Search

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 (

Objectives To determine whether the information provided by short tandem repeat (STR) testing and bone marrow (BM) biopsy specimens following hematopoietic stem cell transplant (HSCT) provides redundant information, leading to test overutilization, without additional clinical benefit. Methods Cases with synchronous STR and flow cytometric immunophenotyping (FCI) testing, as part of the BM evaluation, were assessed for STR/FCI concordance. Results Of 1199 cases (410 patients), we found the overall concordance between STR and FCI was 93%, with most cases (1063) classified as STR–/FCI–. Of all discordant cases, 75 (6%) were STR+/FCI–, with only 5 (6.7%) cases best explained as identification of disease relapse. Eight cases were STR–/FCI+, representing relapsed/residual disease. Analysis of cases 1 year or more from transplant (54% of all cases) indicated only 9 (1.5%) were STR+/FCI–, and none uniquely identified relapse. Conclusions These data suggest that STR analysis performed 1 year or more post-HSCT does not identify unknown cases of relapse. Furthermore, while STR testing is critical for identifying graft failure/rejection within the first year posttransplant, FCI appears superior to STR at detecting late relapses with low-level disease. Therefore, STR testing from patients 1 year or more post-HSCT may be unnecessary, as BM biopsy evaluation is sufficient to identify disease relapse. [ABSTRACT FROM AUTHOR]

Objectives: Patients undergoing autologous hematopoietic stem cell transplant (HCT) are at risk for death and remain understudied relative to those undergoing allogeneic HCT. Cognitive functioning may be a useful indicator of mortality risk. We examined cognition among patients who underwent autologous HCT and its relationship to mortality. Methods: Participants (N = 51; 11 patients deceased) completed tasks of processing speed, working memory, executive-mediated learning, and visual recall using the computerized CogState battery prior to HCT, 30 days post-autologous HCT, and 100 days post-autologous HCT. Results: Slower processing speed (HR = 3.00) and more errors on an executive-mediated visual learning task (HR = 2.78) prior to HCT were associated with an increased risk of death following HCT. Our sample size limited longitudinal analyses of whether cognitive change predicted survival, however descriptive cognitive data of the deceased versus living patient's performances over time suggested different patterns of performance across groups. Conclusions: Pre-HCT cognition may have utility as an indicator of mortality risk following autologous HCT. More research is needed to examine whether cognitive changes after HCT could also predict mortality. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cell transplant (HSCT) is now recognized as a standard treatment option for people with HIV (PWH) who develop high-risk hematologic malignancies. However, the involved polypharmacy can lead to complications from drug interactions and toxicities, affecting the efficacy and safety of chemotherapy and antiretroviral therapy (ART). Managing these patients requires a personalized approach, including the careful selection of ART based on previous therapies and potential interactions, alongside risk assessment for infections. This discussion will address the history of HSCT in PWH and management considerations for this group. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Hematopoietic Stem Cell Transplant (HCT) is a potentially curative treatment for hematologic malignancies, including multiple myeloma. Biomarker investigation can guide identification of HCT recipients at-risk for poor outcomes. MicroRNAs (miRNAs) are a class of non-coding RNAs involved in the modulation and regulation of pathological processes and are emerging as prognostic and predictive biomarkers for multiple health conditions. This pilot study aimed to examine miRNA profiles associated with HCT-related risk factors and outcomes in patients undergoing autologous HCT. Methods: Patients eligible for autologous HCT were recruited and blood samples and HCT-related variables were collected. Differential expression analysis of miRNA was conducted on 24 patient samples to compare changes in miRNA profile in HCT eligible patients before and after transplant. Results: Unsupervised clustering of differentially expressed (p <.05) miRNAs pre- and post- HCT identified clusters of up- and down-regulated miRNAs. Four miRNAs (miR-125a-5p, miR-99b-5p, miR-382–5p, miR-145–5p) involved in hematopoiesis (differentiation of progenitor cells, granulocyte function, thrombopoiesis, and tumor suppression) were significantly downregulated post-HCT. Correlation analyses identified select miRNAs associated with risk factors (such as frailty, fatigue, cognitive decline) and quality of life pre- and post-HCT. Select miRNAs were correlated with platelet engraftment. Conclusion: Future studies should examine miRNA signatures in larger cohorts in association with HCT outcomes; and expand investigations in patients receiving allogeneic transplants. This will lead to identification of biomarkers for risk stratification of HCT recipients. [ABSTRACT FROM AUTHOR]

Post-transplant or hematological cancer patients have a higher risk of mortality after infection with ancestral and early variants of severe acute respiratory syndrome (SARS)-CoV-2. Adoptive cell therapy (ACT) with virus-specific T cells (VSTs) could augment endogenous T cell immunity to avoid disease deterioration before viral clearance. We established a third-party SARS-CoV-2-specific T cell (COVID-T) bank in 2020 (NCT04351659) using convalescent and/or vaccinated donors. In a phase I/II study (NCT04457726), 13 adult and pediatric patients, acutely positive for SARS-CoV-2 and predicted to have a high chance of mortality, were recruited from September 2021 to February 2022. Twelve patients received a single dose of COVID-T cells, matched on at least 1 HLA. A dose of either 75,000 or 150,000 IFN-γ+CD3+ cells/m2 SARS-COV-2-specific T cells did not cause cytokine release syndrome, acute respiratory distress syndrome, or graft-versus-host disease. In the 8 patients who had detectable donor SARS-COV-2-specific T cells after ACT, none progressed to severe disease or died with COVID-19. In contrast, among the other four patients without evidence of donor micro-chimerism, two died of COVID-19. Long-acting third-party VSTs from convalescent or vaccinated donors could be expediently produced and might be clinically useful in future pandemics, particularly before global vaccination is implemented. [ABSTRACT FROM AUTHOR]

AbstractPurposeDesignSample/MethodsFindingsImplicationsTo examine the associations between state positive psychological well-being (PPWB) constructs, mood, and quality of life (QOL) in hematopoietic stem cell transplantation (HSCT) survivors.The study was a secondary analysis of cross-sectional data.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.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.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. [ABSTRACT FROM AUTHOR]

BACKGROUND: The development of tyrosine kinase inhibitors (TKIs) has significantly improved survival rates among patients with Philadelphia chromosome (Ph+) B cell acute lymphoblastic leukemia (B-ALL). Ph-like B-ALL patients lack the BCR::ABL1 translocation but share gene expression profiles with Ph+ B-ALL. The role of TKIs for Ph-like patients pre- and post-hematopoietic stem cell transplantation (HSCT) is not yet clear. CASE: Here we present five cases of pediatric, adolescent, and young adult patients who presented with Ph-like B-ALL or CML in B-ALL blast phase who were treated with personalized TKI regimens pre- and post-HSCT. CONCLUSION: This report describes several novel Ph-like fusions as well as combinations of TKIs with chemotherapy or immunotherapy not yet reported in the pediatric population. This case series provides real-world experience highlighting the potential application of pre- and post-HSCT use of TKIs in a subset of patients with targetable fusions.

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. Identify risk factors and quantify KC cumulative incidence and multiple-incidence burden in CCS. 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. 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. Participant self-reporting of some data including race without skin phototype and past medical history may have impacted analysis. The burden of KC in CCS remains high, but predictable risk factors should guide screening. [ABSTRACT FROM AUTHOR]

Abstract 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.

Background: Hematopoietic stem cell transplantation (HCT) is a curative treatment for various hematologic malignancies and some benign hematologic diseases. However, in addition to chronic graft-versus-host disease, second primary malignancy is also a long-term adverse effect. Materials and Methods: We retrospectively collected long-term follow-up data of 380 patients who had undergone transplantation (autologous in 184 with 126 long-term survivors and allogeneic in 196 patients with 100 long-term survivors) between 2001 and 2021 and analyzed the incidence and types of second primary malignancy. Results: Twelve patients had second primary malignancy, including five with head-and-neck squamous cell carcinoma (SCC), three with myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), one with acute lymphoblastic leukemia (ALL), one with esophageal SCC, one with breast cancer, and one with papillary thyroid cancer. Of eight patients who underwent allogeneic hematopoietic stem cell transplants, five had head and neck, one had esophageal, one had breast, and one had papillary thyroid cancer. Of four patients who underwent autologous transplants, three had MDS/AML, and one had ALL. The cumulative incidence of second malignancy was 6% at 10 years and 16% at 19 years, and the postautologous and postallogeneic transplant rates were 5% versus 7% at 10 years and 15% versus 17% at 19 years. Conclusion: The occurrence of a second malignancy after HCT is a crucial issue of concern, and an early diagnosis is essential for posttransplant patients.

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. [ABSTRACT FROM AUTHOR]

Introduction: This study explored the efficacy of repeat blood cultures in bacteremic acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem cell transplantation (HSCT). Methods: This was a retrospective study of AML patients who experienced febrile neutropenia (FN) and bacteremia following HSCT at the Taussig Cancer Center from January 1, 2019, to December 31, 2022. The primary endpoint was the rate of positive repeat blood cultures following initial positive blood culture. Results: Fifty patients were included in the study. There were 50 occurrences of FN with positive initial blood cultures that were diagnosed following HSCT. Fifty initial sets of blood cultures and 96 sets of repeat blood cultures were drawn between the 50 occurrences of FN. Twelve of 96 (12.5%) repeat blood culture sets were positive for a pathogen, which occurred over nine of 50 (18.0%) episodes of FN. Three of 96 (3.2%) repeat blood culture sets grew a pathogen that differed from the pathogen that grew in the preceding positive blood culture. Conclusion: Among bacteremic AML patients in the post‐HSCT period, the yield of repeat blood cultures for detecting previously detected and new pathogens was low. [ABSTRACT FROM AUTHOR]

This case involves a 53‐year‐old female with concurrent acute myeloid leukemia (AML) and multiple myeloma. She underwent cytarabine and daunorubicin (7+3) induction chemotherapy followed by cytarabine (HiDAC) consolidation, with an early AML relapse requiring azacitidine and venetoclax therapy. She achieved complete remission and incomplete count recovery. Following fludarabine, melphalan, and thymoglobulin induction chemotherapy, she underwent an allogeneic stem cell transplant with failure to engraft, requiring autologous stem cell rescue, buffy coat, and granulocyte transfusions, eventually presenting with a diffuse skin rash consistent with Steven‐Johnson syndrome and toxic epidermal necrolysis, persistent neutropenic fevers and positive blood cultures. [ABSTRACT FROM AUTHOR]

Pediatric Hematopoietic Stem Cell Transplant (HSCT) profoundly affects various dimensions of parents' lives. Effective coping strategies are essential for improving psychological well-being and overall quality of life. Therefore, this study aimed to explore parental coping strategies with their child's HSCT challenges. This qualitative study was conducted in Iran from February to November 2023, utilizing conventional content analysis with purposive sampling. For data collection, unstructured interviews were conducted, followed by in-depth semi-structured interviews with open-ended questions. Saturation was reached after analyzing qualitative data from 20 participants. Data analysis unveiled a main theme labeled "harmony in hardship". This overarching concept encapsulates the participants' endeavors to cope with the various hurdles and complexities stemming from their child's HSCT. This theme consisted of five categories: "emotional release", "positive coping", "avoidance coping", "spiritual coping", and "seeking support". Parents utilized multifaceted coping strategies to manage the complexities of their child's HSCT journey. Understanding these mechanisms is crucial as they can positively influence parents' psychological well-being and improve their overall quality of life. Healthcare professionals should recognize the diverse coping strategies employed by parents of children undergoing HSCT and provide tailored interventions and support. Furthermore, implementing structured support programs and training initiatives for healthcare professionals can enhance their capacity to meet the diverse needs of parents during this challenging journey. • Pediatric HSCT profoundly impacts parents' lives. • The traumatic nature of before, during, and post-HSCT periods poses coping challenges for parents. • Our findings described the multifaceted coping strategies parents use to manage their child's medical journey. • Supporting parents in their coping efforts can help to create a more supportive and holistic care environment. [ABSTRACT FROM AUTHOR]

Background: Hematopoietic stem cell transplantation (hereafter "HCT") is a physically and psychologically difficult treatment for patients with hematological cancers. This study examined relationships among patients' reports of pre-transplant social isolation, social constraints, and psychological distress. Method: We used baseline data from a multisite randomized controlled trial evaluating the effects of expressive helping writing to reduce physical and emotional symptoms in HCT patients. We collected data prior to randomization and before either allogenic or autologous HCT using validated scales to assess social constraints, social isolation, anxiety, and depressive symptoms. We analyzed data using bivariate analysis and multivariate linear regression. We also explored whether social isolation mediated the effect of social constraints on both of our outcomes: anxiety and depressive symptoms. Results: Among 259 adults recruited prior to transplant, 43.6% were women (mean age = 57.42 years, SD = 12.34 years). In multivariate analysis controlling for relevant covariates, both social isolation (β = 0.24, p < 0.001) and social constraints (β = 0.28, p < 0.001) were associated with anxiety. When both social constraints and social isolation were in the model, only greater social isolation (β = 0.79, p < 0.001) was associated with depressive symptoms. Social isolation fully mediated the association between social constraints and anxiety and depressive symptoms. Conclusion: For patients awaiting either allogenic or autologous HCT, the negative association between social constraints and anxiety and depressive symptoms may be related, in part, to the mechanism of perceived social isolation. Interventions prior to and during HCT are needed to support patients' psychological health and sense of social connectedness. [ABSTRACT FROM AUTHOR]

This letter discusses the importance of accurately and efficiently measuring CD34+ stem cell counts in peripheral blood for hematopoietic stem cell transplantation (HSCT). The authors describe a case in which there was a discrepancy between the results of the hematopoietic progenitor cell (HPC) count and the flow cytometric CD34+ cell count, indicating interference in the flow cytometric analysis. They conducted alternative staining methods and washing techniques to resolve the issue and ultimately confirmed the presence of CD34+ stem cells. The authors emphasize the value of HPC count as a quality control parameter and highlight the importance of careful review and communication in patient treatment. [Extracted from the article]

ObjectivesThis practice parameter was revised collaboratively by the American College of Radiology (ACR) and the American Radium Society (ARS). This practice parameter provides updated reference literature regarding both clinical-based conventional total body irradiation and evolving volumetric modulated total body irradiation.MethodsThis practice parameter was developed according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website ( https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards ) by the Committee on Practice Parameters-Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with the ARS.ResultsThis practice parameter provides a comprehensive update to the reference literature regarding conventional total body irradiation and modulated total body irradiation. Dependence on dose rate remains an active area of ongoing investigation in both the conventional setting (where instantaneous dose rate can be varied) and in more modern rotational techniques, in which average dose rate is the relevant variable. The role of imaging during patient setup and the role of inhomogeneity corrections due to computer-based treatment planning systems are included as evolving areas of clinical interest notably surrounding the overall dose inhomogeneity. There is increasing emphasis on the importance of evaluating mean lung dose as it relates to toxicity during high-dose total body irradiation regimens.ConclusionsThis practice parameter can be used as an effective tool in designing and evaluating a total body irradiation program that successfully incorporates the close interaction and coordination among the radiation oncologists, medical physicists, dosimetrists, nurses, and radiation therapists.

Abstract Background Total body irradiation (TBI) for hematopoietic stem cell transplant (HSCT) has certain distinct advantages, such as uniform dose distribution and lack of drug resistance, but it is not widely available in resource-constrained settings. To overcome the limitations of in-house radiotherapy services in hematology centers, we evaluated the feasibility of conducting HSCT programs in coordination with two physically distant centers using a reduced-intensity TBI protocol. Methods Thirty-two patients with a median age of 20.5 years were included in the study. Fifteen patients were diagnosed with aplastic anemia, 10 patients with acute myeloid leukemia (AML), 3 patients with acute lymphocytic leukemia (ALL), and 4 patients with other hematological conditions. Conditioning regimens used were fludarabine plus cyclophosphamide in 29 cases, fludarabine-cytarabine ATG in 2 cases, and busulfan plus fludarabine in 1 case. The TBI dose was 3 Gy in 28 cases and 2 Gy in 4 cases. Patients were followed monthly after TBI, and the major toxicities were recorded. Results The median follow-up was 22 months. The most common acute complication was acute graft-versus-host disease (GVHD), which occurred in 15.6% of patients. The major late complications were chronic GVHD (9.3%), Cytomegalovirus (CMV) infection (34.3%), and CMV-induced secondary graft failure (6.2%). Seventy-five percent of patients were alive, 21.9% were dead, and 1 patient was lost to follow-up. Conclusions HSCT based on TBI is feasible even if the center lacks a radiotherapy facility by coordinating with a remote radiotherapy facility. without compromising the patient's outcome.

Abstract Chronic disseminated candidiasis (CDC) is a severe but rarely seen fungal infection presenting in patients with hematologic malignancies after a prolonged duration of neutropenia. A high index of suspicion is required to diagnose CDC as standard culture workup is often negative. While tissue biopsy is the gold standard of diagnosis, it is frequently avoided in patients with profound cytopenias and increased bleeding risks. A presumptive diagnosis can be made in patients with recent neutropenia, persistent fevers unresponsive to antibiotics, imaging findings of hypoechoic, non-rim enhancing target-like lesions in the spleen and liver, and mycologic evidence. Here, we describe the case of an 18-year-old woman with relapsed B-cell acute lymphoblastic leukemia treated with re-induction chemotherapy who subsequently developed CDC with multi-organ involvement. The diagnosis was made based on clinical and radiologic features with positive tissue culture from a skin nodule and hepatic lesion. The patient was treated for a total course of 11 months with anti-fungal therapy, most notably amphotericin B and micafungin, and splenectomy. After initial diagnosis, the patient was monitored with monthly CT abdomen imaging that showed disease control after 5 months of anti-fungal therapy and splenectomy. The diagnosis, treatment, and common challenges of CDC are outlined here to assist with better understanding, diagnosis, and treatment of this rare condition.

We report a case of Enterocytozoon bieneusi infection in a pediatric hematopoietic stem cell transplant recipient in Argentina. Spores were visualized in feces using Calcofluor White and modified trichrome stainings. PCR and sequencing identified E. bieneusi genotype D in fecal samples and liver samples, confirming extraintestinal dissemination of the parasite.

Sickle cell disease (SCD) results from a single base pair change in the sixth codon of the β-globin chain of hemoglobin, which promotes aggregation of deoxyhemoglobin, increasing rigidity of red blood cells and causing vaso-occlusive and hemolytic complications. Allogeneic transplant of hematopoietic stem cells (HSCs) can eliminate SCD manifestations but is limited by absence of well-matched donors and immune complications. Gene therapy with transplantation of autologous HSCs that are gene-modified may provide similar benefits without the immune complications. Much progress has been made, and patients are realizing significant clinical improvements in multiple trials using different approaches with lentiviral vector-mediated gene addition to inhibit hemoglobin aggregation. Gene editing approaches are under development to provide additional therapeutic opportunities. Gene therapy for SCD has advanced from an attractive concept to clinical reality.

Neutrophils are essential effector cells for mediating rapid host defense and their insufficiency arising from therapy-induced side-effects, termed neutropenia, can lead to immunodeficiency-associated complications. In autologous hematopoietic stem cell transplantation (HSCT), neutropenia is a complication that limits therapeutic efficacy. Here, we report the development and in vivo evaluation of an injectable, biodegradable hyaluronic acid (HA)-based scaffold, termed HA cryogel, with myeloid responsive degradation behavior. In mouse models of immune deficiency, we show that the infiltration of functional myeloid-lineage cells, specifically neutrophils, is essential to mediate HA cryogel degradation. Post-HSCT neutropenia in recipient mice delayed degradation of HA cryogels by up to 3 weeks. We harnessed the neutrophil-responsive degradation to sustain the release of granulocyte colony stimulating factor (G-CSF) from HA cryogels. Sustained release of G-CSF from HA cryogels enhanced post-HSCT neutrophil recovery, comparable to pegylated G-CSF, which, in turn, accelerated cryogel degradation. HA cryogels are a potential approach for enhancing neutrophils and concurrently assessing immune recovery in neutropenic hosts.

Background: Total body irradiation (TBI) for hematopoietic stem cell transplant (HSCT) has certain distinct advantages, such as uniform dose distribution and lack of drug resistance, but it is not widely available in resource-constrained settings. To overcome the limitations of in-house radiotherapy services in hematology centers, we evaluated the feasibility of conducting HSCT programs in coordination with two physically distant centers using a reduced-intensity TBI protocol. Methods: Thirty-two patients with a median age of 20.5 years were included in the study. Fifteen patients were diagnosed with aplastic anemia, 10 patients with acute myeloid leukemia (AML), 3 patients with acute lymphocytic leukemia (ALL), and 4 patients with other hematological conditions. Conditioning regimens used were fludarabine plus cyclophosphamide in 29 cases, fludarabine-cytarabine ATG in 2 cases, and busulfan plus fludarabine in 1 case. The TBI dose was 3 Gy in 28 cases and 2 Gy in 4 cases. Patients were followed monthly after TBI, and the major toxicities were recorded. Results: The median follow-up was 22 months. The most common acute complication was acute graft-versus-host disease (GVHD), which occurred in 15.6% of patients. The major late complications were chronic GVHD (9.3%), Cytomegalovirus (CMV) infection (34.3%), and CMV-induced secondary graft failure (6.2%). Seventy-five percent of patients were alive, 21.9% were dead, and 1 patient was lost to follow-up. Conclusions: HSCT based on TBI is feasible even if the center lacks a radiotherapy facility by coordinating with a remote radiotherapy facility. without compromising the patient's outcome. [ABSTRACT FROM AUTHOR]

Introduction: Dental examination and stabilization are performed prior to allogeneic hematopoietic cell transplantation to decrease infection risk during neutropenia. Burden of dental disease and treatment need is not well characterized in this population. Objectives: This report describes the dental status of a cohort of patients within the Chronic Graft‐versus‐Host Disease Consortium and treatment rendered prior to transplant. Methods: The cohort included 486 subjects (Fred Hutchinson: n = 245; Dana‐Farber: n = 241). Both centers have institutional‐based dental clearance programs. Data were retrospectively abstracted from medical records by calibrated oral health specialists. Results: The median age at transplant was 55.9 years, 62.1% were male, and 88% were white. Thirteen patients were edentulous (2.7%). The mean teeth among dentate patients before clearance was 26.0 (SD, 4.6). Dental findings included untreated caries (31.2%), restorations (91.6%), endodontically treated teeth (48.1%), and dental implants (5.7%). Pretransplant procedures during clearance included endodontic therapy (3.6%; mean = 0.1 teeth), restorations (25.1%; mean = 0.7), dental prophylaxis (59.2%), scaling/root planing (5.1%), and extraction (13.2%; mean = 0.3). The mean teeth after clearance was 25.6 (SD, 5.0). Conclusions: Retrospective analysis of pre‐AlloHCT dental data in subjects at two large transplant centers identified low levels of dental need. Findings suggest high access to care. [ABSTRACT FROM AUTHOR]

Purpose: Hematopoietic stem cell transplant (HSCT) is an intense form of treatment, resulting in major symptom burden but can prove curative. The quality of life (QOL) is a major endpoint for these patients as the survival rate in them has improved over time. The aim of the study is to assess the QOL and symptom burden of hematological malignancy patients at admission to hospital for HSCT, at 1 month and at 3 months following HSCT. Methods: This prospective observational study was done on hematological malignancy patients who were admitted for HSCT in a regional cancer center. The study subjects were assessed by the Functional Assessment of Cancer Therapy–Bone Marrow Transplant Scale (FACT–BMT Scale), Edmonton Symptom Assessment Scale-revised (r-ESAS), and Depression, Anxiety and Stress Scale—21 Items (DASS-21) at the time of hospital admission for transplantation, on day 30 (~ 1 month) and day100 (~ 3 months) of transplantation. Results: A total of 68 patients were included in this study. FACT–BMT scores have decreased from baseline (F0) to the first follow-up (F1) and then increased in the third follow-up (F2). The maximum r-ESAS mean score was for tiredness among all other symptoms at F0 as well as at F1 and at F2. The DASS 21 scores for depression, anxiety, and stress were maximum during F1 and minimum during F2. Conclusion: Symptom burden is maximum during the first month of BMT, which improves later and QOL becomes improved with time. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate corneal epithelial changes and related factors in chronic ocular graft-versus-host disease (oGVHD) patients. Methods: 21 patients (35 eyes) with chronic oGVHD and 8 patients (12 eyes) without oGVHD after bone marrow transplantation were recruited for assessment involving in vivo confocal microscopy (IVCM) analysis, ocular surface parameter determination and tear cytokine level analysis. The IVCM corneal epithelial scoring system was used to evaluate corneal epithelial changes. Results: There was a significant difference in the corneal epithelial score (p = .001) between the two groups. The corneal epithelial scores were significantly correlated with the corneal fluorescein staining scores (CFS, r = 0.463, p < .001), Schirmer's test (r = 0.389, p = .009) and tear cytokine levels of EGF (r = 0.491, p < .001) and APRIL (r = 0.318, p = .030). Conclusions: The depth of corneal epithelial defects can be estimated by the CFS. Corneal epithelial changes of chronic oGVHD are considered to be associated with lacrimal deficiency and a lack of EGF. [ABSTRACT FROM AUTHOR]

Background: Assessing the risk of multidrug-resistant colonization and infections is pivotal for optimizing empirical therapy in hematopoietic stem cell transplants (HSCTs). Limited data exist on extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) colonization in this population. This study aimed to assess whether ESBL-E colonization constitutes a risk factor for ESBL-E bloodstream infection (BSI) and to evaluate ESBL-E colonization in HSCT recipients. Methods: A retrospective analysis of ESBL-E colonization and BSI in HSCT patients was conducted from August 2019 to June 2022. Weekly swabs were collected and cultured on chromogenic selective media, with PCR identifying the β-lactamase genes. Pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS) assessed the colonizing strains' similarities. Results: Of 222 evaluated HSCT patients, 59.45% were colonized by ESBL-E, with 48.4% at admission. The predominant β-lactamase genes were blaTEM (52%) and blaSHV (20%). PFGE analysis did not reveal predominant clusters in 26 E. coli and 15 K. pneumoniae strains. WGS identified ST16 and ST11 as the predominant sequence types among K. pneumoniae. Thirty-three patients developed thirty-five Enterobacterales-BSIs, with nine being third-generation cephalosporin-resistant. No association was found between ESBL-E colonization and ESBL-BSI (p = 0.087). Conclusions: Although the patients presented a high colonization rate of ESBL-E upon admission, no association between colonization and infection were found. Thus, it seems that ESBL screening is not a useful strategy to assess risk factors and guide therapy for ESBL-BSI in HSCT-patients. [ABSTRACT FROM AUTHOR]

Hepatic complications are an acknowledged cause of mortality and morbidity among patients undergoing hematopoietic stem cell transplantation. In this study, we aimed to evaluate the potential role in the prediction of liver injury of five selected microRNAs (miRNAs)—miR-122-5p, miR-122-3p, miR-15b-5p, miR-99b-5p, and miR-125a-5p—in the setting of autologous hematopoietic stem cell transplantation (ASCT). A total of 66 patients were included in the study: 50 patients (75.8%) with multiple myeloma (MM) and 16 (24.2%) with lymphoma. Blood samples were collected after the administration of the conditioning regimen, on the day of transplant (day 0). The expression levels of selected miRNAs were quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) using the miRCURY LNA miRNA Custom PCR Panels (QIAGEN). In a multivariate logistic regression analysis adjusted for age, sex, and the administered conditioning regimen, two miRNAs, hsa-miR-122-5p (odds ratio, OR 2.10, 95% confidence interval, CI: 1.29–3.42, p = 0.0029) and hsa-miR-125a-5p (OR 0.27, 95% CI: 0.11–0.71, p = 0.0079), were independent for hepatic toxicity occurrence during the 14 days after transplant. Our model in 10-fold cross-validation preserved its diagnostic potential with a receiver operating characteristics area under the curve (ROC AUC) of 0.75, 95% CI: 0.63–0.88 and at optimal cut-off reached 72.0% sensitivity and 74.4% specificity. An elevated serum level of miR-122-5p and decreased level of miR-125a-5p on day 0 are independent risk factors for hepatotoxicity in ASCT recipients, showing promise in accurately predicting post-ASCT complications. Identifying patients susceptible to complications has the potential to reduce procedure costs and optimize the selection of inpatient or outpatient procedures. [ABSTRACT FROM AUTHOR]

Objective Anxiety, negatively affects the response to transplantation and the recovery process after transplantation. Anxiety prevalence is high pre and post transplantation but no information is known about during transplantation. This study was conducted to determine anxiety and adverse events during hematopoietic stem cell transplantation (HSCT) and to explain the association between these two conditions. Methods The sample consisted of 93 patients with cancer who received hematopoietic stem cell transplantation at the Bone Marrow Transplant Centre in Türkiye. The data were collected using a patient information form and the State Anxiety Inventory (STAI-S). Significance between the descriptive characteristics of the participants and the scale was calculated using a one-way ANOVA and Student-T test. Logistic regression analysis was performed to determine the effect of adverse events on the level of anxiety. Results We found that there was a significant difference between the variables of age (F = 2.497 p = 0.020), gender, years after diagnosis (F= 1.381 p = 0.035), the state of believing that transplant will be successful and previous transplant history, and the STAI-S mean score. The Nagelkerke R2 value of the model was 0.167. The goodness of fit of the model was assessed using Hosmer and Lemeshow's test (X2 = 8.900, p = 0.203). When analyzing the adverse events during HSCT that affected the occurrence of anxiety, we found that nausea and vomiting increased the anxiety score by 6.1-fold (β: 0.613, p = 0.010), abdominal pain by 4.4-fold (β: 0.449, p = 0.030), and tachycardia by 2.6-fold (β: 0.267, p = 0.020). Conclusions The results of this study showed that patients experienced nausea and vomiting, hypertension and abdominal pain during stem cell transplantation, respectively; anxiety level was above the moderate level; nausea and vomiting, abdominal pain and palpitations increased anxiety. Preventing anxiety during stem cell transplant can reduce adverse effects depend on HSCT. [ABSTRACT FROM AUTHOR]

Takayasu arteritis (TA) is a large-vessel vasculitis that rarely presents in infancy. Casitas B-lineage lymphoma (CBL) syndrome is a rare genetic disorder due to heterozygous CBL gene germline pathogenic variants that is characterized by a predisposition to develop juvenile myelomonocytic leukemia (JMML). Vasculitis, including TA, has been reported in several patients. Herein, we describe a patient with CBL syndrome, JMML, and TA, developing long-term remission of this vasculitis after allogeneic hematopoietic stem cell transplant (HSCT), and perform a literature review of CBL syndrome with vasculitis or vasculopathy. We report a female patient with growth delay, developmental issues, and congenital heart disease who was admitted at 14 months of age with massive splenomegaly, lymphadenopathy, fever, and hypertension. Body imaging studies revealed arterial stenosis and wall inflammation of the aorta and multiple thoracic and abdominal branches. Whole exome sequencing revealed a pathogenic variant in CBL with loss of heterozygosity in blood cells, diagnosing CBL syndrome, complicated by JMML and TA. Allogeneic HSCT induced remission of JMML and TA, permitting discontinuation of immunosuppression after 12 months. Six years later, her TA is in complete remission off therapy. A literature review identified 18 additional cases of CBL syndrome with vasculitis or vasculopathy. The pathogenesis of vasculitis in CBL syndrome appears to involve dysregulated T cell function and possibly increased angiogenesis. This case advances the understanding of vascular involvement in CBL syndrome and of the genetic, immune, and vascular interplay in TA, offering insights for treating CBL syndrome and broader TA. [ABSTRACT FROM AUTHOR]

We studied patients diagnosed with aspergillosis based on positive bronchoalveolar lavage (BAL) Aspergillus galactomannan (GM) who had follow-up BAL sampling within 180 days. GM trend and clinical outcome were concordant in only 60% (30/50). While useful for the initial diagnosis, BAL GM trending does not always correlate with treatment response. [ABSTRACT FROM AUTHOR]

Introduction: Cytomegalovirus (CMV) infection is a major clinical issue after allogeneic hematopoietic stem cell transplantation (HSCT). The CMV envelope glycoproteins are key in viral pathogenesis; the glycoprotein B (gB) encoded by the UL55 gene might be an important determinant of viral virulence and disease severity marker in patients treated with allogeneic HSCT. Our aim was to investigate the molecular diversity of CMV gB and inquire into the associations between UL55 gene variations and clinical manifestations in adult patients treated with allogeneic HSCT. Results: The most prevalent genotypes were gB1 and gB4 (11/27, 40.7%). Patients with genotype gB1 infection had earlier platelet engraftment (p < 0.033) and less frequent minimal/measurable residual disease post HSCT than those without this genotype. Patients with gB4 glycoprotein infection had a significantly lower CD4+/CD8+ ratio at D90 (p < 0.026). Interestingly, patients with gB5 glycoprotein infection had shorter overall survival from base condition diagnosis (p < 0.042), as well as shorter overall survival after HSCT (p < 0.036). Acute GvHD was noted more frequently in those with mixed-genotype infection (p = 0.047). Material and Methods: The study included fifty-nine adult patients treated with allogeneic HSCT. Peripheral venous blood was sampled typically per week, with detection of CMV performed by quantitative real-time PCR. Multiplex nested PCR was used to determine specific gB genotypes, which were then statistically compared vis-à-vis specific clinical variables. Conclusions: Our study points to variations in the viral UL55 locus imparting both beneficial (earlier platelet engraftment, less frequent MRD post HSCT) and adverse effects (shorter overall survival, more frequent acute GvHD, less frequent 100% chimerism at day 90) to the transplanted host. Comprehensive molecular investigations are necessary to validate this apparent duality, as the potential benefits of CMV could perhaps be utilized for the benefit of the patient in the future. [ABSTRACT FROM AUTHOR]

Traditional weight-based dosing of rabbit anti-thymocyte globulin (rATG) used in allogeneic hematopoietic cell transplantation (HCT) to prevent graft-versus-host disease (GVHD) and graft rejection leads to variable exposures. High exposures induce delayed CD4+immune reconstitution (CD4+IR) and greater mortality. We sought to determine the impact of rATG exposure in children and young adults receiving various types of EX-VIVO T-cell–depleted (EX-VIVO-TCD) HCT. Patients receiving their first EX-VIVO-TCD HCT (CliniMACS CD34+, Isolex or soybean lectin agglutination), with removal of residual T cells by E-rosette depletion (E-) between 2008 and 2018 at Memorial Sloan Kettering Cancer Center were retrospectively analyzed. rATG exposure post-HCT was estimated (AU*d/L) using a validated population pharmacokinetic model. Previously defined rATG-exposures, <30, 30–55, ≥55 AU*d/L, were related with outcomes of interest. Cox proportional hazard and cause-specific models were used for analyses. In total, 180 patients (median age 11 years; range 0.1–44 years) were included, malignant 124 (69%) and nonmalignant 56 (31%). Median post-HCT rATG exposure was 32 (0–104) AU*d/L. Exposure <30 AU*d/L was associated with a 3-fold greater probability of CD4+IR (P < 0.001); 2- to 4-fold lower risk of death (P = 0.002); and 3- to 4-fold lower risk of non-relapse mortality (NRM) (P = 0.02). Cumulative incidence of NRM was 8-fold lower in patients who attained CD4+IR compared with those who did not (P < 0.0001). There was no relation between rATG exposure and aGVHD (P = 0.33) or relapse (P = 0.23). Effect of rATG exposure on outcomes was similar in three EX-VIVO-TCD methods. Individualizing rATG dosing to target a low rATG exposure post-HCT while maintaining total cumulative exposure may better predict CD4+IR, reduce NRM and increase overall survival, independent of the EX-VIVO-TCD method. [ABSTRACT FROM AUTHOR]

Background: Prolonged periods of immunosuppression during hematopoietic stem cell transplant (HSCT) can result in serious infectious complications and contribute to transplant‐related morbidity and mortality. Adherence to standardized pre and postinfection screening guidelines, prescribed medications, and early identification of infectious symptoms through comprehensive patient and family education are crucial to minimizing infectious complications. Advanced practice nurses (APNs) are key members of the multidisciplinary care team in the HSCT specialty, maintaining a specialized skillset and scope of practice which includes a holistic based, preventative medicine and risk mitigation approach. Methods: This review sought to describe the role of the APN in HSCT care and to further examine existing APN led models of care which focus on infection prevention and education throughout the HSCT treatment journey. Results: No studies specifically examined the APN role in infectious diseases risk assessment, screening, and management throughout the HSCT journey were identified throughout our review, however, there was considerable evidence to demonstrate the benefits of APN led care in the oncology and solid organ transplantation specialty which led to improvements in continuity of care, overall patient outcomes, and multidisciplinary team collaboration. The key themes identified in our review, were the role of the APN in the delivery of comprehensive patient and family education, the role of the APN in supporting, mentoring, and educating junior medical and nursing teams, the collaboration between the APN and the multidisciplinary care team, and the role of the APN in prompt recognition, triage, and management of treatment related complications, such as infection. [ABSTRACT FROM AUTHOR]

This study aims to perform an extensive review of the literature that evaluates various factors that affect the survival rates of patients with severe combined immunodeficiency (SCID) after hematopoietic stem cell transplantation (HSCT) in developed and developing countries. An extensive search of the literature was made in four different databases (PubMed, Embase, Scopus, and Web of Science). The search was carried out in December 2022 and updated in July 2023, and the terms such as "hematopoietic stem cell transplantation," "bone marrow transplant," "mortality," "opportunistic infections," and "survival" associated with "severe combined immunodeficiency" were sought based on the MeSH terms. The language of the articles was "English," and only articles published from 2000 onwards were selected. Twenty-three articles fulfilled the inclusion criteria for review and data extraction. The data collected corroborates that early HSCT, but above all, HSCT in patients without active infections, is related to better overall survival. The universal implementation of newborn screening for SCID will be a fundamental pillar for enabling most transplants to be carried out in this "ideal scenario" at an early age and free from infection. HSCT with an HLA-identical sibling donor is also associated with better survival rates, but this is the least common scenario. For this reason, transplantation with matched unrelated donors (MUD) and mismatched related donors (mMRD/Haploidentical) appear as alternatives. The results obtained with MUD are improving and show survival rates similar to those of MSD, as well as they do not require manipulation of the graft with expensive technologies. However, they still have high rates of complications after HSCT. Transplants with mMRD/Haplo are performed just in a few large centers because of the high costs of the technology to perform CD3/CD19 depletion and TCRαβ/CD19 depletion or CD34 + selection techniques in vitro. The new possibility of in vivo T cell depletion using post-transplant cyclophosphamide could also be a viable alternative for performing mMRD transplants in centers that do not have this technology, especially in developing countries. [ABSTRACT FROM AUTHOR]

Objectives: Pediatric Hematopoietic Stem Cell Transplant (HSCT) profoundly impacts the physical, psychological, and social aspects of parents' lives. Thus, this study aimed to explore the experiences of parents living with a child with cancer who undergoes HSCT. Methods: This qualitative study involved 20 parents of children with cancer who were undergoing HSCT at a referral hospital in Iran. Purposive sampling was used to select the participants from February 2023 to November 2023. In-depth semi-structured interviews, featuring open-ended questions, were utilized for data collection. Data analysis was performed using conventional content analysis. Results: Data analysis revealed two main themes. "Surrounded by hardships" and "Self-actualization." The first theme encompassed participants' experiences of facing difficulties in life after being aware of their child's need for HSCT. This theme consisted of four categories: "uncertainty about the child's future," "exhaustion from the child's treatment process," "worrying about the healthy child(ren)," and "helplessness." The second theme "self-actualization" included with two categories: "transformation in life's philosophy" and "acquisition of new capabilities." These categories highlighted the positive outcomes experienced by the participants following their child's HSCT. Conclusion: Our findings underscore the importance of healthcare providers being attuned to parents' experiences throughout their child's HSCT trajectory. It is crucial for healthcare providers to encourage parents to articulate their concerns and feelings and seek support from healthcare providers, family, and friends. The development of psychological support services in healthcare settings can facilitate tailored interventions to alleviate parents' difficulties. [ABSTRACT FROM AUTHOR]

Chronic disseminated candidiasis (CDC) is a severe but rarely seen fungal infection presenting in patients with hematologic malignancies after a prolonged duration of neutropenia. A high index of suspicion is required to diagnose CDC as standard culture workup is often negative. While tissue biopsy is the gold standard of diagnosis, it is frequently avoided in patients with profound cytopenias and increased bleeding risks. A presumptive diagnosis can be made in patients with recent neutropenia, persistent fevers unresponsive to antibiotics, imaging findings of hypoechoic, non-rim enhancing target-like lesions in the spleen and liver, and mycologic evidence. Here, we describe the case of an 18-year-old woman with relapsed B-cell acute lymphoblastic leukemia treated with reinduction chemotherapy who subsequently developed CDC with multi-organ involvement. The diagnosis was made based on clinical and radiologic features with positive tissue culture from a skin nodule and hepatic lesion. The patient was treated for a total course of 11 months with anti-fungal therapy, most notably amphotericin B and micafungin, and splenectomy. After initial diagnosis, the patient was monitored with monthly CT abdomen imaging that showed disease control after 5 months of anti-fungal therapy and splenectomy. The diagnosis, treatment, and common challenges of CDC are outlined here to assist with better understanding, diagnosis, and treatment of this rare condition. [ABSTRACT FROM AUTHOR]