Diagnosis and Management of Aplastic Anemia

Guinan, Eva C.

doi:10.1182/asheducation-2011.1.76

Cited by 42 publications

(28 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Successful outcomes of allogeneic hematopoietic stem cell transplantation correlate well with close HLA matching between the patient and the selected donor unit (14,24). Also, in many diseases early treatment including hematopoietic stem cell transplantation soon after diagnosis, correlates with superior outcomes (25). Listing donors and units with the corresponding high resolution HLA type can dramatically accelerate the identification of optimally compatible donors.…”

Section: Discussionmentioning

confidence: 99%

High-throughput, high-fidelity HLA genotyping with deep sequencing

Wang

Krishnakumar

Wilhelmy

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

175

144

View full text Add to dashboard Cite

Human leukocyte antigen (HLA) genes are the most polymorphic in the human genome. They play a pivotal role in the immune response and have been implicated in numerous human pathologies, especially autoimmunity and infectious diseases. Despite their importance, however, they are rarely characterized comprehensively because of the prohibitive cost of standard technologies and the technical challenges of accurately discriminating between these highly related genes and their many allelles. Here we demonstrate a high-resolution, and cost-effective methodology to type HLA genes by sequencing, which combines the advantage of long-range amplification, the power of high-throughput sequencing platforms, and a unique genotyping algorithm. We calibrated our method for HLA-A, -B, -C, and -DRB1 genes with both reference cell lines and clinical samples and identified several previously undescribed alleles with mismatches, insertions, and deletions. We have further demonstrated the utility of this method in a clinical setting by typing five clinical samples in an Illumina MiSeq instrument with a 5-d turnaround. Overall, this technology has the capacity to deliver low-cost, high-throughput, and accurate HLA typing by multiplexing thousands of samples in a single sequencing run, which will enable comprehensive disease-association studies with large cohorts. Furthermore, this approach can also be extended to include other polymorphic genes.hematopoietic stem cell transplantation | sequence-based typing H uman leukocyte antigen (HLA) genes encode cell-surface proteins that bind and display fragments of antigens to T lymphocytes. This helps to initiate the adaptive immune response in higher vertebrates and thus is critical to the detection and identification of invading microorganisms (1). Six of the HLA genes (HLA-A, -B, -C, -DQA1, -DQB1, and -DRB1) are extremely polymorphic and constitute the most important set of markers for matching patients and donors for bone marrow transplantation (2, 3). Specific HLA alleles have been found to be associated with a number of autoimmune diseases, such as multiple sclerosis (4), narcolepsy (5), celiac disease (6), rheumatoid arthritis (7), and type I diabetes (3,8). Alleles have also been noted to be protective in infectious diseases such as HIV (9, 10), and numerous animal studies have shown that these genes are often the major contributors to disease susceptibility or resistance (11-13).HLA genes are among the most polymorphic in the human genome, and the changes in sequence affect the specificity of antigen presentation and histocompatibility in transplantation. A variety of methodologies have been developed for HLA typing at the protein and nucleic acid level. Whereas earlier HLA typing methods distinguished HLA antigens, modern methods such as sequence-based typing (SBT) determine the nucleotide sequences of HLA genes for higher resolution. However, due to cost and time constraints, HLA sequencing technologies have traditionally focused on the most polymorphic regions encoding the peptide-...

show abstract

Section: Discussionmentioning

confidence: 99%

High-throughput, high-fidelity HLA genotyping with deep sequencing

Wang

Krishnakumar

Wilhelmy

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

175

144

View full text Add to dashboard Cite

show abstract

“…The phenotype of the Recql4 Δ/Δ hematopoietic system, with the exception of the sparing of the megakaryocyte lineage, shares many of the key features of aplastic anemia in humans (64,65). The genetic causes of aplastic anemia are largely unknown, and the diagnosis is largely by exclusion.…”

Section: Discussionmentioning

confidence: 99%

The Rothmund-Thomson syndrome helicase RECQL4 is essential for hematopoiesis

Smeets¹,

DeLuca²,

Wall³

et al. 2014

J. Clin. Invest.

View full text Add to dashboard Cite

“…1 These causes might include hypocellular ALL, which occurs in 1-2% of cases of childhood ALL; in such cases an overt leukemia usually develops within 3-9 months of the apparent BM failure (BMF). 2,3 The neutropenia is usually more pronounced than the thrombocytopenia and sometimes there is an increase in reticulin within the hypocellular BM.…”

Section: Diagnosismentioning

confidence: 99%

Management of acquired aplastic anemia in children

Korthof

Békássy

Hussein

2013

Bone Marrow Transplant

View full text Add to dashboard Cite

on behalf of the SAA-WP of the EBMT The diagnosis of aplastic anemia in children requires exclusion of a variety of inherited or acquired BM failure syndromes with similar phenotypes. An efficient diagnostic plan is important because time from diagnosis to 'final' treatment is directly related to outcome regardless of the therapeutic option chosen. The gold standard of therapy remains hematopoietic SCT with a graft of BM cells for those children with matched sibling donors. Conversely for children without a sibling donor the high response and markedly improved overall survival rates of combined immunosuppressive therapy have proven robust, especially when horse derived anti-thymocyte globuline plus ciclosporine A are used. Incomplete response, relapse and progression to myelodysplasia/ leukemia however have emerged as significant long-term issues. Improvements in outcome of alternative donor transplantation and the use of established and novel immunosuppressive agents provide multiple alternatives for treating refractory or relapsed patients. Regardless of the type of therapeutic approach, patients require centralized treatment in a center of excellence, ongoing monitoring for recurrence of disease and/or therapy-related immediate side effects and long-term effects.

show abstract

Diagnosis and Management of Aplastic Anemia

Cited by 42 publications

References 50 publications

High-throughput, high-fidelity HLA genotyping with deep sequencing

High-throughput, high-fidelity HLA genotyping with deep sequencing

The Rothmund-Thomson syndrome helicase RECQL4 is essential for hematopoiesis

Management of acquired aplastic anemia in children

Contact Info

Product

Resources

About