Hematopoietic Stem Cell Transplantation Research Articles

Kidney Recovery Prognosis after Allogeneic Hematopoietic Stem-Cell Transplantation

Kidney Recovery Prognosis after Allogeneic Hematopoietic Stem-Cell Transplantation

Enhancing Hematopoietic Stem Cell Transplantation Success: The Crucial Role of Architectural Design in Transplant Units and Hematology Departments

Aim: This paper aims to explore the critical role of architectural design in Hematopoietic Stem Cell Transplantation (HSCT) procedures, focusing on how various aspects of design influence patient outcomes, staff efficiency, infection control, and overall safety. The study seeks to understand how the physical environment impacts both the immediate and long-term recovery of patients undergoing HSCT and to advocate for design principles that enhance patient and caregiver experiences. Discussion: Hematopoietic Stem Cell Transplantation (HSCT) has emerged as a vital therapeutic modality for a diverse spectrum of hematological disorders and malignancies. As medical and technological advancements continue to evolve, the significance of the physical environment in which HSCT procedures are conducted becomes increasingly evident. This paper delves into how architectural design affects patient well-being, staff efficiency, and infection control, emphasizing the importance of creating environments that support psychological well-being. It examines the impact of design on infection prevention, safety during emergencies, and the overall efficiency of healthcare delivery. The discussion also highlights the role of sustainability and green design principles in minimizing the environmental footprint while promoting patient recovery. Conclusions: The paper concludes that architectural design plays a transformative role in enhancing patient experiences and healthcare outcomes in HSCT settings. It underscores the need for a patient-centric approach to design that integrates wellness-focused elements and advanced technology. The study advocates for a collaborative effort among healthcare institutions, architects, designers, and policymakers to create supportive, efficient, and sustainable healthcare environments. By prioritizing these design considerations, healthcare environments can significantly improve the HSCT journey and contribute to the broader realm of healthcare excellence.

Autologous hematopoietic stem cell transplant for systemic sclerosis associated interstitial lung disease.

Over the last 25 years, the role of autologous hematopoietic stem cell transplant (HSCT) in the treatment of diffuse cutaneous systemic sclerosis (dcSSc) has been elucidated. However, multiple critical questions remain regarding this therapy. Of particular interest is the role of HSCT in the treatment of systemic sclerosis (SSc)-associated interstitial lung disease since this is the leading cause of death in SSc. Most clinical trials and observational studies of HSCT for the treatment of dcSSc have reported pulmonary outcomes as secondary outcomes, Also, most studies have excluded patients with significant pulmonary function impairment. Despite these limitations, there is increasing evidence that suggests that HSCT leads to interstitial lung disease stabilization and possibly improvement of lung function based on pulmonary function tests and imaging. HSCT has demonstrated improved long-term outcomes compared to conventional therapies for dcSSC. Future research is needed to refine or expand patient selection, optimize conditioning regimens, and evaluate the potential role of maintenance immunosuppression. We recommend an increased focus on interstitial lung disease since this is the primary cause of death in SSc.

The Management of Hematopoietic Stem Cell Transplant in People with HIV.

Hematopoietic stem cell transplant (HSCT) is now recognized as a standard treatment option for people with HIV (PWH) who develop high-risk hematologic malignancies. However, the involved polypharmacy can lead to complications from drug interactions and toxicities, affecting the efficacy and safety of chemotherapy and antiretroviral therapy (ART). Managing these patients requires a personalized approach, including the careful selection of ART based on previous therapies and potential interactions, alongside risk assessment for infections. This discussion will address the history of HSCT in PWH and management considerations for this group.

A case of visual impairment due to HHV-6 encephalitis after allogeneic hematopoietic stem cell transplantation in childhood acute myeloid leukemia-M2 subtype.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a crucial treatment option for children with M2 subtype acute myeloid leukemia (AML). Human herpesvirus 6 (HHV-6) encephalitis following transplantation is a rare postoperative complication, with a poor prognosis and a high fatality rate in allo-HSCT recipients. In this report, a juvenile patient with AMLwas successfully treated after developing visual impairment as a result of HHV-6B encephalitis during allo-HSCT therapy. HHV-6 encephalitis-associated visual impairment after transplantation is rare, and clinical diagnosis and treatment are challenging, requiring more attention in the future.

Insights into cytomegalovirus-associated T cell receptors in recipients following allogeneic hematopoietic stem cell transplantation

BackgroundCytomegalovirus (CMV) reactivation is a serious problem in recipients of allogeneic hematopoietic stem cell transplantation. Long-term latency depends on specific T cell immune reconstitution, which identifies various pathogens by T cell receptors (TCRs). However, the mechanisms underlying the selection of CMV-specific TCRs in recipients after transplantation remain unclear.MethodsUsing high-throughput sequencing and bioinformatics analysis, the T cell immune repertoire of seven CMV reactivated recipients (CRRs) were analyzed and compared to those of seven CMV non-activated recipients (CNRs) at an early stage after transplant.ResultsThe counts of unique complementarity-determining region 3 (CDR3) were significantly higher in CNRs than in CRRs. The CDR3 clones in the CNRs exhibit higher homogeneity compared to the CRRs. With regard to T cell receptor β-chain variable region (TRBV) and joint region (TRBJ) genotypes, significant differences were observed in the frequencies of TRBV6, BV23, and BV7–8 between the two groups. In addition to TRBV29–1/BJ1–2, TRBV2/BJ2–2, and TRBV12–4/BJ1–5, 11 V-J combinations had significantly different expression levels between CRRs and CNRs.ConclusionsThe differences in TCR diversity, TRBV segments, and TRBV-BJ combinations observed between CNRs and CRRs might be associated with post-transplant CMV reactivation and could serve as a foundation for further research.

Frequency and relationship of HLA allele in Turkish patients with Fanconi anemia

Purpose: Fanconi anemia (FA) is a childhood disorder inherited in an autosomal recessive manner. It is characterized by bone marrow failure, a range of congenital physical abnormalities, increased susceptibility to cancer, chromosomal instability, and heightened sensitivity to cross-linking agents. The aim of this study was to determine the role of the HLA Class I and Class II alleles in genetic susceptibility to Fanconi anemia in Turkish patients. Materials and Methods: In this study, we retrospectively evaluated the HLA-A, -B, and -DRB1 allele frequencies of patients with Fanconi anemia who underwent hematopoietic stem cell transplantation between 2010 and 2021. HLA-A, -B, -DR of all patients and healthy Turkish individuals were genotyped. Results: The study included 86 patients with Fanconi anemia and 300 healthy controls. The most common antigens in patients with Fanconi were HLA-A*02, HLA-B*35 and DRB1*11. Moreover, in the patient group, the HLA-A*23 allele was significantly lower than the control group. When we evaluated the patient group according to gender the HLA-A*01 allele was significantly higher in the female patient group. Conclusion: Our study provides valuable insights into the genetic susceptibility of Turkish patients with Fanconi anemia, focusing on the role of HLA Class I and Class II alleles. HLA-B*14 may be a risk factor and HLA-A*23 may be protective for Fanconi anemia. These results contribute to our understanding of the complex genetic factors underlying Fanconi anemia and may have implications for improved diagnosis, prognosis, and potential therapeutic interventions for affected individuals.

Glycosphingolipids Associated Metabolic Disorders

Lipids play diverse roles in sustaining life, including energy storage, hormonal balance, and cellular communication. Alterations in lipid metabolism can lead to various disorders, including diabetes, atherosclerosis, cancer, and neurodegenerative diseases. Among these disorders, lysosomal storage disorders (LSDs) related to glycosphingolipids metabolism present significant challenges. This review systematically analyzes the current literature on LSDs, focusing on classification, clinical presentations, diagnostic advancements, available treatments, and emerging therapeutic strategies. Glycosphingolipids biosynthesis, particularly its role in viral dissemination and melanin synthesis, underscores its significance in health and disease. Additionally, the review delves into specific LSDs, such as Fabry disease, Gaucher disease, Sandhoff disease, Tay-Sachs disease, and Krabbe disease, highlighting their pathophysiology, prevalence, and treatment options. Enzyme replacement therapy and hematopoietic stem cell transplantation are mainstays in LSD treatment, but gene therapy shows promise. Furthermore, the review explores the role of glycosphingolipids in non-communicable diseases like diabetes, cancer, atherosclerosis, lupus, Alzheimer's, Parkinson's disease, and influenza. Understanding glycosphingolipid metabolism offers insights into disease mechanisms and therapeutic targets, paving the way for improved treatments and ultimately enhancing patient outcomes.

Association between positive affect, flourishing, quality of life, and psychological distress in allogeneic hematopoietic stem cell transplantation

Purpose To examine the associations between state positive psychological well-being (PPWB) constructs, mood, and quality of life (QOL) in hematopoietic stem cell transplantation (HSCT) survivors. Design The study was a secondary analysis of cross-sectional data. Sample/Methods We analyzed self-report data assessing positive affect, flourishing, QOL, depression and anxiety, and PTSD symptoms from 158 allogeneic HSCT recipients at day-100 post-transplant enrolled in supportive care studies. Findings Univariate analysis showed that factors associated with greater levels of various state PPWB constructs include older age, disability status, greater social support, and presence of graft-versus-host disease. Multivariate analysis showed that state PPWB constructs—greater levels of positive affect and flourishing—were significantly associated with better QOL and lower PTSD, anxiety, and depression symptomatology. Implications Our findings suggest that longitudinal studies are needed to examine the links between state PPWB constructs and HSCT outcomes, which may inform population specific interventions and opportunities to improve outcomes.

Which allogeneic hematopoietic cell transplant recipients have an increased risk for delayed-onset clinically significant cytomegalovirus infection after letermovir prophylaxis?

Cytomegalovirus (CMV) reactivation is one of the most common complications after allogeneic hematopoietic stem cell transplantation (HSCT). Letermovir is approved for CMV prophylaxis among high-risk recipients. However, delayed-onset post-prophylaxis clinically significant CMV infection (csCMVi) has been observed, suggesting the potential for extending letermovir prophylaxis beyond the first one hundred days post-HSCT. Retrospective multicenter cohort study of allogeneic HSCT patients from August 2018 to March 2023. The primary aim of this study was to identify the risk factors at day 100 associated with delayed onset csCMVi, in patients who received letermovir prophylaxis up to day 100. Competing risk analysis was used to evaluate incidence with specific risk factors, using Gray's Test comparing groups for each event. Among 166 eligible allogeneic HSCT recipients, the most common primary hematological diagnosis was acute myelogenous leukemia (AML) (42.2%). Twenty-six (15.7%) developed a breakthrough csCMVi. Delayed-onset csCMVi occurred in 23.5%, at a median time of 133 days after SCT. On multivariate analysis, having a matched unrelated donor (odds ratio [OR] 2.46) and a CMV donor negative/recipient positive status (OR 3.47) were associated with delayed onset csCMVi. In contrast, AML had a lower odd of having delayed-onset csCMVi (OR 0.23). Having a matched unrelated donor, a CMV donor negative/recipient positive status, and a non-AML underlying disease were associated with delayed onset csCMVi. Prospective studies are needed to evaluate whether extended letermovir prophylaxis is beneficial for these patients.

HLA Diversity in Transylvanian Ethnic Groups: Consequences for Hematopoietic Cell Transplantation

The HLA profile is essential in cell and tissue transplantation, particularly in patients with autoimmune conditions and infections. Due to the extreme polymorphism in certain HLA loci, it also serves as a key tool for population genetic analysis. This study aimed to identify the allele and haplotype distributions of HLA class I (A, B, and C) and class II (DRB1) genotypes in unrelated hematopoietic stem cell donors. A retrospective analysis was conducted between 2016 and 2020 on 9832 Transylvanian volunteers, divided into Romanian and Hungarian groups based on self-reported ethnicity. Using PCR-SSO for HLA typing, significant differences were found in allele frequencies between ethnic groups. A total of 19 HLA-A, 31 HLA-B, 14 HLA-C, and 13 HLA-DRB1 distinct allele groups were identified between ethnic groups. Notably, B*18, B*51, and C*12 were more frequent in Romanians, while B*44, B*40, and C*07 were more common in Hungarians. Differences in haplotype distributions were also observed, with HLA-A*02~B*18~C*07~DRB1*11 being significantly more frequent in Romanians. Understanding these population-specific HLA profiles can improve donor matching for hematologic diseases, enhancing patient outcomes and access to life-saving hematopoietic stem cell transplantation.

Transplantation for immune dysregulatory disorders: current themes and future expectations.

Primary immune regulatory disorders (PIRDs) are an increasing indication for hematopoietic stem cell transplant (HCT) in pediatric patients. Here, we provide an updated overview of HCT for PIRDs, and discuss future avenues for improvement in outcomes. There are now more than 50 described monogenic PIRDs, which impact all aspects of immune tolerance, regulation, and suppression. Disease characteristics are highly variable, and HCT remains the only option for cure. We review advances in targeted therapies for individual PIRDs, which have significantly improved outcomes and the ability to safely bridge to transplant. Additionally, advances in GVHD prevention, graft manipulation, personalized conditioning regimens, and supportive care have all increased survival after HCT. The high inflammatory state increases the risk of nonengraftment, rejection, and autologous reconstitution. Therapy to reduce the inflammatory state may further improve outcomes. In addition, although younger patients with fewer comorbidities have better outcomes, the clinical courses of these diseases may be extremely variable thereby complicating the decision to proceed to HCT. HCT for PIRDs is a growing consideration in cell therapy. Yet, there remain significant gaps in our understanding of which patients this curative therapy could benefit the most. Here, we review the current data supporting HCT for PIRDs as well as areas for future improvement.

TBI/Cy followed by auto-HSCT is a good choice next to allo-HSCT for patients with T-LBL/ALL

The aim of this retrospective study was to evaluate the efficiency and safety of total body irradiation plus cyclophosphamide (TBI/Cy) followed by autogenetic hematopoietic stem cell transplantation (auto-HSCT) in T-LBL/ALL patients that cannot receive allogeneic hematopoietic stem cell transplant (allo-HSCT). Between 2013 and 2023, 24 patients received auto-HSCT following by TBI/Cy, 26 patients underwent allo-HSCT, all patients achieved completed hematopoietic reconstitution after HSCT. The progression free survival (PFS) and overall survival (OS) had no statistically significant differences between the two groups (P = 0.791, HR 1.127, 95%CI 0.456–2.785; P = 0.456, HR 0.685, 95%CI 0.256–1.828). Although the cumulative incidence of relapse was lower for patients who received allo-HSCT than auto-HSCT (P = 0.033, HR 3.707, 95%CI 1.188–11.570, 2-year relapse 11.5% vs. 33.3%), the incidence of non-relapse mortality (NRM) was higher than that in the auto-HSCT group (P = 0.014, HR 0.000, 95%CI -1.000 - -1.000, 2-year NRM, 23.1% vs. 0%). Trough Landmark analysis, the two groups showed a statistically significant difference in 3-year PFS and 4-year OS curves (Figure S2A&B, P = 0.039, HR 0.426, 95%CI 0.163–1.117; P = 0.014, HR 0.317, 95%CI 0.113–0.887). By COX analysis, poor baseline performance status (ECOG-PS ≥ 2) and CNS involvement were risk factors for PFS and OS. In conclusion, TBI/Cy followed by auto-HSCT is a good choice next to allo-HSCT for patients with T-LBL/ALL.

Oral Chronic Graft-Versus-Host Disease: Pathogenesis, Diagnosis, Current Treatment, and Emerging Therapies.

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.

Letermovir at a Prophylactic Dose for Cytomegalovirus Infection in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Retrospective Study in Japan.

Cytomegalovirus (CMV) infection is a major complication of hematopoietic stem cell transplantation (HSCT). Previous studies in adults demonstrated that letermovir prophylaxis for 100 d after HSCT reduces the occurrence of CMV infection; however, studies in children are limited. In this study, we aimed to examine the incidence of CMV infection in children who underwent allogeneic HSCT with prophylactic letermovir therapy. A single-center retrospective study was conducted among patients aged ≤17 who underwent allogeneic HSCT. We compared the cumulative incidence of CMV infection, mainly monitored by pp65-antigenemia, after HSCT between patients with and without letermovir prophylaxis (10-12 or 5-6 mg/kg/d when co-administered with cyclosporine) using Gray's test. We analyzed 79 patients with a median follow-up period of 126 d. The median age of these patients was 8.3 years (Interquartile range, 3.7-12.4). Prophylactic letermovir was used in 25 patients. Twenty-five patients developed CMV infection, and the cumulative incidence was 38.9% (95% confidence intervals, 25.0-52.5). The cumulative incidence of CMV infection was not significantly different between the letermovir and no-letermovir groups (33.1 vs. 36.6%, p = 0.228). Meanwhile, the cumulative incidence of CMV infection up to 100 d following HSCT was significantly lower in the letermovir group than in the no-letermovir group (8.0 vs. 32.8%, p = 0.026). Most patients experienced no noticeable adverse effects associated with letermovir; however, one patient discontinued letermovir because of nausea and anorexia. In conclusion, the results of this study suggest that letermovir prophylaxis against CMV infection may be effective in children without severe adverse effects.

Chemotherapy and allo-HSCT for young patients with aggressive ATL

Adult T-cell leukemia-lymphoma (ATL) is an aggressive malignancy with a poor prognosis, especially for patients with the aggressive subtype. While conventional chemotherapy offers short-term disease control, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most promising curative approach for young, transplant-eligible patients. This review focuses on current treatment strategies for aggressive ATL in this specific population. We discuss the rationale for early upfront allo-HSCT following induction chemotherapy. The advent of allo-HSCT using alternative donors, particularly haploidentical HCT, has broadened the applicability of early upfront allo-HSCT in patients with aggressive ATL worldwide. Finally, we address emerging therapies that may improve outcomes in the context of allo-HSCT, paving the way for further advancements in the treatment of aggressive ATL.

Treatment of pediatric refractory or relapsed Epstein-Barr virus-associated hemophagocytic syndrome with PD-1 inhibitors.

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a type of pediatric HLH that occurs frequently in Asia. Although immunochemotherapy based on etoposide and hormone has improved survival rates, there are still about 30% of HLH patients that do not respond. The objective of the article is to examine the efficacy and safety of programmed cell death protein 1 (PD-1) inhibitors for children with relapsed/refractory (r/r) EBV-HLH. A retrospective case note review of four pediatric patients with r/r EBV-HLH who were treated with PD-1 inhibitors at Sun Yat-sen Memorial Hospital, Sun Yat-sen University. All four patients responded to PD-1 inhibitors and achieved partial response after their first infusion. Plasma EBV DNA copy number and HLH-related monitoring indicators decreased in all of these patients. All patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), and two were still alive at the last follow-up on December 30, 2022. Two patients died because of transplantation-related complications. Serious side effects included increased liver enzymes and edema in two patients. PD-1 inhibitors are an effective salvage therapy and can provide a bridge to allo-HSCT for pediatric patients with r/r EBV-HLH. However, side effects should be monitered.

Palliative Care Referral in Adult Allogeneic Hematopoietic Stem Cell Transplants: An Integrative Literature Review.

Context: Hematologic malignancies are often unpredictable, aggressive, and may require treatments such as hematopoietic stem cell transplants (HSCT). Although morbidity and mortality are significantly amplified during the HSCT process, palliative care (PC) services are historically underutilized by HSCT providers for issues such as symptom management, prognosis understanding, goals of care, and advanced care planning. Objective: This review aimed to assess the impact of PC on the adult HSCT standard of care and examine the effects on patients' quality of life during the acute phase of allogeneic HSCT. Methodology: We conducted an integrative literature search through PubMed and CINAHL databases and utilized the PRISMA guidelines for formal review. The authors reviewed a total of 19 full-text articles. Results: Four major themes were generated from a review of the evidence: (1) Physical and Psychosocial HSCT symptoms, (2) Misconceptions of PC, (3) PC Integration on Quality of Life, and (4) Early PC integration and HSCT recipients. The consensus suggests that interdisciplinary PC during HSCT enhances the quality of care. Conclusion: Discussion of this evidence further exemplifies the need to identify unmet palliative needs earlier so that PC may be integrated before the severe consequences of HSCT. Future work should focus on investigating and evaluating effective and efficient integration of HSCT and PC specialties to optimize the quality of care.

Soluble MICA concentrations and genetic variability of MICA and its NKG2D receptor as factors affecting Graft-versus-Host Disease development after allogeneic haematopoietic stem cell transplantation

Despite new treatment strategies, graft-versus-host disease (GvHD) remains a formidable complication after allogeneic hematopoietic stem cell transplantation (HSCT). This study aimed to investigate the impact of polymorphisms and expression of MICA and NKG2D receptor on the development of GvHD in allogeneic HSCT recipients. Soluble MICA (sMICA) concentration was measured in serum collected 30 days after transplantation and the genetic variability of MICA and NKG2D genes was evaluated. The frequency of NKG2D+NK cells was determined by flow cytometry before and (21, 30, 60 and 90 days) after transplantation. Recipients with acute GvHD grades II-IV carried the NKG2D rs1049174 C allele more frequently than controls or patients with no or mild disease. Patients with chronic GvHD had higher frequency of NKG2D expressing NK cells posttransplant, reflecting increased activity of their NK cells. Although no direct relationship between MICA SNPs and GvHD were observed, the presence of MICA rs1051792 GG genotype correlated with elevated sMICA levels and increased serum level of sMICA was associated with higher risk of chronic GvHD. Our findings suggest that sMICA concentration may serve as a potential biomarker for chronic GvHD and emphasize the impact of genetic variability of NKG2D and its surface expression on the HSCT outcome.

A limited sampling model to estimate the area under the curve of mycophenolic acid in hematopoietic stem cell transplantation recipients.

Relationship between the areas under the curve (AUC) of mycophenolic acid (MPA) and the likelihood of rejection is well-established in solid organ transplantation recipients. In hematopoietic stem cell transplantation (HSCT), MPA AUC is also linked to graft versus host disease. This study aimed to develop a simplified method to estimate MPA AUC0-12 in Chinese patients undergoing allogeneic HSCT (allo-HSCT). Intensive sampling was conducted in 22 patients who were orally administered mycophenolate mofetil. Plasma concentrations of total MPA were measured, and a model predicting AUC0-12 using data from these 22 patients was constructed through regression analysis. The accuracy of the most suitable model was assessed in an additional 20 patients. None of the individual MPA concentrations showed a strong correlation with AUC0-12 (r2<0.7). Models utilizing 4 or more concentrations were found to effectively estimate MPA AUC0-12 (r2>0.87). The most operationally feasible model demonstrated good predictive performance with a mean absolute percentage error (APE%)<20%. Single MPA concentrations showed poor correlation with MPA AUC0-12. A model utilizing 4 oral concentrations (0, 0.5, 1, and 4h postdose) over a 12-h period could effectively estimate MPA AUC0-12 with precise results and minimal bias.