Treatment of Severe Aplastic Anemia With Porcine Antihuman Lymphocyte Globulin.
Abstract Aplastic anemia (AA) is a bone marrow failure syndrome characterized with pancytopenia. Hematopoietic stem cell decreased, immune abnormalities and bone marrow microenvironment are the major pathogenesis of AA. Hematopoietic stem cell transplantation and immune-suppressive therapy are the first-line therapy for AA. Porcine anti-lymphocyte globulins (p-ALG) is a new product developed in China. Several studies have shown that p-ALG had a good role on AA. In this paper, we review the results of p-ALG on AA, including response rates, survival and side effects. PMID: 32183661 [PubMed - as supplied by publ...
Source: Current Pharmaceutical Design - March 17, 2020 Category: Drugs & Pharmacology Authors: Lv Q, Huiqin Z, Xiao N, Chunyan L, Zonghong S, Huaquan W Tags: Curr Pharm Des Source Type: research

Cancers, Vol. 12, Pages 597: mTOR and STAT3 Pathway Hyper-Activation is Associated with Elevated Interleukin-6 Levels in Patients with Shwachman-Diamond Syndrome: Further Evidence of Lymphoid Lineage Impairment
vo Corey Borgatti Cipolli Bezzerri Keywords: STAT3; mTOR; Bone Marrow Failure Syndromes; lymphocytes (Source: Cancers)
Source: Cancers - March 5, 2020 Category: Cancer & Oncology Authors: Vella D ’Aversa Api Breveglieri Allegri Giacomazzi Busilacchi Fabrizzi Cestari Sorio Bedini D ’Amico Bronte Poloni Benedetti Bovo Corey Borgatti Cipolli Bezzerri Tags: Article Source Type: research

Cancers, Vol. 12, Pages 597: mTOR and STAT3 Pathway Hyper-Activation is Associated with evated Interleukin-6 Levels in Patients with Shwachman-Diamond Syndrome: Further Evidence of Lymphoid Lineage Impairment
nte Antonella Poloni Antonio Benedetti Chiara Bovo Seth J. Corey Monica Borgatti Marco Cipolli Valentino Bezzerri Shwachman–Diamond syndrome (SDS) is a rare inherited bone marrow failure syndrome, resulting in neutropenia and a risk of myeloid neoplasia. A mutation in a ribosome maturation factor accounts for almost all of the cases. Lymphoid involvement in SDS has not been well characterized. We recently reported that lymphocyte subpopulations are reduced in SDS patients. We have also shown that the mTOR-STAT3 pathway is hyper-activated in SDS myeloid cell populations. Here we show that mTOR-STAT3 ...
Source: Cancers - March 5, 2020 Category: Cancer & Oncology Authors: Antonio Vella Elisabetta D ’Aversa Martina Api Giulia Breveglieri Marisole Allegri Alice Giacomazzi Elena Marinelli Busilacchi Benedetta Fabrizzi Tiziana Cestari Claudio Sorio Gloria Bedini Giovanna D ’Amico Vincenzo Bronte Antonella Poloni Antonio Be Tags: Article Source Type: research

Improving quality of life in hematopoietic stem cell transplant survivors through a positive psychology intervention
For some patients with advanced hematologic malignancies, non-malignant diseases and bone marrow failure syndromes, hematopoietic stem cell transplantation (HSCT) provides a potential for cure.1 Approximately 50,0002,3 HSCTs are performed worldwide and the number of transplants is projected to increase significantly in the next decade.4,5 Although recent advances in transplantation medicine have improved the morbidity and mortality following HSCT, the transplantation process is intensive and prior studies show a higher risk of treatment-related sequelae (e.g., cardiac disease, secondary malignancies, chronic graft vs. (Sou...
Source: Biology of Blood and Marrow Transplantation - February 20, 2020 Category: Hematology Authors: Hermioni L. Amonoo, Chareeni Kurukulasuriya, Kate Chilson, Lynn Onstad, Jeff C. Huffman, Stephanie J. Lee Source Type: research

Improving Quality of Life in Hematopoietic Stem Cell Transplantation Survivors Through a Positive Psychology Intervention
For some patients with advanced hematologic malignancies, nonmalignant diseases, and bone marrow failure syndromes, hematopoietic stem cell transplantation (HSCT) provides a potential for cure [1]. Approximately 50,000 HSCTs are performed worldwide [2,3], and the number of transplantations is projected to increase significantly in the next decade [4,5]. Although recent advances in transplantation medicine have improved morbidity and mortality following HSCT, the transplantation process is intensive, and previous studies have shown a higher risk of treatment-related sequelae (eg, cardiac disease, secondary malignancies, chr...
Source: Biology of Blood and Marrow Transplantation - February 20, 2020 Category: Hematology Authors: Hermioni L. Amonoo, Chareeni Kurukulasuriya, Kate Chilson, Lynn Onstad, Jeff C. Huffman, Stephanie J. Lee Source Type: research

Utility of clinical comprehensive genomic characterisation for diagnostic categorisation in patients presenting with hypocellular bone marrow failure syndromes.
In conclusion, genomic characterisation can improve diagnostic categorisation of patients presenting with hypoplastic BMF syndromes and should be routinely performed in this group of patients. PMID: 32054657 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - February 13, 2020 Category: Hematology Authors: Blombery P, Fox L, Ryland GL, Thompson ER, Lickiss J, McBean M, Yerneni S, Hughes D, Greenway A, Mechinaud F, Wood EM, Lieschke GJ, Szer J, Barbaro P, Roy J, Wight J, Lynch E, Martyn M, Gaff C, Ritchie D Tags: Haematologica Source Type: research

Tracking HSCs and their progeny using whole genome sequencing
Despite decades of progress in our understanding of hematopoiesis through the study of animal models and transplantation in humans, investigating physiological human hematopoiesis directly has remained challenging. Questions on the clonal structure of the human hematopoietic stem cell (HSC) pool, such as “how many HSCs are there?” and “do all HSC clones actively produce all blood cell types in equal proportions?” have remained open. These questions have inherent value for understanding normal human physiology, but also directly inform our comprehension of the process by which the system is s ubverte...
Source: Experimental Hematology - January 30, 2020 Category: Hematology Authors: Henry Lee-Six, David G. Kent Source Type: research

Tracking hematopoietic stem cells and their progeny using whole-genome sequencing
Despite decades of progress in our understanding of hematopoiesis through the study of animal models and transplantation in humans, investigating physiological human hematopoiesis directly has remained challenging. Questions on the clonal structure of the human hematopoietic stem cell (HSC) pool, such as “how many HSCs are there?” and “do all HSC clones actively produce all blood cell types in equal proportions?” remain open. These questions have inherent value for understanding normal human physiology, but also directly inform our comprehension of the process by which the system is subverte d to dr...
Source: Experimental Hematology - January 30, 2020 Category: Hematology Authors: Henry Lee-Six, David G. Kent Tags: Review Source Type: research

Epidemiology of aplastic anemia: a study of 1324 cases.
Conclusion: Younger age, male predominance and higher consanguinity point toward genetic factors in AA etiology among the South Asian population. PMID: 31906834 [PubMed - in process] (Source: Hematology)
Source: Hematology - January 9, 2020 Category: Hematology Tags: Hematology Source Type: research

Anesthetic Management of a Patient With Fanconi Anemia.
Authors: Nagano S, Tsukamoto M, Yokoyama T Abstract Fanconi anemia (FA) is a type of bone marrow failure syndrome based on an autosomal recessive inherited trait with increased predisposition for other cancers. It is extremely rare and is characterized by short stature, polydactyly, and pancytopenia. At present, the only effective treatment for FA is allogeneic hematopoietic stem cell transplantation (SCT). Chemotherapy is necessary prior to allogeneic SCT. Dental treatment is usually performed before chemotherapy to reduce potential infections. We experienced the anesthetic management of a 4-year-old boy diagnosed...
Source: Anesthesia Progress - January 2, 2020 Category: Anesthesiology Tags: Anesth Prog Source Type: research

Idiopathic aplastic anemia vs hypocellular myelodysplastic syndrome.
Authors: Durrani J, Maciejewski JP Abstract Proper diagnostic distinction of bone marrow failure syndromes can often be challenging. In particular, for older patients with idiopathic aplastic anemia (AA), differential diagnosis includes myelodysplastic syndrome (MDS), which can atypically present in a hypocellular form. In addition to blasts and overt dysplasia, the presence of chromosomal abnormalities and a spectrum of somatic mutations may be revealing. Both clonal cytogenetic aberrations and somatic mutations most typically correspond to a clonal myelodysplasia, but clonal somatic mutations have also recently b...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Monitoring and treatment of MDS in genetically susceptible persons.
Authors: Davies SM Abstract Genetic susceptibility to myelodysplastic syndrome (MDS) occurs in children with inherited bone marrow failure syndromes, including Fanconi anemia, Shwachman Diamond syndrome, and dyskeratosis congenita. Available evidence (although not perfect) supports annual surveillance of the blood count and bone marrow in affected persons. Optimal treatment of MDS in these persons is most commonly transplantation. Careful consideration must be given to host susceptibility to DNA damage when selecting a transplant strategy, because significant dose reductions and avoidance of radiation are necessary...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Unlicensed umbilical cord blood units provide a safe and effective graft source for a diverse population: A study of 2456 umbilical cord blood recipients.
Allogeneic hematopoietic stem cell transplantation (HCT) is a curative procedure for patients with some hematologic malignancies, bone marrow failure syndromes, and genetic diseases.1 The optimal donor is often an HLA-matched related donor (MRD), however only 30% of patients have a match in their family. There are over 20 million adult volunteer donors enrolled in the Be The Match ® (BTM) international unrelated donor registry, but it remains difficult for Black, Hispanic, and Caucasian patients of non-Western European ancestry to identify a matched unrelated donor (MUD) in the registry. (Source: Biology of Blood and M...
Source: Biology of Blood and Marrow Transplantation - November 19, 2019 Category: Hematology Authors: Karen Ballen, Brent R. Logan, Pintip Chitphakdithai, Michelle Kuxhausen, Stephen R. Spellman, Alexia Adams, Rebecca J. Drexler, Merry Duffy, Ann Kemp, Roberta King, Aleksandar Babic, Colleen Delaney, Chatchada Karanes, Joanne Kurtzberg, Lawrence Petz, And Source Type: research

Characterization and genotype-phenotype correlation of patients with Fanconi anemia in a multi-ethnic population.
Abstract Fanconi anemia, an inherited bone marrow failure syndrome, caused by mutations in DNA repair genes, is characterized by congenital anomalies, aplastic anemia, high risk of malignancies and extreme sensitivity to alkylating agents. We aimed to study the clinical presentation, molecular diagnosis and genotype-phenotype correlation among patients with Fanconi anemia from the Israeli inherited bone marrow failure registry. Overall, 111 patients of Arab (57%) and Jewish (43%) descent were followed for a median of 15 (range 0.1-49) years; sixty-three percent were offspring of consanguineous parents. One-hundred...
Source: Haematologica - September 26, 2019 Category: Hematology Authors: Steinberg-Shemer O, Goldberg TA, Yacobovich J, Levin C, Koren A, Revel-Vilk S, Ben-Ami T, Kuperman AA, Shkalim Zemer V, Toren A, Kapelushnik J, Ben-Barak A, Miskin H, Krasnov T, Noy-Lotan S, Dgany O, Tamary H Tags: Haematologica Source Type: research

Modeling hematopoietic disorders in zebrafish [AT A GLANCE]
ABSTRACT Zebrafish offer a powerful vertebrate model for studies of development and disease. The major advantages of this model include the possibilities of conducting reverse and forward genetic screens and of observing cellular processes by in vivo imaging of single cells. Moreover, pathways regulating blood development are highly conserved between zebrafish and mammals, and several discoveries made in fish were later translated to murine and human models. This review and accompanying poster provide an overview of zebrafish hematopoiesis and discuss the existing zebrafish models of blood disorders, such as myeloid and ly...
Source: DMM Disease Models and Mechanisms - September 6, 2019 Category: Biomedical Science Authors: Konantz, M., Schürch, C., Hanns, P., Müller, J. S., Sauteur, L., Lengerke, C. Tags: Zebrafish as a Disease Model AT A GLANCE Source Type: research

DKC1 is a transcriptional target of GATA1 and drives upregulation of telomerase activity in normal human erythroblasts.
Abstract Telomerase is a ribonucleoprotein complex that maintains the length and integrity of telomeres to enable ongoing cellular proliferation. Understanding the regulation of telomerase in hematopoietic cells is relevant to the pathogenesis of leukemia where telomerase is constitutively activated, as well as bone marrow failure syndromes that feature telomerase insufficiency. Past studies showing high levels of telomerase in human erythroblasts and a prevalence of anemia in disorders of telomerase insufficiency provide rationale for investigating telomerase regulation in erythroid cells. Here it is shown for th...
Source: Haematologica - August 14, 2019 Category: Hematology Authors: Richards LA, Kumari A, Knezevic K, Thoms JA, von Jonquieres G, Napier CE, Ali Z, O'Brien R, Marks-Bluth J, Maritz MF, Pickett HA, Morris J, Pimanda JE, MacKenzie KL Tags: Haematologica Source Type: research

Implications of revertant somatic mosaicism in bone marrow failure syndromes
We present examples of RM of haematopoietic cells in the context of inherited BMF syndromes with dramatically different clinical outcomes. Diamond Blackfan Anaemia (DBA) is an inherited BMF disorder caused by mutations/deletions in ribosomal proteins. We have a 9 year old male who required regular transfusions until he became transfusion independent at age 4. We identified a 184kb deletion on chromosome 12 encompassing 11 genes including RPS26 (known DBA gene). (Source: Experimental Hematology)
Source: Experimental Hematology - August 1, 2019 Category: Hematology Authors: Parvathy Venugopal, Milena Babic, Christopher Barnett, Sarah Bray, Anna Brown, Jesse Cheah, Richard D'Andrea, Jinghua Feng, Miriam Fine, Amee George, Michael Guandalini, Christopher Hahn, Ross Hannan, David Lawrence, Sarah Moore, Kerry Philips, Nicola Pop Tags: 3141 Source Type: research

Serum ferritin levels at diagnosis predict prognosis in patients with low blast count myelodysplastic syndromes.
pathic Bone Marrow Failure Syndromes Abstract Serum ferritin, a marker of systemic iron status, is considered a prognostic factor for patients with myelodysplastic syndromes (MDS), despite the lack of supporting evidence. We investigated the association between serum ferritin levels at diagnosis and the prognoses of Japanese MDS patients with bone marrow blasts 
Source: International Journal of Hematology - July 29, 2019 Category: Hematology Authors: Kawabata H, Usuki K, Shindo-Ueda M, Kanda J, Tohyama K, Matsuda A, Araseki K, Hata T, Suzuki T, Kayano H, Shimbo K, Chiba S, Ishikawa T, Arima N, Nohgawa M, Miyazaki Y, Kurokawa M, Arai S, Mitani K, Takaori-Kondo A, Japanese National Research Group on Idi Tags: Int J Hematol Source Type: research

Strategies for elevating hematopoietic stem cells expansion and engraftment capacity
Publication date: Available online 25 June 2019Source: Life SciencesAuthor(s): Mehdi Derakhshani, Hossein Abbaszadeh, Ali Akbar Movassaghpour, Amir Mehdizadeh, Majid Ebrahimi-Warkiani, Mehdi YousefiAbstractHematopoietic stem cells (HSCs) are a rare cell population in adult bone marrow, mobilized peripheral blood, and umbilical cord blood possessing self-renewal and differentiation capability into a full spectrum of blood cells. Bone marrow HSC transplantation has been considered as an ideal option for certain disorders treatment including hematologic diseases, leukemia, immunodeficiency, bone marrow failure syndrome, genet...
Source: Life Sciences - June 25, 2019 Category: Biology Source Type: research

Diagnosis and management of childhood aplastic anaemia
Aplastic anaemia (AA) is a rare and heterogeneous disorder. AA results in pancytopenia and a hypocellular bone marrow in the absence of an abnormal infiltrate, major dysplasia or marrow fibrosis. In children, most cases are idiopathic and caused by T lymphocyte-mediated destruction of haemopoietic stem and progenitor cells (HSPC's). Inherited bone marrow failure syndromes (IBMFS) account for around 20% of cases and have to be excluded. This can be challenging but has specific implications for management. (Source: Paediatrics and Child Health)
Source: Paediatrics and Child Health - June 21, 2019 Category: Pediatrics Authors: Katherine Clesham, Neha Bhatnagar, Sujith Samarasinghe Tags: Symposium: haematology Source Type: research

Soluble NKG2D Ligands Are Potential Biomarkers and Sentinels of Immune-Mediated Bone Marrow Injury in Bone Marrow Failure Syndromes
Immune-mediated processes are considered important in the pathogenesis of bone marrow failure syndromes (BFS). We previously reported that natural killer group 2D (NKG2D) ligands were expressed on pathological blood cells of patients with BFS and that NKG2D immunity may be involved in bone marrow failure. In addition to membranous NKG2D ligands on the cell surface, soluble NKG2D ligands can exist in plasma. We therefore examined the relationship between soluble NKG2D ligands and blood cell counts in 86 patients with BFS, including aplastic anemia, myelodysplastic syndrome with single lineage dysplasia, and paroxysmal noctu...
Source: Acta Haematologica - June 19, 2019 Category: Hematology Source Type: research

Soluble NKG2D Ligands Are Potential Biomarkers and Sentinels of Immune-Mediated Bone Marrow Injury in Bone Marrow Failure Syndromes.
Abstract Immune-mediated processes are considered important in the pathogenesis of bone marrow failure syndromes (BFS). We previously reported that natural killer group 2D (NKG2D) ligands were expressed on pathological blood cells of patients with BFS and that NKG2D immunity may be involved in bone marrow failure. In addition to membranous NKG2D ligands on the cell surface, soluble NKG2D ligands can exist in plasma. We therefore examined the relationship between soluble NKG2D ligands and blood cell counts in 86 patients with BFS, including aplastic anemia, myelodysplastic syndrome with single lineage dysplasia, an...
Source: Acta Haematologica - June 19, 2019 Category: Hematology Authors: Murata S, Mushino T, Hosoi H, Kuriyama K, Nishikawa A, Nagakura S, Horikawa K, Yonemura Y, Nakakuma H, Sonoki T, Hanaoka N Tags: Acta Haematol Source Type: research

Clonal Hematopoiesis and Risk of Acute Myeloid Leukemia
Publication date: Available online 24 May 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Pinkal Desai, Duane Hassane, Gail J. RobozAbstractAcute Myeloid Leukemia, the most common form of acute leukemia in adults, is an aggressive hematopoietic stem cell malignancy that is associated with significant morbidity and mortality. Though AML generally presents de novo, risk factors include exposure to chemotherapy and/or radiation, as well as both familial and acquired bone marrow failure syndromes. Clonal Hematopoiesis (CH) refers to an expansion of blood or marrow cells resulting from somatic mutations ...
Source: Best Practice and Research Clinical Haematology - May 25, 2019 Category: Hematology Source Type: research

Telomerase insufficiency induced telomere erosion accumulation in successive generations in dyskeratosis congenita family
ConclusionsOur study identified three clinical pathologicTERT mutations and implied that telomere erosion might be accumulated through successive generations, contributing to the severity of DC in the younger generation. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - May 22, 2019 Category: Genetics & Stem Cells Authors: Caixia He, Shuang Jing, Congling Dai, Chaofeng Tu, Zhenhua Tan, Juan Du, Guang ‐Xiu Lu, Ge Lin, Sicong Zeng Tags: ORIGINAL ARTICLE Source Type: research

Novel variants in Iranian individuals suspected to have inherited red blood cell disorders, including bone marrow failure syndromes.
Abstract PMID: 31097629 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - May 16, 2019 Category: Hematology Authors: Neishabury M, Mehri M, Fattahi Z, Najmabadi H, Azarkeivan A Tags: Haematologica Source Type: research

Eltrombopag maintains human hematopoietic stem and progenitor cells under inflammatory conditions mediated by IFN-{gamma}
The proinflammatory cytokine interferon- (IFN-) has been implicated in human hematopoietic stem and progenitor cell (HSPC) depletion in immune-mediated bone marrow failure syndromes. We show that IFN- specifically prevents full engagement of thrombopoietin (TPO), a primary positive regulator of HSPC survival, to its receptor (c-MPL) via steric occlusion of the low-affinity binding site, contributing to perturbation of TPO-induced signaling pathways and decreased survival of human HSPCs. Eltrombopag, a synthetic small molecule mimetic of TPO that interacts with c-MPL at a position distinct from the extracellular binding sit...
Source: Blood - May 9, 2019 Category: Hematology Authors: Alvarado, L. J., Huntsman, H. D., Cheng, H., Townsley, D. M., Winkler, T., Feng, X., Dunbar, C. E., Young, N. S., Larochelle, A. Tags: Hematopoiesis and Stem Cells Source Type: research

The IL-12 Cytokine and Receptor Family in Graft-vs.-Host Disease
Allogeneic hematopoietic cell transplantation (allo-HCT) is performed with curative intent for high risk blood cancers and bone marrow failure syndromes; yet the development of acute and chronic graft-versus-host disease (GVHD) remain preeminent causes of death and morbidity. The IL-12 family of cytokines is comprised of IL-12, IL-23, IL-27, IL-35 and IL-39. This family of cytokines is biologically distinct in that they are composed of functional heterodimers, which bind to cognate heterodimeric receptor chains expressed on T cells. Of these, IL-12 and IL-23 share a common β subunit cytokine, p40, as well as a common ...
Source: Frontiers in Immunology - May 8, 2019 Category: Allergy & Immunology Source Type: research

Hereditary Myeloid Malignancies
Publication date: Available online 3 May 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Hind Rafei, Courtney D. DiNardoAbstractMyelodysplastic syndromes and acute myeloid leukemia are sporadic for the majority of cases affecting the elderly population. Inherited cases, however, do occur. Genetic predispositions to myeloid malignancies can be classified into three categories: familial cancer syndromes associated with increased risk of various malignancies including myelodysplasia and acute myeloid leukemia such as Li-Fraumeni syndrome and constitutional mismatch repair deficiency (CMMRD); germline m...
Source: Best Practice and Research Clinical Haematology - May 5, 2019 Category: Hematology Source Type: research

26. Uncovering the genetic etiology of inherited bone marrow failure syndromes using a custom-designed NGS panel
Introduction: Inherited bone marrow failure syndromes (IBMFSs) are a group of heterogeneous disorders characterized by failure to generate enough blood cells in bone marrow. IBMFSs account for ∼30% of pediatric bone marrow failure and are associated with developmental abnormalities and increased cancer risk. We have developed and clinically validated a large NGS-based panel to facilitate the diagnosis of IBMFSs. (Source: Cancer Genetics and Cytogenetics)
Source: Cancer Genetics and Cytogenetics - April 1, 2019 Category: Genetics & Stem Cells Authors: Fumin Lin, Fengqi Chang, Kajia Cao, Helge Hartung, Michele Lambert, Lea Surrey, Minjie Luo, Michele Paessler, Kristin Zelley, Daniel Gallo, Elizabeth Denenberg, Edward Romasko, Xiaonan Zhao, Tim Olson, Marilyn Li Source Type: research

MDS overlap disorders and diagnostic boundaries
Myelodysplastic syndromes (MDS) are clonal diseases defined by clinical, morphologic, and genetic features often shared by related myeloid disorders. The diagnostic boundaries between these diseases can be arbitrary and not necessarily reflective of underlying disease biology or outcomes. In practice, measures that distinguish MDS from related disorders may be difficult to quantify and can vary as disease progression occurs. Patients may harbor findings that are not consistent with a single diagnostic category. Several overlap disorders have been formally described, such as the myelodysplastic/myeloproliferative neoplasms ...
Source: Blood - March 7, 2019 Category: Hematology Authors: Tanaka, T. N., Bejar, R. Tags: Hematopoiesis and Stem Cells, Myeloid Neoplasia, Review Articles, Review Series, Clinical Trials and Observations Source Type: research

18 F-FLT PET/MRI for bone marrow failure syndrome-initial experience
Conclusion18F-FLT PET can be used to noninvasively assess whole-body bone marrow proliferative activity and DWI may reflect the different aspects of bone marrow pathophysiology from18F-FLT PET.18F-FLT PET/MRI is useful for the diagnosis and monitoring of BMFS, except for the differentiation between non-severe AA and hypo-MDS, and the prediction of progression to leukemia. (Source: EJNMMI Research)
Source: EJNMMI Research - February 15, 2019 Category: Radiology Source Type: research

The Hematopoietic Cell Transplant Comorbidity Index predicts survival after allogeneic transplant for nonmalignant diseases
In conclusion, this is the largest study to date reporting on patients with nonmalignant diseases demonstrating HCT-CI scores ≥3 that had inferior survival after HCT, except for patients with hemoglobinopathies. Our findings suggest that using the HCT-CI score, in addition to disease-specific factors, could be useful when developing treatment plans for nonmalignant diseases. (Source: Blood)
Source: Blood - February 14, 2019 Category: Hematology Authors: Thakar, M. S., Broglie, L., Logan, B., Artz, A., Bunin, N., Burroughs, L. M., Fretham, C., Jacobsohn, D. A., Loren, A. W., Kurtzberg, J., Martinez, C. A., Mineishi, S., Nelson, A. S., Woolfrey, A., Pasquini, M. C., Sorror, M. L. Tags: Transplantation, Clinical Trials and Observations Source Type: research

Dynamics of the Gut Microbiota in Children Receiving Selective or Total Gut Decontamination Treatment During Hematopoietic Stem Cell Transplantation
Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment option for patients with various life-threatening diseases such as high-risk hematological malignancies, acquired or inborn bone marrow failure syndromes, severe immune deficiencies, and hemoglobinopathies. Graft-versus-Host disease (GvHD) is a severe and frequent complication of HSCT, characterized by severe organ damage due the initiation of an immune response of donated tissue (the graft) towards host tissue. The exact pathophysiology of GvHD is not known. (Source: Biology of Blood and Marrow Transplantation)
Source: Biology of Blood and Marrow Transplantation - February 4, 2019 Category: Hematology Authors: Vincent Bekker, Romy D. Zwittink, Cornelis W. Knetsch, Ingrid M.J.G. Sanders, Dagmar Berghuis, Peter J. Heidt, Jaak M.J.J. Vossen, Willem M. de Vos, Clara Belzer, Robbert G.M. Bredius, Peter J. van ‘t Hof, Arjan C. Lankester, Ed J. Kuijper Source Type: research

What are the most promising new agents in myelodysplastic syndromes?
Purpose of review Myelodysplastic syndromes (MDS) are a diverse group of clonal disorders of hematopoietic stem or progenitor cells that represent the most common class of acquired bone marrow failure syndromes in adults. Despite significant improvement in the pathologic insight into this group of disorders, therapeutic options remain limited and allogeneic hematopoietic stem-cell transplantation is the only treatment that can induce long-term remission in patients with MDS. The goals of therapy for MDS are based on disease prognostication, with a focus of minimizing transfusion dependence and preserving quality of life ...
Source: Current Opinion in Hematology - February 1, 2019 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Multidisciplinary, evidence-based consensus guidelines for human papillomavirus (HPV) vaccination in high-risk populations, Spain, 2016.
CONCLUSIONS: Data concerning non-routine HPV vaccination in populations with a high risk of HPV infection and associated lesions were scarce. We have developed a document to evaluate and establish evidence-based guidelines on HPV vaccination in high-risk populations in Spain, based on best available scientific evidence. PMID: 30782268 [PubMed - in process] (Source: Euro Surveill)
Source: Euro Surveill - February 1, 2019 Category: Infectious Diseases Authors: Martínez-Gómez X, Curran A, Campins M, Alemany L, Rodrigo-Pendás JÁ, Borruel N, Castellsagué X, Díaz-de-Heredia C, Moraga-Llop FA, Del Pino M, Torné A Tags: Euro Surveill Source Type: research

Reduced Intensity Alternative Donor Transplantation with Post-Transplant Cyclophosphamide Is Highly Effective in Inherited Immune Deficiencies and Bone Marrow Failure Syndromes
Allogeneic Bone Marrow Transplantation (alloBMT) is the only cure for many primary immune deficiencies (PID) and inherited bone marrow failure syndromes (IBMFS). There has been great success using HLA-matched related donors; however, use of alternative donors has been associated with increased graft failure, graft versus host disease (GVHD), and transplant related mortality (TRM). BMT using reduced intensity conditioning (RIC), alternative donors, and post-transplantation cyclophosphamide (PT/Cy) has been previously reported by our institution with no TRM, and low rates of graft failure and GVHD. (Source: Biology of Blood ...
Source: Biology of Blood and Marrow Transplantation - January 31, 2019 Category: Hematology Authors: Orly R. Klein, Samantha Bapty, Allen R. Chen, Christopher Gamper, Mary Josephine Holuba, Howard Lederman, Nicolas J. Llosa, Nancy Robey, Elias T. Zambidis, Kenneth R. Cooke, Heather J. Symons Tags: 464 Source Type: research

Disease modelling of bone marrow failure syndromes using iPS cell-derived hematopoietic stem progenitor cells
Aplastic anemia (AA) is a life-threatening bone marrow failure (BMF) disorder, resulting in bone marrow hypoplasia, infection and hemorrhage, and severe peripheral pancytopenia. Although the most cases of AA are acquired and are associated with the autoimmune destruction of hematopoietic stem progenitor cells (HSPCs) in the BM, in some cases the BMF is caused by genetic or inherited anomalies that impair hematopoiesis [1]. The destruction or dysfunction of HSPCs in the BM of patients with BMFSs limits to study of these disorders since the use of conventional  in vitro HSPC culture or in vivo animal mode...
Source: Experimental Hematology - January 18, 2019 Category: Hematology Authors: Mahmoud I. Elbadry, J. Luis Espinoza, Shinji Nakao Source Type: research

Disease modeling of bone marrow failure syndromes using iPSC-derived hematopoietic stem progenitor cells
Aplastic anemia (AA) is a life-threatening bone marrow failure (BMF) disorder, resulting in bone marrow hypoplasia, infection and hemorrhage, and severe peripheral pancytopenia. Although the most cases of AA are acquired and associated with the autoimmune destruction of hematopoietic stem progenitor cells (HSPCs) in the BM, in some cases, the BMF is caused by genetic or inherited anomalies that impair hematopoiesis [1]. The destruction or dysfunction of HSPCs in the BM of patients with BMF syndromes (BMFSs) limits the study of these disorders because the use of conventional in vitro HSPC culture or in vivo animal models fo...
Source: Experimental Hematology - January 18, 2019 Category: Hematology Authors: Mahmoud I. Elbadry, J. Luis Espinoza, Shinji Nakao Source Type: research

A diagnosis of discernment: Identifying a novel ATRX mutation in myelodysplastic syndrome with acquired α-thalassemia
Publication date: Available online 9 January 2019Source: Cancer GeneticsAuthor(s): Jedrzej Wykretowicz, Yeohan Song, Brooke McKnight, Sung Won Choi, John Magenau, Radhika Takiar, Paul El Tomb, David Ginsburg, Dale Bixby, Rami KhoriatyAbstractMyelodysplastic syndromes (MDS) are a heterogeneous category of myeloid neoplasms that represent the most common class of acquired bone marrow failure syndromes in adults. MDS is typically associated with a hypoproliferative macrocytic anemia, but atypical findings on initial diagnostic evaluations can raise concern for a distinct pathophysiological process and lead to the investigatio...
Source: Cancer Genetics - January 10, 2019 Category: Cancer & Oncology Source Type: research

A diagnosis of discernment: Identifying a novel ATRX mutation in myelodysplastic syndrome with acquired α-thalassemia
Myelodysplastic syndromes (MDS) are a heterogeneous category of myeloid neoplasms that represent the most common class of acquired bone marrow failure syndromes in adults. MDS is typically associated with a hypoproliferative macrocytic anemia, but atypical findings on initial diagnostic evaluations can raise concern for a distinct pathophysiological process and lead to the investigation of alternative etiologies. Here, we report a case of MDS with a concomitant hypoproliferative microcytic and hypochromic anemia that led to the identification of acquired hemoglobin H due to a novel somatic ATRX mutation. (Source: Cancer Ge...
Source: Cancer Genetics and Cytogenetics - January 9, 2019 Category: Genetics & Stem Cells Authors: Jedrzej Wykretowicz, Yeohan Song, Brooke McKnight, Sung Won Choi, John Magenau, Radhika Takiar, Paul El Tomb, David Ginsburg, Dale Bixby, Rami Khoriaty Tags: Case Report Source Type: research

Human iPSC-based model of severe congenital neutropenia reveals elevated UPR and DNA damage in CD34+ cells preceding leukemic transformation
Severe congenital neutropenia (CN) is a mono-lineage pre-leukemia bone marrow failure syndrome, characterized by early onset of neutropenia and severe infections owing to promyelocytic maturational arrest in the bone marrow [1,2]. CN is a heterogeneous disease caused by mutations in a number of genes, including ELANE [3] (most common [1]), HAX1 [4], CSF3R [5,6], JAGN1 [7], G6PC3 [8], TCIRG1 [9] and others. In most cases, ELANE mutations are missense mutations that are distributed throughout all five exons of the ELANE gene, although a majority of mutations are found in exons 4 and 5 [10]. (Source: Experimental Hematology)
Source: Experimental Hematology - January 4, 2019 Category: Hematology Authors: Benjamin Dannenmann, Azadeh Zahabi, Perihan Mir, Benedikt Oswald, Regine Bernhard, Maksim Klimiankou, Tatsuya Morishima, Cornelia Zeidler, Lothar Kanz, Nico Lachmann, Thomas Moritz, Karl Welte, Julia Skokowa Source Type: research

Clinical features of dyskeratosis congenita in mainland China: case reports and literature review.
Abstract Dyskeratosis congenita (DC) is a rare-inherited bone marrow failure syndrome associated with multi-system disorder. To summarize the clinical features, epidemiology, and treatment of DC in mainland China, we retrospectively reviewed the medical records of two patients diagnosed with DC at our hospital and published reports on other DC patients in mainland China. The clinical features of 82 DC patients were summarized. The median age of onset was 5 years, but the median age at diagnosis was 16 years. Bone marrow failure occurred at a high rate of 44% and early, with a median onset age of 6 y...
Source: International Journal of Hematology - January 3, 2019 Category: Hematology Authors: Li F, Li W, Qiao X, Xie X Tags: Int J Hematol Source Type: research

Late Mortality after Allogeneic BMT in Childhood for Bone Marrow Failure Syndromes and Severe Aplastic Anemia
Children with bone marrow failure syndromes and severe aplastic anemia (SAA) are treated with allogeneic blood or marrow transplantation (BMT). However, there is a paucity of studies examining late mortality risk after allogeneic BMT performed in childhood for bone marrow failure syndromes and SAA and how the risk differs between the diseases. We investigated cause-specific late mortality in 2y-survivors of allogeneic BMT for bone marrow failure syndromes and SAA performed before age 22 between 1974 and 2010 at one of two U.S. (Source: Biology of Blood and Marrow Transplantation)
Source: Biology of Blood and Marrow Transplantation - December 20, 2018 Category: Hematology Authors: Anna S ällfors Holmqvist, Yanjun Chen, Jessica Wu, Kevin Battles, Liton Francisco, Lindsey Hageman, Michelle Kung, Emily Ness, Mariel Parman, Jeanette Falck Winther, Joseph Rosenthal, Mukta Arora, Saro H Armenian, Smita Bhatia Source Type: research

Peering through zebrafish to understand inherited bone marrow failure syndromes.
Abstract Inherited bone marrow failure syndromes are experiments of nature characterized by impaired hematopoiesis with cancer and leukemia predisposition. The mutations associated with inherited bone marrow failure syndromes affect fundamental cellular pathways, such as DNA repair, telomere maintenance, or proteostasis. How these disturbed pathways fail to produce sufficient blood cells and lead to leukemogenesis are not understood. The rarity of inherited cytopenias, paucity of affected primary human hematopoietic cells, and sometime inadequacy of murine or induced pluripotential stem cell models constitute obst...
Source: Haematologica - December 20, 2018 Category: Hematology Authors: Oyarbide U, Topczewski J, Corey SJ Tags: Haematologica Source Type: research

Late Mortality after Allogeneic Bone Marrow Transplantation in Childhood for Bone Marrow Failure Syndromes and Severe Aplastic Anemia
Children with bone marrow failure syndromes and severe aplastic anemia (SAA) are treated with allogeneic blood or marrow transplantation (BMT). However, there is a paucity of studies examining late mortality risk after allogeneic BMT performed in childhood for bone marrow failure syndromes and SAA and evaluating how this risk differs between these diseases. We investigated cause-specific late mortality in 2-year survivors of allogeneic BMT for bone marrow failure syndromes and SAA performed before age 22 years between 1974 and 2010 at 2 US transplantation centers. (Source: Biology of Blood and Marrow Transplantation)
Source: Biology of Blood and Marrow Transplantation - December 20, 2018 Category: Hematology Authors: Anna S ällfors Holmqvist, Yanjun Chen, Jessica Wu, Kevin Battles, Liton Francisco, Lindsey Hageman, Michelle Kung, Emily Ness, Mariel Parman, Jeanette Falck Winther, Joseph Rosenthal, Mukta Arora, Saro H. Armenian, Smita Bhatia Source Type: research

Mechanism of BAALC-Mediated Leukemogenesis Downstream of RUNX1-Mutations in Severe Congenital Neutropenia
Severe congenital neutropenia (CN) is a pre-leukemic bone marrow failure syndrome. We recently reported a high frequency of cooperating RUNX1 and CSF3R mutations in CN patients that developed AML or MDS. To study the mechanism of leukemia development in CN, we established a model for step-wise leukemia progression in CN using iPSC-based hematopoietic differentiation in combination with CRISPR/Cas9-mediated gene editing of iPSCs. Using this model, we confirmed that co-acquisition of CSF3R and RUNX1 mutations is necessary and sufficient to induce leukemia in CN. We also identified BAALC (brain and acute leukemia, cytoplasmic...
Source: Blood - November 21, 2018 Category: Hematology Authors: Dannenmann, B., Klimiankou, M., Oswald, B., Ritter, M. U., Nasri, M., Solovyeva, A., Kanz, L., Zeidler, C., Welte, K., Skokowa, J. Tags: 201. Granulocytes, Monocytes, and Macrophages: Regulation of Myelopoiesis and Neutrophil Lineage Mutations: Biological Mechanism and Clinical Implications Source Type: research

Targeting Autophagy as a Therapeutic Pathway in Diamond-Blackfan Anemia
Diamond-Blackfan anemia (DBA) is a congenital disorder characterized by the failure of erythroid progenitor differentiation, severely curtailing red blood cell production. Because many DBA patients fail to respond to corticosteroid therapy, there is considerable need for therapeutics for this disorder. We previously used unbiased drug screens in induced pluripotent stem cells (iPSCs) which identified SMER28 as a potential therpauetic for DBA. SMER28 acts by selectively modulating autophagy, but has distinct effects from the mTOR inhibitor rapamycin, highlighting the need for further study. Autophagy and mitophagy are criti...
Source: Blood - November 21, 2018 Category: Hematology Authors: Doulatov, S. Tags: New Approaches to Correcting the Defect in Inherited Bone Marrow Failure Syndromes Source Type: research

TGF-B Inhibition Rescues Hematopoietic Defects in Fanconi Anemia
Four different combinations of double knock-out mouse strains have been created (SMAD3-/- Fancd2-/-) consisting of combinations of the individual knock-out strains on either the C57BL/6 or 129/Sv background. Sets of breeding experiments were carried out and the frequency of detection of double knock-out mice was significantly below the expected frequency of detecting DKO mice by breeding double heterozygotes (1 out of 16 or 6.25%). In fact, DKO mice were detected at a frequency ranging from 3.4% to 0.54%. Mice of all four DKO genotypes showed resistance of bone marrow hematopoietic progenitor cells to canonical TGF-β ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Greenberger, J. S. Tags: New Approaches to Correcting the Defect in Inherited Bone Marrow Failure Syndromes Source Type: research

Enhancing a Wnt-Telomere Feedback Loop Restores Intestinal Stem Cell Function in Dyskeratosis Congenita
Patients with dyskeratosis congenita (DC) suffer from stem cell failure in numerous organs, including the skin, intestine, blood, lung, and liver, due to hypomorphic loss-of-function mutations in proteins that promote telomere elongation or capping. Few therapeutic options exist for this disorder, and while patients are treated with bone marrow transplantation to restore hematopoietic function, this does not address the multi-organ failure, and in some cases can exacerbate it. We generated isogenic DC patient and disease allele-corrected induced pluripotent stem (iPS) cell lines using clustered regularly interspaced short ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Lengner, C. Tags: New Approaches to Correcting the Defect in Inherited Bone Marrow Failure Syndromes Source Type: research

Eltrombopag Improves Hematopoiesis in Patients with Low to Intermediate-2 Risk Myelodysplastic Syndrome (MDS)
In conclusion, our results suggest that EPAG is well-tolerated and effective in restoring hematopoiesis in patients with low to intermediate-2 risk MDS, particular with a prior history of hypoplastic bone marrow failure syndromes. EPAG was discontinued for robust response in the majority of responders but declining blood cell counts were observed in about 50% of them. Variants in MCG were more common at study entry compared to patients with aplastic anemia (Yoshizato, NEJM, 2015). However, EPAG appears not to selectively promote expansion of clones harboring MCGs in this patient population.DisclosuresTownsley: National Ins...
Source: Blood - November 21, 2018 Category: Hematology Authors: Vicente, A., Gutierrez-Rodrigues, F., Giudice, V., Wu, Z., Kajigaya, S., Fernandez Ibanez, M. d. P., Albitar, M., Weinstein, B., Calvo, K. R., Townsley, D. M., Scheinberg, P., Dunbar, C. E., Young, N. S., Winkler, T. Tags: 637. Myelodysplastic Syndromes-Clinical Studies: Novel Therapeutics I Source Type: research