Cyclophosphamide and Thiotepa Increases Risk of Transplant-Associated Thrombotic Microangiopathy.

Transplant associated thrombotic microangiopathy (TA-TMA) is a complication of hematopoietic cell transplant (HCT) associated with endothelial injury resulting in severe end organ damage, acute and long-term morbidity, and mortality. Myeloablative conditioning is a known risk factor, though specific causative agents have not been identified. We hypothesized that the combination of cyclophosphamide and thiotepa (CY + TT) is particularly toxic to the endothelium, placing patients at elevated risk for TA-TMA.

Diagnosing and Grading of Sinusoidal Obstructive Syndrome after Hematopoietic Stem Cell Transplant of Children, Adolescent and Young Adults treated in a Pediatric Institution with Pediatric Protocols.

Sinusoidal obstructive syndrome (SOS), or veno-occlusive disease, of the liver has been recognized as a complex, life-threatening complication in the posthematopoietic stem cell transplant (HSCT) setting. The diagnostic criteria for SOS have evolved over the last several decades with a greater understanding of the underlying pathophysiology, with 2 recent diagnostic criteria introduced in 2018 (European Society of Bone Marrow Transplant [EBMT] criteria) and 2020 (Cairo criteria). We sought out to evaluate the performance characteristics in diagnosing and grading SOS in pediatric patients of the 4 different diagnostic criteria (Baltimore, Modified Seattle, EBMT, and Cairo) and severity grading systems (defined by the EBMT and Cairo criteria).

Relevance of lymphocyte proliferation to PHA in severe combined immunodeficiency (SCID) and T cell lymphopenia.

Severe combined immunodeficiency (SCID) is characterized by a severe deficiency in T cell numbers. We analyzed data collected (n = 307) for PHA-based T cell proliferation from the PIDTC SCID protocol 6901, using either a radioactive or flow cytometry method. In comparing the two groups, a smaller number of the patients tested by flow cytometry had <10% of the lower limit of normal proliferation as compared to the radioactive method (p = 0.

Posttransplantation late complications increase over time for patients with SCID: A Primary Immune Deficiency Treatment Consortium (PIDTC) landmark study.

Background: The Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children in the United States and Canada onto a retrospective multicenter natural history study of hematopoietic cell transplantation (HCT).

Objective: We investigated outcomes of HCT for severe combined immunodeficiency (SCID).

Methods: We evaluated the chronic and late effects (CLE) after HCT for SCID in 399 patients transplanted from 1982 to 2012 at 32 PIDTC centers.

Measuring the effect of newborn screening on survival after haematopoietic cell transplantation for severe combined immunodeficiency: a 36-year longitudinal study from the Primary Immune Deficiency Treatment Consortium.

Background: Severe combined immunodeficiency (SCID) is fatal unless durable adaptive immunity is established, most commonly through allogeneic haematopoietic cell transplantation (HCT). The Primary Immune Deficiency Treatment Consortium (PIDTC) explored factors affecting the survival of individuals with SCID over almost four decades, focusing on the effects of population-based newborn screening for SCID that was initiated in 2008 and expanded during 2010-18.

Methods: We analysed transplantation-related data from children with SCID treated at 34 PIDTC sites in the USA and Canada, using the calendar time intervals 1982-89, 1990-99, 2000-09, and 2010-18.

Lentiviral Gene Therapy for Artemis-Deficient SCID.

Background: The DNA-repair enzyme Artemis is essential for rearrangement of T- and B-cell receptors. Mutations in , which encodes Artemis, cause Artemis-deficient severe combined immunodeficiency (ART-SCID), which is poorly responsive to allogeneic hematopoietic-cell transplantation.

Methods: We carried out a phase 1-2 clinical study of the transfusion of autologous CD34+ cells, transfected with a lentiviral vector containing , in 10 infants with newly diagnosed ART-SCID.

Impact of Genetic Diagnosis on the Outcome of Hematopoietic Stem Cell Transplant in Primary Immunodeficiency Disorders.

To evaluate the relationship between knowledge of genetic diagnosis before HSCT and outcome, we reviewed all HSCTs for primary immune deficiencies (PID) performed at UCSF from 2007 through 2018. SCID, a distinct entity identified since 2010 in California by newborn screening and treated early, was considered separately. The underlying genetic condition was known at the time of HSCT in 85% of cases.

A pilot trial of prophylactic defibrotide to prevent serious thrombotic microangiopathy in high-risk pediatric patients.

Background: Transplant-associated thrombotic microangiopathy (TA-TMA) is an endothelial injury complication of hematopoietic stem cell transplant (HSCT) leading to end-organ damage and high morbidity and mortality. Defibrotide is an anti-inflammatory and antithrombotic agent that may protect the endothelium during conditioning.

Procedure: We hypothesized that prophylactic use of defibrotide during HSCT conditioning and acute recovery could prevent TA-TMA.

Hematopoietic Cell Transplantation Cures Adenosine Deaminase 2 Deficiency: Report on 30 Patients.

Purpose: Deficiency of adenosine deaminase 2 (DADA2) is an inherited inborn error of immunity, characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency, lymphoproliferation, immune cytopenias, and bone marrow failure (BMF). Tumor necrosis factor (TNF-α) blockade is the treatment of choice for the vasculopathy, but often fails to reverse refractory cytopenia. We aimed to study the outcome of hematopoietic cell transplantation (HCT) in patients with DADA2.

International retrospective study of allogeneic hematopoietic cell transplantation for activated PI3K-delta syndrome.

Background: Activated phosphoinositide 3-kinase delta syndrome (APDS) is a combined immunodeficiency with a heterogeneous phenotype considered reversible by allogeneic hematopoietic cell transplantation (HCT).

Objectives: This study sought to characterize HCT outcomes in APDS.

Methods: Retrospective data were collected on 57 patients with APDS1/2 (median age, 13 years; range, 2-66 years) who underwent HCT.

Transplant-associated thrombotic microangiopathy in pediatric patients: pre-HSCT risk stratification and prophylaxis.

Transplant-associated thrombotic microangiopathy (TA-TMA) is an endothelial injury syndrome that complicates hematopoietic stem cell transplant (HSCT). Morbidity and mortality from TA-TMA remain high, making prevention critical. We describe our retrospective single-center experience of TA-TMA after pediatric allogeneic HSCT and present a novel pre-HSCT risk-stratification system and prophylaxis regimen.

Unknown cytomegalovirus serostatus in primary immunodeficiency disorders: A new category of transplant recipients.

Background: Cytomegalovirus (CMV) serostatus of recipient (R) and donor (D) influences hematopoietic stem cell transplant (HSCT) outcome. However, it is not a reliable indicator of CMV infection in primary immunodeficiency disorder (PIDD) recipients who are unable to make adequate antigen-specific immunoglobulin (Ig) or who receive intravenous Ig (IVIg) prior to testing.

Objective: Since no data exist on PIDD with unknown CMV serostatus, we aimed to evaluate the relationship between pre-HSCT recipient and donor serostatus and incidence of CMV infection in recipients with unknown serostatus.

Reduced Toxicity Conditioning for Nonmalignant Hematopoietic Cell Transplants.

Allogeneic hematopoietic cell transplantation (HCT) for children with nonmalignant disorders is challenged by potential drug-related toxicities and poor engraftment. This retrospective analysis expands on our single pediatric medical center experience with targeted busulfan, fludarabine, and intravenous (IV) alemtuzumab as a low-toxicity regimen to achieve sustained donor engraftment. Sixty-two patients received this regimen for their first HCT for a nonmalignant disorder between 2004 and 2018.

Low Exposure Busulfan Conditioning to Achieve Sufficient Multilineage Chimerism in Patients with Severe Combined Immunodeficiency.

After allogeneic hematopoietic cell transplantation (HCT), the minimal myeloid chimerism required for full T and B cell reconstitution in patients with severe combined immunodeficiency (SCID) is unknown. We retrospectively reviewed our experience with low-exposure busulfan (cumulative area under the curve, 30 mg·hr/L) in 10 SCID patients undergoing either first or repeat HCT from unrelated or haploidentical donors. The median busulfan dose required to achieve this exposure was 5.

Secondary Hypogammaglobulinemia After Rituximab for Neuromyelitis Optica: A Case Report.

A 17-year-old male with history of neuromyelitis optica and seizures presented to the pulmonology clinic for evaluation of recurrent pneumonias. He had received rituximab for the past 6 years. Over the past 2 years, he experienced four episodes of pneumonia.

Optimal Antiretroviral Prophylaxis in Infants at High Risk of Acquiring HIV: A Systematic Review.

Introduction: The risk of perinatal HIV infection can be dramatically reduced through maternal antiretroviral (ARV) therapy and infant ARV postnatal prophylaxis. The 2013 World Health Organization guidelines recommended 4-6 weeks of nevirapine or zidovudine as postnatal prophylaxis, with possible extension to 12 weeks for high-risk breastfed infants. A systematic review was undertaken to determine if there is evidence for the World Health Organization to recommend enhanced or extended prophylaxis for high-risk infants.

Low Birth Weight in Human Immunodeficiency Virus-Exposed Uninfected Infants in Bronx, New York.

Background: Prevention of mother-to-child transmission of human immunodeficiency virus (HIV) with antiretroviral therapy (ART) has been highly successful. However, HIV-exposed uninfected (HIV-EU) infants might be at increased risk for low birth weight and/or preterm birth. We compared the birth weights and gestational ages of HIV-EU infants to those of HIV-unexposed control infants in Bronx, New York, an epicenter of the HIV epidemic in the United States.

Fulminant Sepsis Due to Granulibacter bethesdensis in a 4-Year-Old Boy With X-Linked Chronic Granulomatous Disease.

Granulibacter bethesdensis is a Gram-negative bacillus described as a pathogen exclusively in patients with chronic granulomatous disease, a phagocytic disorder that impairs the ability to clear catalase-producing organisms. Granulibacter usually causes chronic and recurrent lymphadenopathies. We report the fatal case of a 4-year-old boy with chronic granulomatous disease, who presented with sepsis after a few days of abdominal pain and diarrhea.

Multivariable analysis to determine if HIV-1 Tat dicysteine motif is associated with neurodevelopmental delay in HIV-infected children in Malawi.

Background: HIV-1 Tat protein is implicated in HIV-neuropathogenesis. Tat C31S polymorphism (Tat(CS)) has been associated with milder neuropathology in vitro and in animal models but this has not been addressed in a cohort of HIV-infected adults or children.

Methods: HIV viral load (VL) in plasma and cerebrospinal fluid (CSF) were determined and plasma HIV tat gene was sequenced.

Microbiological and Genetic Characterization of Carbapenem-Resistant Klebsiella pneumoniae Isolated From Pediatric Patients.

This manuscript reports the clinical, microbiological, and genetic characteristics of carbapenem-resistant K. pnuemoniae isolates from pediatric patients at a tertiary-care children's hospital. Although there is an extensive body of literature describing carbapenem-resistant Klebsiella infections in adults, pediatric data are comparatively limited.