Assessment of Biventricular Systolic and Diastolic Function Using Conventional and Strain Echocardiography in Children with Sickle Cell Disease Surviving 1-year After Hematopoietic Stem Cell Transplant.

Hematopoietic stem cell transplant (HSCT) is a potentially curative therapy for children with sickle cell disease (SCD). The effects of HSCT on ventricular function are not well characterized in children with SCD. Echocardiograms from children with SCD who underwent HSCT between 2007 and 2017 were retrospectively analyzed before and 1-year after HSCT. Left ventricular (LV) volumes, mass, and ejection fraction were calculated by the 5/6 area*length method. LV end-diastolic and systolic dimensions, septal, and posterior wall thickness, and fractional shortening were measured by M-mode. Mitral and tricuspid inflow Dopplers (E and A waves) as well as mitral, tricuspid, and septal tissue Dopplers (E', A') were assessed. E/A, E'/A' and E/E' ratios were calculated. Biventricular strain imaging was performed using speckle-tracking echocardiography. Peak global systolic longitudinal and circumferential LV strain, and global longitudinal right ventricular strain, as well as early and late diastolic strain rate, were measured on LV apical 4-chamber, LV short-axis mid-papillary, and RV apical views, respectively. Forty-seven children (9.7 ± 5.5 years, 60% male) met inclusion criteria. Pre-HSCT, subjects had mild LV dilation with normal LV systolic function by conventional measure of ejection fraction and fractional shortening. There was a significant reduction in LV volume, mass, and ejection fraction after HSCT, but measurements remained within normal range. LV longitudinal and circumferential strain were normal pre-HSCT and showed no significant change post-HSCT. RV strain decreased after HSCT, but the absolute change was small, and mean values were normal both pre- and post-HSCT. Conventional measures of diastolic function were all normal pre-HSCT. Post-HSCT there was a reduction in select parameters, but all parameters remained within normal range. Early and late diastolic strain rate parameters showed no significant change from pre- to post-HSCT. At one-year after HSCT in children with SCD conventional measures of systolic and diastolic function are within normal limits. Except for a small decrease in RV systolic strain with values remaining within normal limits, systolic strain and diastolic strain rate values did not significantly change 1-year after HSCT.

The Road More or Less Traveled- Examining the Role of Consolidative Allogeneic Hematopoietic Stem Cell Transplantation After Chimeric Antigen Receptor T Cell Therapy in B-cell ALL.

Treatment with CD19-targeted chimeric antigen receptor T cell therapy (CD19-CART) has improved salvage rates in children and adults with relapsed and/or refractory B-cell acute lymphoblastic leukemia (ALL). However, not all patients treated with CD19-CAR T cells achieve long-term remission. The role of allogeneic hematopoietic stem cell transplantation as consolidative therapy remains undefined. We aim to review the current literature published to date regarding prognostic markers indicating durable ALL response to CD19-CART and risk factors for relapse after CD19-CART to identify patient cohorts who may benefit from consolidative hematopoietic stem cell transplantation.

Association between positive affect, flourishing, quality of life, and psychological distress in allogeneic hematopoietic stem cell transplantation.

PURPOSE: To examine the associations between state positive psychological well-being (PPWB) constructs, mood, and quality of life (QOL) in hematopoietic stem cell transplantation (HSCT) survivors. DESIGN: The study was a secondary analysis of cross-sectional data. SAMPLE/METHODS: We analyzed self-report data assessing positive affect, flourishing, QOL, depression and anxiety, and PTSD symptoms from 158 allogeneic HSCT recipients at day-100 post-transplant enrolled in supportive care studies. FINDINGS: Univariate analysis showed that factors associated with greater levels of various state PPWB constructs include older age, disability status, greater social support, and presence of graft-versus-host disease. Multivariate analysis showed that state PPWB constructs-greater levels of positive affect and flourishing-were significantly associated with better QOL and lower PTSD, anxiety, and depression symptomatology. IMPLICATIONS: Our findings suggest that longitudinal studies are needed to examine the links between state PPWB constructs and HSCT outcomes, which may inform population specific interventions and opportunities to improve outcomes.

Invasive fungal infections are rare in pediatric and young adult autologous hematopoietic stem cell transplant patients.

BACKGROUND: Pediatric and young adult patients undergoing autologous hematopoietic stem cell transplant (auto-HSCT) face a crucial, yet understudied, risk of invasive fungal infections (IFI), especially compared to allogeneic transplants. This gap underscores the need for research in pediatric patients undergoing auto-HSCT. Our objective was to evaluate the incidence of IFI in pediatric and young adult patients during the first year after auto-HSCT. MATERIALS AND METHODS: We conducted a single-center retrospective analysis of 150 pediatric and young adult auto-HSCT patients who underwent transplant from January 2013 to January 2023. We focused on IFI incidence within the first-year post transplant, using the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria for IFI identification. RESULTS: Among the 150 patients analyzed, with 240 unique transplant episodes, the primary indication was neuroblastoma (37.3%), and micafungin was extensively used for prophylaxis (82.7%). There was an absence of IFI from yeast and mold species, suggesting a low IFI risk in this cohort. The incidence of IFI in pediatric auto-HSCT recipients receiving micafungin primary antifungal prophylaxis is rare. CONCLUSIONS: The findings advocate for further research to refine prophylaxis guidelines and highlight the need for individualized risk assessment to optimize post-transplant care.

Wiskott-Aldrich Syndrome: A Report of a Rare X-Linked Disorder.

Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive genetic disorder marked by eczema, thrombocytopenia, and immunodeficiency. The associated immune dysregulation increases the risk of autoimmune disorders and lymphoid malignancies. WAS results from mutations in the WAS protein gene on the short arm of the X chromosome. Here, we present the case of a seven-month-old male, born to non-consanguineous parents with no significant birth or family history. The child had height, weight, and head circumference below the third percentile for age and presented with recurrent mild upper respiratory infections, mild eczema, and thrombocytopenia. Despite symptomatic treatment and clinical improvement, platelet counts continued to decline. A provisional diagnosis of immune thrombocytopenia was made, and intravenous immunoglobulin was administered, which halted the downward trend but did not improve platelet counts. Autoimmune testing revealed strong positivity for antinuclear antibodies (ANA). Given the early-onset thrombocytopenia, anemia, and failure to thrive, autoimmune lymphoproliferative syndrome was suspected. However, T cell subset analysis was normal. A bone marrow biopsy suggested myelodysplastic syndrome or myeloproliferative neoplasm, but molecular studies were negative. Due to the early-onset autoimmunity and strongly positive ANA, genetic testing via whole exome sequencing confirmed the diagnosis of WAS.

Pattern of Immune Reconstitution Post Allogeneic Stem Cell Transplant: Data From a Resource Constraint Country.

OBJECTIVE: To determine the Pattern of immune reconstitution (IR) post allogeneic stem cell transplant at six months. STUDY DESIGN: Prospective observational study. Place and duration of the study: This study was conducted at The Armed Forces Bone Marrow Transplant Centre (AFMBTC) Rawalpindi, Pakistan, from May 2022 to December 2022. METHODOLOGY: After approval from the institutional review board, informed/written consents were taken from patients. All patients (both genders, irrespective of age) undergoing allogeneic hematopoietic stem cell transplant were included in the study. Patients undergoing haplo-identical or autologous bone marrow transplants were excluded from the study. Innate immune reconstitution was checked by complete blood count and adaptive immune reconstitution at six months was checked lymphocyte subset analysis and serum immunoglobulin levels. Data was entered in pre-designed proforma and was analyzed using IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp. RESULTS: This study analyzes 43 patients, including 67% (n=29) males. The median age at the time of HSCT was 11.19 years. Cellular and humoral reconstitution at six months after transplant was used to assess immune reconstitution. Innate immune reconstitution was checked by complete blood count for count recovery (Neutrophil engraftment), and adaptive immune reconstitution (cellular/humoral) at six months was checked lymphocyte subset analysis and serum immunoglobulin levels. By using chi-square, significant associations were found as pre-transplant condition regimen with CD4 (PChi= 0.001), GVHD prophylaxis with CD4 (PChi= 0.04), source of stem cells with CD19 (PChi= 0.008), patient-donor gender disparity with CD19 (PChi= 0.05), GVHD treatment low CD19 (PChi= 0.04), patient-donor relationship with IgA(PChi= 0.007), IgG (PChi= 0.001), and IgM (PChi= 0.001), gender of the patient with IgA (PChi= 0.04). CONCLUSION: Our data suggested that at post-transplant six months, there was adequate immune reconstitution except for CD4 and CD4:CD8 ratio. Therefore, post-transplant, six months in Allo-HSCT could be considered for immunization.

Unprecedented Megakaryocytic Blast Phase Transformation in Chronic Myeloid Leukemia After 16 Years of Tyrosine Kinase Inhibitor Therapy.

We report the case of a 51-year-old Japanese man with chronic myeloid leukemia (CML) initially diagnosed in the chronic phase. For 16 years, the patient maintained chronic phase (CP) under treatment with first- and second-generation tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib, and bosutinib, none of which resulted in ABL1 mutations. However, despite long-term disease stability, the patient experienced an abrupt progression to the megakaryocytic blast phase (MBP), a rare and aggressive form of CML. In response to this progression, ponatinib, a third-generation TKI, was introduced as a fourth-line therapy. Remarkably, within 7 months of initiating ponatinib, the patient achieved a deep molecular response (DMR), evidenced by a reduction in BCR::ABL1 transcript levels to undetectable levels (MR5.0). This molecular remission enabled the patient to proceed with an allogeneic bone marrow transplantation from a human leukocyte antigen (HLA) 8/8-allele-matched unrelated donor. Post-transplantation, the patient has maintained DMR for 14 months without recurrence, despite the challenges posed by graft-versus-host disease. This case illustrates the critical role of third-generation TKIs like ponatinib in managing advanced CML phases, especially when previous therapies fail. It also emphasizes the necessity of vigilant long-term monitoring during the chronic phase to detect and address any signs of disease progression promptly.

Preadmission Penicillin Allergy Evaluation Before Hematopoietic Stem Cell Transplantation Optimizes Febrile Neutropenia Treatment and Inpatient Resource Utilization.

Febrile neutropenia is a common complication of conditioning chemotherapy for hematopoietic stem cell transplant (HSCT), but a major barrier for optimal treatment of febrile neutropenia is historical penicillin allergies. Our group recently published a development of a clinical pipeline for delabeling penicillin allergies in adult patients planned to undergo hematopoietic stem cell transplant (HSCT). In this retrospective cohort study, we followed patients to evaluate their outcomes during inpatient admission for HSCT. We hypothesized that, among patients planned for HSCT with a self-reported penicillin allergy, completing penicillin allergy testing (amoxicillin ingestion challenge with or without concomitant penicillin skin testing) prior to HSCT admission would be associated with differences in inpatient treatment for febrile neutropenia (including antibiotic selection and timing of antibiotic administration) and improved inpatient resource utilization (including nursing and inpatient physician consults). We identified patients with a self-reported penicillin allergy who answered a penicillin allergy questionnaire and were subsequently admitted to our institution for HSCT. We divided the cohort into 2 groups: patients whose penicillin allergy was evaluated prior to admission (EPTA) and patients whose penicillin allergy was not evaluated prior to admission (NEPTA). We then performed comparison between the 2 groups for general clinical outcomes of HSCT admission (duration of admission, need for ICU transfer, readmission rate, etc.), febrile neutropenia treatment, and inpatient resource utilization. Statistics were calculated using the nonparametric 2-tailed Fisher exact test for categorical outcomes and the nonparametric 2-tailed Mann-Whitney U test for numerical outcomes. Within our cohort, 35 patients completed penicillin allergy testing prior to HSCT admission (EPTA) and 44 patients did not (NEPTA). Demographics were similar between these groups, and there was no significant difference in the rate of febrile neutropenia during HSCT admission (EPTA 64% versus NEPTA 66%, P = 1.00). EPTA patients were significantly more likely to receive standard first-line antibiotics (cefepime or ceftazidime) for febrile neutropenia (EPTA 95% versus NEPTA 65%, P = .015) and time between febrile neutropenia onset and antibiotic administration was shorter (EPTA mean 66 mins versus NEPTA mean 121 mins, P = .0058). No patients in the EPTA group experienced an immediate hypersensitivity reaction (hives, anaphylaxis, etc.) or severe cutaneous adverse reaction (SCAR) during HSCT admission. EPTA patients were also significantly less likely to require 1:1 nursing for antibiotic test doses, challenges, and desensitizations (EPTA 0% versus NEPTA 49%, P < .0001); less likely to require inpatient allergy consult (EPTA 0% versus NEPTA 12%, P = .031); and less likely to require inpatient antimicrobial stewardship consult (EPTA 0% versus NEPTA 13%, P = .013) during their HSCT admission. In summary, patients who completed penicillin allergy testing prior to HSCT admission were more likely to receive first-line antibiotics and received antibiotics more rapidly for treatment of febrile neutropenia. Furthermore, patients who completed penicillin allergy testing prior to HSCT admission were less likely to require 1:1 nursing, inpatient allergy consults, and inpatient antimicrobial stewardship consults during HSCT admission.

Management of resistant and refractory cytomegalovirus infections after transplantation.

INTRODUCTION: Cytomegalovirus (CMV) is a classic opportunistic infection in transplant recipients. Treatment-refractory CMV infections are of concern, with growing identification of strains that have developed genetic mutations which confer resistance to standard antiviral therapy. Resistant and refractory CMV infections are associated with worse patient outcomes, prolonged hospitalization, and increased healthcare costs. AREAS COVERED: This article provides a comprehensive practical overview of resistant and refractory CMV infections in transplant recipients. We review the updated definitions for these infections, antiviral pharmacology, mechanisms of drug resistance, diagnostic workup, management strategies, and host-related factors including immune optimization. EXPERT OPINION: Resistant and refractory CMV infections are a significant contributor to post-transplant morbidity and mortality. This is likely the result of a combination of prolonged antiviral exposure and active viral replication in the setting of intensive pharmacologic immunosuppression. Successful control of resistant and refractory infections in transplant recipients requires a combination of immunomodulatory optimization and appropriate antiviral drug choice with sufficient treatment duration.

Palliative Care Referral in Adult Allogeneic Hematopoietic Stem Cell Transplants: An Integrative Literature Review.

Context: Hematologic malignancies are often unpredictable, aggressive, and may require treatments such as hematopoietic stem cell transplants (HSCT). Although morbidity and mortality are significantly amplified during the HSCT process, palliative care (PC) services are historically underutilized by HSCT providers for issues such as symptom management, prognosis understanding, goals of care, and advanced care planning. Objective: This review aimed to assess the impact of PC on the adult HSCT standard of care and examine the effects on patients' quality of life during the acute phase of allogeneic HSCT. Methodology: We conducted an integrative literature search through PubMed and CINAHL databases and utilized the PRISMA guidelines for formal review. The authors reviewed a total of 19 full-text articles. Results: Four major themes were generated from a review of the evidence: (1) Physical and Psychosocial HSCT symptoms, (2) Misconceptions of PC, (3) PC Integration on Quality of Life, and (4) Early PC integration and HSCT recipients. The consensus suggests that interdisciplinary PC during HSCT enhances the quality of care. Conclusion: Discussion of this evidence further exemplifies the need to identify unmet palliative needs earlier so that PC may be integrated before the severe consequences of HSCT. Future work should focus on investigating and evaluating effective and efficient integration of HSCT and PC specialties to optimize the quality of care.

Epidemiology and risk factors for the development of cicatrizing conjunctivitis in chronic ocular graft-versus-host disease.

PURPOSE: To evaluate the incidence of chronic cicatrizing conjunctivitis (CCC) and its associated risk factors in the context of chronic ocular graft-vs-host disease (coGVHD). METHODS: A retrospective chart review of individuals diagnosed with coGVHD following hematopoietic stem cell transplantation (HSCT) who were seen at the Bascom Palmer Eye Institute between May 2010 and November 2021 was performed. Data regarding baseline demographic characteristics, systemic co-morbidities, lid margin abnormalities, ocular cicatricial changes, transplant information, immunosuppressive therapy, and GVHD severity assessments were collected. The incidence of cicatricial conjunctivitis was estimated with Kaplan-Meier survival analysis. A Cox regression model was used to assess the contribution of demographic and systemic variables to the development of CCC. RESULTS: 167 individuals were included (53.9 ± 14.7 years old; 60.5 % male). 65 individuals presented with features suggestive of CCC an average of 60.9 ± 53.8 months after HSCT, with 60-month and 120-month incidences of 29.3 % and 48.9 %, respectively. Multivariable analysis demonstrated that age younger than 50 at the time of the first eye visit was associated with a higher chance of CCC development (Hazard Ratio (HR): 2.14, 95 % Confidence Interval (CI): 1.16-3.97, p = 0.02). CONCLUSION: Clinically detected cicatrizing conjunctivitis is an ocular manifestation of coGVHD, with an incidence that increases over time. Younger individuals may be at higher risk for CCC development.

Keratinocyte carcinomas in survivors of childhood cancer: A report from the childhood cancer survivor study.

BACKGROUND: Childhood cancer survivors (CCS) are at increased risk for keratinocyte carcinomas (KC) however, the long-term incidence of single and multiple KC is not well established. OBJECTIVE: Identify risk factors and quantify KC cumulative incidence and multiple-incidence burden in CCS. METHODS: KC were identified among Childhood Cancer Survivor Study participants, a cohort of 5-year cancer survivors diagnosed <21 years of age between 1970 and 1999 in North America. Cumulative incidence was estimated and multivariable models assessed relative rates of KC associated with survivor and treatment characteristics. RESULTS: Among 25,658 participants, 1446 developed 5363 KC (93.5% basal cell carcinoma, 6.7% squamous cell carcinoma; mean age 37.0 years (range 7.3-67.4), mean latency 25.7 years; 95.3% White and 88.4% with radiotherapy). Mean lesion count was 3.7 with 26.1% experiencing ≥4. Radiotherapy imparted a 4.5-fold increase in the rate of any KC and 9.4-fold increase in the rate of ≥4 KC. Allogeneic and autologous hematopoietic cell transplant were associated with a 3.4- and 2.3-fold increased rate of KC, respectively. LIMITATIONS: Participant self-reporting of some data including race without skin phototype and past medical history may have impacted analysis. CONCLUSIONS: The burden of KC in CCS remains high, but predictable risk factors should guide screening.

Hematopoietic stem cell gene therapy improves outcomes in a clinically relevant mouse model of multiple sulfatase deficiency.

Multiple sulfatase deficiency (MSD) is a severe, lysosomal storage disorder caused by pathogenic variants in the gene SUMF1, encoding the sulfatase modifying factor formylglycine-generating enzyme. Patients with MSD exhibit functional deficiencies in all cellular sulfatases. The inability of sulfatases to break down their substrates leads to progressive and multi-systemic complications in patients, similar to those seen in single-sulfatase disorders such as metachromatic leukodystrophy and mucopolysaccharidoses IIIA. Here, we aimed to determine if hematopoietic stem cell transplantation with ex vivo SUMF1 lentiviral gene therapy could improve outcomes in a clinically relevant mouse model of MSD. We first tested our approach in MSD patient-derived cells and found that our SUMF1 lentiviral vector improved protein expression, sulfatase activities, and glycosaminoglycan accumulation. In vivo, we found that our gene therapy approach rescued biochemical deficits, including sulfatase activity and glycosaminoglycan accumulation, in affected organs of MSD mice treated post-symptom onset. In addition, treated mice demonstrated improved neuroinflammation and neurocognitive function. Together, these findings suggest that SUMF1 HSCT-GT can improve both biochemical and functional disease markers in the MSD mouse.

Microvascular remodeling after autologous stem cell transplant in an overlap of systemic sclerosis and systemic lupus erythematosus: A case report.

Microvascular remodeling and capillary repopulation can occur after autologous hematopoietic stem cell transplant (HSCT) in patients with systemic sclerosis and systemic lupus erythematosus (SLE). We aim to report evidence for microvascular remodeling after autologous HSCT as observed by nailfold videocapillaroscopy (NVC). We describe a rare occurrence of features consistent with systemic sclerosis and SLE in a 33-year-old female with a complex clinical course refractory to conventional treatments, ultimately requiring autologous HSCT. We performed NVC before and after HSCT using optical video and light microscopy. At the microvascular level, morphologic changes in the capillary vascular bed were observed after HSCT. Pretransplant damage in capillary structure was noted as evidenced on NVC with architectural loss, ramifications, capillary drop, and decreased density. Posttransplant NVC revealed an increase in capillary density with evidence of microvascular remodeling. Further studies on the clinical use and impact of microvascular remodeling on disease progression are needed and looking into the application of NVC scoring to assess clinical response would be meaningful.

Ongoing randomized clinical trials on HSCT in multiple sclerosis.

Autologous hematopoietic stem cell transplantation (AHSCT) is emerging as a potent treatment for highly active relapsing remitting multiple sclerosis (RRMS), potentially surpassing the efficacy of traditional disease-modifying therapies (DMTs). Phase II and III randomized controlled trials (RCTs) have demonstrated AHSCT's superiority in reducing relapse rates and delaying disability progression compared to standard DMTs. Despite the evolution of treatment guidelines, questions persist regarding patient selection criteria and optimal conditioning regimens. Notably, ongoing clinical trials in the United Kingdom, the United States, Italy, and Norway aim to address these uncertainties by evaluating the safety, efficacy, and long-term outcomes of AHSCT vs. high efficacy DMTs in both DMT-experienced and treatment-naïve patients with active RRMS or aggressive multiple sclerosis (MS). These trials promise to provide valuable insights into the positioning of AHSCT within the treatment landscape of MS.

Utility of Serial Microbial Cell-free DNA Sequencing for Inpatient and Outpatient Pathogen Surveillance Among Allogeneic Hematopoietic Stem Cell Transplant Recipients.

Background: This study characterizes the clinical utility and validity of the Karius test (KT), a plasma microbial cell-free DNA sequencing platform, as an infection surveillance tool among hematopoietic stem cell transplant (HCT) recipients, including monitoring for cytomegalovirus (CMV) and detecting infections relative to standard microbiologic testing (SMT). Methods: A prospective, observational cohort study was performed among adult HCT recipients as inpatients and outpatients. Serial KTs were performed starting with 1 sample within 14 days before HCT, then weekly from 7-63 days posttransplant then monthly from 3-12 months post-HCT. Diagnostic performance of KT versus CMV polymerase chain reaction was evaluated with positive percent agreement and negative percent agreement. Infectious events (<12 months post-HCT) were extracted from medical records. For infectious events without positive SMT, 2 clinicians adjudicated KT results to determine if any detections were a probable cause. Difference in time from KT pathogen detection and infection onset was calculated. Results: Of the 70 participants, mean age was 49.9 years. For CMV surveillance, positive percent agreement was 100% and negative percent agreement was 90%. There was strong correlation between CMV DNA and KT molecules per microliter (r 2: 0.84, P < .001). Of the 32 SMT+/KT+ infectious events, KT identified 26 earlier than SMT (median: -12 days) and an additional 5 diagnostically difficult pathogens identified by KT but not SMT. Conclusions: KT detected CMV with high accuracy and correlation with quantitative polymerase chain reaction. Among infectious events, KT demonstrated additive clinical utility by detecting pathogens earlier than SMT and those not detected by SMT.

A call to address penicillin allergy labels in patients with hematopoietic stem cell transplants: How to avoid rash decisions.

Among patients with hematopoietic stem cell transplants, infections, particularly multidrug-resistant infections, pose a grave threat. In this setting, penicillin allergy labels are both common and harmful. Though the majority of patients who report penicillin allergy can actually tolerate penicillin, penicillin allergy labels are associated with use of alternative antibiotics, which are often more broad spectrum, less effective, and more toxic. In turn, they are associated with more severe infections, multidrug-resistant infections, Clostridium difficile, and increased mortality. Evaluating penicillin allergy labels can immediately expand access to preferred therapeutic options, which are critical to care in patients with recent hematopoietic stem cell transplants. Point-of-care assessment and clinical decision tools now exist to aid the nonallergist in assessment of penicillin allergy. This can aid in expanding use of other beta-lactam antibiotics and assist in risk-stratifying patients to determine a testing strategy. In patients with low-risk reaction histories, direct oral challenges can be employed to efficiently delabel patients across clinical care settings. We advocate for multidisciplinary efforts to evaluate patients with penicillin allergy labels prior to transplantation.

A Case of Chronic Granulomatous Disease Masquerading As Tubercular Lymphadenitis in an Infant.

Chronic granulomatous disease (CGD) is a rare inborn error of immunity characterized by recurrent fungal and bacterial infections due to defective nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. This case report describes an 11-month-old female who was initially diagnosed with tubercular lymphadenitis and presented with fever and bilateral neck swelling. Despite receiving anti-tubercular treatment (ATT) and intravenous antibiotics, the patient experienced recurrent infections and abscesses, prompting further investigation. Laboratory tests revealed normal immunoglobulin levels but abnormal nitroblue tetrazolium (NBT) and dihydrorhodamine (DHR) tests, indicating CGD. Genetic analysis (clinical exome by next-generation sequencing) confirmed a novel NCF2 gene mutation associated with autosomal recessive CGD. This patient was treated with prophylactic antibiotics and antifungals and subsequently underwent successful hematopoietic stem cell transplantation (HSCT). This highlights the diagnostic challenges associated with CGD, particularly in tuberculosis-endemic regions such as India, emphasizing the importance of considering primary immunodeficiency disorders in patients with recurrent infections. Early diagnosis and appropriate treatment, including HSCT, can significantly improve patient outcomes. The patient remained infection-free on prophylactic antimicrobials for 1.5 years post-discharge, demonstrating the potential for a favorable prognosis with timely intervention and comprehensive management.

18FDG PET/CT imaging of adenovirus-associated acute interstitial nephritis after allogeneic bone marrow transplantation.

Adenovirus-associated acute interstitial nephritis (AAIN) should always be considered in the differential diagnosis of acute kidney failure following allogeneic bone marrow transplant. Although not intended for the definitive diagnosis of AAIN, 18FDG PET/CT can be a helpful noninvasive diagnostic tool, especially when a biopsy is not feasible.

Specific antigen-based stratification of membranous nephropathy in patients after haematopoietic stem cell allotransplantation - a case series and literature review.

BACKGROUND: Nephrotic syndrome (NS) is a rare complication that can occur after haematopoietic stem cell transplantation (HSCT). In patients with membranous nephropathy (MN) who have undergone allogeneic HSCT, a new antigen called protocadherin FAT1 has been identified. Our objective is to present a case series of MN patients after HSCT with a novel antigen-based stratification. CASE PRESENTATIONS: Patients who developed full-blown NS due to MN after an HSCT were enrolled in the University Hospital Centre Zagreb study. The first two patients were treated with an HSCT for acute myeloid leukaemia, and both developed NS after cessation of graft versus host disease (GVHD) prophylaxis. The first patient had reduced kidney function, while the second had completely preserved function. Kidney biopsy showed MN with only subepithelial deposits. A thorough examination revealed that there was no secondary cause of the disease. The patients achieved complete remission after undergoing immunosuppression treatment. The third patient underwent HSCT for acute lymphoblastic leukaemia. He developed both acute and chronic GVHD and also experienced avascular hip necrosis. After sixteen years, the patient developed NS with preserved kidney function. The kidney specimen showed membranous nephropathy (MN) with mesangial and subepithelial deposits. Extensive research was conducted, but no secondary cause for the MN was detected. All three cases tested negative for anti-PLA2R antibodies. Biopsy tissue samples were analysed using laser microdissection and tandem mass spectrometry of glomeruli for the detection of different specific antigens. Patients one and two tested positive for FAT1, whereas patient three tested positive for PCSK6. CONCLUSIONS: MN can develop at various time intervals after HSCT. Specific antigen testing can help establish the relationship between MN and HSCT. In the future, serum testing for anti-FAT1 antibodies in HSCT patients could be significant in diagnosing FAT1-associated MN, similar to how anti-PLA2R antibodies are significant in diagnosing PLA2R-associated MN.