Immunomodulatory Effects of Bendamustine in Hematopoietic Cell Transplantation.
Ontology highlight
ABSTRACT:
SUBMITTER: Stokes J
PROVIDER: S-EPMC8038415 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Life-threatening risks associated with HLA-mismatched unrelated donor hematopoietic cell transplantation limit its general application for the treatment of blood diseases. The increased risks might be explained by undetected genetic variation within the highly polymorphic major histocompatibility complex (MHC) region. We retrospectively assessed each of 1108 MHC region single nucleotide polymorphisms (SNPs) in 2628 patients and their HLA-mismatched unrelated donors to determine whether SNPs are associated with the risk of mortality, disease-free survival, transplant-related mortality, relapse, and acute and chronic graft-versus-host disease (GVHD). Multivariate analysis adjusted for HLA mismatching and nongenetic variables associated with each clinical end point. Twelve SNPs were identified as transplantation determinants. SNP-associated risks were conferred by either patient or donor SNP genotype or by patient-donor SNP mismatching. Risks after transplantation increased with increasing numbers of unfavorable SNPs. SNPs that influenced acute GVHD were independent of those that affected risk of chronic GVHD and relapse. HLA haplotypes differed with respect to haplotype content of (un)favorable SNPs. Outcome after HLA-mismatched unrelated donor transplantation is influenced by MHC region variation that is undetected with conventional HLA typing. Knowledge of the SNP content of HLA haplotypes provides a means to estimate risks prior to transplantation and to lower complications through judicious selection of donors with favorable MHC genetics.
| S-EPMC3591807 | biostudies-literature
Project description:Immunomodulatory drugs (IMiDs) are effective therapeutics for multiple myeloma (MM), where in different clinical settings they exert their function both directly on MM cells and indirectly by modulating immune cell subsets, although with not completely defined mechanisms. Here we studied the role of IMiDs in the context of autologous hematopoietic stem cell transplantation on the T cell subset distribution in the bone marrow of newly diagnosed MM patients. We found that after transplantation pro-tumor Th17-Th1 and Th22 cells and their related cytokines were lower in patients treated with IMiDs during induction chemotherapy compared to untreated patients. Of note, lower levels of IL-17, IL-22, and related IL-6, TNF-α, IL-1β, and IL-23 in the bone marrow sera correlated with treatment with IMiDs and favorable clinical outcome. Collectively, our results suggest a novel anti-inflammatory role for IMiDs in MM.
| S-EPMC6348257 | biostudies-literature
Project description:Chemotherapeutic agents without cross-resistance to prior therapies may enhance PBSC collection and improve patient outcomes by exacting a more potent direct antitumor effect before autologous stem cell transplant. Bendamustine has broad clinical activity in transplantable lymphoid malignancies, but concern remains over the potential adverse impact of this combined alkylator-nucleoside analog on stem cell mobilization. We performed a prospective, nonrandomized phase II study including 34 patients with multiple myeloma (MM) (n=34; International Staging System (ISS) stages I (35%), II (29%) and III (24%); not scored (13%)) to evaluate bendamustine's efficacy and safety as a stem cell mobilizing agent. Patients received bendamustine (120?mg/m2 IV days 1, 2), etoposide (200?mg/m2 IV days 1-3) and dexamethasone (40?mg PO days 1- 4) (bendamustine, etoposide and dexamethasone (BED)) followed by filgrastim (10??g/kg/day SC; through collection). All patients (100%) successfully yielded stem cells (median of 21.60 × 106/kg of body weight; range 9.24-55.5 × 106/kg), and 88% required a single apheresis. Six nonhematologic serious adverse events were observed in 6 patients including: neutropenic fever (1, grade 3), bone pain (1, grade 3) and renal insufficiency (1, grade 1). In conclusion, BED safely and effectively mobilizes hematopoietic stem cells.
| S-EPMC5052091 | biostudies-literature
Project description:Sickle cell disease (SCD) is a severe autosomal recessively inherited disorder of the red blood cell characterized by erythrocyte deformation caused by the polymerization of the abnormal hemoglobin, which leads to erythrocyte deformation and triggers downstream pathological changes. These include abnormal rheology, vaso-occlusion, ischemic tissue damage, and hemolysis-associated endothelial dysfunction. These acute and chronic physiologic disturbances contribute to morbidity, organ dysfunction, and diminished survival. Hematopoietic cell transplantation (HCT) from HLA-matched or unrelated donors or haploidentical related donors or genetically modified autologous hematopoietic progenitor cells is performed with the intent of cure or long-term amelioration of disease manifestations. Excellent outcomes have been observed following HLA-identical matched related donor HCT. The majority of SCD patients do not have an available HLA-identical sibling donor. Increasingly, however, they have the option of undergoing HCT from unrelated HLA matched or related haploidentical donors. The preliminary results of transplantation of autologous hematopoietic progenitor cells genetically modified by adding a non-sickling gene or by genomic editing to increase expression of fetal hemoglobin are encouraging. These approaches are being evaluated in early-phase clinical trials. In performing HCT in patients with SCD, careful consideration must be given to patient and donor selection, conditioning and graft-vs.-host disease regimen, and pre-HCT evaluation and management during and after HCT. Sociodemographic factors may also impact awareness of and access to HCT. Further, there is a substantial decisional dilemma in HCT with complex tradeoffs between the possibility of amelioration of disease manifestations and early or late complications of HCT. The performance of HCT for SCD requires careful multidisciplinary collaboration and shared decision making between the physician and informed patients and caregivers.
| S-EPMC7813811 | biostudies-literature
Project description:A second allogeneic transplantation after a prior allogeneic (allo-allo) or autologous (auto-allo) hematopoietic cell transplantation (HCT) is usually performed for graft failure, disease recurrence, secondary malignancy, and, as planned, auto-allo transplantation for some diseases.We sought to describe the costs of second allogeneic HCT and evaluate their relationship with patient characteristics and posttransplantation complications. Clinical information and medical costs for the first 100 days after transplantation of 245 patients (allo-allo, 55; auto-allo, 190) who underwent a second HCT between 2004 and 2010 were collected.Median costs of the second allogeneic HCT were U.S. $151,000 (range, U.S. $62,000-405,000) for the allo-allo group and U.S. $109,000 (range, U.S. $26,000-490,000) for the auto-allo group. Median length of hospital stay was 23 days (range, 0-76) for the allo-allo group and 9 days (range, 0-96) for the auto-allo group. Only the year of transplantation and posttransplantation complications were significantly associated with costs in both groups when both pre- and posttransplantation variables were considered. The overall costs of the second HCT were higher than the first in the allo-allo group. For the auto-allo group, there was no difference between the costs whether preformed as a planned tandem or as salvage for relapse.Our results suggest that second allogeneic HCT is costly, particularly if it follows a prior allogeneic transplantation, and is driven by the costs of complications.
| S-EPMC3696423 | biostudies-other
Project description:Graft versus host disease (GVHD) remains one of the leading causes of morbidity and mortality associated with conventional allogeneic hematopoietic stem cell transplantation (HCT). The use of T-cell depletion significantly reduces this complication. Recent prospective and retrospective data suggest that, in patients with AML in first complete remission, CD34+ selected grafts afford overall and relapse-free survival comparable to those observed in recipients of conventional grafts, while significantly decreasing GVHD. In addition, CD34+ selected grafts allow older patients, and those with medical comorbidities or with only HLA-mismatched donors to successfully undergo transplantation. Prospective data are needed to further define which groups of patients with AML are most likely to benefit from CD34+ selected grafts. Here we review the history of T-cell depletion in AML, and techniques used. We then summarize the contemporary literature using CD34+ selection in recipients of matched or partially mismatched donors (7/8 or 8/8 HLA-matched), and provide a summary of the risks and benefits of using T-cell depletion.
| S-EPMC4470141 | biostudies-literature
Project description:BackgroundLong-term survivors of allogeneic hematopoietic stem cell transplantation (alloHSCT) are at a substantial risk of developing medical late effects. We aimed to determine the incidence of metabolic syndrome (MS), cardiovascular (CV) events, bone density loss, and fractures in a cohort of patients who underwent alloHSCT for hematologic disorders. The potential risk factors for MS, CV events, bone density loss, and fractures, as well as the sufficiency of existing monitoring measures in our institution, were also evaluated.MethodsA single-center, retrospective study was conducted. We included patients who underwent alloHSCT at the Singapore General Hospital between January 2011 and December 2016, were at least 21 years old, and had a minimum follow-up period of 6 months. Patients with MS-related data comprised the CV study population, whereas patients with bone loss-related data comprised the skeletal study population. Associations between risk factors and the development of MS or bone loss were assessed using a univariate analysis followed by multivariate logistic regression. All analyses were performed using SPSS version 23.ResultsA total of 91 patients were included in the CV study population, of which 13 (14.3%) had preexisting MS, 17 (18.7%) developed MS, and 5 (5.5%) developed CV events after alloHSCT. Thirty-one patients were included in the skeletal study population, of which 2 (6.5%) had preexisting bone loss, 23 (71.0%) developed osteopenia or osteoporosis, and 2 (6.5%) had a fracture. After adjusting for preexisting MS, pretransplant abdominal obesity (p=0.002), elevated triglyceride (p<0.001), and fasting hyperglycemia (p<0.001) significantly predicted MS on multivariate analyses. Only female sex predicted the risk of bone loss after alloHSCT on multivariate analyses after adjusting for preexisting osteopenia (p=0.02). Of the 174 patients who underwent alloHSCT during the study period, 83 (47.7%) and 143 (82.2%) patients had no MS-related data and bone loss-related data, respectively.ConclusionLong-term alloHSCT survivors are at an increased risk of MS, CV complications, and bone loss. This underscores the importance of close monitoring and timely interventions to reduce long-term morbidity and mortality.
| S-EPMC9847294 | biostudies-literature
Project description:The goal of this review is to look at the role of endothelial damage and dysfunction in the initiation and development of early complications that appear after hematopoietic cell transplantation (HCT). These early complications share overlapping clinical manifestations and the suspicion of underlying endothelial damage. Several studies using different approaches, such as animal and in vitro models, the analysis of soluble biomarkers and clinical findings have provided evidence of this endothelial dysfunction. Historically, the first complication in which the role of endothelial damage was elucidated was the veno-oclusive disease/sinusoidal obstructive syndrome. In the last two decades, increasing evidence of the implication of the endothelium in the pathophysiology of other syndromes such as capillary leak syndrome, transplant-associated microangiopathy, or even graft versus host disease has accumulated. This knowledge opens up potential pharmacologic interventions to prevent/and/or treat endothelial damage and, therefore, to improve the outcome of patients receiving HCT.
| S-EPMC8432381 | biostudies-literature
Project description:Due to its negative impact on the outcome of stem cell transplant (SCT) and solid organ transplant patients (SOT) CMV has been called "the troll of transplantation". One of the greatest advances in the management of SCT has been the introduction of the preemptive strategy. Since its introduction, the incidence of the viremia, as expected, remains unchanged but there has been a marked decline in the incidence of early CMV disease. However, in spite of the advances in prevention of CMV disease, CMV is still today an important cause of morbidity and mortality. Late CMV disease is still occurring in a significant proportion of patients and the so-called indirect effects of CMV are causing significant morbidity and mortality. Fortunately there have been several advances in the development of new antivirals, adoptive immunotherapy and DNA-CMV vaccines that might transform the management of CMV in the near future.
| S-EPMC4928522 | biostudies-literature
Project description:Histone deacetylase inhibitors are currently the most studied drugs because of their beneficial effects on inflammatory response. Emerging data from numerous basic studies and clinical trials have shown that histone deacetylase inhibitors can suppress immune-mediated diseases, such as graft-vs.-host disease (GVHD), while retaining beneficial graft-vs.-leukemia (GVL) effects. These drugs prevent and/or treat GVHD by modifying gene expression and inhibiting the production of proinflammatory cytokines, regulating the function of alloreactive T cells, and upregulating the function and number of regulatory T cells. Some of these drugs may become new immunotherapies for GVHD and other immune diseases.
| S-EPMC7959724 | biostudies-literature