Infection and transplantation

CD5+ diffuse large B-cell lymphoma (DLBCL) is a rare subtype characterized by an inferior outcome. While dose-dense therapy shows promising activity, the optimal management remains to be determined. To evaluate the benefit of consolidative autologous hematopoietic stem cell transplantation (ASCT), we retrospectively reviewed the medical records of 47 consecutive patients with newly diagnosed de novo CD5+ DLBCL. Of 19 patients ≤ 70 of age with age-adjusted International Prognostic Index 2-3, eight underwent upfront ASCT, and nine did not, despite preserved organ function and response after induction therapy...

We report 5 children with bone marrow failure (BMF) after primary varicella zoster virus (VZV) infection or VZV vaccination, highlighting the highly variable course. Two patients were treated with intravenous immunoglobulins; one had a slow hematologic recovery, and the other was rescued by allogeneic hematopoietic stem cell transplantation (HSCT). Of the 2 patients treated with immunosuppressive therapy with antithymocyte globulin and cyclosporine, one had a complete response, and the other was transplanted for nonresponse...

Human allogeneic pancreatic islet transplantation is a life-changing treatment for patients with severe Type 1 Diabetes (T1D) who suffer from hypoglycemia unawareness and high risk of severe hypoglycemia. However, intensive immunosuppression is required to prevent immune rejection of the graft, that may in turn lead to undesirable side effects such as toxicity to the islet cells, kidney toxicity, occurrence of opportunistic infections, and malignancies. The shortage of cadaveric human islet donors further limits islet transplantation as a treatment option for widespread adoption...

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hematological disorder of immune dysregulation associated with significant challenges in diagnosis and management. Described as primary HLH secondary to genetic defects or more commonly secondary to infections, it can also occur secondary to malignancy, i.e., malignancy-associated hemophagocytic lymphohistiocytosis (M-HLH). A five-year-old male child presented with left cervical adenopathy and a high-spiking fever for two weeks. He had pallor, anasarca, multiple enlarged and matted cervical lymph nodes, respiratory distress, and hepatomegaly...

Cytomegalovirus (CMV) infection is associated with increased morbidity and mortality in hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients, with traditional anti-CMV therapies limited by their associated toxicities and the development of resistance. Clinical providers are often faced with challenging and complicated CMV infections that require multiple courses of antiviral therapies. Increasingly, advanced practice providers (APPs) are playing an important role in the day-to-day management of transplant recipients with CMV infection, including resistant/refractory CMV and other complex CMV syndromes...

BACKGROUND: Endoscopic features of intestinal transplant-associated microangiopathy (iTAM) have not been comprehensively investigated. This study aimed to examine the endoscopic characteristics of patients diagnosed with iTAM. METHODS: This retrospective analysis included 14 patients pathologically diagnosed with iTAM after stem cell transplantation for hematolymphoid neoplasms (n = 13) or thalassemia (n = 1). The sex, age at diagnosis, endoscopic features, and prognosis of each patient were assessed...

BACKGROUND: Posaconazole is a vital drug to treat and prevent invasive fungal infections. Several factors, such as sex, body weight, total serum proteins, dietary intake, and severe mucositis, affect posaconazole pharmacokinetics (PKs). However, the relevance of other factors that affect the PKs of posaconazole in hematopoietic stem cell transplantation (HSCT) is unknown. This study explored factors influencing the PKs of posaconazole in HSCT recipients and nontransplant patients with hematological diseases...

The role of viral diversity in the pathogenesis of BK polyomavirus (BKPyV)-associated disease is poorly understood. Here, we report near full-length BKPyV genome sequences from two allogeneic hematopoietic cell transplant recipients infected with BKPyV genotype II, which is uncommon in the USA.

This study evaluated the cost-effectiveness of maribavir versus investigator-assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, or cidofovir) for post-transplant refractory cytomegalovirus (CMV) infection with or without resistance. A two-stage Markov model was designed using data from the SOLSTICE trial (NCT02931539), real-world multinational observational studies, and published literature. Stage 1 (0-78 weeks) comprised clinically significant CMV (csCMV), non-clinically significant CMV (n-csCMV), and dead states; stage 2 (78 weeks-lifetime) comprised alive and dead states...

Antibody-mediated rejection (AMR) is a common cause of graft failure after pig-to-nonhuman primate organ transplantation, even when the graft is from a pig with multiple genetic modifications. The specific factors that initiate AMR are often uncertain. We report two cases of pig kidney transplantation into immunosuppressed baboons in which we identify novel factors associated with the initiation of AMR. In the first, membranous nephropathy was the initiating factor that was then associated with the apparent loss of the therapeutic anti-CD154 monoclonal antibody in the urine when severe proteinuria was present...

INTRODUCTION: Immune reconstitution (IR) kinetics of paediatric patients underwent haploidentical haematopoietic stem cell transplantation (HSCT) with post-transplant cyclophosphamide (PTCy) have not been extensively studied. We compared IR patterns of children receiving HSCT from haploidentical (n = 92) and HLA-matched donors (n = 36), and analysed risk factors for viral infection in these patients. METHODS: We prospectively measured lymphocyte subset numbers before HSCT and at 1, 3, 6 and 12 months after HSCT...

Background: The mechanisms underlying the increased mortality of secondary infections during the immunosuppressive phase of sepsis remain elusive. Objectives: We sought to investigate the role of Siglec-F+ neutrophils on splenic T lymphocytes in the immunosuppressed phase of sepsis and on secondary infection in PICS mice, and to elucidate the underlying mechanisms. Methods: We established a mouse model of sepsis-induced immunosuppression followed by secondary infection with LPS or E. coli. The main manifestation of immunosuppression is the functional exhaustion of splenic T lymphocytes...

INTRODUCTION: In view of ever-increasing end-stage renal disease (ESRD) population but inadequate availability of suitable donors, ABO-incompatible (ABOi) transplantation can be an important void filler. However, at present, ABOi transplantation is limited to a few centers in India and there is a lack of adequate experience and expertise to guide this program to other centers in the country. METHODS: Data of all the ABOi transplants performed from 2012 to 2021 in a tertiary care hospital was retrospectively analyzed...

INTRODUCTION: There is a paucity of studies on asymptomatic bacteriuria (ASB) among kidney transplant recipients (KTR) in developing countries. This study assessed the clinical profile, risk factors, outcomes, and impact of treatment of ASB in KTRs with a normal genitourinary tract. METHODS: Consecutive KTRs from 2009 to 2018 with no clinical or radiological evidence of obstructive uropathy were included. Urinary tract infection (UTI) after ASB was defined as occurrence of cystitis, pyelonephritis, or urosepsis, with ASB being the first bacteriuric episode...

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening condition due to extensive and uncontrolled immune activation. There is sparse literature on HLH in kidney transplant recipients. We report a case of a 27-year -old male kidney transplant recipient who presented with dengue fever and acute allograft dysfunction. Following improvement in allograft function with supportive treatment, he was found to have worsening pancytopenia with unusually high serum ferritin levels. Bone marrow aspiration performed for pancytopenia revealed hemophagocytosis...

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BACKGROUND: Emerging risk factors highlight the need for an updated understanding of cryptococcosis in the United States. OBJECTIVE: Describe the epidemiological trends and clinical outcomes of cryptococcosis in three patient groups: people with HIV (PWH), non-HIV-infected and non-transplant (NHNT) patients, and patients with a history of solid organ transplantation. METHODS: We utilized data from the Merative Medicaid Database to identify individuals aged 18 and above with cryptococcosis based on the International Classification of Diseases, Tenth Revision diagnosis codes from January 2017 to December 2019...

Previous work has shown that innate immune sensing of tumors involves the host STING pathway, which leads to IFN-β production, dendritic cell (DC) activation, and T cell priming against tumor antigens. This observation has led to the development of STING agonists as a potential cancer therapeutic. However, despite promising results in mouse studies using transplantable tumor models, clinical testing of STING agonists has shown activity in only a minority of patients. Thus, further study of innate immune pathways in anti-tumor immunity is paramount...

Reactivation or primary infection with double stranded DNA viruses is common in recipients of solid organ transplants and is associated with significant morbidity and mortality. Treatment with conventional anti-viral medications is limited by toxicities, resistance, and lack of effective options for adenovirus and BKPyV. Virus-specific T-cells (VSTs) have been shown to be an effective treatment for infections with adenovirus, BKPyV, cytomegalovirus (CMV), and Epstein-Barr virus (EBV). Most of these studies have been conducted in stem cell recipients and no large studies have been published in the solid organ transplant population to date...

Post-transplant lymphoproliferative disorder (PTLD) is a rare complication of solid organ transplantation, and cytotoxic chemotherapy is associated with treatment-related morbidity and mortality. Current treatment takes a sequential, risk-stratified approach, patients with low-risk disease following initial immunotherapy can avoid escalation to immunochemotherapy. TIDaL is a prospective, single-arm phase 2 trial investigating the activity and tolerability of ibrutinib combined with risk-stratified therapy for first-line treatment of PTLD...