Dataset Information

Individualization of Hematopoietic Stem Cell Transplantation Using Alpha/Beta T-Cell Depletion.

ABSTRACT: Allogeneic hematopoietic stem cell transplantation (HSCT) is associated with several potentially lethal complications. Higher levels of CD3+ T-cells in the graft have been associated with increased risk of graft-versus-host disease (GVHD), but also beneficial graft-versus-leukemia effect and reduced infections. To tackle post-transplant complications, donor lymphocyte infusions have been used but with an increased risk of GVHD. To reduce this risk, we performed depletion of ?? T-cells and treated 12 patients post-HSCT suffering from infections and/or poor immune reconstitution. The ?? T-cell depleted cell products were characterized by flow cytometry. The median log depletion of ?? T-cells was -4.3 and the median yield of ?? T-cells was 73.5%. The median CD34+ cell dose was 4.4 × 10⁶/kg. All 12 patients were alive 3 months after infusion and after 1 year, two patients had died. No infusion-related side effects were reported and no severe acute GVHD (grade III-IV) developed in any patient post-infusion. Overall, 3 months after infusion 11 out of 12 patients had increased levels of platelets and/or granulocytes. In conclusion, we describe the use of ?? T-cell depleted products as stem cell boosters with encouraging results.

SUBMITTER: Radestad E

PROVIDER: S-EPMC6378311 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Individualization of Hematopoietic Stem Cell Transplantation Using Alpha/Beta T-Cell Depletion.

Rådestad Emelie E Sundin Mikael M Törlén Johan J Thunberg Sarah S Önfelt Björn B Ljungman Per P Watz Emma E Mattsson Jonas J Uhlin Michael M

Frontiers in immunology 20190211

Allogeneic hematopoietic stem cell transplantation (HSCT) is associated with several potentially lethal complications. Higher levels of CD3+ T-cells in the graft have been associated with increased risk of graft-versus-host disease (GVHD), but also beneficial graft-versus-leukemia effect and reduced infections. To tackle post-transplant complications, donor lymphocyte infusions have been used but with an increased risk of GVHD. To reduce this risk, we performed depletion of αβ T-cells and treate ...[more]

PMID: 30804948

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Project description:UnlabelledNew 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 β-cell function still has limitations. The aim of the study was to select the optimal quantitative index to assess pre-existing β-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 (Δβ-score > 0) and a nonresponder group (Δβ-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 β-cell reserves, and they were predictive for the clinical response after auto-HSCT.SignificanceThe β-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 β-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.

Project description:Hematopoietic stem cell transplantation (HSCT) requires significant infrastructure. Little is known about HSCT use and the factors associated with it on a global level.To determine current use of HSCT to assess differences in its application and to explore associations of macroeconomic factors with transplant rates on a global level.Retrospective survey study of patients receiving allogeneic and autologous HSCTs for 2006 collected by 1327 centers in 71 participating countries of the Worldwide Network for Blood and Marrow Transplantation. The regional areas used herein are (1) the Americas (the corresponding World Health Organization regions are North and South America); (2) Asia (Southeast Asia and the Western Pacific Region, which includes Australia and New Zealand); (3) Europe (includes Turkey and Israel); and (4) the Eastern Mediterranean and Africa.Transplant rates (number of HSCTs per 10 million inhabitants) by indication, donor type, and country; description of main differences in HSCT use; and macroeconomic factors of reporting countries associated with HSCT rates.There were 50 417 first HSCTs; 21 516 allogeneic (43%) and 28 901 autologous (57%). The median HSCT rates varied between regions and countries from 48.5 (range, 2.5-505.4) in the Americas, 184 (range, 0.6-488.5) in Asia, 268.9 (range, 5.7-792.1) in Europe, and 47.7 (range, 2.8-95.3) in the Eastern Mediterranean and Africa. No HSCTs were performed in countries with less than 300,000 inhabitants, smaller than 960 km(2), or having less than US $680 gross national income per capita. Use of allogeneic or autologous HSCT, unrelated or family donors for allogeneic HSCT, and proportions of disease indications varied significantly between countries and regions. In linear regression analyses, government health care expenditures (r(2) = 77.33), HSCT team density (indicates the number of transplant teams per 1 million inhabitants; r(2) = 76.28), human development index (r(2) = 74.36), and gross national income per capita (r(2) = 74.04) showed the highest associations with HSCT rates.Hematopoietic stem cell transplantation is used for a broad spectrum of indications worldwide, but most frequently in countries with higher gross national incomes, higher governmental health care expenditures, and higher team densities.

Dataset Information

Individualization of Hematopoietic Stem Cell Transplantation Using Alpha/Beta T-Cell Depletion.

Publications

Individualization of Hematopoietic Stem Cell Transplantation Using Alpha/Beta T-Cell Depletion.

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