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Background Continuing antifungal prophylaxis (AFPx) to prevent invasive mold infections (IMIs) in recipients of allogeneic hematopoietic cell transplantation (alloHCT) after primary hospital discharge from alloHCT admission varies among transplant centers despite recommendations to continue prophylaxis through day +75. Characteristics driving AFPx prescribing at hospital discharge and outcomes are unknown. Methods In this retrospective analysis, we reviewed patients continuing AFPx vs no AFPx at hospital discharge. We included patients with a hospital stay ≥7 days and ≤40 days. We excluded patients with a history of IMI prior to alloHCT, new IMI during admission, or death prior to discharge. Our primary objective was incidence of probable or proven IMI per the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Our secondary objectives were nonrelapse mortality at day +100, overall survival at day +100, and characteristics driving AFPx discontinuation at hospital discharge. Results Of the 430 patients identified, 387 met inclusion criteria. At discharge, 56% (217/387) continued AFPx, and 44% (170/387) had no AFPx. At day +100, 3 probable IMI cases occurred in the group with continued AFPx vs 1 probable IMI case in the no-AFPx group (no proven IMI). Univariate analysis showed no difference in cumulative incidence of probable IMI (P =.440), nonrelapse mortality (P =.072), and overall survival (P =.855) between groups. Multivariable logistic regression demonstrated that patients were less likely to continue AFPx if they had a diagnosis other than acute myeloid leukemia, a length of stay ≤30 days, acute graft-vs-host disease grade 0 or 1, and corticosteroid use ≤5 days. Conclusions There was no difference in probable IMI at day +100 after alloHCT based on continuing vs discontinuing AFPx at hospital discharge after alloHCT admission supporting a risk-adapted prophylaxis approach. [ABSTRACT FROM AUTHOR]

Purpose: This study examines the risk of severe oral mucositis (SOM) in graft-versus-host disease prophylaxis (GVHD) compared to other agents in hematopoietic cell transplantation patients. Methods: A comprehensive search of four databases, including PubMed, Embassy, Web of Science, and Scopus, was conducted to identify studies reporting frequency and severity of oral mucositis in association with GVHD prophylactic regimens. RevMan 5.4 was used to perform the meta-analysis. Risk of bias assessment was carried out using the Rob-2 tool for randomized clinical trials (RCTs) and ROBINS-I tool for observational studies. Results: Twenty-five papers, including 11 RCTs and 14 observational studies, met the inclusion criteria. The pooled results from eight RCTs showed a higher risk of SOM in patients receiving MTX or MTX-inclusive GVHD prophylaxis versus non-MTX alternatives (RR = 1.50, 95% CI [1.20, 1.87], I2 = 36%, P = 0.0003). Mycophenolate mofetil (MMF) and post-transplant cyclophosphamide (Pt-Cy) consistently showed lower risk of mucositis than MTX. Folinic acid (FA) rescue and mini-dosing of MTX were associated with reduced oral mucositis severity. Conclusion: Patients receiving MTX have a higher SOM risk compared to other approaches to prevent GVHD, which should be considered in patient care. When appropriate, MMF, FA, and a mini-dose of MTX may be an alternative that is associated with less SOM. This work also underlines the scarcity of RCTs on MTX interventions to provide the best evidence-based recommendations. [ABSTRACT FROM AUTHOR]

This article examines the use of axicabtagene ciloleucel (axi-cel), a CAR T-cell therapy, as a second-line treatment for large B-cell lymphoma (LBCL) in a real-world setting. The study analyzes data from patients who received axi-cel at a single center and evaluates various outcomes such as survival rates, response rates, and side effects. The results indicate that axi-cel is effective and well-tolerated, providing valuable insights for its use in clinical practice. However, larger studies with longer follow-up are needed to further validate its efficacy and practicality. [Extracted from the article]

Neutropenic ulcerations are characterized by mucosal ulcerations which occur in the presence of neutropenia, suggesting a direct link between neutropenia and mucosal ulceration. An oral ulcer can be labeled as “neutropenic” only if the patients have primary (typically congenital) or secondary neutropenia, and neutropenia is the sole causative factor. Oral mucosal ulcers observed in patients undergoing oncologic therapy may also be termed as “neutropenic ulcers”, but the pathogenesis of these oral ulcers more likely involves mucosal events related to trauma, microbial factors, and direct cytotoxicity. In cancer patients, the early appearance of oral ulcers is often attributed to oral mucositis which is a condition primarily caused by the direct mucosal cytotoxicity of chemotherapeutic agents and radiation therapy. Oral ulcers that develop later during or after active cancer therapy may result from intraoral trauma and typically manifest on non-keratinized areas of the oral mucosa which are more susceptible to mucosal damage. In patients undergoing chemotherapy, factors such as disturbances in mucosal barrier function as well as bone marrow suppression lead to reduced neutrophil count and function, and can contribute to the development of oral ulcers. While the etiology of oral ulcers in cancer therapy receiving patients can vary, it is important to emphasize that the host’s response plays a crucial role in the progression and repair process of these lesions. This narrative review presents the etiopathogenesis, clinical presentation, and potential management approaches for oral ulcerations in neutropenic patients, with a particular focus on clarifying the usage of the term “neutropenic ulcer” since this term lacks diagnostic specificity and can be misleading in clinical practice regarding the underlying causes and treatment strategies. [ABSTRACT FROM AUTHOR]

We conducted a retrospective analysis of WT1-mutated acute myeloid leukemia (AML) patients who underwent allogeneic stem cell transplant. Thirty-seven patients with WT1-mutated AML were identified. Primary induction failure (40%) and early relapse rate (18%) after idarubicin/cytarabine (7 + 3) chemotherapy were observed. All patients with induction failure subsequently achieved CR with additional chemotherapy. There was no significant difference between outcomes after myeloablative vs. reduced intensity (Fludarabine/Melphalan [Flu/Mel]) conditioning regimens. RFS but not OS was significantly better in patients who received FLAG-IDA prior to transplant and/or a fludarabine-containing conditioning. In an independent ex vivo study, WT1-mutated AML samples exhibited greater sensitivity to fludarabine (p = 0.026) and melphalan (p = 0.0005) than non-WT1-mutated AML samples while there was no difference between sensitivity to cytarabine. Our data favor using a fludarabine-based induction for AML with WT1 mutation instead of 7 + 3. Fludarabine conditioning regimens for alloHCT showed better RFS but not OS. [ABSTRACT FROM AUTHOR]

This study presents follow-up of a prior study of patients with chronic symptomatic oral chronic graft-versus-host-disease (cGVHD) managed with photobiomodulation therapy (PBM therapy for 1 month. Here, we report long-term follow-up of a series of patients where PBM therapy in patients with oral cGVHD for maintenance follows the initial period of PBM therapy for continuing management. Patients and methods: We report continuing follow-up of 7 cases of oral cGVHD that were treated with PBM therapy. PBM therapy was continued in these patients with the goal of determining the best management schedule of PBM to maintain or improve control of each patient's symptoms and signs of oral cGVHD. Results: Oral sensitivity and mucosal changes of cGVHD were controlled with a continuing schedule of PBM therapy of up to 6–8-week treatment intervals in patients with continuing GVHD. These findings suggest that PBM therapy represents an additional approach for continuing management of oral cGVHD and that the frequency of treatment should be individualized for each patient to provide best control of oral findings. In one case weekly PBM treatment was continued, while in others, management on a monthly or bimonthly basis was associated with control of the oral condition. PBM may be individualized and provided based upon best control of the symptoms and signs of oral GVHD. [ABSTRACT FROM AUTHOR]

Introduction: Despite advances in therapy for multiple myeloma, patients have continued to experience relapse. We sought to better understand this. Objective: To identify factors that predict early relapse in patients with multiple myeloma who receive autologous hematopoietic peripheral stem cell transplant (HSCT). Methods: Retrospective analysis of Kaiser Permanente Southern California patients who received HSCTs between 2008 and 2012. Results: A total of 141 patients were included. Factors found to be associated with inferior progression-free survival were disease status less than complete response at the time of HSCT, no use of maintenance therapy after HSCT, International Staging System stage III, and high Freiburg Comorbidity Index. Disease status less than complete response, stage III, higher Freiburg Comorbidity Index, no use of maintenance therapy, and male sex were the most predictive factors for early relapse (< 18 months). Discussion: Our results identified a subgroup of high-risk individuals with multiple myeloma who will continue to do poorly after HSCT with the best available treatment using a combination of proteasome inhibitors and immunomodulatory drugs. These results highlight the need for consideration of alternative therapy in such instances. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to assess the impact of palifermin on oral mucositis (OM) and its sequelae in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) who were conditioned with fractionated total body irradiation (FTBI) and etoposide.Methods: This retrospective chart review study compared the effect of palifermin on the development of OM in patients who received this agent during an allo-HSCT (n = 99) to those who did not (n = 30). The primary end points were severity and duration of OM. Secondary end points included requirements for opioids, total parenteral nutrition (TPN), and intensive oral care; incidence of infection; length of hospital stay; and overall survival.Results: There was no significant difference in the incidence of all grades of OM, but incidence of severe OM was decreased in palifermin-exposed patients (34 vs 80 %, p < 0.0001). In patients who developed OM (all grades), the median duration of OM was shorter in palifermin-exposed patients (13 vs 18 days, p = 0.0001); there was no difference in the median duration of severe OM. Patients who received palifermin used less opioids and required a shorter duration of intensive oral care. There was no difference in duration of TPN, incidence of infection, length of hospital stay, and overall survival.Conclusions: Our findings demonstrated a significant benefit with the use of palifermin for allo-HSCT recipients who were conditioned with FTBI and etoposide. Palifermin can potentially improve quality of life for this patient population and reduce complications and resources used during the transplant process. A randomized clinical trial is required to confirm these results. [ABSTRACT FROM AUTHOR]

The functional status of cytotoxic T lymphocyte (CTL) populations recognizing cytomegalovirus intermediate-early antigen (IE1) and pp65 polypeptides was investigated in peripheral blood mononuclear cells from hematopoietic stem-cell transplant (HSCT) and solid organ transplant recipients. Combined flow-based CD107a/b degranulation/mobilization and intracellular cytokine (ICC) assays using peptide libraries as antigens indicated that a significantly higher proportion of pp65-specific CTLs were in a more mature functional state, compared with IE1-specific CTLs. Degranulation/multiple cytokine ICC assays also indicated that a significantly higher proportion of pp65-specific than IE1-specific CTLs secreted both interferon-g and tumor necrosis factor- a and possessed greater cytotoxic potential. These results support our earlier findings of functional differences between CTLs recognizing individual epitopes within the IE1 and pp65 antigens in healthy donors and HSCT recipients and extend them to a broader array of human leukocyte antigen-restricted responses to those antigens. We also provide evidence of a relationship between cytotoxic function and the ability of cytomegalovirus-specific CTLs to secrete multiple cytokines. [ABSTRACT FROM AUTHOR]

Entrainment of ventricular tochycardia (VT) may be manifest as fixed and progressive QRS fusion with ventricular and, rarely, atrial pacing. Only a single example of spontaneous VT entrainment by another rhythm, rapid atrioventricular nodal tachycardia, has been reported. This article describes an example of fixed and progressive QRS fusion between conducted sinus rhythm and VT consistent with entrainment. In contrast to entrainment with pacing, entrainment of VT by sinus rhythm occurred with drug-mediated arrhythmia slowing and demonstrated progressive QBS fusion at a constant cycle length. However, it did not demonstrate unfused but entrained QRS complexes. The resulting short PB interval and wide QRS mimicked a preexcited rhythm. [ABSTRACT FROM AUTHOR]

The use of granulocyte transfusions during amphotericin B treatment of invasive fungal infections in granulocytopenic patients is controversial because of concern about pulmonary complications from leukostasis. Moreover, the administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) to patients with active infections has been questioned because of reports that this cytokine inhibits neutrophil migration into areas of inflammation. We report a case in which the combined use of amphotericin B, granulocyte transfusions, and GM-CSF was safe and life-saving in a pancytopenic patient with disseminated fusarium infection. Histologic evidence of the migration of neutrophils into an area of active infection was found. [ABSTRACT FROM PUBLISHER]