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The impact of pulmonary function in patients undergoing autologous stem cell transplantation.

ABSTRACT: High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is an established therapy for patients with hematological malignancies. The age of patients undergoing auto-HSCT, and therefore the co-morbidities, has increased during the last decades. However, the assessment of organ dysfunction prior auto-HSCT has not been well undertaken. Therefore, we analyzed retrospectively the association of clinical factors, lung and cardiac function with outcome and complications after conditioning with BEAM (BCNU/carmustin, etoposide, cytarabine, melphalan) and high-dose melphalan of patients undergoing auto-HSCT. In this study, we included 629 patients treated with auto-HSCT (334 conditioned with BEAM and 295 with high-dose melphalan) at our institution between 2007 and 2017. The median follow-up for patients conditioned with BEAM was 52 months (range:0.2-152) and with high-dose melphalan 50 months (range:0.5-149). In the multivariate analysis, we identified progressive disease, CO-diffusion capacity corrected for hemoglobin (DLCOcSB)<60% of predicted, Karnofsky performance status (KPS)≤80%, HCT-CI score≥4 and age>70 years to be associated with decreased overall survival (OS) in patients treated with BEAM. Similarly, DLCOcSB<60% of predicted, HCT-CI score ≥4 and age>60 years were identified in patients treated with high-dose melphalan. Abnormalities in DLCOcSB<60% of predicted were associated with chemotherapy with lung toxic substances, mediastinal radiotherapy, KPS≤80%, current/previous smoking and treatment at the intensive care unit. Patients with decreased DLCOcSB<60% of predicted had more frequently non-relapse mortality, including pulmonary cause of death. In summary, we have identified DLCOcSB<60% of predicted as an independent risk factor associated with decreased OS in patients conditioned with BEAM and high-dose melphalan prior auto-HSCT.

SUBMITTER: Duque-Afonso J

PROVIDER: S-EPMC8579263 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Multiple sclerosis is an immune mediated disease of the central nervous system. High-dose immunosuppression therapy followed by autologous hematopoietic stem cell transplantation (HDI/AHSCT) has emerged in the past few years as a new treatment strategy in patients with severe MS and refractory to conventional treatment. We characterized the molecular profile of T cells during immune reconstitution of these patients. Total RNA of CD4+ and CD8+ T cells from eight MS patients before transplantation and four patients at 6 months, 1 and 2 years after transplantation was processed for DNA microarray analysis. We investigated the molecular and biological function of DEG using bioinformatics tools and selected genes involved with immune response to measure quantitative gene expression by Real-time PCR. In CD8+ T cells, we measured the levels of expression of 23 genes modulated after transplantation: nine transcriptional factors (LEF1, FOXD1, CEBPD, JUN, JUNB, RELB, IFI16, AEBP1) including the translational factor PDCD4, the chemokine CCR7 and adhesion molecule L Selectin, three TNF superfamily members (TNFRSF4, TNFRSF19L, LT?), seven genes involved with molecular signaling (SOCS1, SOCS3, DGKH, CSNK1L1, IKB?, IKB?, IKB?), and the immune cell receptors CD47 and SIRPG. In CD4+ T cells, we evaluated the relative level of expression of STAT3, FcRL3, PDCD1, DGKH, CSNK1L1, L Selectin, CCR7 and PIAS3 that were all modulated after transplantation. We found significantly transcriptional changes in both T cells subsets during the first 2 years post-transplantation, but the analysis of CD8+ T cells revealed more extensive changes of genes involved in effector immune responses. In order to study the transcriptional changes in T cell subsets from MS patients submitted HID/HSCT, immunomagnetically purified CD4+ and CD8+ T-cells from the peripheral blood of 8 patients before transplantation and 4 patients 6 months, 1 year and 2 years after tranplantation, as well as from 4 healthy controls were isolated and processed the microarray assay according Agilent's protocol. The differential expressed genes, molecular characterization and networks analysis were evaluated using robust bioinformatic tools, then the real time PCR was done to validate the 27 immune related-genes.

Project description:New strategies of autologous hematopoietic stem cell transplantation (auto-HSCT) have gained much interest for the treatment of type 1 diabetes mellitus. However, assessing the clinical response and residual ?-cell function still has limitations. The aim of the study was to select the optimal quantitative index to assess pre-existing ?-cell function and to explore its predictive function for clinical response after auto-HSCT therapy. In this study, all of the patients who had undergone auto-HSCT were clustered into a responder group (??-score > 0) and a nonresponder group (??-score ? 0). We compared their quantitative metabolic indexes at baseline and performed receiver-operating characteristic (ROC) analysis to analyze the correlations between the indexes and clinical response. Kaplan-Meier analysis was conducted to compare the cumulative response durations in each quartile of the selected indexes. In an average of 15.13 ± 6.15 months of follow-up, 44 of 112 patients achieved a clinical response. The responder group had lower levels of fasting plasma glucose and quantitative insulin sensitivity check index (QUICKI) but higher levels of fasting C-peptide, fasting insulin, and homeostasis model assessments for insulin resistance (HOMA-IR). ROC analysis showed that HOMA-IR had the largest area under the curve (0.756), which was similar to that of QUICKI. Kaplan-Meier analysis further confirmed that the third quartile (1.3371-1.7018) of HOMA-IR or the second quartile (0.3523-0.3657) of QUICKI was preferential for a prolonged response. In conclusion, HOMA-IR and QUICKI could be optimal measurements for ?-cell reserves, and they were predictive for the clinical response after auto-HSCT.The ?-score was comprehensive and reliable in evaluating clinical response after autologous hematopoietic stem cell transplantation (HSCT). The homeostasis model assessments for insulin resistance and the quantitative insulin sensitivity check index could serve as precise assessments for residual ?-cell function and good predictors of clinical response. They might be used to select optimal clinical trial participants or predict the clinical response after auto-HSCT.

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The impact of pulmonary function in patients undergoing autologous stem cell transplantation.

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