Unlabelled: Hematopoietic cell transplantation (HCT) is a promising treatment for hematologic malignancies, but intensive conditioning leads to immunosuppression and susceptibility to healthcare-associated infections (HAI). Despite standard prevention measures, bloodstream infections (BSI) impact a significant percentage of immunocompromised HCT patients. Incidence of BSI can be mitigated by chlorhexidine gluconate (CHG) bathing-an underutilized infection-prevention strategy.
View Article and Find Full Text PDFWe describe the case of a 27-year-old male, previously healthy though with a social history notable for recreational cocaine use, who developed bone marrow failure due to aplastic anemia (AA) with associated serous fat atrophy (SFA). After the SFA was corrected with nutritional supplementation, the patient underwent successful allogeneic, haploidentical stem cell transplantation with a regimen designed to treat AA. To our knowledge, this is the first case of hematopoietic stem cell transplantation (HSCT) performed following correction of SFA.
View Article and Find Full Text PDFBackground: Almost all acquired severe aplastic anaemia is immune mediated and characterised by hypocellular bone marrow and ≥2 affected haematopoietic lineages. The optimal preparartive regimen for unrelated donor transplantation remains to be established. We aimed to study long-term outcomes after unrelated donor transplantation for severe aplastic anaemia with de-escalation of cyclophosphamide (Cy) dose in steps of 50 mg/kg (150, 100, 50, 0 mg/kg) in combination with total body irradiation (TBI) 2 Gy, anti-thymocyte globulin (ATG) and fludarabine.
View Article and Find Full Text PDFChronic graft-versus-host disease (cGVHD) is a debilitating, autoimmune-like syndrome that can occur after allogeneic hematopoietic stem cell transplantation. Constitutively activated B cells contribute to ongoing alloreactivity and autoreactivity in patients with cGVHD. Excessive tissue damage that occurs after transplantation exposes B cells to nucleic acids in the extracellular environment.
View Article and Find Full Text PDFPurpose: Sclerotic chronic GVHD (scGVHD) is characterized by progressive skin fibrosis and frequent refractoriness to available therapies. Aberrant activation of Hedgehog signaling in dermal fibroblasts has been implicated in scGVHD. Here, we report the results of two phase I/II studies (NCT03415867, GETH-TC; NCT04111497, FHD) that evaluated glasdegib, a smoothened antagonist, as a novel therapeutic agent in refractory scGVHD.
View Article and Find Full Text PDFThe use of electronic health/medical record (EMR) systems has streamlined medical practice and improved efficiency of clinical care in recent years. However, EMR systems are not generally well designed to support research and tracking of longitudinal outcomes across populations, which are particularly important in hematopoietic stem cell transplantation (HCT) and immune effector cell therapy (IEC), where data reporting to registries and regulatory agencies are often required. Since its formation in 2014, the HCT EMR user group has worked with a large EMR vendor (Epic) to develop many functionalities within the EMR to improve the care of HCT/IEC patients and facilitate the capture of HCT/IEC data in an easily interoperable format.
View Article and Find Full Text PDFAlloreactivity can drive autoimmune syndromes. After allogeneic hematopoietic stem cell transplantation (allo-HCT), chronic graft-versus-host disease (cGVHD), a B cell-associated autoimmune-like syndrome, commonly occurs. Because donor-derived B cells continually develop under selective pressure from host alloantigens, aberrant B cell receptor (BCR) activation and IgG production can emerge and contribute to cGVHD pathobiology.
View Article and Find Full Text PDFAllogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment for hematologic malignancies and nonmalignant disorders. Rapid immune reconstitution (IR) following allogeneic HCT has been shown to be associated with improved clinical outcomes and lower infection rates. A global phase 3 trial (ClinicalTrials.
View Article and Find Full Text PDFPurpose: To evaluate clinical outcomes and patterns of failure, specifically in regards to the central nervous system (CNS), in patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT) using total body irradiation (TBI)-based conditioning regimens.
Methods And Materials: All adult patients (aged ≥18 years) with ALL undergoing allogeneic HSCT using TBI-based conditioning regimens treated from 1995 to 2020 at Duke University Medical Center were evaluated. Various patient, disease, and treatment-related factors were collected, including CNS prophylaxis and treatment interventions.
J Natl Compr Canc Netw
February 2023
The NCCN Guidelines for Hematopoietic Cell Transplantation (HCT) provide an evidence- and consensus-based approach for the use of autologous and allogeneic HCT in the management of malignant diseases in adult patients. HCT is a potentially curative treatment option for patients with certain types of malignancies; however, recurrent malignancy and transplant-related complications often limit the long-term survival of HCT recipients. The purpose of these guidelines is to provide guidance regarding aspects of HCT, including pretransplant recipient evaluation, hematopoietic cell mobilization, and treatment of graft-versus-host disease-a major complication of allogeneic HCT-to enable the patient and clinician to assess management options in the context of an individual patient's condition.
View Article and Find Full Text PDFOmidubicel is an umbilical cord blood (UCB)-derived ex vivo-expanded cellular therapy product that has demonstrated faster engraftment and fewer infections compared with unmanipulated UCB in allogeneic hematopoietic cell transplantation. Although the early benefits of omidubicel have been established, long-term outcomes remain unknown. We report on a planned pooled analysis of 5 multicenter clinical trials including 105 patients with hematologic malignancies or sickle cell hemoglobinopathy who underwent omidubicel transplantation at 26 academic transplantation centers worldwide.
View Article and Find Full Text PDFNumerous recent advancements in T-cell based immunotherapies have revolutionized the treatment of hematologic malignancies. In the race towards the first approved allogeneic cellular therapy product, there is growing interest in utilizing natural killer (NK) cells as a platform for off-the-shelf cellular therapies due to their scalable manufacturing potential, potent anti-tumor efficacy, and superior safety profile. Allogeneic NK cell therapies are now being actively explored in the setting of hematopoietic stem cell transplantation and adoptive transfer.
View Article and Find Full Text PDFDespite the exciting advancement of novel therapies, chronic graft-versus-host disease (cGVHD) remains the most common cause of non-relapse mortality after allogeneic hematopoietic stem cell transplantation (HCT). Frontline treatment of cGVHD involves systemic steroids, which are associated with significant morbidities. We previously found that inhibition of spleen tyrosine kinase (SYK) with fostamatinib preferentially eradicated aberrantly activated B cells in both ex vivo studies of cGVHD patient B cells, as well as in vivo mouse studies.
View Article and Find Full Text PDFOmidubicel is an advanced cell therapy derived from umbilical cord blood (UCB) for use in allogeneic hematopoietic cell transplantation (HCT). A recent randomized phase 3 clinical trial demonstrated faster engraftment, shorter length of hospital stays, and lower rates of infection with omidubicel compared with standard UCB transplantation in patients with high-risk hematologic malignancies. Despite the proven clinical benefits of omidubicel, its impact on health-related quality of life (HRQL) from the patient's perspective has not been described.
View Article and Find Full Text PDFBackground: Relapsed severe aplastic anaemia is a marrow failure disorder with high morbidity and mortality. It is often treated with bone marrow transplantation at relapse post-immunosuppressive therapy, but under-represented minorities often cannot find a suitably matched donor. This study aimed to understand the 1-year overall survival in patients with relapsed or refractory severe aplastic anaemia after haploidentical bone marrow transplantation.
View Article and Find Full Text PDFAllogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for both malignant and nonmalignant hematologic diseases; however, reported rates of treatment-related mortality approach 30%. Outcomes are worse in patients who begin HCT with functional impairments. To detect such impairments, a geriatric assessment (GA) is recommended in adults age ≥65 years.
View Article and Find Full Text PDFPrimary myelofibrosis (PMF) is a BCR-ABL1 negative myeloproliferative neoplasm characterized by clonal proliferation of myeloid cells. This leads to reactive bone marrow fibrosis, ultimately resulting in progressive marrow failure, hepatosplenomegaly, and extramedullary hematopoiesis. PMF is considered the most aggressive of the BCR-ABL1 negative myeloproliferative neoplasms with the least favorable prognosis.
View Article and Find Full Text PDFPatients undergoing allogeneic (allo) and autologous (auto) hematopoietic cell transplantation (HCT) require extensive hospitalizations or daily clinic visits for the duration of their transplantation. Home HCT, wherein patients live at home and providers make daily trips to the patient's residence to perform assessments and deliver any necessary interventions, may enhance patient quality of life and improve outcomes. We conducted the first study of home HCT in the United States to evaluate this model in the US healthcare setting and to determine the effect on clinical outcomes and quality of life.
View Article and Find Full Text PDFHematopoietic cell transplant (HCT) is an increasingly common and curative treatment strategy to improve survival among individuals with malignant and nonmalignant diseases, with over one million HCTs having been performed worldwide. Neurocognitive dysfunction is a common and untoward consequence of HCT for many recipients, although few studies have examined the profile of neurocognitive impairments in HCT or their association with clinical features, such as frailty, or the incidence of pre-HCT neurocognitive impairments across all ages, which may influence post-HCT neurocognitive impairments. We examined the pattern and correlates of pre-transplant neurocognitive dysfunction in a prospective sample of adults undergoing HCT.
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