LabMedica

Download Mobile App
Recent News Expo Clinical Chem. Molecular Diagnostics Hematology Immunology Microbiology Pathology Technology Industry Focus

High-Res Genotyping Improves Survival for Stem Cell Transplantation

By LabMedica International staff writers
Posted on 25 Apr 2019
Print article
Image: The PacBio RS II sequencer uses single molecule, real time (SMRT) sequencing technology (Photo courtesy of Pacific Biosciences).
Image: The PacBio RS II sequencer uses single molecule, real time (SMRT) sequencing technology (Photo courtesy of Pacific Biosciences).
Allogeneic hematopoietic cell transplantation (HCT) provides a curative treatment option for individuals with hematologic diseases. Recipients and donors are considered to be compatible or “well matched” if they share a high degree of genetic similarity at their human leukocyte antigen (HLA) loci.

HCT was limited to using HLA-identical related donors. Improved knowledge of the transplant process and therapeutic drug development, coupled with increased resolution of HLA typing and a significantly larger pool of volunteer unrelated donors (VUDs) worldwide, has meant that HCT with a VUD now offers comparable survival.

A team of scientists working with the Anthony Nolan Research Institute (London, UK) carried out a large retrospective study consisting of VUD–recipient HCT pairs transplanted between 1996 and 2011. The cohort comprised 891 adult and pediatric patients with hematologic malignancies from 32 UK allogeneic centers were included. Primary outcomes included overall survival (OS), non-relapse mortality (NRM), disease relapse, and acute graft-versus-host disease (aGVHD). Reporting of chronic GVHD follow-up data were insufficient to perform this analysis.

The team used methods of DNA-based HLA typing used previously included sequence specific oligonucleotide probing, Sanger sequencing-based typing, and reference strand-mediated conformational analysis. Retrospective UHR HLA typing of the cohort was performed for the six classic HLA loci using Pacific Biosciences Single Molecule Real-Time sequencing. To determine if there were viable alternatives to a 12/12 ultra-high resolution (UHR) HLA match, they chose to test the HLA-DPB1 T cell epitope (TCE) model of permissible mismatching in this data set.

The scientists reported that of 891 bone marrow donors and their respective, they found that when patients were matched at 12 alleles across six HLA genes, five-year survival was 55% compared to 40% for patients with any degree of mismatch. In addition, they found that 29% of patients who were previously thought to be matched via HLA typing methods that included Sanger sequencing and sequencing-specific oligonucleotide probing, actually had at least one mismatch when they were retrospectively analyzed using long-read sequencing on the Pacific Biosciences RS II platform. And, five-year survival among these patients was also lower at 30%.

Neema P Mayor, PhD, Head of Immunogenetics and lead author of the study, said, “We thought all of these individuals had been well matched, but they were not as well-matched as we had previously thought. Then, when the team analyzed the outcomes, they found that the individuals with mismatches that we didn't know about did significantly worse.” The study was published in the March 2019 issue of the journal Biology of Blood and Marrow Transplantation.

Related Links:
Anthony Nolan Research Institute

Gold Member
Chagas Disease Test
CHAGAS Cassette
Verification Panels for Assay Development & QC
Seroconversion Panels
New
Respiratory Bacterial Panel
Real Respiratory Bacterial Panel 2
New
HIV Test
Anti-HIV (1/2) Rapid Test Kit

Print article

Channels

Clinical Chemistry

view channel
Image: The tiny clay-based materials can be customized for a range of medical applications (Photo courtesy of Angira Roy and Sam O’Keefe)

‘Brilliantly Luminous’ Nanoscale Chemical Tool to Improve Disease Detection

Thousands of commercially available glowing molecules known as fluorophores are commonly used in medical imaging, disease detection, biomarker tagging, and chemical analysis. They are also integral in... Read more

Immunology

view channel
Image: The cancer stem cell test can accurately choose more effective treatments (Photo courtesy of University of Cincinnati)

Stem Cell Test Predicts Treatment Outcome for Patients with Platinum-Resistant Ovarian Cancer

Epithelial ovarian cancer frequently responds to chemotherapy initially, but eventually, the tumor develops resistance to the therapy, leading to regrowth. This resistance is partially due to the activation... Read more

Microbiology

view channel
Image: The lab-in-tube assay could improve TB diagnoses in rural or resource-limited areas (Photo courtesy of Kenny Lass/Tulane University)

Handheld Device Delivers Low-Cost TB Results in Less Than One Hour

Tuberculosis (TB) remains the deadliest infectious disease globally, affecting an estimated 10 million people annually. In 2021, about 4.2 million TB cases went undiagnosed or unreported, mainly due to... Read more

Pathology

view channel
Image: The ready-to-use DUB enzyme assay kits accelerate routine DUB activity assays without compromising data quality (Photo courtesy of Adobe Stock)

Sensitive and Specific DUB Enzyme Assay Kits Require Minimal Setup Without Substrate Preparation

Ubiquitination and deubiquitination are two important physiological processes in the ubiquitin-proteasome system, responsible for protein degradation in cells. Deubiquitinating (DUB) enzymes contain around... Read more

Technology

view channel
Image: The HIV-1 self-testing chip will be capable of selectively detecting HIV in whole blood samples (Photo courtesy of Shutterstock)

Disposable Microchip Technology Could Selectively Detect HIV in Whole Blood Samples

As of the end of 2023, approximately 40 million people globally were living with HIV, and around 630,000 individuals died from AIDS-related illnesses that same year. Despite a substantial decline in deaths... Read more

Industry

view channel
Image: The collaboration aims to leverage Oxford Nanopore\'s sequencing platform and Cepheid\'s GeneXpert system to advance the field of sequencing for infectious diseases (Photo courtesy of Cepheid)

Cepheid and Oxford Nanopore Technologies Partner on Advancing Automated Sequencing-Based Solutions

Cepheid (Sunnyvale, CA, USA), a leading molecular diagnostics company, and Oxford Nanopore Technologies (Oxford, UK), the company behind a new generation of sequencing-based molecular analysis technologies,... Read more
Sekisui Diagnostics UK Ltd.