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Does Mesenchymal Stromal Cell Count in Pre-autologous Hematopoietic Stem Cell Transplant Peripheral Blood and Apheresis Product Predict for Infectious Complications in the Post-transplant Period?

ABSTRACT: Mesenchymal stromal cells (MSC) have gained attention in the recent past considering their multipotentiality and organ-healing properties. Exogenous administration of MSC in the pre-hematopoietic stem cell transplant (HSCT) setting has been reported to enhance engraftment, heal graft-vs-host disease and increase infections in the post-HSCT period. In this study, we aimed to determine the effect of endogenous pre-HSCT MSC on the post-HSCT infectious complications in patients undergoing autologous-HSCT. The study included patients undergoing autologous-HSCT (n = 25; multiple myeloma-20, lymphoma-5). MSC were analyzed and quantified by flow cytometry in the peripheral blood (PB) at baseline, and in both PB and apheresis product (AP) following mobilization with growth factors. Pre-HSCT MSC (PB/AP) were correlated with the post-HSCT duration of febrile neutropenia and duration of antimicrobial drugs using Pearson's correlation co-efficient, and with the mucositis grade using Spearman's rank correlation. Pre-HSCT MSC (baseline and post-mobilization) correlated positively with the longer duration of febrile neutropenia and duration of antimicrobials used in the post-HSCT period (p < 0.05). Pre-HSCT MSC failed to correlate with post-HSCT engraftment and onset/severity/duration of oral and gastrointestinal mucositis. Endogenous pre-HSCT MSC counts might predict for increased infectious complications in the post autologous-HSCT setting.

SUBMITTER: Jain A

PROVIDER: S-EPMC8239070 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Does Mesenchymal Stromal Cell Count in Pre-autologous Hematopoietic Stem Cell Transplant Peripheral Blood and Apheresis Product Predict for Infectious Complications in the Post-transplant Period?

Jain Ankur A Khadwal Alka A Sachdeva Man Updesh Singh MUS Bose Praveen P Lad Deepesh D Bhattacharya Shalmoli S Prakash Gaurav G Malhotra Pankaj P Varma Neelam N Varma Subhash S

Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion 20210228 3

Mesenchymal stromal cells (MSC) have gained attention in the recent past considering their multipotentiality and organ-healing properties. Exogenous administration of MSC in the pre-hematopoietic stem cell transplant (HSCT) setting has been reported to enhance engraftment, heal graft-vs-host disease and increase infections in the post-HSCT period. In this study, we aimed to determine the effect of endogenous pre-HSCT MSC on the post-HSCT infectious complications in patients undergoing autologous ...[more]

PMID: 34267471

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Project description:Autologous hematopoietic stem cell transplantation (AHCT) improves survival in patients with multiple myeloma (MM) but is associated with morbidity and nonrelapse mortality (NRM). Hematopoietic cell transplant comorbidity index (HCT-CI) was shown to predict risk of NRM and survival after allogeneic transplantation. We tested the utility of HCT-CI as a predictor of NRM and survival in patients with MM undergoing AHCT. We analyzed outcomes of 1156 patients of AHCT after high-dose melphalan reported to the Center for International Blood and Marrow Transplant Research. Individual comorbidities were prospectively collected at the time of AHCT. The impact of HCT-CI and other potential prognostic factors, including Karnofsky performance score (KPS), on NRM and survival were studied in multivariate Cox regression models. HCT-CI score was 0, 1, 2, 3, and >3 in 42%, 18%, 13%, 13%, and 14% of the study cohort, respectively. Subjects were stratified into 3 risk groups: HCT-CI score of 0 (42%) versus HCT-CI score of 1 to 2 (32%) versus HCT-CI score > 2 (26%). Higher HCT-CI was associated with lower KPS < 90 (33% of subjects score of 0 versus 50% in HCT-CI score > 2). HCT-CI score > 2 was associated with melphalan dose reduction (22% versus 10% in score 0 cohort). One-year NRM was low at 2% (95% confidence interval, 1% to 4%) and did not correlate with HCT-CI score (P = .9). On multivariate analysis, overall survival was inferior in groups with HCT-CI score of 1 to 2 (relative risk, 1.37, [95% confidence interval, 1.01 to 1.87], P = .04) and HCT-CI score > 2 (relative risk, 1.5 [95% confidence interval, 1.09 to 2.08], P = .01). Overall survival was also inferior with KPS < 90 (P < .001), IgA subtype (P ≤ .001), those receiving >1 pretransplant induction regimen (P = .007), and those with resistant disease at the time of AHCT (P < .001). AHCT for MM is associated with low NRM, and death is predominantly related to disease progression. Although a higher HCT-CI score did not predict NRM, it was associated with inferior survival.

Project description:High-risk neuroblastoma has a poor prognosis, and research studies have shown that increasing the intensity of therapy improves outcomes. Autologous hematopoietic cell transplant (aHCT) as consolidation therapy confers a significant survival advantage but is accompanied by significant morbidity. Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication caused by endothelial injury that often leads to hemolytic anemia, microthrombotic platelet consumption, and renal injury. Here we investigated the incidence, potential risk factors, and sequelae of TA-TMA in patients with high-risk neuroblastoma. We conducted a retrospective chart review of all patients (n = 141) with neuroblastoma in our institutions who underwent aHCT from 2000 to 2017. Ten patients (7%) developed TA-TMA. The patients in the TA-TMA group were similar to the rest of the subjects in demographics, disease burden, prior therapies, renal function, and timing of transplant. The type of conditioning regimen was the only statistically significant pretransplant variable (P < .001). Six of 15 patients (40%) intended to receive tandem transplants (cyclophosphamide/thiotepa and then carboplatin/etoposide/melphalan (CEM)), 4 of 68 patients (6%) who received conditioning with single CEM, and none of the 56 patients who received busulfan/melphalan were diagnosed with TA-TMA. Patients with TA-TMA were more likely to require intensive care unit transfer, have a longer length of stay in the hospital, and experience a delay or change in their subsequent therapy. In our cohort overall, patients with a delay in therapy after transplant appeared to have a worse overall survival, although the difference was not statistically significant. Because of this high incidence and significant morbidity, we have implemented standardized screening for TA-TMA during and after transplant. We anticipate that screening will lead to earlier intervention and decreased severity of disease.

Project description:BackgroundPulmonary complications, including infections, are highly prevalent in patients after hematopoietic cell transplantation with chronic graft-vs-host disease. These comorbid diseases can make the diagnosis of early lung graft-vs-host disease (bronchiolitis obliterans syndrome) challenging. A quantitative method to differentiate among these pulmonary diseases can address diagnostic challenges and facilitate earlier and more targeted therapy.Study design and methodsWe conducted a single-center study of 66 patients with CT chest scans analyzed with a quantitative imaging tool known as parametric response mapping. Parametric response mapping results were correlated with pulmonary function tests and clinical characteristics. Five parametric response mapping metrics were applied to K-means clustering and support vector machine models to distinguish among posttransplantation lung complications solely from quantitative output.ResultsCompared with parametric response mapping, spirometry showed a moderate correlation with radiographic air trapping, and total lung capacity and residual volume showed a strong correlation with radiographic lung volumes. K-means clustering analysis distinguished four unique clusters. Clusters 2 and 3 represented obstructive physiology (encompassing 81% of patients with bronchiolitis obliterans syndrome) in increasing severity (percentage air trapping 15.6% and 43.0%, respectively). Cluster 1 was dominated by normal lung, and cluster 4 was characterized by patients with parenchymal opacities. A support vector machine algorithm differentiated bronchiolitis obliterans syndrome with a specificity of 88%, sensitivity of 83%, accuracy of 86%, and an area under the receiver operating characteristic curve of 0.85.InterpretationOur machine learning models offer a quantitative approach for the identification of bronchiolitis obliterans syndrome vs other lung diseases, including late pulmonary complications after hematopoietic cell transplantation.

Dataset Information

Does Mesenchymal Stromal Cell Count in Pre-autologous Hematopoietic Stem Cell Transplant Peripheral Blood and Apheresis Product Predict for Infectious Complications in the Post-transplant Period?

Publications

Does Mesenchymal Stromal Cell Count in Pre-autologous Hematopoietic Stem Cell Transplant Peripheral Blood and Apheresis Product Predict for Infectious Complications in the Post-transplant Period?

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