications and survival outcomes. Methods: A retrospective analysis was conducted on 163 pediatric allo-HSCT recipients. Serum magnesium levels were measured at defined intervals post-transplant, and outcomes were correlated with CD4+ T cell recovery, time to engraftment, incidence of graft-versus-host disease (GVHD), and survival within 12 months. Iron status, including siderosis severity, was evaluated using imaging and laboratory parameters obtained from clinical records. Results: Patients who died within 12 months post-transplant exhibited significantly lower magnesium levels. Hypomagnesemia was associated with delayed CD4+ T cell recovery, prolonged engraftment, and an increased risk of acute GVHD. A strong inverse correlation was observed between magnesium levels and the severity of siderosis. Iron overload appeared to exacerbate magnesium deficiency. Additionally, the coexistence of hypomagnesemia and siderosis significantly increased the risk of immune dysfunction and early mortality. No significant association was found with chronic GVHD. Conclusions: Hypomagnesemia is a significant, early predictor of poor outcomes in pediatric allo-HSCT, particularly in the context of iron overload, underscoring the need for early intervention, including iron chelation and MRI, to improve outcomes. Full article

This paper conducts a literature review on the role of natural killer cells in haploidentical hematopoietic stem cell transplantation. Theoretical concepts related to KIR genes are introduced regarding their structure, nomenclature, genetic organization, polymorphism, and inheritance pattern, types of KIR proteins and receptors, HLA ligands for KIR receptors, and the definition of different NK alloreactivity prediction models for the donor of haploidentical hematopoietic stem cell transplantation and the recipient. These models include the following and consider incompatibility: ligand–ligand, receptor–ligand, gene–gene, and KIR haplotype models or the KIR-B donor group. These models consider the presence or absence of specific ligands or receptors and/or KIR genes in the donor and recipient to predict alloreactivity. Determining the best model for predicting KIR alloreactivity and its significance in donor selection algorithms for haploidentical transplantation is still under investigation. Full article

Background: Acinetobacter, specifically A. baumannii, are becoming a great threat to hospitalized patients due to increasing antibiotic resistance. The aim of this study was to describe the epidemiology, clinical characteristics, antimicrobial susceptibility pattern and outcome of Acinetobacter infections in pediatric cancer patients and hematopoietic stem cell transplant (HSCT) recipients in Poland. Methods: A total of 125 episodes of Acinetobacter species infections were reported in patients <18 years treated in Polish pediatric hematology and oncology centers over a period from 2012 to 2023. Infections were subdivided into oncohematological disease (OHD) group (n = 106; 84.8%) and HSCT group (n = 19; 15.2%). Each episode represented a separate infection event; therefore, a patient who was infected more than once during the course of treatment was counted for each infection episode. Results: A. baumannii is the most common Acinetobacter species in all groups. The most common diagnoses in OHD group were acute lymphoblastic leukemia (ALL) (n = 32; 30.2%) and acute myeloid leukemia (AML) (n = 13; 12.3%). The most common underlying diseases that were indication for HSCT were hemophagocytic lymphohistiocytosis (n = 3; 15.8%) and neuroblastoma (n = 3; 15.8%). Mortality was significantly higher in the HSCT group compared to the OHD group. In the OHD group, deaths did not correlate with the type of antibiotic, with an exception for gentamicin, which correlated with higher mortality. In the HSCT group, deaths did not correlate with the type of antibiotic, except for levofloxacin that was correlated with a higher mortality rate. Conclusions: Acinetobacter infections are a great danger to immunocompromised patients. More research is needed in order to prevent and treat antibiotic-resistant bacteria. Full article

Respiratory syncytial virus (RSV) represents one of the main respiratory infections found among immunocompromised patients. Objective: The study analyzes the incidence of RSV infection in different populations of immunocompromised patients as organ transplant recipients (lung, other solid organs, hematopoietic stem cells) and oncologic patients (solid organ malignancy and hematological malignancy) compared to a group of non-immunocompromised patients. We also assessed the prevalence of viral, bacterial, and mycotic coinfection. Moreover, we aimed at evaluating the efficacy of ribavirin treatment in terms of mortality reduction. Methods: We conducted a retrospective analysis on a total of 466 transplant patients undergoing bronchoscopy with bronchoalveolar lavage for suspected viral disease or surveillance between 2016 and 2023, compared to 460 controls. Results: The incidence of RSV was significantly higher in immunocompromised patients, particularly in those with lung and bone marrow transplants. Among RSV+ patients, a higher prevalence of viral (influenza virus), bacterial (S. pneumoniae, M. pneumoniae, Nocardia spp.), and fungal (Aspergillus spp.) coinfections were observed. The efficacy of ribavirin in reducing mortality did not show significant differences compared to supportive therapy alone. Conclusions: The results of our exploratory study suggest that immunocompromised patients are particularly vulnerable to RSV infection and coinfections. Our hypothesis-generating data warrant the need for future studies aimed at exploring preventive and therapeutic strategies for RSV infection in these high-risk patient groups. Full article

Background: Allogeneic hematopoietic stem cell transplant (Allo-HSCT) recipients are still at increased risk of severe COVID-19 infection. Vaccination is a critical strategy to protect this population. This real-world prospective cohort study aimed to evaluate the immune response and clinical outcomes of COVID-19 vaccines in Allo-HSCT recipients. Methods: Allo-HSCT recipients (median age: 48 years) who received either the BNT162b2 or CoronaVac vaccines were included. Antibodies against the SARS-CoV-2 spike protein were quantitatively measured using the chemiluminescent microparticle immunoassay. Patient- and vaccine-related factors affecting antibody responses were analyzed. Adverse events, including graft-versus-host disease (GVHD) and post-vaccine infections, were recorded. Results: Among 95 Allo-HSCT recipients, 86.3% achieved adequate antibody responses following COVID-19 vaccination. Patients receiving ≥3 vaccine doses showed significantly higher antibody titers compared to those with only 2 doses (OR: 0.11; 95% CI: 0.02–0.53; p = 0.006 **). The use of Ruxolitinib or Ibrutinib was associate with increased odds of low antibody response (OR: 38.39; 95% CI: 3.14–468.95; p = 0.004 **). Hypogammaglobulinemia (low serum IgG levels) was associated with a reduced antibody response (OR: 0.17; 95% CI: 0.03–0.96; p = 0.045 *), while no significant correlation was found between serum IgA levels and antibody responses (p = 0.672). Three cases of post-vaccine GVHD were observed, and no fatalities related to COVID-19 occurred during the study. Conclusions: COVID-19 vaccination is safe and effective in Allo-HSCT recipients, with stronger responses especially following ≥3 vaccine doses. Patients receiving GVHD treatment or with hypogammaglobulinemia exhibited impaired responses, emphasizing the need for tailored vaccination strategies and close monitoring in this population. Full article

Background: Secondary immunodeficiencies in allo-HSCT (allogeneic hematopoietic stem cell transplantation) recipients increase the risk of viral reactivation, making vaccinations a vital issue. There is a paucity of data on the use of recombinant vaccine against herpes zoster (RZV) after allo-HSCT. Methods: This analysis included 149 recipients of allo-HSCT, transplanted in 2012–2022, mainly due to hematological malignancies (>95%). RZV was used from 2021 to 2023 according to the current recommendations of ACIP. The ELISA method was used to assess the VZV IgG antibody titers. Results: VZV reactivation was diagnosed in 49 out of 149 (33%) patients before vaccination, including 5 (3%) patients with reactivation within the first year after transplantation and the remaining 44 (30%) within the subsequent three years. At that time, the majority of patients were not receiving acyclovir prophylaxis. The most common clinical manifestation of reactivation was involvement of intercostal nerves, diagnosed in 40 (81%) patients. Twenty-one recipients (median age: 41) received two doses of RZV (at a median time of 34 months after transplantation, range 12–84 months), the majority of them at an interval of 1 month. The serological post-vaccination response was confirmed in 12 recipients, with a ratio of 2.38–8.3 (median 5.095). The median number of total CD3+CD4+cells in vaccinated patients was 451/μL. Despite vaccination, four patients (19%, three with confirmed serological response) developed herpes zoster. Conclusions: Herpes zoster occurred mainly in the late period after allo-HSCT after completion of acyclovir prophylaxis in over 30% of recipients. The preliminary results indicate that RZV vaccination after allo-HSCT was safe and more than 80% effective at preventing HZ, but some vaccinated individuals did experience HZ. Full article

Adenovirus (AdV) infections can lead to significant morbidity and increased mortality in immunocompromised populations such as hematopoietic stem cell and solid organ transplant recipients. This review evaluates currently available and emerging therapies for AdV infections. Cidofovir, while most commonly used, is limited by its variable efficacy and nephrotoxicity. This led to the development of brincidofovir, which has a better safety profile and great in vitro potency against AdV. The use of ribavirin and ganciclovir has been reported in the literature, but their use is limited due to inconsistent efficacy. Immune-based approaches, such as adoptive T-cell therapy, have shown promise in achieving viral clearance and improving survival but remain constrained by challenges related to manufacturing complexity and risks of graft-versus-host disease. This review underscores the need for standardized treatment protocols as well as comparative studies to identify optimal dosing and timing to initiate treatment. Future research should focus on individualized treatment approaches and the development of novel therapeutic agents to address the unmet clinical needs of AdV management. Full article

Background: Invasive fungal disease is a significant cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (alloHSCT) recipients. Posaconazole, a broad-spectrum triazole, is widely used as prophylaxis. Methods: We conducted a monocentric, retrospective study to present real-world data on posaconazole trough levels in paediatric alloHSCT patients. The main objective was to determine the required daily dose of posaconazole in paediatric patients. We analysed factors influencing posaconazole levels, and the association between posaconazole levels and breakthrough fungal infection. Results: Among 102 allogeneic HSCT recipients, we measured posaconazole plasma concentrations in 548 blood samples. The required daily doses to reach a target range of 0.7–2.0 mg/L were 15.22 (suspension), 7.52 (tablet), and 7.84 mg/kg (intravenous). Patients aged < 13 years needed higher doses to achieve the target range. The presence of enteral symptoms during prophylaxis was associated with lower plasma concentrations (p < 0.001), while co-administration of proton pump inhibitors did not (p = 0.09). Eight breakthrough infections occurred; low levels of posaconazole (<0.7 mg/L) were observed in five out of eight cases. The Cox regression model showed that higher mean plasma concentrations decreased the hazard of breakthrough infections. Conclusions: The tablet and intravenous formulations of posaconazole outperformed the suspension in terms of predictability. Our analyses on breakthrough infections and posaconazole plasma levels suggest an exposure–response relationship. Full article

Polyomaviruses (PyVs) are non-enveloped double-stranded DNA viruses that can cause significant morbidity in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients, particularly BK polyomavirus (BKPyV) and JC polyomavirus (JCPyV). BKPyV is primarily associated with hemorrhagic cystitis (HC), while JCPyV causes progressive multifocal leukoencephalopathy (PML). The pathogenesis of these diseases involves viral reactivation under immunosuppressive conditions, leading to replication in tissues such as the kidney, bladder, and central nervous system. BKPyV-HC presents as hematuria and urinary symptoms, graded by severity. PML, though rare after allo-HSCT, manifests as neurological deficits due to JCPyV replication in glial cells. Diagnosis relies on nucleic acid amplification testing for DNAuria or DNAemia as well as clinical criteria. Management primarily involves supportive care, as no antiviral treatments have proven consistently effective for either virus and need further research. This review highlights the virology, clinical presentations, and management challenges of PyV-associated diseases post-allo-HSCT, emphasizing the need for improved diagnostic tools and therapeutic approaches to mitigate morbidity and mortality in this vulnerable population. Full article

Background/Objectives: Hematopoietic stem cell transplantation (HSCT) can potentially cure hematological malignancies; however, post-transplant patients have a high risk of infection owing to their immunocompromised status. Vaccination against pathogens, such as diphtheria, tetanus, pertussis, and polio, is essential post-transplantation, but neither the long-term efficacy of vaccines nor the optimal vaccination schedule has been fully established. Methods: In this prospective observational study, we assessed the short- and long-term immunogenicity of three doses of the diphtheria, tetanus, acellular pertussis, and inactivated poliovirus (DTaP-IPV) vaccines or DTaP vaccines in 29 adult allogeneic HSCT (allo-HSCT) recipients, with antibody levels measured at baseline, 1–3 months post-vaccination, and 1-year after vaccine completion. Results: At baseline, a substantial proportion of patients lacked protective antibody levels for the targeted pathogens. However, within 1–3 months post-vaccination, seropositivity rates significantly increased, reaching 78–100% for diphtheria, tetanus, pertussis, and poliovirus. Despite this, antibody levels significantly declined 1-year post-vaccination, especially for pertussis, with only 58–65% of patients maintaining protective levels. In contrast, 85–96% of patients retained protective levels for diphtheria, tetanus, and poliovirus, although antibody values also decreased. Compared to human leukocyte antigen (HLA)-mismatched cases, HLA-matched cases showed significantly higher antibody levels for diphtheria, pertussis, and poliovirus types 1 and 3. Conclusions: This study demonstrates the short-term effectiveness of DTaP-IPV and DTaP vaccines in adult allo-HSCT patients but emphasizes the challenge of maintaining long-term immunity. Given the difficulties in sustaining long-term vaccine efficacy in allo-HSCT recipients, particularly in HLA-mismatched cases, re-evaluating the current vaccination schedule may be necessary to maintain protection. Full article

BK polyomavirus (BKPyV) is a pathogen responsible for infectious complications in hematopoietic stem cell transplant (HSCT) recipients. This review aims to give an insight into recent data about the structure and genomic organization, epidemiology, clinical manifestations, diagnosis, and current treatment options of BKPyV infections in children after HSCT. News regarding viral replication and pathogenesis include the generation of miRNA, new mechanisms of viral shedding by releasing infectious particles via extracellular vesicles, and human bladder microvascular endothelial cells probably acting as viral reservoirs enabling low-level viral replication and persistence. In studies conducted over the past five years, BKPyV hemorrhagic cystitis (BKPyV-HC) has a prevalence rate of 4 to 27% in children undergoing HSCT. Diagnostics still has unsolved dilemmas like whole blood or plasma samples as well as the standardization of molecular methods to allow for reporting in international units. In terms of treatment, new approaches have been used in the past five years, including the use of mesenchymal stem cells (MSCs), virus-specific T cells (VSTs), and recombinant human keratinocyte growth factor (rH-KGF), although the efficacy of some of these treatments has only been documented in isolated studies. This complication continues to pose a substantial clinical challenge, characterized by an absence of effective preventive and therapeutic measures. Full article

Invasive aspergillosis (IA) is a significant cause of morbidity and mortality in patients with hematological malignancy (HM) and hematopoietic stem cell transplant (HSCT) recipients. Aspergillus terreus is associated with worse outcomes than non-terreus Aspergillus species. Since the introduction of anti-mold azoles in 2002, there have been limited data on the etiology of IA. We retrospectively compared characteristics, antifungal treatments, and outcomes between patients with HM or HSCT infected with A. terreus and those with non-terreus Aspergillus between July 1993 and July 2023. We also examined trends over time in rates of A. terreus and outcomes of this infection. A total of 699 patients with culture-documented IA were analyzed, 537 with non-terreus species and 162 with A. terreus. Types of underlying malignancy, neutropenia, graft-versus-host disease, and anti-mold prophylaxis were similar between the groups. ICU stays and mechanical ventilation were more common among patients with A. terreus (p = 0.002 and 0.003, respectively). The rate of A. terreus decreased significantly from 35.9% during 1993–2003 to 11.2% during 2004–2013 and 16.7% during 2014–2023 (p < 0.0001 each). IA caused by A. terreus showed significant improvements in response to therapy and in overall and IA-associated mortality in the last two decades compared to the first (p < 0.0001). In conclusion, the increased use of anti-mold azoles after 2003 improved outcomes for HM patients with IA caused by A. terreus. Full article

Myeloid chimerism better reflects donor stem cell engraftment than whole-blood chimerism in assessing graft function following allogeneic hematopoietic stem cell transplant (HCT). We describe our experience with 130 patients aged younger than 18 years, treated with allogeneic HCT using bone marrow or PBSC from HLA-matched donors for non-malignant diseases, whose pre-transplant conditioning therapy included alemtuzumab and who were monitored with lineage-specific chimerism after transplant. At 6 years post-transplant, overall survival (OS) was 91.1% and event-free survival (EFS) was 81.5%, with no grade III-IV acute GvHD or chronic GVHD observed. Recipient T-cells did not contribute to graft loss. Mixed T-cell chimerism (MC) did not affect EFS, and there was no connection between T-cell chimerism and myeloid chimerism in patients with MC or graft loss. MC significantly correlated with virus infection; more children with MC were CMV seropositive than those with complete chimerism (CC). Additionally, MC was more common in patients with CMV viramia post-transplant. CD8 T-cell reconstitution was affected by viral reactivation, including CMV, with CD8 T-cell counts higher in the MC group than in the CC group. Mixed T-cell chimerism is due to autologous, virus-specific, predominantly CD8, T-cell expansion, and is protective and not deleterious to the recipient. Full article

Hematopoietic stem cell transplantation (HSCT) is a standard method for treating a number of pathologies, primarily blood diseases. Timely restoration of the immune system after HSCT is a critical factor associated with the development of complications such as relapses or secondary tumors and various infections, as well as the graft-versus-host reaction in allogeneic transplantation, which ultimately affects the survival of patients. Introduction into the recipient’s body of immune system cells that are incapable of sensitization by recipient antigens during the period of immune reconstitution can increase the rate of restoration of the immune system, as well as reduce the risk of complications. This review presents the results of studies on cell therapy with various cell subpopulations of both bone marrow and mesenchymal origin during HSCT. Full article

Cytomegalovirus (CMV) infection in solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients may increase the risk of rejection or allograft dysfunction, other infection(s), and morbidity and mortality. Treatment can be challenging due to medication-associated toxicities. Maribavir (MBV) is a promising option for the treatment of resistant or refractory (R/R) CMV infection in lieu of foscarnet (FOS), which has long been the recommended therapy for (val)ganciclovir-resistant infection. This was a single-center retrospective study of clinical outcomes of patients who received MBV compared to a control group who received FOS for an episode of CMV infection. Each cohort consisted of 27 episodes of CMV infection. Twenty patients in the MBV cohort and from the FOS cohort cleared the infection, with five and three patients developing MBV or FOS resistance, respectively. There were no statistically significant differences in failure of therapy as evidenced by persistent DNAemia (p = 0.56) or development of antiviral resistance (p = 0.24). In conclusion, MBV was as effective as FOS for the treatment of R/R CMV infection and was better tolerated without increased risk of antiviral resistance. Full article