Non-malignant Hematological Diseases Research Articles

Intrabone infusion for allogeneic umbilical cord blood transplantation in children.

Umbilical cord blood transplantation (UCBT) has been used to treat malignant and non-malignant diseases. UCBT offers the advantages of easy procurement and acceptable partial HLA mismatches, but also shows delayed hematopoietic and immunological recoveries. We postulated that an intrabone (IB) infusion of cord blood could provide a faster short- and long-term engraftment in a pediatric population with malignant and non-malignant hematologic diseases. We conducted this phase I-II single arm, exploratory clinical trial (NCT01711788) from 2012 to 2016 in a single center. Fifteen patients aged from 1.9 to 16.4 years received an IB UCBT. Median time to neutrophils and platelet recoveries were 18 days (range: 13-36 days) and 42 days (range: 26-107 days), respectively. Rate of severe acute GVH grade was low, with only one patient with grade III aGVH. Relapse occurred in 5 patients (38.5%) and TRM occurred in 1 patient. This leads to 6 years EFS and OS of 66.7% and 80% respectively. In conclusion, IB UCBT is safe and well-tolerated in children and hematological recovery compared similarly to the results obtained with IV UCBT.

Impact of Influenza Infection Among Adult and Pediatric Populations With Hematologic Malignancy and Hematopoietic Stem Cell Transplant: A Systematic Review and Meta-Analysis

PurposeInfluenza is increasingly recognized as a leading cause of morbidity and mortality in patients with hematologic malignancies and recipients of hematopoietic stem cell transplantation (HSCT). However, the impact of influenza on this population has not been previously evaluated in a systematic review. This study systematically reviewed and summarized the outcomes of influenza infection as to in-hospital influenza-related mortality, development of lower respiratory tract infection and acute respiratory distress syndrome, need for hospitalization, intensive care unit admission, and mechanical ventilation. MethodsWe conducted a systematic search of literature using the PubMed and EMBASE databases for articles published from January 1989 through January 19, 2020, reporting laboratory-confirmed influenza in patients of any age with hematologic malignancies and HSCT. Time from transplantation was not included in the search criteria. The impact of antiviral therapy on influenza outcomes was not assessed due to heterogeneity in antiviral treatment provision across the studies. Patients with influenza-like illness, solid-tumor cancers, or nonmalignant hematologic diseases were excluded from the study. A random-effects meta-analysis was performed to estimate the prevalences and 95% CIs of each outcome of interest. A subgroup analysis was carried out to assess possible sources of heterogeneity and to evaluate the potential impact of age on the influenza infection outcomes. Heterogeneity was assessed using the I2 statistic. FindingsData from 52 studies providing data on 1787 patients were included in this analysis. During seasonal epidemics, influenza-related in-hospital mortality was 16.60% (95% CI, 7.49%–27.7%), with a significantly higher death rate in adults compared to pediatric patients (19.55% [95% CI, 10.59%–29.97%] vs 0.96% [95% CI, 0%–6.77%]; P < 0.001). Complications from influenza, such as lower respiratory tract infection, developed in 35.44% of patients with hematologic malignancies and HSCT recipients, with a statistically significant difference between adults and children (46.14% vs 19.92%; P < 0.001). However, infection resulted in a higher hospital admission rate in pediatric patients compared to adults (61.62% vs 22.48%; P < 0.001). For the 2009 H1N1 pandemic, no statistically significant differences were found between adult and pediatric patients when comparing the rates of influenza-related in-hospital mortality, lower respiratory tract infection, and hospital admission. Similarly, no significant differences were noted in any of the outcomes of interest when comparing H1N1 pandemic with seasonal epidemics. ImplicationsRegardless of influenza season, patients, and especially adults, with underlying hematologic malignancies and HSCT recipients with influenza are at risk for severe outcomes including lower respiratory tract infection and in-hospital mortality.

La infección fúngica en el paciente pediátrico inmunodeprimido

In recent years, immunodeficiency condition has experienced a rise among children, who are at risk of invasive fungal infections (IFI) due to their health condition. Cancer, non-malignant hematological diseases, as primary immunodeficiencies, hematopoietic stem cell transplantation (HSCT), extreme prematurity, or critically ill condition in Pediatric Intensive Care Unit (PICU) are some immunosuppressive situations in children. The use of oncologic therapies, including immunotherapy and monoclonal antibodies, for the treatment of the aforementioned health conditions has led to an increase in morbidity and mortality rates of IFI in children.The underlying diseases and their management, comorbidities, the diagnostic tests used (both molecular and imaging), as well as the treatment used can be significantly different between adult patients and children admitted to PICU or with cancer. In pediatrics, the treatment of IFI is based primarily on pharmacokinetic studies performed in adults. In higher risk patients prophylaxis should be considered and, in the case of an IFI diagnosis, an antifungal treatment should be administered as early as possible, supported by the reversion of the immune dysfunction and surgery when appropriate.

Chimerism Monitoring Techniques after Hematopoietic Stem Cell Transplantation: An Overview of the Last 15 Years of Innovations.

Chimerism analysis is a well-established method for monitoring the state of hematopoietic stem cell transplantation (HSCT) over time by analyzing peripheral blood or bone marrow samples of the recipient in several malignant and non-malignant hematologic diseases. From a clinical point of view, a continuous monitoring is fundamental for an effective early therapeutic intervention. This paper provides a comparative overview of the main molecular biology techniques which can be used to study chimerism after bone marrow transplantation, focusing on their advantages and disadvantages. According to the examined literature, short tandem repeats (STR) analysis through simple PCR coupled with capillary electrophoresis (STR-PCR) is the most powerful method which guarantees a high power of differentiation between different individuals. However, other methods such as real-time quantitative PCR (qPCR), digital PCR (dPCR), and next-generation sequencing (NGS) technology were developed to overcome the technical limits of STR-PCR. In particular, these other techniques guarantee a higher sensitivity, which allows for the detection of chimerism at an earlier stage, hence expanding the window for therapeutic intervention. After a comparative evaluation of the various techniques, it seems clear that STR-PCR still remains the gold standard option for chimerism study, even if it is likely that both dPCR and NGS could supplement or even replace the common methods of STR analysis.

Significance of Stem Cells in Forensic Dentistry

In forensic point of view and for genetic study, biological samples collected at a crime scene serve as a significant tool, in order to resolve crimes by identifying the person. In some scenarios, individual identification gets masked by chimera persons, where the chimera person cells will have different DNA. The use of biological traces which are recorded by a person’s touch while handling items raises the chance of forensic study system. Therefore, DNA profiling can be obtained from items that were touched, which inturn becomes an useful means for forensic mode of investigation. Chimerism investigations are recognized processes to examine the condition of Hematopoietic Stem Cell Transplantation (HSCT) to analyze peripheral blood and recipient’s bone marrow samples for non-malignant and malignant hematologic diseases. In adults, ectomesenchymal cells identified in oral and maxillofacial tissues are promising for future dental stem cell therapies, because the oral tissues area rich source for stem cells. Dental stem cells have various expressive profiles and exist in specific niches. Apart from these applications, this review article highlights dental stem cells significances in forensic dental investigations.

Selective T-cell depletion targeting CD45RA as a novel approach for HLA-mismatched hematopoietic stem cell transplantation in pediatric nonmalignant hematological diseases.

Severe aplastic anemia and congenital amegakaryocytic thrombocytopenia are rare bone marrow failure syndromes. Treatment for aplastic anemia consists of hematopoietic stem cell transplantation (HSCT) from a matched sibling donor or immunosuppressant drugs if there is no donor available. Congenital amegakaryocytic thrombocytopenia is a rare autosomal recessive disease that causes bone marrow failure and has limited treatment options, except for transfusion support and HSCT. In the absence of a suitable matched sibling donor, matched-unrelated, haploidentical, or mismatched donors may be considered. A 2-step partial T-cell-depletion strategy can remove CD45RA+ naïve T cells responsible for graft-versus-host disease (GvHD) while preserving memory T cells. Five patients underwent transplantation using this strategy with rapid neutrophil and platelet recovery. Acute and chronic GvHD ≥ grade 2 appeared in two and one patient, respectively. No severe infections were observed before day + 100. A high (60%) incidence of transplant-associated microangiopathy was observed. Three patients (60%) remain alive, with a median follow-up of 881 (range 323-1248) days. CD45RA-depleted HSCT is a novel approach for patients lacking a suitable matched donor; however, further improvements are needed.

Bone marrow transplantation patients in the intensive care unit

Die allogene hämatopoetische Stammzelltransplantation (HSZT) stellt für viele Patienten mit maligner, aber auch nichtmaligner hämatologischer Grunderkrankung die einzige Chance auf Heilung dar. Dies gilt insbesondere für Patienten, die genetisch bedingt ein hohes Rezidivrisiko haben oder sich refraktär auf eine konventionelle Therapie zeigen. Durch die allogene HSZT eröffnet sich für diese Patienten eine Langzeitperspektive bei ansonsten infauster Prognose. Diese Therapieform ist jedoch mit einer nicht unerheblichen Morbidität und Mortalität assoziiert. Ein Teil der Patienten wird aufgrund von infektiösen, immunologischen und/oder toxischen Komplikationen intensivpflichtig. Nach wie vor ist unklar, ob Patienten in solchen klinischen Situationen von einer Intensivtherapie mit mechanischer Beatmung und Nierenersatztherapie profitieren, da die Mortalität der Betroffenen hoch ist. Diese Arbeit beschreibt die wichtigsten Komplikationen und mögliche Behandlungsstrategien von allogen blutstammzelltransplantierten Patienten auf der Intensivstation.

Impact of donor and recipient Epstein-Barr Virus serostatus on outcomes of allogeneic hematopoietic cell transplantation: a systematic review and meta-analysis

Allogeneic hematopoietic cell transplant (allo-HCT) is a potentially curative therapeutic strategy that showed encouraging long-term outcomes in hematological diseases. A number of factors can influence post-transplant clinical outcomes. While Epstein-Barr virus (EBV) constitutes a trigger for development of various adverse conditions, no clinical study yet has been powered to assess the effect of EBV serostatus on the clinical outcomes in allo-HCT population. To systematically summarize and analyze the impact of donor and recipient EBV serostatus on transplant outcomes in allo-HCT recipients, meta-analyses were conducted. Selected endpoints were overall survival (OS), relapse-free survival (RFS), relapse incidence (RI), non-relapse mortality (NRM), acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD), and de novo cGVHD. Three studies with 26,650 patients, transplanted for acute leukemias, lymphomas, chronic hematological malignancies, or non-malignant hematological diseases were included in the meta-analysis. In the whole population, with a total of 53,300 donors and recipients, the rate of EBV seropositivity was 85.1%, including 86.6% and 83.6% among transplant recipients and healthy donors, respectively. Donor EBV seropositivity increased the risk of cGVHD by 17%, de novo cGVHD by 14%, and aGHVD by 5%. Recipient EBV seropositivity increased the risk of cGVHD by 12%, de novo cGVHD by 17%; increased NRM by 11%, increased RI by 11%, decreased OS by 14%, and decreased RFS by 11%. In performed meta-analyses, donor and recipient EBV seropositivity was found to have a significant impact on transplant outcomes in patients after allo-HCT.

Bone Marrow Failure Syndromes, Overlapping Diseases with a Common Cytokine Signature.

Bone marrow failure (BMF) syndromes are a heterogenous group of non-malignant hematologic diseases characterized by single- or multi-lineage cytopenia(s) with either inherited or acquired pathogenesis. Aberrant T or B cells or innate immune responses are variously involved in the pathophysiology of BMF, and hematological improvement after standard immunosuppressive or anti-complement therapies is the main indirect evidence of the central role of the immune system in BMF development. As part of this immune derangement, pro-inflammatory cytokines play an important role in shaping the immune responses and in sustaining inflammation during marrow failure. In this review, we summarize current knowledge of cytokine signatures in BMF syndromes.

Natural-killer cell cytotoxicity as a diagnostic and prognostic marker for adult patients with secondary hemophagocytic lymphohistiocytosis: a prospective phase II observational study.

Background:Hemophagocytic lymphohistiocytosis (HLH) can be life-threatening if not detected and treated appropriately. The diagnosis of HLH can be confusing due to other similar febrile diseases that present with cytopenia. Natural-killer cell (NK)-cytotoxicity is an important diagnostic parameter for primary HLH; however, its role in secondary HLH in adults has not been well-elucidated.Methods:We prospectively enrolled 123 adult patients with febrile conditions accompanied by cytopenia or marrow hemophagocytosis. A diagnosis of HLH was based on HLH-2004 criteria and treated based on HLH-94 protocol. NK-cytotoxicity was calculated at the time of diagnosis by K562-cell direct lysis using flow-cytometry.Results:HLH (n = 60) was determined to be caused by Epstein–Barr virus (EBV) (n = 11), infection other than EBV (n = 16), malignancies (n = 19), and unknown (n = 14). Febrile diseases other than HLH (n = 63) were diagnosed as autoimmune disease (n = 22), malignancies (n = 21), infection (n = 12), non-malignant hematological diseases (n = 6), and unknown (n = 2). A lower NK-cytotoxicity level was observed at diagnosis in patients with HLH, compared with other causes of febrile disease (12.1% versus 26.2%, p < 0.001). However, NK-cytotoxicity had a borderline effect on diagnosis of HLH, with an area under receiver operation characteristic curve of 0.689. It also showed no significant role for the prediction of survival outcome. Multivariate analysis revealed that malignant disease and high ferritin level were related with poor survival outcome. In non-malignant disease subgroups, old age, EBV-association, and low NK-cytotoxicity were related with poor survival.Conclusions:Febrile disease with cytopenia was associated with decreased NK-cytotoxicity, especially in adults with HLH; however, its diagnostic role for adult HLH is still arguable. The diagnostic criteria for adult HLH should be further discussed.Trial registration:Clinical Research Information Service [Internet]; Osong (Chungcheongbuk-do), Korea, Centers for Disease Control and Prevention, Ministry of Health and Welfare (Republic of Korea); https://cris.nih.go.kr/cris/index.jsp; Feb, 16th 2016; KCT0001886 (KC15TISE0936);

Extracellular Vesicles from Red Blood Cells and Their Evolving Roles in Health, Coagulopathy and Therapy.

Red blood cells (RBCs) release extracellular vesicles (EVs) including both endosome-derived exosomes and plasma-membrane-derived microvesicles (MVs). RBC-derived EVs (RBCEVs) are secreted during erythropoiesis, physiological cellular aging, disease conditions, and in response to environmental stressors. RBCEVs are enriched in various bioactive molecules that facilitate cell to cell communication and can act as markers of disease. RBCEVs contribute towards physiological adaptive responses to hypoxia as well as pathophysiological progression of diabetes and genetic non-malignant hematologic disease. Moreover, a considerable number of studies focus on the role of EVs from stored RBCs and have evaluated post transfusion consequences associated with their exposure. Interestingly, RBCEVs are important contributors toward coagulopathy in hematological disorders, thus representing a unique evolving area of study that can provide insights into molecular mechanisms that contribute toward dysregulated hemostasis associated with several disease conditions. Relevant work to this point provides a foundation on which to build further studies focused on unraveling the potential roles of RBCEVs in health and disease. In this review, we provide an analysis and summary of RBCEVs biogenesis, composition, and their biological function with a special emphasis on RBCEV pathophysiological contribution to coagulopathy. Further, we consider potential therapeutic applications of RBCEVs.

Optimization of the criteria for cord blood unit selection for transplantation in recipients of the different age groups: current view and prospects in Ukraine

Umbilical cord blood has been widely used to treat both malignant and non-malignant hematological diseases for over 30 years. During this time, more than 40,000 successful hematopoietic stem cell (HSC) transplantations of umbilical cord blood have been performed. However, today in Ukraine there is no public umbilical cord blood bank established for unrelated HSC transplantation to patients with oncohematological disorders (both children and adults). In this regard, the HSC units must be purchased abroad or the patients are sent to foreign clinics for high-cost treatment. The organization of a public umbilical cord blood bank in Ukraine would help in a short time to meet the needs of patients with oncohematological disorders for donor HSCs for unrelated transplantation and save significant funds for the treatment of patients abroad. According to the experience of the world's leading oncohematological centers, when it is impossible to find either a related or haploidentical donor or in all available registries – a unrelated transplant, the search continues in the registers of public cord blood banks and an umbilical cord blood unit that matches the criteria is usually found. The optimal choice of umbilical cord blood unit is crucial to maximize the likelihood of successful transplant engraftment and recipient survival after the transplantation, so the criteria for cord blood unit selection for unrelated transplantation are a bit broader than those used when matching donor-recipient pairs. The review presents the main criteria for cord blood unit selection according to the assessment of its quality, cell dose, HLA matching for unrelated transplantation to recipients of different age groups in accordance with international guidelines developed by the National Marrow Donor Program (NMDP), USA Center for International Blood and Brain Transplantation Research (CIBMTR), in collaboration with the NMDP Council Advisory Group, as well as in accordance with the American Society for Transplantation and Cellular Therapy (ASTCT) and the Seventh Edition of the NetCord-FACT International Standards for Cord Blood Collection, Banking, and Release for Administration.

Secondary oral cancer following hematopoietic cell transplantation.

The aim of this retrospective study was to determine the incidence and the clinical outcome of secondary oral cancer (SOC) and to assess potential risk factors in a large cohort of patients (n = 908), who received allogeneic hemopoietic cell transplantation (HCT) either for a malignant (n = 733) or nonmalignant hematologic disease (n = 175). The median follow-up of 438 transplant survivors was 17 years. Twelve patients developed SOC at a median of 13.5 years since HCT and at a median age of 47 years. The 35-year cumulative incidence function of SOC development was 3.47%. In univariate analysis, factors associated with increased incidence of SOC were reduced intensity conditioning and chronic graft-versus-host disease (cGvHD). On multivariate analysis, nonmalignant disease and duration of oral cGvHD ≥15 months were independent risk factors for SOC development. Nonmalignant disease recipients had 3.94× higher than expected rate of SOC (95% confidence interval, 1.50-10.39%, p = 0.0055). Recipients whose oral cGvHD persisted for more than ≥15 months had 58.6× higher than expected rate of SOC (95% confidence interval, 13.3-258.1%), p < 0.0001). This study demonstrates that oral cGvHD and a diagnosis of nonmalignant hematologic disease are strong risk factors in the SOC development.

Survival in Patients Who Underwent HLA-Haploidentical Stem Cell Transplantation in Two Centers in Colombia

Introduction: Allogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for several malignant and non-malignant hematological diseases. However, sometimes it is challenging to find human leukocyte antigen (HLA)-matched related or unrelated donors, especially in minority populations such as Hispanics. Transplantation of T cell replete HLA haploidentical graft (HaploHCT) followed by a high dose post-transplantation cyclophosphamide (PTCy) to eradicate alloreactive T cells is an option for populations with low donor availability. HaploHCT has emerged as an effective and safe strategy in this population (Luznik L et al. BBMT 2008), but data in Hispanics is scarce. Objective: The aim of our study was to describe the clinical characteristics and assess overall survival at 100 days, 1- and 3-years of patients who underwent haploHCT in two Colombian reference centers. Methods: An observational retrospective study was conducted at two tertiary referral centers in Colombia. Patients who underwent haploHCT at Clinica FOSCAL and Centro Medico Imbanaco between January 2013 and January 2020 were selected. Demographic and clinical characteristics where analyzed using descriptive statistics. The Kaplan-Meier method was used to assess overall survival (OS) rates and the log-rank test was used to compare survival rates between groups. All data were analyzed using R statistical software®. Results: Seventy-six patients were included. Mean age at transplantation was 34 years (range 18-60). Forty-two (57.89%) patients were female. Average body mass index was 19.86kg/m2. The majority of patients (57%) had a pre-transplantation ECOG performance status of 2. The most common indication for haploHCT was acute lymphoblastic leukemia (55.26%), followed by acute myeloid leukemia (23.64%). A sibling was the donor in 69.74% of the cases. Forty-seven (61.84%) patients were ABO-matched group. Peripheral blood stem cells were the graft source in 96% of the patients. The average number of infused CD34+ cells was 11.15 x 106/kg. Fludarabine-melphalan was the most commonly used conditioning regimen (57%), followed by fludarabine-busulfan-thiotepa (39%). Graft-versus-host disease (GVHD) prophylaxis consisted of PTCy (50 mg/kg/day) on days 3 and 4 after HCT and a calcineurin inhibitor plus mycophenolate mofetil from day 5 to day 35 post-HCT. Median time to neutrophil engraftment (neutrophils &amp;gt; 0,5x109/L) was 15 days (range 10-33), while platelet engraftment, defined as as the second day of unsupported platelet count of ≥20 × 109, occurred at a median time of 13 days (range 5-38) post-transplantation. On day 28 post-HSCT, 93.4% of the patients had achieved 100% chimerism. OS was 91% (95%CI 84-97.5) at 100 days, 81% (95%CI 72-90) at 1-year, and 77% (95%CI 68-88) at 3-years after HaploHCT. C onclusion: The results of our haploHCT retrospective study in a Hispanic population are comparable to several other cohorts that have reported similar outcomes of haploHCT compared to HLA-matched HCT. The OS rates reported in our study suggest that haploHCT is a viable option in patients without an HLA-matched related or unrelated donor available, especially in populations with lower rates of suitable donors. Acknowledgements: We deeply thank Gonzalo Gutiérrez García, M.D. for his leadership and guidance implementing the haploHCT program in Clinica FOSCAL. Disclosures Peña: Roche: Honoraria. Salazar:Janssen: Honoraria; Novartis: Honoraria. Sandoval-Sus:MorphoSys US: Consultancy; Janssen: Consultancy; Massive Bio: Consultancy; Celgene: Speakers Bureau. Sossa:Novo: Honoraria; Takeda: Honoraria; Astellas: Honoraria; Roche: Honoraria.

Outcomes of Patients with Hematologic Malignancies and COVID-19 Infection: A Report from the ASH Research Collaborative Data Hub

Outcomes of Patients with Hematologic Malignancies and COVID-19 Infection: A Report from the ASH Research Collaborative Data Hub

Effect of Pegcetacoplan on Quality of Life in Patients with Paroxysmal Nocturnal Hemoglobinuria from the Pegasus Phase 3 Trial Comparing Pegcetacoplan to Eculizumab

Effect of Pegcetacoplan on Quality of Life in Patients with Paroxysmal Nocturnal Hemoglobinuria from the Pegasus Phase 3 Trial Comparing Pegcetacoplan to Eculizumab

Categorized Hematologic Response to Pegcetacoplan Versus Eculizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria: Post Hoc Analysis of Data from a Phase 3 Randomized Trial (PEGASUS)

Categorized Hematologic Response to Pegcetacoplan Versus Eculizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria: Post Hoc Analysis of Data from a Phase 3 Randomized Trial (PEGASUS)

INCIDENCE AND RISK FACTORS FOR ORAL MUCOSITIS AFTER BONE MARROW TRANSPLANTATION PATIENTS UNDER LOW INTENSITY LASER THERAPY: A LONGITUDINAL STUDY

Bone marrow transplantation (BMT) has been used to treat numerous malignant and non-malignant hematological diseases, genetic and immunological diseases with a high risk of oral mucositis (OM) due to the action of antineoplastic drugs. As photobiomodulation therapy (FBMT) with low-level laser is a proven non-invasive treatment for OM, the objective of this study was to evaluate the incidence of OM in patients on BMT undergoing FBM. 53 patients undergoing treatment received FBMT (red laser, 2J, 20s, 100mW) as a preventive protocol. If MO was observed, an infrared laser (4J, 40s, 100W) was administered. The following data were collected from patients' medical records: sex, age, chemotherapy protocol (QT) and type of BMT. An incidence of 34% was observed in the population studied (20% grade I, 11.3% grade II and 1.9% grade III). Prevention protocols using FBMT significantly reduced the incidence of oral mucositis (p = 0.004). Now, young patients with myeloid leukemia, the time between QT and BMT (p = 0.010) and time of QT (p = 0.018) were directly associated with the increased incidence of oral mucositis. It was concluded that low-intensity preventive laser therapy was associated with a reduction in the incidence of oral mucositis, showing the importance of this therapy in the management of patients undergoing BMT.

Efficacy and safety of hepatitis B re-vaccination in children after completion of chemotherapy and(or) hematopoietic stem cell transplantation

Objective: To assess the anti-hepatitis B surface antibody (HBsAb) titers in children after completion of chemotherapy and (or) hematopoietic stem cell transplantation (HSCT), evaluate the efficacy and safety of the current hepatitis B re-vaccination schedule. Methods: A total of 239 children who completed their chemotherapy and (or) HSCT and visited the vaccination clinic of Shanghai Children's Medical Center from March 2017 to July 2019 were enrolled in this study. According to the previous diseases, patients were divided into leukemia group (85 cases), lymphoma group (30 cases), solid tumor group (49 cases) and non-malignant hematological disease group (75 cases). According to the treatment of previous diseases, the patients were divided into chemotherapy group (126 cases), HSCT group (89 cases) and chemotherapy plus HSCT group (24 cases). HBsAb titers were assessed both at the time of diagnosis and after completion of treatment and some children who were HBsAb seronegative were re-vaccinated with 3 doses of hepatitis B vaccine, the vaccine-related adverse reactions were monitored. HBsAb titers were measured again one month after the completion of inoculation. HBsAb titers were defined as negative at levels <10 U/L and positive at ≥ 10 U/L. Chi-square test or Fisher exact test was used to compare the difference of negative conversion rate of hepatitis B antibody between groups, and Logistic regression was used to explore the risk factors of hepatitis B antibody negative conversion. Results: Among 239 patients, there were 143 males and 96 females. At the time of diagnosis, 179 patients (74.9%) were HBsAb seropositive and 60 patients (25.1%) were HBsAb seronegative. After completion of chemotherapy and (or) HSCT, 133 of 179 children with HBsAb seropositive (74.3%) at diagnosis became HBsAb seronegative. Univariate analysis showed significant differences at the negative conversion rates of HBsAb between different disease groups (χ²=10.211，P=0.015), different treatments groups (χ²=14.899，P<0.01) and different HBsAb titers groups before treatment (χ²=32.117，P<0.01). Logistic regression showed that HSCT (chemotherapy group as the reference, odds ratio (OR）=2.999, 95% confidence interval (CI) 1.276-7.050，P=0.012) and HBsAb titers<328.2 U/L before treatment (HBsAb titers≥328.2 U/L group as the reference, OR=6.397， 95% CI3.159-12.954，P<0.01) were risk factors for negative conversion of HBsAb. Among 48 patients whose HBsAb was seronegative after completion of chemotherapy and (or) HSCT and re-vaccinated with hepatitis B vaccine, 47 (97.9%) cases became HBsAb seropositivie. No serious adverse effects or complications were reported among these patients. Conclusions: After completion of chemotherapy and (or) HSCT, most children completely lose their protective humoral immunity against hepatitis B. Hepatitis B re-vaccination schedule can be efficiently and safely applied in those patients.

Evaluating Thymic Function After Human Hematopoietic Stem Cell Transplantation in the Personalized Medicine Era

Hematopoietic stem cell transplantation (HSCT) is an effective treatment option for several malignant and non-malignant hematological diseases. The clinical outcome of this procedure relies to a large extent on optimal recovery of adaptive immunity. In this regard, the thymus plays a central role as the primary site for de novo generation of functional, diverse, and immunocompetent T-lymphocytes. The thymus is exquisitely sensitive to several insults during HSCT, including conditioning drugs, corticosteroids, infections, and graft-vs.-host disease. Impaired thymic recovery has been clearly associated with increased risk of opportunistic infections and poor clinical outcomes in HSCT recipients. Therefore, better understanding of thymic function can provide valuable information for improving HSCT outcomes. Recent data have shown that, besides gender and age, a specific single-nucleotide polymorphism affects thymopoiesis and may also influence thymic output post-HSCT, suggesting that the time of precision medicine of thymic function has arrived. Here, we review the current knowledge about thymic role in HSCT and the recent work of genetic control of human thymopoiesis. We also discuss different transplant-related factors that have been associated with impaired thymic recovery and the use of T-cell receptor excision circles (TREC) to assess thymic output, including its clinical significance. Finally, we present therapeutic strategies that could boost thymic recovery post-HSCT.