Marrow Transplant Recipients Research Articles

Pharmacokinetic Model of Drug Interaction of Tacrolimus with Combined Administration of CYP3A4 Inhibitors Voriconazole and Clarithromycin After Bone Marrow Transplantation.

A pharmacokinetic model has been developed to quantify the drug-drug interactions of tacrolimus with concentration-dependent inhibition of cytochrome P450 (CYP) 3A4 from voriconazole and clarithromycin based on the CYP3A5 and CYP2C19 genotypes. This retrospective study recruited unrelated bone marrow transplant recipients receiving oral tacrolimus concomitantly with voriconazole and clarithromycin. The published population pharmacokinetic model that implemented genotypes of CYP3A5 (tacrolimus) and CYP2C19 (voriconazole) was integrated. The tested CYP3A4 inhibition models (Sigmoid efficacy maximum [Emax], Emax, log-linear, and linear) were a function of competitive inhibition of voriconazole and mechanism-based inhibition of clarithromycin in a virtual enzyme compartment. The total tacrolimus trough concentrations were 119 points, with a median of 4.3 (range: 2.0-9.9) ng/mL (n = 3). The final model comprised the Sigmoid Emax model for voriconazole and clarithromycin, which depicted time-course alterations in tacrolimus concentration and clearance when given voriconazole and clarithromycin. These findings could facilitate the model-informed precision dosing of tacrolimus after unrelated bone marrow transplant.

Quality of Life in 74 Recipients of Allogeneic Bone Marrow Transplantation

Quality of Life in 74 Recipients of Allogeneic Bone Marrow Transplantation

A qualitative study on blood and marrow transplant recipients' perceptions of health professional roles following BMT and preferences for ongoing care.

Survivors of blood and marrow transplantation (BMT) require life-long follow-up involving both tertiary transplant and primary care services. This paper explores the attitudes and preferences of BMT survivors and their carers regarding the transition from BMT centre care to primary care. This qualitative study involved semi-structured interviews with BMT survivors and carers from New South Wales, Australia. Interviews were audio-recorded, transcribed verbatim and thematically analysed. Twenty-two BMT survivors and six carers were interviewed. Two themes emerged: (1) 'Relationships with health professionals' and (2) 'Challenges of long-term care'. Participants, particularly rural/regional survivors, had diverse views on the availability of community BMT expertise and identified a range of strategies to optimise care for BMT survivors. These results highlight the importance BMT survivors and carers place on their relationships with, and ongoing access to, specialised BMT teams for long-term care. While some are happy to receive community-based care, concerns exist about the capacity of primary care providers, particularly in rural and regional areas. Improved support, communication and coordination between BMT centres and primary care may help facilitate a person-centred, sustainable shared care model. Provider education, use of telehealth and clear delineation of roles and responsibilities may assist in this transition. As BMT survivors live longer post-treatment, transitions of care and sustainable long-term care models are needed. A shared care approach, integrating specialised BMT teams and local primary care, may optimise outcomes but requires further development to balance accessibility, preferences, and specialised care needs.

The Conserved YPX3L Motif in the BK Polyomavirus VP1 Protein Is Important for Viral Particle Assembly but Not for Its Secretion into Extracellular Vesicles.

The BK polyomavirus (BKPyV) is a small DNA non-enveloped virus whose infection is asymptomatic in most of the world's adult population. However, in cases of immunosuppression, the reactivation of the virus can cause various complications, and in particular, nephropathies in kidney transplant recipients or hemorrhagic cystitis in bone marrow transplant recipients. Recently, it was demonstrated that BKPyV virions can use extracellular vesicles to collectively traffic in and out of cells, thus exiting producing cells without cell lysis and entering target cells by diversified entry routes. By a comparison to other naked viruses, we investigated the possibility that BKPyV virions recruit the Endosomal-Sorting Complexes Required for Transport (ESCRT) machinery through late domains in order to hijack extracellular vesicles. We identified a single potential late domain in the BKPyV structural proteins, a YPX3L motif in the VP1 protein, and used pseudovirions to study the effect of point mutations found in a BKPyV clinical isolate or known to ablate the interaction of such a domain with the ESCRT machinery. Our results suggest that this domain is not involved in BKPyV association with extracellular vesicles but is crucial for capsomere interaction and thus viral particle assembly.

Irradiate the knowledge gap: Empowering residents for blood product selection at Albany Medical Center.

e23236 Background: Transfusion-associated graft versus host disease (ta-GvHD) poses risks for immunocompromised patients. Indications for irradiated blood products include hematological malignancies and bone marrow transplant cases. In instances of severe acute pancytopenia, the initial contact at the emergency room (ER) is typically a nurse, followed by the ER physician. Patients referred from the local private practice, New York Oncology and Hematology (NYOH) office to our local hospital, Albany Medical Center (AMC), often bring comprehensive paper charts, but those coming directly from home frequently lack necessary documents, relying on the medical teams' expertise to ensure appropriate blood product selection. We aim to improve understanding of transfusion products and their indications. Methods: An initial pre-survey questionnaire was sent to internal medicine residents. Of the 33 responses received, 87.9% were aware of the need for irradiated blood products in hematological malignancies, 66.6% knew it was not required for solid tumors, and only 57.6% knew about the need for CAR-T patients. Additionally, only 15.2% knew where to find information on selecting irradiated blood products at AMC. The analysis highlighted a significant knowledge gap in transfusing irradiated blood products for hematological and oncological malignancies. In response, a user-friendly educational resource was created and displayed in residents' conference rooms during inpatient rotations, with plans for intermittent educational sessions over the next months. A comprehensive educational initiative addressed this aspect of patient care within the inpatient service, distributing detailed materials and discussions with the internal medicine residents at AMC. The focus was on emphasizing the critical requirement for irradiated blood products in specific clinical scenarios, particularly when managing patients with hematological malignancies and other conditions where irradiated blood is medically indicated. Results: A follow-up survey, conducted four months after distributing educational material on medicine floors, included responses from 27 internal medicine residents. Notably, 100% and 88.9% were knowledgeable about the necessity of irradiated blood products in hematological malignancies and bone marrow transplant recipients, respectively. Additionally, 24 out of 27 residents were aware that irradiated products are unnecessary for solid tumor malignancies in adult patients. All residents knew where to find information on blood product selection at AMC, and 92.6% found the education material helpful. Conclusions: Improved knowledge among residents underscores our commitment to patient care. We aim to extend education on irradiated blood product necessity beyond our residency program. Our long-term vision is to broaden this critical knowledge across the healthcare community at AMC.

Respiratory Syncytial Virus Infections in Recipients of Bone Marrow Transplants: A Systematic Review and Meta-Analysis.

Human Respiratory Syncytial Virus (RSV) is a common cause of respiratory tract infections. Usually associated with infants and children, an increasing amount of evidence suggests that RSV can cause substantial morbidity and mortality in immunocompromised individuals, including recipients of bone marrow transplantation (BMT). The present systematic review was therefore designed in accordance with the PRISMA guidelines to collect available evidence about RSV infections in BMT recipients. Three medical databases (PubMed, Embase, and MedRxiv) were therefore searched for eligible observational studies published up to 30 September 2023 and collected cases were pooled in a random-effects model. Heterogeneity was assessed using I2 statistics. Reporting bias was assessed by means of funnel plots and regression analysis. Overall, 30 studies were retrieved, including 20,067 BMT cases and 821 RSV infection episodes. Of them, 351 were lower respiratory tract infections, and a total of 78 RSV-related deaths were collected. A pooled attack rate of 5.40% (95% confidence interval [95%CI] 3.81 to 7.60) was identified, with a corresponding incidence rate of 14.77 cases per 1000 person-years (95%CI 9.43 to 20.11), and a case fatality ratio (CFR) of 7.28% (95%CI 4.94 to 10.60). Attack rates were higher in adults (8.49%, 95%CI 5.16 to 13.67) than in children (4.79%, 95%CI 3.05 to 7.45), with similar CFR (5.99%, 95%CI 2.31 to 14.63 vs. 5.85%, 95%CI 3.35 to 10.02). By assuming RSV attack rates as a reference group, influenza (RR 0.518; 95%CI 0.446 to 0.601), adenovirus (RR 0.679, 95%CI 0.553 to 0.830), and human metapneumovirus (RR 0.536, 95%CI 0.438 to 0.655) were associated with a substantially reduced risk for developing corresponding respiratory infection. Despite the heterogeneous settings and the uneven proportion of adult and pediatric cases, our study has identified high attack rates and a substantial CFR of RSV in recipients of BMT, stressing the importance of specifically tailored preventive strategies and the need for effective treatment options.

Long-term lymphocyte subset number reconstitution is unique but comparable between umbilical cord blood and unrelated bone marrow transplantation.

The number of umbilical cord blood transplantation (U-CBT) procedures has been growing annually, but little research has been done on long-term immune recovery after U-CBT. Infection risk is high in U-CBT recipients, and this can be partially attributed to immature immunocompetent cells in umbilical cord blood. In this study, we analyzed lymphocyte subset (LST) number to determine the long-term recovery timeline. We included 36 U-CBT and 10 unrelated bone marrow transplantation (U-BMT) recipients who survived more than 2years after transplantation, and followed them for up to 10years post-transplant. Recovery kinetics in the early phase post-transplant was different for each LST. Recovery of CD19+ B cells was faster after U-CBT than after U-BMT in the first 5years after transplantation. Although CD4+ T cells increased in the first several months after U-CBT, long-term cell count recovery was impaired in approximately 20% of patients. Thus, although the LST recovery pattern after U-CBT was unique, LST number recovery was statistically comparable between U-CBT and U-BMT past 5years post-transplantation.

Aromatase deficiency in transplanted bone marrow cells improves vertebral trabecular bone quantity, connectivity, and mineralization and decreases cortical porosity in murine bone marrow transplant recipients.

Estradiol is an important regulator of bone accumulation and maintenance. Circulating estrogens are primarily produced by the gonads. Aromatase, the enzyme responsible for the conversion of androgens to estrogen, is expressed by bone marrow cells (BMCs) of both hematopoietic and nonhematopoietic origin. While the significance of gonad-derived estradiol to bone health has been investigated, there is limited understanding regarding the relative contribution of BMC derived estrogens to bone metabolism. To elucidate the role of BMC derived estrogens in male bone, irradiated wild-type C57BL/6J mice received bone marrow cells transplanted from either WT (WT(WT)) or aromatase-deficient (WT(ArKO)) mice. MicroCT was acquired on lumbar vertebra to assess bone quantity and quality. WT(ArKO) animals had greater trabecular bone volume (BV/TV p = 0.002), with a higher trabecular number (p = 0.008), connectivity density (p = 0.017), and bone mineral content (p = 0.004). In cortical bone, WT(ArKO) animals exhibited smaller cortical pores and lower cortical porosity (p = 0.02). Static histomorphometry revealed fewer osteoclasts per bone surface (Oc.S/BS%), osteoclasts on the erosion surface (ES(Oc+)/BS, p = 0.04) and low number of osteoclasts per bone perimeter (N.Oc/B.Pm, p = 0.01) in WT(ArKO). Osteoblast-associated parameters in WT(ArKO) were lower but not statistically different from WT(WT). Dynamic histomorphometry suggested similar bone formation indices' patterns with lower mean values in mineral apposition rate, label separation, and BFR/BS in WT(ArKO) animals. Ex vivo bone cell differentiation assays demonstrated relative decreased osteoblast differentiation and ability to form mineralized nodules. This study demonstrates a role of local 17β-estradiol production by BMCs for regulating the quantity and quality of bone in male mice. Underlying in vivo cellular and molecular mechanisms require further study.

Adverse Events Associated with Infusion of Cellular Therapy Products in Pediatric Blood and Marrow Transplant Recipients

Adverse Events Associated with Infusion of Cellular Therapy Products in Pediatric Blood and Marrow Transplant Recipients

Development of a Patient Itinerary for Chimeric Antigen Receptor T Cell (CAR-T) Therapy and Blood and Marrow Transplant (BMT) Recipients and Donors

Development of a Patient Itinerary for Chimeric Antigen Receptor T Cell (CAR-T) Therapy and Blood and Marrow Transplant (BMT) Recipients and Donors

Real-world effectiveness of fidaxomicin in patients at high risk of Clostridioides difficile recurrence.

Compare the real-world impact of fidaxomicin (FDX) and vancomycin (VAN) on Clostridioides difficile infection (CDI) recurrence in a high-risk patient population. A retrospective, matched-cohort study evaluating hospitalized patients with CDI from January 1, 2016, to November 1, 2022, within a tertiary academic medical center. Adult patients with at least 1 prior CDI case who received either FDX or VAN for non-fulminant CDI while admitted, and had at least 1 additional risk factor for recurrence. Risk factors included age >70, solid organ or bone marrow transplant recipients, broad-spectrum antibiotic use within 30 days, or receipt of chemotherapy/immune-modulating agents within 30days of admission. FDX and VAN patients were matched according to risk factors. A total of 415 patient admissions were identified. After the exclusion of 92 patients for fulminant CDI, diarrhea from another cause, or use of VAN taper therapy, and 15 unmatched patients, 308 patient admissions were included (68 FDX and 240 VAN patients). There were no significant differences in 4-week recurrence (26% vs 23%; OR 1.1; P = .51), 90-day CDI readmission (29% vs 23%; P = .65), or 90-day all-cause readmission (54% vs 53%; P = .91). There was a significant 17% decrease in 90-day mortality associated with the use of FDX (OR .3; P = .04). In a real-world high-risk patient population, the use of FDX compared to oral VAN did not result in decreased CDI recurrence within 4 weeks or fewer hospital readmissions within 90 days. Further research is needed to better assess the value of FDX in this patient population.

Early detection, reactivation of cytomegalovirus DNA & immediate early (IE)-mRNA expression in hematopoietic stem cell-transplant patients

BackgroundHuman cytomegalovirus (HCMV) reactivation is a major cause of morbidity and mortality among stem cell transplant recipients post-transplantation. AimHCMV immediate-early messenger RNA (IE-mRNA) was evaluated as marker of post-transplant HCMV reactivation in bone marrow transplant recipients. Methodology: An in-house real-time reverse transcriptase PCR targeting IE-mRNA was developed to estimate HCMV mRNA levels post-transplantation. Blood samples collected in K2-EDTA tubes from patients (n = 162) admitted with Department of Clinical Hematology were transported in cold condition for routine HCMV DNA screening. For HCMV IE-mRNA quantification, peripheral blood mononuclear cells (PBMCs) were separated from whole blood and stored in RNA later at −70 °C until testing. Samples were collected weekly once for first 3 weeks post-transplantation and thereafter from week 4–12, samples were collected twice weekly. A total of 2467 samples were collected from 162 study participants. ResultsThirty five patients (21.6 %) had post-transplant HCMV reactivation. Twenty five patients with complete follow-up were selected for monitoring HCMV DNA. HCMV IE-mRNA PCR was performed for 15 patients and 7(46.6 %) patients had detectable mRNA levels. HCMV IE-mRNA was detected in all patients with increasing HCMV DNA levels except for one patient in whom IE-mRNA appeared 3 days before HCMV DNA was detected. One patient had detectable HCMV IE-mRNA during declining HCMV DNA level. However the patient showed an increased HCMV DNA one week later, indicating the importance of HCMV mRNA in predicting HCMV replication. ConclusionQuantification of HCMV IE-mRNA may be a valuable tool to predict progression of HCMV infection post-transplantation, with further prospective studies needed for validation.

Consensus document of the Spanish Society of Paediatric Infectious Diseases and the Advisory Committee on Vaccines of the Spanish Association of Pediatrics for vaccination of immunosuppressed individuals

The number of people with immunosuppression is increasing considerably due to their greater survival and the use of new immunosuppressive treatments for various chronic diseases. This is a heterogeneous group of patients in whom vaccination as a preventive measure is one of the basic pillars of their wellbeing, given their increased risk of contracting infections. This consensus, developed jointly by the Sociedad Española de Infectología Pediátrica (Spanish Society of Pediatric Infectious Diseases) and the Advisory Committee on Vaccines of the Asociación Española de Pediatría (Spanish Association of Paediatrics), provides guidelines for the development of a personalised vaccination schedule for patients in special situations, including general recommendations and specific recommendations for vaccination of bone marrow and solid organ transplant recipients, children with inborn errors of immunity, oncologic patients, patients with chronic or systemic diseases and immunosuppressed travellers.

Documento de consenso de la Sociedad Española de Infectología Pediátrica y el Comité Asesor de Vacunas de la Asociación Española de Pediatría para la vacunación en inmunodeprimidos

The number of people with immunosuppression is increasing considerably due to their greater survival and the use of new immunosuppressive treatments for various chronic diseases. This is a heterogeneous group of patients in whom vaccination as a preventive measure is one of the basic pillars of their wellbeing, given their increased risk of contracting infections. This consensus, developed jointly by the Sociedad Española de Infectología Pediátrica (Spanish Society of Pediatric Infectious Diseases) and the Advisory Committee on Vaccines of the Asociación Española de Pediatría (Spanish Association of Paediatrics), provides guidelines for the development of a personalised vaccination schedule for patients in special situations, including general recommendations and specific recommendations for vaccination of bone marrow and solid organ transplant recipients, children with inborn errors of immunity, oncologic patients, patients with chronic or systemic diseases and immunosuppressed travellers.

Peripheral Blood Haploidentical Allogeneic Stem Cell Transplantation in Older Adults with Acute Myeloid Leukemia and Myelodysplastic Syndromes Demonstrates Long Term Survival, Results from Australia and New Zealand Transplant and Cellular Therapies

There is a limited body of evidence for haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in older patients. Previous studies have used a high proportion of bone marrow–derived grafts and a variety of conditioning regimens. In Australia and New Zealand, haplo-HCST is predominantly performed using peripheral blood (PB) with universal use of post-transplantation cyclophosphamide (PTCy). To characterize the outcomes of older recipients undergoing haplo-HSCT for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Data were collected through the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) for patients aged 65 or older receiving a PB haplo-HSCT for AML/MDS between January 2010 and July 2020. A total of 44 patients were included in the analysis. The median follow-up time was 377 days. The median age was 68 (range 65-74) with a median Karnofsky performance status of 90. Thirty patients (68.2%) had AML, whereas 14 (31.8%) had MDS. The median donor age was 40. The most common conditioning regimen was nonmyeloablative fludarabine, cyclophosphamide, and total body irradiation (75%); the remainder of the patients received either melphalan- or busulfan-based regimens, and the majority were reduced intensity, with only 2 patients undergoing myeloablative conditioning. All patients received post-transplantation cyclophosphamide and mycophenolate mofetil, with the majority also receiving tacrolimus (90.5%) and the remainder receiving cyclosporine (9.5%). No patients received anti-thymocyte globulin. Neutrophil engraftment was achieved in 97.6% of patients at a median of 18 days, whereas platelet engraftment was achieved in 92.7% of patients at a median of 28 days. The cumulative incidences of cytomegalovirus (CMV) reactivation and CMV disease were 52.5% and 5.1% at 1 year. The incidence of grade 2-4 acute Graft Versus Host Disease (GVHD) was 18.2%. The incidence of chronic GVHD at 2 years was 40.7%, with extensive chronic GVHD occurring in 17.7% of patients. The incidences of relapse and non-relapse mortality (NRM) at 2 years were 8.8% and 20.7% respectively. The leading causes of death were infection (64.7%) followed by relapse (14.2%). The 2-year overall survival was 74%. Relapse free survival and GVHD free, relapse free survival at 2 years was 70% and 48%. Haplo-HSCT using a peripheral blood graft and PTCy GVHD prophylaxis demonstrates long-term disease control with acceptable rates of NRM for older patients with AML/MDS.

Efficacy of Sinopharm Vaccine Among Stem Cell Transplant Recipients During Two Peaks of Delta and Omicron variants of COVID-19.

Considering the dearth of research on the complications of Sinopharm coronavirus disease 2019 (COVID-19) vaccine in immunocompromised individuals and the lack of available data on COVID-19 vaccination from Iran. This study aimed to investigate the efficacy of vaccine of Sinopharm COVID-19 vaccine and its complications in bone marrow transplant (BMT) recipients. This was a retrospective cross-sectional study conducted on 250 patients with BMT who were referred to Montaserieh Hospital, Mashhad, Iran. Among them, 53 cases who received at least two doses of Sinopharm COVID-19 vaccine from March to January 2021 were entered in this study. The data were extracted from a student dissertation (Code:4000370). Sinopharm vaccine side effects were reported only in 7.7% of the patients, and shingles was the only serious side effect of the Sinopharm vaccine, which was observed only in one case. The results also revealed that Sinopharm COVID-19 vaccine side effects were not related to age or gender. Infection with the Delta variant of COVID-19 was reported in 7.5% (n=4) and no mortality was reported among them. Vaccine failure was reported in 39.6% of the cases; however, no mortality was reported among patients infected with the Omicron variant of COVID-19. In summary, it seems that Sinopharm COVID-19 vaccine adverse effects were not serious among stem cell transplant recipients. However, it may lead to some severe complications in the population. Vaccine failure against the Delta and Omicron variants of COVID-19 has been reported among more than one-third of BMT patients; however, no mortality was observed among BMT patients infected with the new variants of COVID-19.

Aspergillus fumigatus cytochrome c impacts conidial survival during sterilizing immunity.

Aspergillus fumigatus can cause a life-threatening infection known as invasive pulmonary aspergillosis (IPA), which is marked by fungus-attributable mortality rates of 20%-30%. Individuals at risk for IPA harbor genetic mutations or incur pharmacologic defects that impair myeloid cell numbers and/or function, exemplified by bone marrow transplant recipients, patients that receive corticosteroid therapy, or patients with chronic granulomatous disease (CGD). However, treatments for Aspergillus infections remain limited, and resistance to the few existing drug classes is emerging. Recently, the World Health Organization classified A. fumigatus as a critical priority fungal pathogen. Our cell death research identifies an important aspect of fungal biology that impacts susceptibility to leukocyte killing. Furthering our understanding of mechanisms that mediate the outcome of fungal-leukocyte interactions will increase our understanding of both the underlying fungal biology governing cell death and innate immune evasion strategies utilized during mammalian infection pathogenesis. Consequently, our studies are a critical step toward leveraging these mechanisms for novel therapeutic advances.

Assignment of the antibacterial potential of Ag2O/ZnO nanocomposite against MDR bacteria Proteus mirabilis and Salmonella typhi isolated from bone marrow transplant patients

The rate of infectious diseases started to be one of the major mortality agents in the healthcare sector. Exposed to increased bacterial infection by antibiotic-resistant bacteria became one of the complications that occurred for bone marrow transplant patients. Nanotechnology may provide clinicians and patients with the key to overcoming multidrug-resistant bacteria. Therefore, this study was conducted to clarify the prevalence of MDR bacteria in bone marrow transplant recipients and the use of Ag2O/ZnO nanocomposites to treat participants of diarrhea brought on by MDR bacteria following bone marrow transplantation (BMT). Present results show that pathogenic bacteria were present in 100 of 195 stool samples from individuals who had diarrhea. Phenotypic, biochemical, and molecular analysis clarify that Proteus mirabilis and Salmonella typhi were detected in 21 and 25 samples, respectively. Successful synthesis of Ag2O/ZnO nanocomposites with a particle enables to inhibition of both pathogens. The maximum inhibitory impact was seen on Salmonella typhi. At low doses (10−5 g/l), it prevented the growth by 53.4%, while at higher concentrations (10−1 g/l), Salmonella typhi was inhibited by 95.5%. Regarding Proteus mirabilis, at (10−5 g/l) Ag2O/ZnO, it was inhabited by 78.7%, but at higher concentrations (10−1 g/l), it was inhibited the growth by 94.6%. Ag2O/ZnO nanocomposite was therefore found to be the most effective therapy for MDR-isolated bacteria and offered promise for the treatment of MDR bacterial infections that cause diarrhea.

T-large granular lymphocyte frequencies and correlates in disease states detected by multiparameter flow cytometry in pediatric and young adult population.

T-large granular lymphocytes (T-LGL) characterized by dim CD5 staining, although not completely understood, have unique roles in the immune system. Expansion of peripheral blood (PB) clonal T-LGL populations is associated with various entities in adults. We have previously demonstrated clonal T-LGL proliferations in pediatric immune dysregulation/inflammatory/proliferative conditions. However, T-LGL populations have not been studied in broader spectrum pathologies. In this study we evaluated sizes and correlates of T-LGL populations in the pediatric and young adult populations with various disease states. Lymphocytes including T-LGL were investigated retrospectively by reviewing PB multiparameter flow cytometric data with various indications over a 4-year period. Associations with clinical, laboratory findings, and T-LGL population sizes were sought. Among 520 cases reviewed, 240 were females and 280 males with a mean age of 9years (0-33years); mean T-LGL population constituted 14% (1-67%) in PB T cells. There were significant differences between T-LGL and CD5-bright, regular T cells. T-LGL correlated with CD8 + /DR + (R = 0.570; P < 0.01) and CD8 + /CD11b + (R = 0.597; P < 0.01) expression, indicating activated cytotoxic phenotype. The highest average T-LGL were seen in bone marrow transplant recipients (23.7%), Evans syndrome (23.7%), lymphoma (20.6%), and acute EBV infection (20.4%) cases, all with underlying immune dysregulation pathologies. In pediatric and young adult patients with different clinical conditions, PB T-LGL constitute an average of 14% of the T cells and have a predominantly activated cytotoxic T cell phenotype. Higher relative presence was seen in cases with an immune dysregulation background. These results may serve as a reference for T-LGL research efforts.

Prediction of Coronary Heart Disease Events in Blood or Marrow Transplantation Recipients.

The long-term risk of coronary heart disease (CHD) and clinical models that predict this risk remain understudied in blood or marrow transplantation (BMT) recipients. This study sought to examine the risk of CHD after BMT and identify the associated risk factors. Participants included patients transplanted between 1974 and 2014 at City of Hope, University of Minnesota, or University of Alabama at Birmingham and those who survived≥2 years after BMT. Multivariable logistic regression models assessed CHD risk in BMT survivors compared with a sibling cohort. A self-reported questionnaire and medical records provided information regarding sociodemographics, comorbidities, and therapeutic exposures, which were used to develop a CHD risk prediction nomogram. Overall, 6,677 BMT recipients participated; the mean age at BMT was 43.9 ± 17.7 years, 58.3% were male, and 73.3% were non-Hispanic Whites. The median length of follow-up was 6.9 years (range: 2-46.2 years) from BMT. CHD was reported in 249 participants, with a 20-year cumulative incidence of 5.45% ± 0.39%. BMT survivors had a 1.6-fold greater odds of CHD compared with a sibling cohort (95% CI: 1.09-2.40). A nomogram was then developed to predict the risk of CHD at 10 and 20 years after BMT including age at BMT (HR: 1.06/y; 95% CI: 1.04-1.08), male sex (HR: 1.89; 95% CI: 1.15-3.11), a history of smoking (HR: 1.61; 95% CI: 1.01-2.58), diabetes (HR: 2.45; 95% CI: 1.23-4.89), hypertension (HR: 2.02; 95% CI: 1.15-3.54), arrhythmia (HR: 1.90; 95% CI: 0.89-4.06), and pre-BMT chest radiation (yes vs no: HR: 2.83; 95% CI: 1.20-6.67; unknown vs no: HR: 0.88; 95% CI: 0.34-2.28). The C-statistic was 0.77 in the test set (95% CI: 0.70-0.83). This study identified BMT recipients at high risk for CHD, informing targeted screening for early detection and aggressive control of risk factors.