RESUMEN

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.

RESUMEN

Objectives: This manuscript presents a bibliometric and visualization analysis of Total Body Irradiation (TBI) research, aiming to elucidate trends, gaps, and future directions in the field. This study aims to provide a comprehensive overview of the global research landscape of TBI, highlighting its key contributions, evolving trends, and potential areas for future exploration. Methods: The data for this study were extracted from the Web of Science Core Collection (WoSCC), encompassing articles published up to May 2023. The analysis included original studies, abstracts, and review articles focusing on TBI-related research. Bibliometric indicators such as total publications (TP), total citations (TC), and citations per publication (C/P) were utilized to assess the research output and impact. Visualization tools such as VOS Viewer were employed for thematic mapping and to illustrate international collaboration networks. Results: The analysis revealed a substantial body of literature, with 7,315 articles published by 2,650 institutions involving, 13,979 authors. Full-length articles were predominant, highlighting their central role in the dissemination of TBI research. The authorship pattern indicated a diverse range of scholarly influences, with both established and emerging researchers contributing significantly. The USA led in global contributions, with significant international collaborations observed. Recent research trends have focused on refining TBI treatment techniques, investigating long-term patient effects, and advancing dosimetry and biomarker studies for radiation exposure assessments. Conclusions: TBI research exhibits a dynamic and multifaceted landscape, driven by global collaboration and innovation. It highlights the clinical challenges of TBI, such as its adverse effects and the need for tailored treatments in pediatric cases. Crucially, the study also acknowledges the fundamental science underpinning TBI, including its effects on inflammatory and apoptotic pathways, DNA damage, and the varied sensitivity of cells and tissues. This dual focus enhances our understanding of TBI, guiding future research toward innovative solutions and comprehensive care.

RESUMEN

The field of epigenetics studies the complex processes that regulate gene expression without altering the DNA sequence itself. It is well established that epigenetic modifications are crucial to cellular homeostasis and differentiation and play a vital role in hematopoiesis and immunity. Epigenetic marks can be mitotically and/or meiotically heritable upon cell division, forming the basis of cellular memory, and have the potential to be reversed between cellular fate transitions. Hence, over the past decade, there has been increasing interest in the role that epigenetic modifications may have on the outcomes of allogeneic hematopoietic transplantation and growing enthusiasm in the therapeutic potential these pathways may hold. In this brief review, we provide a basic overview of the types of epigenetic modifications and their biological functions, summarizing the current literature with a focus on hematopoiesis and immunity specifically in the context of allogeneic hematopoietic stem cell transplantation.

Asunto(s)

RESUMEN

Background: Transplant professionals are specialized in providing lifesaving organs to patients in whom organ failure including bone marrow, in a way that gives strong hope to patients and families. We should be aware of that patients with advanced medical conditions must have an advanced care planning (ACP) in place, though it is difficult to balance possible outcomes and hope. Case Description: This case report showed our serious illness conversation program (SICP) could transit gradually a patient with bone marrow transplant (BMT) and palliative care (PC) needs to hospice care. Initially, she had difficulty in accepting the relapse of her hematological disease, with the main focus on disease treatment and blood parameters. After the transition, this patient's symptoms got better, she felt more stable emotionally, her muscle strength improved, and her hope was reignited because she wanted to go to her daughter's wedding. All these have been facilitated by the PC team. Conclusions: In this case, use of SIC can be regarded as a tool to facilitate better communication and so lead to faster and smoother transition to PC and subsequently hospice care. The use of chemotherapy (e.g., vidaza), on the other hand, had important palliative roles including for symptom control, maintaining patient's mobility and quality of life. Despite her condition being gradually deteriorated, her grief could be largely resolved if most of the wishes fulfilled.

RESUMEN

ß3-adrenergic receptor (ß3-AR) is the last ß-adrenoceptor subtype identified. ß3-AR is widely expressed and regulates numerous physiological processes, and it is also a potential target for the treatment of many diseases, including cancers. For some types of cancers, bone marrow transplant (BMT) represents a valid therapeutic support, especially in the case of the necessity of high-dose chemotherapy and radiotherapy. For a successful BMT, it is necessary that a donor's hematopoietic stem cells (HSCs) correctly reach the staminal niche in the recipient's bone marrow (BM) and contribute to restore normal hematopoiesis in order to rapidly repopulate BM and provide all the healthy blood cells of which the patient needs. Generally, it takes a long time. Control and accelerate homing and engraftment of HSCs could represent a helpful approach to avoid the complications and undesirable effects of BMT. The evidence that the ß-adrenergic system has a role in the BM can be found in different studies, and this leads us to hypothesize that studying this field could be interesting to meliorate the most critical aspects of a BMT. Here, we collected the data present in literature about the role of ß3-AR in the BM with the purpose of discovering a possible utility of ß3-AR modulation in regulating HSC trafficking and hematopoiesis.

RESUMEN

Graft versus host disease (GvHD) is a life-threating complication of allogeneic hematopoietic stem cell transplantation, which is initially treated with high dose corticosteroids. Approximately 50% of acute GvHD cases are resistant to steroid treatment, and two-year mortality rates in those steroid-resistant patients exceed 80%. Chronic GvHD necessitates prolonged corticosteroid use, which is typically associated with limited efficacy and troublesome adverse effects. No agent has yet been established as an optimal second line therapy for either acute or chronic GvHD, but mesenchymal stromal cells (MSCs) have shown substantial promise. MSCs promote an immunosuppressive and immunoregulatory environment via multifactorial mechanisms, including: secretion of proteins/peptides/hormones; transfer of mitochondria; and transfer of exosomes or microvesicles containing RNA and other molecules. A large number of clinical studies have investigated MSCs from various sources as a treatment for acute and/or chronic GvHD. MSCs are generally safe and well tolerated, and most clinical studies have generated encouraging efficacy results, but response rates have varied. Confounding factors include variability in MSC donor types, production methodology and dose regimens, as well as variations in study design. It is well-established that extensive culture expansion of primary donor-derived MSCs leads to marked changes in functionality, and that there is a high level of inter-donor variability in MSC properties. However, recent manufacturing innovations may be capable of overcoming these problems. Further adequately powered prospective studies are required to confirm efficacy and establish the place of MSC therapy in the treatment of this condition.

Asunto(s)

RESUMEN

BACKGROUND: We undertook a study to determine the impact of Wiskott Aldrich Syndrome (WAS) and X-linked thrombocytopenia (XLT) and their therapies upon the health-related quality of life (HRQOL) of patients and their families. MATERIALS AND METHODS: We undertook a survey of patients and their families, who self-identified as having either WAS or XLT. We assessed the PedsQL™ 4.0, the parent proxy form, and the family impact module. These results were compared with normative data from previously published reports. RESULTS: Sixty-eight patients (29 patients completed both the PedsQL™ 4.0 and the parent proxy form; 21 completed only the PedsQL™ 4.0; and 18 completed only the parent proxy form) were included. In contrast to patient-reported outcomes, parents of patients who had a bone marrow transplant (BMT) reported that their children had better QOL scores compared with those who did not (82.6 vs. 73.3, p = 0.023). The QOL of patients vs. previously published normative data showed decreases in patient scores for psychosocial health (72.62 vs. 86.58, p = < 0.001), emotional functioning (69.91 vs. 82.64, p = < 0.001), social functioning (77.55 vs. 91.56, p = < 0.001), and school functioning (70.46 vs. 85.67, p = < 0.001). The family impact study revealed deficits in emotional, social, and cognitive functioning, communication, and worry. CONCLUSION: These results show that patients with WAS/XLT are significantly impacted with respect to QOL. BMT offered a better QOL for patients according to parents, but not as reported by the patients. Future studies should incorporate QOL to provide more data and a better understanding of outcomes for long-term survivors and decision-making regarding BMT.

Asunto(s)

RESUMEN

Background and aims: Primary immunodeficiencies (PID) are characterized by recurrent infections and increased risk of malignancies because of the reduced immunological surveillance against cancer cells and oncogenic viruses. Methods: We report the incidence of tumors among 690 patients with PID, diagnosed from 1990 until 2017 in Brescia. Results: Out of 690 patients, 25 patients (3.6%) developed 33 tumors. Of the 25 affected patients, 8 patients suffered from common variable immunodeficiency (CVID), 5 from combined immunodeficiency (CID), 3 from Ataxia-telangectasia (AT), 2 from Hermanksy-Pudlak type 2 (HSP2), 2 from gammaglobulinemia X-linked (XLA), 2 from Wiskott-Aldrich syndrome (WAS), 2 from Hyper IgE syndrome (HIES), 1 from severe combined immunodeficiency (SCID). The age at diagnosis ranged from 1 to 52 years, with a median age of 19.6 years. The time between the diagnosis of PID and onset of tumor was short, often <1 year between diagnosis and the appearance of cancer in the case of CID. Moreover, in two cases of CID, the diagnosis of cancer was made before the diagnosis of PID, so cancer was the onset clinical manifestation. Hematological malignancies were prevalent (22/33, 66.7%) with a minority of solid tumors (11/33, 33.33%). In particular Non-Hodgkin lymphomas were the most frequent (16/33, 48.48%). In total 13 patients survived (52%) and tumor was the main cause of death (7 cases). Two patients underwent BMT once the disease was in remission. Conclusions: Therefore, the correct management of tumors that arise in patients with primitive immunodeficiency still represents a challenge in the pediatric field. For this reason now it is mandatory to collect in a unique international registry the cases of malignancies in PID that could lead to a better understanding of the etiopathogenesis and of the biological and clinical characteristics of these tumors, with the aim of defining adequate preventive measures and guaranteeing an early diagnosis which also creating a shared and specific therapeutic strategy, with the prospect of obtaining a better prognosis for these patients.

RESUMEN

PURPOSE OF REVIEW: The use of prophylactic antibiotics during the neutropenic period in hematopoietic stem cell transplantation has been the standard of care at most institutions for the past 20 years. We sought to review the benefits and risks of this practice. RECENT FINDINGS: Emerging data has highlighted the potential costs of antibacterial prophylaxis, from selecting for antibiotic resistance to perturbing the microbiome and contributing to increase risk for Clostridium difficile and perhaps graft-versus-host-disease, conditions which may lead to poorer outcomes. Though in many studies prophylactic antibiotics improved morbidity and mortality outcomes, the potential harms including antibiotic resistance, Clostridium difficile infection, and alterations of the gut microbiome should be considered. Future studies aimed to better risk-stratify patients and limit the use of broad-spectrum antibiotics are warranted.

Asunto(s)