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Data on antibody response (AR) after vaccination against SARS-CoV2 in hematopoietic stem-cell transplantation setting (HSCT) were initially scarce, mainly due to the exclusion of such patients from approval studies. Shortly after the worldwide application of vaccination against SARS-CoV-2 in vulnerable populations such as patients with hematologic malignancies, limited single-center trials, including HSCT patients, were published. However, there was a great heterogeneity between them regarding the type of underlying malignancy, co-current treatment, type of vaccine, method of AR measurement, and time point of AR measurement. Herein, we present the results of a prospective study on AR after vaccination for SARS-CoV-2 using the BNT162b2 vaccine in a cohort of 54 HSCT recipients—mostly autologous from a single Unit—along with a broad review of the current literature. In our cohort, the AR positivity rate at 1 month was 80.8% and remained positive in 85.7% of patients at 3 months after vaccination. There were only nine non-responders, who were more heavily pretreated and more frequently hypogammaglobulinemic compared to responders. High antibody titers (AT), [AT ≥ 1000 U/mL], were detected in 38.5% and 30.6% of the patients at m1 and m3, respectively. A significant decline in AT between m1 and m3 was demonstrated—p < 0.0001; median AT1 and AT3 were 480.5 and 293 U/mL, respectively. A novel finding of our study was the negative impact of IgA hypogammaglobulinemia on response to vaccination. Other negative significant factors were treatment with anti-CD20 antibody at vaccination and vaccination within 18 months from HSCT. Our data indicate that HSCT recipients elicit a positive response to the BNT162b2 vaccine against SARS-CoV-2 when vaccinated at 6 months post-transplant, and vaccination should be offered to this patient population even within the post-pandemic COVID-19 era. [ABSTRACT FROM AUTHOR]

Data on antibody response (AR) after vaccination against SARS-CoV2 in hematopoietic stem-cell transplantation setting (HSCT) were initially scarce, mainly due to the exclusion of such patients from approval studies. Shortly after the worldwide application of vaccination against SARS-CoV-2 in vulnerable populations such as patients with hematologic malignancies, limited single-center trials, including HSCT patients, were published. However, there was a great heterogeneity between them regarding the type of underlying malignancy, co-current treatment, type of vaccine, method of AR measurement, and time point of AR measurement. Herein, we present the results of a prospective study on AR after vaccination for SARS-CoV-2 using the BNT162b2 vaccine in a cohort of 54 HSCT recipients—mostly autologous from a single Unit—along with a broad review of the current literature. In our cohort, the AR positivity rate at 1 month was 80.8% and remained positive in 85.7% of patients at 3 months after vaccination. There were only nine non-responders, who were more heavily pretreated and more frequently hypogammaglobulinemic compared to responders. High antibody titers (AT), [AT ≥ 1000 U/mL], were detected in 38.5% and 30.6% of the patients at m1 and m3, respectively. A significant decline in AT between m1 and m3 was demonstrated—p < 0.0001; median AT1 and AT3 were 480.5 and 293 U/mL, respectively. A novel finding of our study was the negative impact of IgA hypogammaglobulinemia on response to vaccination. Other negative significant factors were treatment with anti-CD20 antibody at vaccination and vaccination within 18 months from HSCT. Our data indicate that HSCT recipients elicit a positive response to the BNT162b2 vaccine against SARS-CoV-2 when vaccinated at 6 months post-transplant, and vaccination should be offered to this patient population even within the post-pandemic COVID-19 era.

Infectious diarrhoea is common post-allogeneic haematopoietic stem-cell transplantation (alloHSCT). While the epidemiology of Clostridioides difficile infection (CDI) post-alloHSCT has been described, the impact of other diarrhoeal pathogens is uncertain. We reviewed all alloHSCT between 2017 and 2022 at a single large transplant centre; 374 patients were identified and included. The 1-year incidence of infectious diarrhoea was 23%, divided into viral (13/374, 3%), CDI (65/374, 17%) and other bacterial infections (16/374, 4%). There was a significant association between infectious diarrhoea within 1 year post-transplant and the occurrence of severe acute lower gastrointestinal graft-versus-host disease (GVHD, OR = 4.64, 95% CI 2.57–8.38, p < 0.001) and inferior GVHD-free, relapse-free survival on analysis adjusted for age, donor type, stem cell source and T-cell depletion (aHR = 1.64, 95% CI = 1.18–2.27, p = 0.003). When the classes of infectious diarrhoea were compared to no infection, bacterial (OR = 6.38, 95% CI 1.90–21.40, p = 0.003), CDI (OR = 3.80, 95% CI 1.91–7.53, p < 0.001) and multiple infections (OR = 11.16, 95% CI 2.84–43.92, p < 0.001) were all independently associated with a higher risk of severe GI GVHD. Conversely, viral infections were not (OR = 2.98, 95% CI 0.57–15.43, p = 0.20). Non-viral infectious diarrhoea is significantly associated with the development of GVHD. Research to examine whether the prevention of infectious diarrhoea via infection control measures or modulation of the microbiome reduces the incidence of GVHD is needed. [ABSTRACT FROM AUTHOR]

Objective To investigate the nutritional status of hematopoietic stem-cell transplantation patients and the construction and application of nutritional management scheme. Methods This study adopts a prospective research method, taking 120 patients with hematopoietic stem-cell transplantation treated in our hospital from January 2020 to September 2021 as the research objects. Patients were randomly divided into observation group and control group. The patients in the control group take routine nursing guidance, and the patients in the observation group take nutrition intervention mode nursing under team management, Both groups were intervened for 2 weeks. The differences of influencing factors, physiological indexes, immune indexes and prognosis between the two groups were compared. Results After treatment, Hb, ALB, PAB, TP, IBW %, MAMC, complement C3, complement C4, IgA, IgG and IgM in the two groups were significantly increased, and Hb, ALB, PAB, TP, IBW %, MAMC, complement C3, complement C4, IgA, IgG and IgM in the observation group were significantly higher than those in the control group(P＜0. 05). The incidence of malnutrition, acute graft-versus-host disease and infection during transplantation in the observation group were significantly lower than those in the control group(P＜0. 05). Conclusion The nutritional intervention under the team management mode adopted by patients with stem cell transplantation has significantly improved their nutritional and immune indexes. (目的 探讨造血干细胞移植患者营养情况及营养管理方案的构建与应用效果。方法 采取前瞻性研究方法, 选取2020年1月—9月在本院进行治疗的120例造血干细胞移植术患者作为研究对象, 随机分为观察组及对照组, 各60例。对照组患者采取常规营养指导, 观察组患者采取团队管理下的营养干预模式护理。两组患者均干预2周。比较两组患者的影响因素、生理指标、免疫指标、预后之间的差异。结果 经过治疗后, 两组患者的血红蛋白(HB)、白蛋白(ALB)、前蛋白(PAB)、总蛋白(TP)、实际体质量与理想体质量的比值(IBW%)、上臀中部肌围(MAMC)、补体C3、补体C4、免疫球蛋白A(IgA)、免疫球蛋白G(IgG)、免疫球蛋白M(IgM)均显著升高, 且观察组患者的HB、ALB、PAB、TP、IBW%、MAMC、补体C3、补体C4、IgA、IgG、IgM显著高于对照组(P＜0. 05)。观察组患者的营养不良发生率、急性移植物抗宿主病发生率、移植期感染率显著低于对照组(P＜0. 05)。结论 给予造血干细胞移植患者团队管理模式下的营养干预, 能有效营养指标以及免疫指标显著改善。)

Background: Antibiotics, while an essential component of supportive care in allogeneic hematopoietic cell transplantation (allo‐HCT), can have adverse effects and select for antibiotic resistance. Understanding of patterns of use will inform antimicrobial stewardship (AMS) interventions. Methods: Retrospective, single‐center cohort of children undergoing first allo‐HCT (n = 125). Antibiotic prescription and infection data were included from the date conditioning was commenced until 30 days post allo‐HCT. Antibiotic use was reported as length of therapy (LOT) (number of days a patient received an antibiotic) and days of therapy DOT (aggregating all antibiotics prescribed per day). Infections were classified as microbiologically documented infection (MDI) or clinically documented infections. Results: At least one course of antibiotics was administered to 124 (99%) patients. The LOT was 636 per 1000 patient days and DOT was 959 per 1000 patient days. The median duration of cumulative antibiotic exposure per patient was 24 days (interquartile range [IQR] 20–30 days). There were 131 days of fever per 1000 patient days with patients febrile for a median of 4 days (IQR 1–7 days). Piperacillin–tazobactam was used for 116 (94%) of patients with an LOT of 532 per 1000 patient days. A total of 119 MDI episodes occurred in 74 (59%) patients, including blood stream infection in 30 (24%) and a proven/probable invasive fungal infection in 4 (3%). Conclusion: Pediatric HCT patients receive prolonged courses of broad‐spectrum antibiotics relative to the frequency of fever and bacterial infections. This study has identified opportunities for AMS intervention to improve outcomes for our HCT patients. [ABSTRACT FROM AUTHOR]

Aim: to investigate the slime production in isolates of Staphylococcus spp., associated with bacteremia in patients after hematopoietic stem-cell transplantation (HSCT) and to determine the relationship between the slime production and ica genes carriage, as well as the correlation of ica and methicillin resistance.

Transplantation of immature dopaminergic neurons or neural precursors derived from embryonic stem cells (ESCs) into the substantia nigra pars compacta (SNpc) is a potential therapeutic approach for functional restitution of the nigrostriatal pathway in Parkinson's disease (PD). However, further studies are needed to understand the effects of the local microenvironment on the transplanted cells to improve survival and specific differentiation in situ. We have previously reported that the adult SNpc sustains a neurogenic microenvironment. Non-neuralized embryoid body cells (EBCs) from mouse ESCs (mESCs) overexpressing the dopaminergic transcription factor Lmx1a gave rise to many tyrosine hydroxylase (Th+) cells in the intact and damaged adult SNpc, although only for a short-term period. Here, we extended our study by transplanting EBCs from genetically engineered naive human ESC (hESC), overexpressing the dopaminergic transcription factors LMX1A, FOXA2, and OTX2 (hESC-LFO), in the SNpc. Unexpectedly, no graft survival was observed in wild-type hESC EBCs transplants, whereas hESC-LFO EBCs showed viability in the SNpc. Interestingly, neural rosettes, a developmental hallmark of neuroepithelial tissue, emerged at 7- and 15-days post-transplantation (dpt) from the hESC-LFO EBCs. Neural rosettes expressed specification dopaminergic markers (Lmx1a, Otx2), which gave rise to several Th+ cells at 30 dpt. Our results suggest that the SNpc enables the robust initiation of neural differentiation of transplanted human EBCs prompted to differentiate toward the midbrain dopaminergic phenotype. [ABSTRACT FROM AUTHOR]

Mutations in the FLT3 gene are associated with poor prognosis in patients with AML, even after consolidation with allogeneic hematopoietic cell transplantation (alloHCT) in first remission. Treatment failure in FLT3-mutated AML is largely driven by excessive risk of relapse compared to other genetic subtypes, including in patients post-alloHCT. As a result, there is substantial interest in studying posttransplant maintenance therapy in FLT3-mutated AML as an approach to optimize disease control and improve long-term outcomes. Clinical trials utilizing posttransplant FLT3 inhibitors, such as sorafenib and midostaurin, have shown feasibility, safety, and encouraging posttransplant outcomes, and there are ongoing studies using newer-generation tyrosine-kinase inhibitors as posttransplant maintenance therapy. Here, we review the toxicities and efficacy of FLT3 inhibitors as posttransplant maintenance, recommendations on the use of FLT3 inhibitors by international consensus guidelines, and highlight key remaining questions. [ABSTRACT FROM AUTHOR]

Human adenovirus (HAdV) can often lead to fulminant hepatitis in immunocompromised patients, mostly after reactivation of HAdV. Different risk factors, e.g., transplantation and chemotherapy, increase the risk of developing a HAdV hepatitis. We retrospectively analyzed three patients who showed the characteristics of a HAdV hepatitis observed in disseminated disease. In addition to PCR, diagnosis could be proven by pathology, CT scan, and markedly elevated transaminases. All patients had a hemato-oncologic underlying disease. Two had received a stem-cell transplant, and one was under chemotherapy including rituximab. Despite therapy with cidofovir, all patients died. As the incidence of HAdV hepatitis is low, diagnosis may be easily overlooked. No treatment approaches have yet been established. HAdV hepatitis should be considered as a differential diagnosis, especially when risk factors are present. To avoid dissemination, treatment should be initiated as soon as possible. [ABSTRACT FROM AUTHOR]

Background: Germ cell tumors represent, among solid cancers, a potentially curable disease even if up to 20% to 30% of patients (pts) relapse after first‐line treatment especially considering intermediate and poor prognosis groups. In this scenario, patients are candidates for high‐dose chemotherapy and autologous stem‐cells transplantation as second‐line treatment even though stem‐cells mobilization potential can be affected by several cycles and regimens of chemotherapy. To date, plerixafor is authorized in poor mobilizer adult pts diagnosed with lymphoma or multiple myeloma and in pediatric solid tumors or lymphoma. Therefore, the use of plerixafor in adult pts with relapsing/refractory GCT is still off label. Materials and methods: In our study, we describe mobilization and collection of peripheral blood stem cells for 10 pts with germ cell tumors. Six patients underwent plerixafor administration since classified as poor mobilizers based on WBC count (>5.000/μL) and CD34+ cell count (<15/μL) the day before apheresis procedure. Results: On the first day of apheresis, plerixafor administration in poor mobilizers made possible a remarkable boost of CD34+ cells in such a way to overlap that of good mobilizers' (32/μL vs 35/μL, respectively, P >.05). Conclusion: Therefore, in our experience, plerixafor made a good fraction of poor mobilizer patients eligible for mobilization and collection and able to undergo the predicted autologous stem‐cells transplantation; thus, the lack of access to the use of plerixafor in this setting of patients risks jeopardizing an effective treatment, especially in case of poor prognosis. [ABSTRACT FROM AUTHOR]

Transplantation of immature dopaminergic neurons or neural precursors derived from embryonic stem cells (ESCs) into the substantia nigra pars compacta (SNpc) is a potential therapeutic approach for functional restitution of the nigrostriatal pathway in Parkinson’s disease (PD). However, further studies are needed to understand the effects of the local microenvironment on the transplanted cells to improve survival and specific differentiation in situ. We have previously reported that the adult SNpc sustains a neurogenic microenvironment. Non-neuralized embryoid body cells (EBCs) from mouse ESCs (mESCs) overexpressing the dopaminergic transcription factor Lmx1a gave rise to many tyrosine hydroxylase (Th+) cells in the intact and damaged adult SNpc, although only for a short-term period. Here, we extended our study by transplanting EBCs from genetically engineered naive human ESC (hESC), overexpressing the dopaminergic transcription factors LMX1A, FOXA2, and OTX2 (hESC-LFO), in the SNpc. Unexpectedly, no graft survival was observed in wild-type hESC EBCs transplants, whereas hESC-LFO EBCs showed viability in the SNpc. Interestingly, neural rosettes, a developmental hallmark of neuroepithelial tissue, emerged at 7- and 15-days post-transplantation (dpt) from the hESC-LFO EBCs. Neural rosettes expressed specification dopaminergic markers (Lmx1a, Otx2), which gave rise to several Th+ cells at 30 dpt. Our results suggest that the SNpc enables the robust initiation of neural differentiation of transplanted human EBCs prompted to differentiate toward the midbrain dopaminergic phenotype.

Regulatory T cell (Treg) reconstitution is essential for reestablishing tolerance and maintaining homeostasis following stem-cell transplantation. We previously reported that bone marrow (BM) is highly enriched in autophagy-dependent Treg and autophagy disruption leads to a significant Treg loss, particularly BM-Treg. To correct the known Treg deficiency observed in chronic graft-versus-host disease (cGVHD) patients, low dose IL-2 infusion has been administered, substantially increasing peripheral Treg (pTreg) numbers. However, as clinical responses were only seen in ∼50% of patients, we postulated that pTreg augmentation was more robust than for BM-Treg. We show that BM-Treg and pTreg have distinct characteristics, indicated by differential transcriptome expression for chemokine receptors, transcription factors, cell cycle control of replication and genes linked to Treg function. Further, BM-Treg were more quiescent, expressed lower FoxP3, were highly enriched for co-inhibitory markers and more profoundly depleted than splenic Treg in cGVHD mice. In vivo our data are consistent with the BM and not splenic microenvironment is, at least in part, driving this BM-Treg signature, as adoptively transferred splenic Treg that entered the BM niche acquired a BM-Treg phenotype. Analyses identified upregulated expression of IL-9R, IL-33R, and IL-7R in BM-Treg. Administration of the T cell produced cytokine IL-2 was required by splenic Treg expansion but had no impact on BM-Treg, whereas the converse was true for IL-9 administration. Plasmacytoid dendritic cells (pDCs) within the BM also may contribute to BM-Treg maintenance. Using pDC-specific BDCA2-DTR mice in which diptheria toxin administration results in global pDC depletion, we demonstrate that pDC depletion hampers BM, but not splenic, Treg homeostasis. Together, these data provide evidence that BM-Treg and splenic Treg are phenotypically and functionally distinct and influenced by niche-specific mediators that selectively support their respective Treg populations. The unique properties of BM-Treg should be considered for new therapies to reconstitute Treg and reestablish tolerance following SCT.

This article explores the role of the teenage and young adult (TYA) blood and marrow stem-cell transplant clinical nurse specialist (CNS) from the author's perspective, and the challenges of developing a novel role. The article aims to provide insight into the role, and review the benefits of the CNS to patient care, thus highlighting the value of developing such a role within other stem-cell transplant centres in the UK. [ABSTRACT FROM AUTHOR]

Human adenovirus (HAdV) can often lead to fulminant hepatitis in immunocompromised patients, mostly after reactivation of HAdV. Different risk factors, e.g., transplantation and chemotherapy, increase the risk of developing a HAdV hepatitis. We retrospectively analyzed three patients who showed the characteristics of a HAdV hepatitis observed in disseminated disease. In addition to PCR, diagnosis could be proven by pathology, CT scan, and markedly elevated transaminases. All patients had a hemato-oncologic underlying disease. Two had received a stem-cell transplant, and one was under chemotherapy including rituximab. Despite therapy with cidofovir, all patients died. As the incidence of HAdV hepatitis is low, diagnosis may be easily overlooked. No treatment approaches have yet been established. HAdV hepatitis should be considered as a differential diagnosis, especially when risk factors are present. To avoid dissemination, treatment should be initiated as soon as possible.

Systemic sclerosis (SSc) is a rare, difficult to treat disease with profound effects on quality of life and high mortality. Complex and incompletely understood pathophysiologic processes and greatly heterogeneous clinical presentations and outcomes have hampered drug development. This review summarizes the currently available immunosuppressive and antifibrotic therapies and discusses novel approaches for the treatment of SSc. We reviewed the literature using the MEDLINE and ClinicalTrial.gov databases between May and September 2020. Available immunosuppressive and antifibrotic drugs only modestly impact the course of the disease. Most drugs are currently only investigated in the subset of patients with early diffuse cutaneous SSc. In this patient population, hematopoietic stem-cell transplantation is currently the only treatment that has demonstrated reversal of lung involvement, enhanced quality of life and reduced long-term mortality, but carries the risk of short-term treatment-related mortality. A great need to provide better therapeutic options to patients exists also for those patients who have limited cutaneous skin involvement. A better understanding of SSc pathophysiology has enabled the identification of numerous new therapeutic targets. The progress made in the design of clinical trials and outcome parameters will likely result in the improvement of effective management options. [ABSTRACT FROM AUTHOR]

Understanding the mechanisms that sustain immunological nonreactivity is essential for maintaining tissue in syngeneic and allogeneic settings, such as transplantation and pregnancy tolerance. While most transplantation rejections occur due to the adaptive immune response, the proinflammatory response of innate immunity is necessary for the activation of adaptive immunity. Botryllus schlosseri, a colonial tunicate, which is the nearest invertebrate group to the vertebrates, is devoid of T- and B-cell-based adaptive immunity. It has unique characteristics that make it a valuable model system for studying innate immunity mechanisms: (i) a natural allogeneic transplantation phenomenon that results in either fusion or rejection; (ii) whole animal regeneration and noninflammatory resorption on a weekly basis; (iii) allogeneic resorption which is comparable to human chronic rejection. Recent studies in B. schlosseri have led to the recognition of a molecular and cellular framework underlying the innate immunity loss of tolerance to allogeneic tissues. Additionally, B. schlosseri was developed as a model for studying hematopoietic stem cell (HSC) transplantation, and it provides further insights into the similarities between the HSC niches of human and B. schlosseri. In this review, we discuss why studying the molecular and cellular pathways that direct successful innate immune tolerance in B. schlosseri can provide novel insights into and potential modulations of these immune processes in humans.

Background: Reactivation of latent human cytomegalovirus (CMV) in patients undergoing allogeneic stem-cell transplantation (HSCT) predisposes to several clinical complications and is therefore a major cause of morbidity and mortality. Although pentraxin-3 (PTX3) has been previously described to bind both human and murine CMV and mediate several host antiviral mechanisms, whether genetic variation in the PTX3 locus influences the risk of CMV infection is currently unknown.Methods: To dissect the contribution of genetic variation within PTX3 to the development of CMV infection, we analyzed described loss-of-function variants at the PTX3 locus in 394 recipients of HSCT and their corresponding donors and assessed the associated risk of CMV reactivation.Results: We report that the donor, but not recipient, h2/h2 haplotype in PTX3 increased the risk of CMV reactivation after 24 months following transplantation, with a significant effect on survival. Among recipients with h2/h2 donors, CMV seropositive patients as well as those receiving grafts from unrelated donors, regardless of the CMV serostatus, were more prone to develop viral reactivation after transplantation. Most importantly, the h2/h2 haplotype was demonstrated to display an influence toward risk of CMV reactivation comparable to that conferred by the unrelated status of the donor alone.Conclusions: Our findings demonstrate the important contribution of genetic variation in donor PTX3 to the risk of CMV reactivation in patients undergoing HSCT, highlighting a promising prognostic value of donor PTX3 to predict risk of CMV reactivation in this clinical setting.

Abstract Purpose It has been proposed that changes in the permeability of Bruch's membrane play a role in the pathogenesis of age-related macular degeneration (AMD). This paper investigates, in an in vivo porcine model, the migration of fluorescent latex beads across the Bruch's membrane after subretinal injection. Methods Forty-one healthy eyes of 33 three-month-old domestic pigs received a subretinal injection of 0.5, 1.0, 2.0, or 4.0 μm fluorescent latex beads. Between three hours and five weeks after injection evaluations were performed with fundus photographs and histology. Fluorescent beads were identified in unstained histologic sections using the rhodamine filter with the light microscope. Results The fluorescent latex beads relocated from the subretinal space. Intact beads up to 2.0 μm were found in the choroid, sclera, and extrascleral space. The smaller beads were also found inside choroidal and extrascleral blood vessels. In contrast, the larger beads of 4.0 μm did not pass the Bruch's membrane. Conclusion Subretinally implanted beads up to 2.0 μm pass the Bruch's membrane intact and cross the blood-ocular barrier. The intact beads are found in the choroid, sclera and inside blood vessels. The results give reason to consider the role of subretinal clearance and passage of Bruch's membrane in the development of AMD. Highlights • Subretinally injected solid particles of 0.5–2 μm pass the Bruch's membrane. • Particles that pass the Bruch's membrane are found intact in the choroid, sclera and bloodvessels. • Subretinally injected solid particles of 4 μm are stopped at the Bruch's membrane. • The transport properties of Bruch's membrane should be considered in formation of drusen. [ABSTRACT FROM AUTHOR]

Abstract Objectives Because commensal viruses are defined by the immunologic tolerance afforded to them, any immunomodulation, such as is received during haematopoietic stem-cell transplantation, may shift the demarcation between innocuous viral resident and disease-causing pathogen. Methods We analysed by deep-sequencing the plasma virome of 40 allogeneic haematopoietic stem-cell transplantation patients 1 month after transplantation. Because human pegivirus (HPgV) was highly prevalent, we performed a 1-year screening of 122 plasma samples by specific real-time reverse transcription PCR assay. We used the log-rank test and the Gray test to assess association with outcomes, and the Mann-Whitney test and multivariable linear regression model to assess association with T-cell reconstitution. Results Polyomaviruses (PyV) (20/40 patients), anelloviruses (16/40), pegiviruses (14/40) and herpesviruses (14/40) were most frequently identified, including ten cytomegalovirus; three Epstein-Barr virus; two herpes simplex virus type 1; one human herpesvirus 6b and one human herpesvirus 7; 18 Merkel cell–PyV; two BK-PyV; three PyV-6; and one JC-PyV. Papillomavirus and adenovirus were identified in 11 and two patients, respectively. The HPgV specific real-time reverse transcription PCR screening identified 51 of 122 positive samples, high virus loads and persistent infections up to 1 year after transplantation. Comparison between patients with or without HPgV infection at time of transplantation did not reveal a significant difference in infections, engraftment, survival, graft vs. host disease, relapse or immune reconstitution. Conclusions The blood virome after allogeneic haematopoietic stem-cell transplantation includes several DNA viruses, notably herpesviruses and PyV. Among RNA viruses, HPgV is highly prevalent and persists for several months, and it thus may deserve special attention in further research on immune reconstitution. [ABSTRACT FROM AUTHOR]

Background: Reactivation of latent human cytomegalovirus (CMV) in patients undergoing allogeneic stem-cell transplantation (HSCT) predisposes to several clinical complications and is therefore a major cause of morbidity and mortality. Although pentraxin-3 (PTX3) has been previously described to bind both human and murine CMV and mediate several host antiviral mechanisms, whether genetic variation in the PTX3 locus influences the risk of CMV infection is currently unknown. Methods: To dissect the contribution of genetic variation within PTX3 to the development of CMV infection, we analyzed described loss-of-function variants at the PTX3 locus in 394 recipients of HSCT and their corresponding donors and assessed the associated risk of CMV reactivation. Results: We report that the donor, but not recipient, h2/h2 haplotype in PTX3 increased the risk of CMV reactivation after 24 months following transplantation, with a significant effect on survival. Among recipients with h2/h2 donors, CMV seropositive patients as well as those receiving grafts from unrelated donors, regardless of the CMV serostatus, were more prone to develop viral reactivation after transplantation. Most importantly, the h2/h2 haplotype was demonstrated to display an influence toward risk of CMV reactivation comparable to that conferred by the unrelated status of the donor alone. Conclusions: Our findings demonstrate the important contribution of genetic variation in donor PTX3 to the risk of CMV reactivation in patients undergoing HSCT, highlighting a promising prognostic value of donor PTX3 to predict risk of CMV reactivation in this clinical setting. [ABSTRACT FROM AUTHOR]

We relate our experience with the Cook (Cook Medial Inc., Bloomington, IN, USA), triple-lumen hyperalimentation (HAS) catheter for treatment related to autologous stem-cell transplant. Nineteen HAS catheters were implanted in the right jugular vein, and tunneled to the right anterior chest wall, under imaging guidance. Retrospectively, we reviewed each catheter. Three patient's experienced “ballooning” of the middle (white) lumen of the HAS catheter during routine use. We assessed, time in situ, follow-up imaging, chemotherapy regimen, possibility of systemic or device infection, tissue pathology of the patient's malignancy, and other factors to attempt to determine if there were any associations that could explain the catheter lumen failure. After this pilot study of the HAS-catheter in these 19 patients, we discontinued use of this device at our facility due to mechanical problems of ballooned and obstructed middle lumens. There was no obvious cause, or association, detected to explain the ballooning identified.

It has been reported that transplanting native cells would lack efficiency without producing artificial cell-tissue, due to the exaggerated oxidative stress in doxorubicin-induced cardiomyopathy. We attempted to activate cardiac progenitor cells (CPCs) by delivering resveratrol to mitochondria using a mitochondrial drug delivery system (MITO-Porter system). We first evaluated the viability of H9c2 cells (a cardio myoblast cell line) after doxorubicin treatment, where H9c2 cells were co-cultured with or without the mitochondria activated CPCs (referred to herein as MITO cell). We next evaluated the survival rate of doxorubicin treated mice, with or without the injection of MITO cells into the myocardium. Finally, we examined the molecular mechanism of the cell therapy by detecting oxidative stress and the induction of apoptosis in addition to quantification of the mRNA and protein levels about oxidative phosphorylation (OXPHOS). The MITO cell transplanted mice lived significantly longer than the conventional CPC transplanted ones. Oxidative stress and massive cell death were both significantly reduced in the MITO cell transplanted hearts, in which the expression levels of OXPHOS protein and gene were also higher than the control group. In doxorubicin-induced cardiomyopathy, the transplantation of MITO cells, which possess activated mitochondria, is more efficient compared to conventional CPC transplantation. [ABSTRACT FROM AUTHOR]

Abstract: The objective of the current retrospective study was to compare differences in rate of breakthrough infections for ciprofloxacin vs levofloxacin prophylaxis in autologous hematopoietic stem‐cell transplant (HSCT) patients treated for multiple myeloma. This was a retrospective, cohort study comparing autologous HSCT recipients treated for multiple myeloma who received ciprofloxacin prophylaxis vs levofloxacin prophylaxis. A total of 297 patients, 143 levofloxacin‐ and 154 ciprofloxacin‐treated were included. There was a significantly higher incidence of bloodstream infections in the ciprofloxacin group (24/154) compared to the levofloxacin group (10/143), P = .03, primarily caused by a statistically higher incidence of gram‐positive bloodstream infections (ciprofloxacin [21/154] vs levofloxacin [8/143]; P < .01). Clinically relevant differences exist between fluoroquinolone agents used for prophylaxis. Levofloxacin prophylaxis was more effective than ciprofloxacin prophylaxis to reduce the incidence of bloodstream infections in this study. [ABSTRACT FROM AUTHOR]

Survival for transformed follicular lymphoma (tFL) has improved in the rituximab era and the need for upfront stem cell transplantation (SCT) is unclear. We evaluated the outcomes for all patients treated with first-line chemotherapy for histologically-proven tFL at our institution from 2003–2013 (n = 87). The majority of patients (89.7%) did not receive a SCT as part of first-line management. With a median follow-up of 7.8 years the 5-year overall survival (OS) for all patients was 61.7%. Patients treated with R-CHOP without upfront SCT (n = 55/87) had a 5-year OS of 64.3%. In a Cox regression analysis of the entire cohort (n = 87) International Prognostic Index (IPI) risk group and presence of B symptoms at transformation were independently associated with OS in multivariate analysis (MVA). Our analysis confirms the improved survival of tFL in the rituximab era even in the absence of upfront SCT consolidation. [ABSTRACT FROM PUBLISHER]