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Expansion of Haematopoietic Stem and Progenitor Cells: Paving the Way for Next-Generation Haematopoietic Stem Cell Transplantation.

ABSTRACT: Haematopoietic stem cell transplantation (HSCT) is now an established practice with over 70,000 transplants performed annually, and over 1.5 million around the world so far. The practice of HSCT has improved over the years due to advances in conditioning regiments, preparatory practices for patients leading up to the transplant, graft versus host disease (GVHD) and infection prophylaxis, as well as a better selection of patients. However, in many instances, the stem cells supplied to the patient may not be adequate for optimal transplantation outcomes. This may be seen in a few areas including umbilical cord blood transplantation, inadequate bone marrow, peripheral blood stem cell harvest, or gene therapy. Growing and expanding HSCs in culture would provide an increase in cell numbers prior to stem cell infusion and accelerate haematopoietic recovery, resulting in improved outcomes. Several new technologies have emerged in recent years, which have facilitated the expansion of haematopoietic stem and progenitor cells (HSPCs) in culture with good outcomes in vitro, in vivo, and in clinical trials. In this review, we will outline some of the reasons for the expansion of HSPCs as well as the new technologies facilitating the advances in HSCT.

SUBMITTER: Bari S

PROVIDER: S-EPMC10427230 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Expansion of Haematopoietic Stem and Progenitor Cells: Paving the Way for Next-Generation Haematopoietic Stem Cell Transplantation.

Bari Sudipto S Chong Paul P Hwang William Ying Khee WYK

Blood cell therapy 20191125 4

Haematopoietic stem cell transplantation (HSCT) is now an established practice with over 70,000 transplants performed annually, and over 1.5 million around the world so far. The practice of HSCT has improved over the years due to advances in conditioning regiments, preparatory practices for patients leading up to the transplant, graft versus host disease (GVHD) and infection prophylaxis, as well as a better selection of patients. However, in many instances, the stem cells supplied to the patient ...[more]

PMID: 37588101

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Project description:Identification of targetable molecular changes is essential for selecting appropriate treatment in patients with advanced lung adenocarcinoma. Methods: In this study, a Sanger sequencing plus Fluorescence In Situ Hybridization (FISH) sequential approach was compared with a Next-Generation Sequencing (NGS)-based approach for the detection of actionable genomic mutations in an experimental cohort (EC) of 117 patients with advanced lung adenocarcinoma. Its applicability was assessed in small biopsies and cytology specimens previously tested for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutational status, comparing the molecular changes identified and the impact on clinical outcomes. Subsequently, an NGS-based approach was applied and tested in an implementation cohort (IC) in clinical practice. Using Sanger and FISH, patients were classified as EGFR-mutated (n = 22, 18.8%), ALK-mutated (n = 9, 7.7%), and unclassifiable (UC) (n = 86, 73.5%). Retesting the EC with NGS led to the identification of at least one gene variant in 56 (47.9%) patients, totaling 68 variants among all samples. Still, in the EC, combining NGS plus FISH for ALK, patients were classified as 23 (19.7%) EGFR; 20 (17.1%) KRAS; five (4.3%) B-Raf proto-oncogene (BRAF); one (0.9%) Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2); one (0.9%) STK11; one (0.9%) TP53, and nine (7.7%) ALK mutated. Only 57 (48.7%) remained genomically UC, reducing the UC rate by 24.8%. Fourteen (12.0%) patients presented synchronous alterations. Concordance between NGS and Sanger for EGFR status was very high (κ = 0.972; 99.1%). In the IC, a combined DNA and RNA NGS panel was used in 123 patients. Genomic variants were found in 79 (64.2%). In addition, eight (6.3%) EML4-ALK, four (3.1%), KIF5B-RET, four (3.1%) CD74-ROS1, one (0.8%) TPM3-NTRK translocations and three (2.4%) exon 14 skipping MET Proto-Oncogene (MET) mutations were detected, and 36% were treatable alterations. Conclusions: This study supports the use of NGS as the first-line test for genomic profiling of patients with advanced lung adenocarcinoma.

Dataset Information

Expansion of Haematopoietic Stem and Progenitor Cells: Paving the Way for Next-Generation Haematopoietic Stem Cell Transplantation.

Publications

Expansion of Haematopoietic Stem and Progenitor Cells: Paving the Way for Next-Generation Haematopoietic Stem Cell Transplantation.

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