Search Results (95)

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

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

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

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

This review explores the complex relationship between gut dysbiosis and hematological malignancies, focusing on graft-versus-host disease (GvHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. We discuss how alterations in microbial diversity and composition can influence disease development, progression, and treatment outcomes in blood cancers. The mechanisms by which the gut microbiota impacts these conditions are examined, including modulation of immune responses, production of metabolites, and effects on intestinal barrier function. Recent advances in microbiome-based therapies for treating and preventing GvHD are highlighted, with emphasis on full ecosystem standardized donor-derived products. Overall, this review underscores the growing importance of microbiome research in hematology–oncology and its potential to complement existing treatments and improve outcomes for thousands of patients worldwide. Full article

Background: Pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) face several risk factors influencing transplantation success, including nutritional status as measured by body mass index (BMI). Methods: This study analyzed BMI data collected from patients transplanted between 2003 and 2023, and aimed to evaluate whether deviations from normal BMI are associated with poorer clinical outcomes. BMI levels assessed before and after first-line treatment and pre-transplantation were analyzed retrospectively to determine a correlation with survival and post-transplant complications. Results: Underweight patients had significantly lower 12- and 36-month overall survival rates compared to normal-weight and overweight patients (p = 1.22 × 10⁻⁸ and p = 8.88 × 10⁻⁸, respectively). Event-free survival was also lower for underweight patients at all time points. A higher pre-transplant BMI increases the risk of acute graft-versus-host disease (GVHD, p = 0.00068). Otherwise, pre-transplant BMI was not significantly correlated with early TRCs and cGVHD. As secondary objectives, this study identified differences in BMI across primary disease groups, with solid tumor patients having the highest BMI and myelodysplastic syndrome patients having the lowest. BMI cut-offs were identified to predict or protect against serious outcomes, including delayed engraftment, TRCs, and acute and chronic GVHD. Conclusions: This study highlights the importance of nutritional assessment and management in pediatric patients undergoing allo-HSCT to optimize post-transplant outcomes, as deviations from a normal BMI can significantly impact post-transplant health. These findings underscore the importance of integrating BMI assessment throughout the entire pre-HSCT therapeutic course to identify patients at higher risk for complications and to define more effective nutritional management strategies. Full article

Background: Graft-versus-host disease (GvHD) is an overactive systemic inflammatory response that can arise following allogeneic hematopoietic stem cell transplantation (HSCT). This condition occurs when the transplanted donor immune cells recognize the recipient’s tissues as foreign and trigger an immune response against them. The ocular surface (eyelids, conjunctiva, meibomian glands, lacrimal glands, and cornea) is particularly involved in GvHD, and its response to existing treatments, including potent immunosuppressants and new targeted therapies, is undesirable, with such treatments often being ineffective. Human allogeneic umbilical cord blood platelet lysate stands out as a potent adjunct to conventional therapies for ocular surface disorders related to severe Dry Eye Disease. This study aimed to evaluate the safety and efficacy of umbilical cord blood platelet lysate eyedrops for the treatment of severe ocular surface disorders in graft-versus-host disease patients who have received previous unsuccessful treatments. Methods: This study was a prospective, non-comparative, interventional case series study involving 22 patients (10 females and 12 males) aged 25–46 years with severe ocular surface disorders that were unresponsive to standard treatments. The GvHD patients were categorized based on the severity of their ocular surface disorders into three groups: Group I: five patients with severe Dry Eye Disease and filamentary keratitis; Group II: eight patients suffering from severe blepharo-kerato-epitheliopathy; Group III: nine patients with corneal ulcers. Fresh umbilical cord blood (UCB) was obtained from healthy donors and subjected to centrifugation using a novel PRP preparation kit provided by Sciacca (AG) Cord blood bank, Italy in a one-step process. In all groups, the outcomes before and after treatment were evaluated by means of the OSDI (Ocular Surface Disease Index), SANDE (Symptom Assessment in Dry Eye) questionnaire, VAS (Visual Analogue Scale), slit lamp examination, Esthesiometry, Lissamine Green Staining, the NIBUT (Non-Invasive Break-Up Time) and BUT, fluorescein staining with digital photography and Oxford classification, the Schirmer Test, the Best Corrected Visual Acuity (BCVA), and Meibography. In Group III at each evaluation time, the size of the ulcer and its relative reduction compared to the baseline size were recorded. Clinical variables, such as corneal inflammation, conjunctivalization, corneal neovascularization, or pain, were also considered individually. Results: We observed a significant improvement in the SANDE, VAS, and OSDI scores; Schirmer Test; BUT; BCVA; and Oxford classification after treatment with allogeneic cord blood serum eyedrops. Nevertheless, pain and inflammation reduced markedly over time until complete healing in all cases. The mean reduction in the ulcer surface area (compared to baseline values) was significantly higher at all assessment points (p = 0.001 for day 7 and p < 0.001 for subsequent time points every 30 days for 90 days). At the last check-up (after 90 days of treatment), the number of ulcers (Group III, nine patients) with a reduction in size of greater than 50% was eight (88.8%), of which seven ulcers were completely healed. None of the patients experienced treatment-related local or systemic adverse events. In this study, using a relatively large number of cases, we demonstrated that the use of umbilical cord blood platelet lysate eyedrops is a safe, feasible, and effective curative approach for severe ocular surface disease in patients with GvHD. Conclusions: Our pilot study highlights the remarkable effectiveness of allogeneic cord blood serum eyedrops in patients with severe ocular surface disorders following GvHD who have shown an inadequate response to the usual treatments. It is mandatory to design future studies on the efficacy of this therapeutic approach for acute ocular, mucosal, and cutaneous GvHD. Full article

Chronic graft-versus-host disease (cGvHD) is a multisystem disorder that occurs in recipients of allogeneic hematopoietic (alloHCT) stem cell transplants and is characterized by both inflammatory and fibrotic manifestations. It begins with the recognition of host tissues by the non-self (allogeneic) graft and progresses to tissue inflammation, organ dysfunction and fibrosis throughout the body. Oral cavity manifestations of cGVHD include mucosal features, salivary gland dysfunction and fibrosis. This review synthesizes current knowledge on the pathogenesis, diagnosis and management of oral cGVHD, with a focus on emerging trends and novel therapeutics. Data from various clinical studies and expert consensus are integrated to provide a comprehensive overview. Full article

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential cure for myelodysplastic neoplasms (MDSs) and other hematologic malignancies. This study investigates post-transplantation genetic evolution and telomere dynamics in hematopoietic cells, with a focus on clonal hematopoiesis (CH). We conducted a longitudinal analysis of 21 MDS patients who underwent allo-HSCT between September 2009 and February 2015. Genetic profiles of hematopoietic cells from both recipients and donors were compared at equivalent pre- and post-transplantation time points. Targeted sequencing identified CH-associated mutations, and real-time quantitative PCR measured telomere length. Furthermore, we compared CH incidence between recipients and age-matched controls from the GENIE cohort from routine health checkups. Post-allo-HSCT, 38% of recipients developed somatic mutations not detected before transplantation, indicating de novo CH originating from donor cells. Compared to age-matched healthy controls, recipients showed a significantly higher incidence of CH, suggesting increased susceptibility to genetic changes post-transplant. Telomere length analysis also revealed accelerated shortening in transplanted cells, highlighting the heightened stress and proliferation demands in the new microenvironment. Our findings reveal a notable incidence of donor-derived CH in allo-HSCT recipients, alongside significant telomere attrition. This suggests the potential influence of the marrow microenvironment on genetic and molecular changes in hematopoietic cells. Full article

The acquisition or reactivation of Epstein–Barr virus (EBV) after allogeneic Hematopoietic Stem Cell Transplant (HSCT) can be associated with complications including the development of post-transplant lymphoproliferative disorder (PTLD), which is associated with significant morbidity and mortality. A number of risk factors for PTLD have been defined, including T-cell depletion, and approaches to monitoring EBV, especially in high-risk patients, with the use of preemptive therapy upon viral activation have been described. Newer therapies for the preemption or treatment of PTLD, such as EBV-specific cytotoxic T-cells, hold promise. Further studies to help define risks, diagnosis, and treatment of EBV-related complications are needed in this at-risk population. Full article

Hepatic graft-versus-host disease (GVHD) significantly impacts morbidity and mortality among allogeneic hematopoietic stem cell transplant recipients. However, the relationship between clinical and immunopathological phenotypes and their influence on clinical outcomes in hepatic GVHD is not well understood. In this study, we aimed to study the implications of portal T-cell infiltration on the clinical outcomes in hepatic GHVD and its similarities to autoimmune liver disease. We analyzed 78 patients with biopsy-confirmed hepatic GVHD (n = 38) or autoimmune liver disease (n = 40) between 2016 and 2021. The cholestatic variant was defined by an R-value < 2.0, based on the ratio of alanine aminotransferase to alkaline phosphatase. The primary outcome was the biochemical response at 4 (early) and 8–12 (late) weeks after corticosteroid treatment. In hepatic GVHD patients, the hepatitic variant (n = 19) showed greater CD3⁺ T-cell infiltration than the cholestatic variant (n = 19; p < 0.001). No significant differences were observed in the infiltration of CD20⁺, CD38⁺, or CD68⁺ cells. The hepatitic variant had significantly better early and late responses and higher liver-related event-free survival than the cholestatic variants (p < 0.05). Concerning autoimmune liver diseases, the autoimmune hepatitis (AIH) group had significantly more portal T-cell infiltration and better treatment responses than the primary biliary cholangitis (PBC) group. In conclusion, higher portal T-cell infiltration may be associated with better clinical outcomes in patients with hepatic GVHD. Additionally, this study highlights similarities in portal T-cell infiltration and treatment response patterns between AIH and the hepatitic variant, as well as PBC and the cholestatic variant. Full article