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Article ; Online: Auditory training for tinnitus treatment: a scoping review.

Barros, Anna Carolina Marques Perrella de / Lopes, Rhayane Vitória / Gil, Daniela / Carmo, Andreia Cristina Feitosa do / Onishi, Ektor Tsuneo / Branco-Barreiro, Fátima Cristina Alves

Brazilian journal of otorhinolaryngology

2023 Volume 90, Issue 1, Page(s) 101361

Abstract: ... Level C), low (Level D), or very low (Level D-) based on the Critically Appraised Topics.: Results ... obtained quality evidence levels ranging from limited to high (C‒A) and studies that applied multisensory ...

Abstract	Objectives: Our study aimed to verify the evidence of auditory training employed in the audiological treatment of tinnitus in adults and older adults. Methods: Scoping review based on a search for articles in journals available in MEDLINE (PubMed), Embase (Elsevier), LILACS (BVS), and Cochrane Library. Titles and abstracts of the retrieved articles were assessed by peers, following the eligibility criteria; they were afterward read in full text, and the references were hand searched in the results found. Studies' level of evidence was classified into very high (Level A+), high (Level A), moderate (Level B), limited (Level C), low (Level D), or very low (Level D-) based on the Critically Appraised Topics. Results: 2160 records were identified in the searching stage and 15 studies were eligible for data extraction. Study design, sample characterization, auditory training tasks, sound stimuli, outcome measures, and results were extracted. Frequency discrimination training was the most frequent strategy, followed by auditory attentional skills training and multisensory training. Almost all studies with daily auditory training sessions reported significant benefits demonstrated in at least one outcome measure. Studies that used auditory discrimination training and attentional auditory skill stimulation to treat tinnitus obtained quality evidence levels ranging from limited to high (C‒A) and studies that applied multisensory training or attentional training combined with counseling and passive listening in tinnitus patients reached a high-quality evidence level (A). Conclusion: Recent studies had higher levels of evidence and considered attentional factors and multisensory pathways in auditory training strategies.
MeSH term(s)	Aged ; Humans ; Acoustic Stimulation/methods ; Attention ; Auditory Perception ; Tinnitus/therapy ; Tinnitus/psychology ; Adult
Language	English
Publishing date	2023-11-17
Publishing country	Brazil
Document type	Journal Article ; Review
ZDB-ID	2428110-4
ISSN	1808-8686 ; 1808-8694
ISSN (online)	1808-8686
ISSN	1808-8694
DOI	10.1016/j.bjorl.2023.101361
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Article ; Online: Surmounting chemotherapy and radioresistance in chondrosarcoma: molecular mechanisms and therapeutic targets.

Onishi, Anne C / Hincker, Alexander M / Lee, Francis Y

Sarcoma

2010 Volume 2011, Page(s) 381564

Abstract: Chondrosarcoma, a primary malignancy of bone, has eluded successful treatment with modern chemotherapeutic and radiation regimens. To date, surgical resection of these tumors remains the only curative treatment offered to patients with this diagnosis. ... ...

Abstract	Chondrosarcoma, a primary malignancy of bone, has eluded successful treatment with modern chemotherapeutic and radiation regimens. To date, surgical resection of these tumors remains the only curative treatment offered to patients with this diagnosis. Understanding and exploring the nature of chemotherapy and radiation resistance in chondrosarcoma could lead to new molecular targets and more directed therapy for these notoriously difficult-to-treat tumors. Here we review the most current hypotheses regarding the molecular mechanisms mediating chemotherapy and radiation resistance and the future direction of chondrosarcoma therapy research.
Language	English
Publishing date	2010-12-30
Publishing country	Egypt
Document type	Journal Article
ZDB-ID	1338527-6
ISSN	1369-1643 ; 1357-714X
ISSN (online)	1369-1643
ISSN	1357-714X
DOI	10.1155/2011/381564
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Article ; Online: Surmounting Chemotherapy and Radioresistance in Chondrosarcoma

Francis Y. Lee / Alexander M. Hincker / Anne C. Onishi

Sarcoma, Vol

Molecular Mechanisms and Therapeutic Targets

2011 Volume 2011

Keywords	Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Oncology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Hindawi Publishing Corporation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Ribose sugars generate internal glycation cross-links in horse heart myoglobin.

Bokiej, Magdalena / Livermore, Andrew T / Harris, Andrew W / Onishi, Anne C / Sandwick, Roger K

Biochemical and biophysical research communications

2011 Volume 407, Issue 1, Page(s) 191–196

Abstract: Glycation of horse heart metmyoglobin with d-ribose 5-phosphate (R5P), d-2-deoxyribose 5-phosphate (dR5P), and d-ribose with inorganic phosphate at 37°C generates an altered protein (Myo-X) with increased SDS-PAGE mobility. The novel protein product has ... ...

Abstract	Glycation of horse heart metmyoglobin with d-ribose 5-phosphate (R5P), d-2-deoxyribose 5-phosphate (dR5P), and d-ribose with inorganic phosphate at 37°C generates an altered protein (Myo-X) with increased SDS-PAGE mobility. The novel protein product has been observed only for reactions with the protein myoglobin and it is not evident with other common sugars reacted over a 1 week period. Myo-X is first observed at 1-2 days at 37°C along with a second form that is consistent in mass with that of myoglobin attached to several sugars. MALDI mass spectrometry and other techniques show no evidence of the cleavage of a peptide from the myoglobin chain. Apomyoglobin in reaction with R5P also exhibited this protein form suggesting its occurrence was not heme-related. While significant amounts of O(2)(-) and H(2)O(2) are generated during the R5P glycation reaction, they do not appear to play roles in the formation of the new form. The modification is likely due to an internal cross-link formed during a glycation reaction involving the N-terminus and an internal amine group; most likely the neighboring Lys133. The study shows the unique nature of these common pentose sugars in spontaneous glycation reactions with proteins.
MeSH term(s)	Animals ; Glycosylation ; Heme/chemistry ; Horses ; Metmyoglobin/chemistry ; Metmyoglobin/metabolism ; Myocardium/metabolism ; Myoglobin/biosynthesis ; Myoglobin/chemistry ; Oxidation-Reduction ; Ribose/chemistry ; Ribose/metabolism ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Chemical Substances	Myoglobin ; Metmyoglobin (12772-23-5) ; Heme (42VZT0U6YR) ; Ribose (681HV46001)
Language	English
Publishing date	2011-03-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2011.02.138
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Article: Ribose sugars generate internal glycation cross-links in horse heart myoglobin

Bokiej, Magdalena / Livermore, Andrew T / Harris, Andrew W / Onishi, Anne C / Sandwick, Roger K

Biochemical and biophysical research communications. 2011 Apr. 1, v. 407, no. 1

2011

Abstract: Glycation of horse heart metmyoglobin with d-ribose 5-phosphate (R5P), d-2-deoxyribose 5-phosphate (dR5P), and d-ribose with inorganic phosphate at 37°C generates an altered protein (Myo-X) with increased SDS–PAGE mobility. The novel protein product has ... ...

Abstract	Glycation of horse heart metmyoglobin with d-ribose 5-phosphate (R5P), d-2-deoxyribose 5-phosphate (dR5P), and d-ribose with inorganic phosphate at 37°C generates an altered protein (Myo-X) with increased SDS–PAGE mobility. The novel protein product has been observed only for reactions with the protein myoglobin and it is not evident with other common sugars reacted over a 1 week period. Myo-X is first observed at 1–2days at 37°C along with a second form that is consistent in mass with that of myoglobin attached to several sugars. MALDI mass spectrometry and other techniques show no evidence of the cleavage of a peptide from the myoglobin chain. Apomyoglobin in reaction with R5P also exhibited this protein form suggesting its occurrence was not heme-related. While significant amounts of O₂ ⁻ and H₂O₂ are generated during the R5P glycation reaction, they do not appear to play roles in the formation of the new form. The modification is likely due to an internal cross-link formed during a glycation reaction involving the N-terminus and an internal amine group; most likely the neighboring Lys133. The study shows the unique nature of these common pentose sugars in spontaneous glycation reactions with proteins.
Keywords	crosslinking ; glycation ; heart ; horses ; hydrogen peroxide ; matrix-assisted laser desorption-ionization mass spectrometry ; myoglobin ; pentoses ; phosphates ; polyacrylamide gel electrophoresis ; ribose ; superoxide anion
Language	English
Dates of publication	2011-0401
Size	p. 191-196.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	205723-2
ISSN	0006-291X ; 0006-291X
ISSN (online)	0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2011.02.138
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Article ; Online: Green Tea Polyphenols Modify the Gut Microbiome in db/db Mice as Co-Abundance Groups Correlating with the Blood Glucose Lowering Effect.

Chen, Tingting / Liu, Anna B / Sun, Shili / Ajami, Nadim J / Ross, Matthew C / Wang, Hong / Zhang, Le / Reuhl, Kenneth / Kobayashi, Koichi / Onishi, Janet C / Zhao, Liping / Yang, Chung S

Molecular nutrition & food research

2019 Volume 63, Issue 8, Page(s) e1801064

Abstract: Scope: The effects of green tea polyphenols, Polyphenon E (PPE), and black tea polyphenols, theaflavins (TFs), on gut microbiota and development of diabetes in db/db mice are investigated and compared.: Methods and results: Supplementation of PPE (0 ... ...

Abstract	Scope: The effects of green tea polyphenols, Polyphenon E (PPE), and black tea polyphenols, theaflavins (TFs), on gut microbiota and development of diabetes in db/db mice are investigated and compared. Methods and results: Supplementation of PPE (0.1%) in the diet of female db/db mice for 7 weeks decreases fasting blood glucose levels and mesenteric fat while increasing the serum level of insulin, possibly through protection against β-cell damage. However, TFs are less or not effective. Microbiome analysis through 16S rRNA gene sequencing shows that PPE and TFs treatments significantly alter the bacterial community structure in the cecum and colon, but not in the ileum. The key bacterial phylotypes responding to the treatments are then clustered into 11 co-abundance groups (CAGs). CAGs 6 and 7, significantly increased by PPE but not by TFs, are negatively associated with blood glucose levels. The operational taxonomic units in these CAGs are from two different phyla, Firmicutes and Bacteroidetes. CAG 10, decreased by PPE and TFs, is positively associated with blood glucose levels. Conclusion: Gut microbiota respond to tea polyphenol treatments as CAGs instead of taxa. Some of the CAGs associated with the blood glucose lowering effect are enriched by PPE, but not TFs.
MeSH term(s)	Animals ; Biflavonoids/pharmacology ; Blood Glucose/metabolism ; Body Weight/drug effects ; Catechin/analogs & derivatives ; Catechin/pharmacology ; Female ; Gastrointestinal Microbiome/drug effects ; Gastrointestinal Microbiome/genetics ; Gastrointestinal Microbiome/physiology ; Hypoglycemic Agents/pharmacology ; Insulin/blood ; Insulin-Secreting Cells/drug effects ; Insulin-Secreting Cells/pathology ; Mice, Mutant Strains ; Organ Size/drug effects ; Polyphenols/pharmacology ; RNA, Ribosomal, 16S ; Tea/chemistry
Chemical Substances	Biflavonoids ; Blood Glucose ; Hypoglycemic Agents ; Insulin ; Polyphenols ; RNA, Ribosomal, 16S ; Tea ; theaflavin (1IA46M0D13) ; Catechin (8R1V1STN48) ; polyphenon E (T432289GYZ)
Language	English
Publishing date	2019-01-30
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2160372-8
ISSN	1613-4133 ; 1613-4125
ISSN (online)	1613-4133
ISSN	1613-4125
DOI	10.1002/mnfr.201801064
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Article ; Online: Direct evidence for inhibition of mitochondrial permeability transition pore opening by sevoflurane preconditioning in cardiomyocytes: comparison with cyclosporine A.

Onishi, Anna / Miyamae, Masami / Kaneda, Kazuhiro / Kotani, Junichiro / Figueredo, Vincent M

European journal of pharmacology

2012 Volume 675, Issue 1-3, Page(s) 40–46

Abstract: To assess whether sevoflurane preconditioning is associated with inhibition of mitochondrial permeability transition pore (MPTP), the effects of sevoflurane were compared with those of cyclosporine A, a known inhibitor of MPTP opening. Isolated perfused ... ...

Abstract	To assess whether sevoflurane preconditioning is associated with inhibition of mitochondrial permeability transition pore (MPTP), the effects of sevoflurane were compared with those of cyclosporine A, a known inhibitor of MPTP opening. Isolated perfused guinea pig hearts underwent 30 min global ischemia and 120 min reperfusion (control). Sevoflurane preconditioning was elicited by administration of 2% sevoflurane for 10 min with 10 min washout before ischemia (sevoflurane). A preconditioning-like cardioprotection was also induced by administering cyclosporine A (0.2 μM) for 15 min, starting 5 min before ischemia and for 10 min after the onset of reperfusion (cyclosporine A). Left ventricular developed and end-diastolic pressures, coronary flow and infarct size were measured. Expressions of Akt and glycogen synthase kinase 3β (GSK3β), known mediators of inhibition of MPTP opening, were determined by Western blot analysis. GSK3β inhibition was achieved with LY294002. The effects of sevoflurane and cyclosporine A on calcium-induced MPTP opening in isolated calcein-loaded mitochondria were assessed. After ischemia-reperfusion, sevoflurane and cyclosporine A had higher left ventricular developed pressure. Infarct size was significantly reduced in sevoflurane and cyclosporine A vs. control. This was abolished by LY294002 in sevoflurane, but not in cyclosporine A. Akt and GSK3β phosphorylation after reperfusion were significantly increased in sevoflurane and cyclosporine A. Ca²⁺-induced reduction in calcein fluorescence was significantly attenuated in sevoflurane and cyclosporine A. Preconditioning agents, sevoflurane and cyclosporine A increase the threshold of calcium-induced MPTP opening to a similar extent. This effect by sevoflurane, but not cyclosporine A is at least partially mediated by GSK3β inactivation.
MeSH term(s)	Animals ; Calcium Signaling/drug effects ; Cardiotonic Agents/pharmacology ; Chromones/pharmacology ; Cyclosporine/pharmacology ; Enzyme Inhibitors/pharmacology ; Glycogen Synthase Kinase 3/antagonists & inhibitors ; Glycogen Synthase Kinase 3/metabolism ; Glycogen Synthase Kinase 3 beta ; Guinea Pigs ; Immunosuppressive Agents/pharmacology ; In Vitro Techniques ; Ischemic Preconditioning, Myocardial ; Male ; Methyl Ethers/pharmacology ; Mitochondria, Heart/drug effects ; Mitochondria, Heart/metabolism ; Mitochondrial Membrane Transport Proteins/antagonists & inhibitors ; Mitochondrial Membrane Transport Proteins/metabolism ; Morpholines/pharmacology ; Myocardial Infarction/pathology ; Myocardial Infarction/prevention & control ; Myocytes, Cardiac/drug effects ; Myocytes, Cardiac/enzymology ; Myocytes, Cardiac/metabolism ; Phosphorylation/drug effects ; Protein Processing, Post-Translational/drug effects ; Proto-Oncogene Proteins c-akt/metabolism ; Ventricular Function, Left/drug effects
Chemical Substances	Cardiotonic Agents ; Chromones ; Enzyme Inhibitors ; Immunosuppressive Agents ; Methyl Ethers ; Mitochondrial Membrane Transport Proteins ; Morpholines ; mitochondrial permeability transition pore ; 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (31M2U1DVID) ; sevoflurane (38LVP0K73A) ; Cyclosporine (83HN0GTJ6D) ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Glycogen Synthase Kinase 3 (EC 2.7.11.26)
Language	English
Publishing date	2012-01-30
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80121-5
ISSN	1879-0712 ; 0014-2999
ISSN (online)	1879-0712
ISSN	0014-2999
DOI	10.1016/j.ejphar.2011.11.040
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Article: Green Tea Polyphenols Modify the Gut Microbiome in db/db Mice as Co‐Abundance Groups Correlating with the Blood Glucose Lowering Effect

Chen, Tingting / Liu, Anna B / Sun, Shili / Ajami, Nadim J / Ross, Matthew C / Wang, Hong / Zhang, Le / Reuhl, Kenneth / Kobayashi, Koichi / Onishi, Janet C / Zhao, Liping / Yang, Chung S

Molecular nutrition & food research. 2019 Apr., v. 63, no. 8

2019

Abstract: SCOPE: The effects of green tea polyphenols, Polyphenon E (PPE), and black tea polyphenols, theaflavins (TFs), on gut microbiota and development of diabetes in db/db mice are investigated and compared. METHODS AND RESULTS: Supplementation of PPE (0.1%) ... ...

Abstract	SCOPE: The effects of green tea polyphenols, Polyphenon E (PPE), and black tea polyphenols, theaflavins (TFs), on gut microbiota and development of diabetes in db/db mice are investigated and compared. METHODS AND RESULTS: Supplementation of PPE (0.1%) in the diet of female db/db mice for 7 weeks decreases fasting blood glucose levels and mesenteric fat while increasing the serum level of insulin, possibly through protection against β‐cell damage. However, TFs are less or not effective. Microbiome analysis through 16S rRNA gene sequencing shows that PPE and TFs treatments significantly alter the bacterial community structure in the cecum and colon, but not in the ileum. The key bacterial phylotypes responding to the treatments are then clustered into 11 co‐abundance groups (CAGs). CAGs 6 and 7, significantly increased by PPE but not by TFs, are negatively associated with blood glucose levels. The operational taxonomic units in these CAGs are from two different phyla, Firmicutes and Bacteroidetes. CAG 10, decreased by PPE and TFs, is positively associated with blood glucose levels. CONCLUSION: Gut microbiota respond to tea polyphenol treatments as CAGs instead of taxa. Some of the CAGs associated with the blood glucose lowering effect are enriched by PPE, but not TFs.
Keywords	Bacteroidetes ; Firmicutes ; bacterial communities ; black tea ; blood glucose ; blood serum ; cecum ; colon ; community structure ; diabetes ; diet ; females ; green tea ; ileum ; insulin ; intestinal microorganisms ; islets of Langerhans ; mice ; microbiome ; phylotype ; ribosomal RNA ; sequence analysis ; theaflavins
Language	English
Dates of publication	2019-04
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	2160372-8
ISSN	1613-4133 ; 1613-4125
ISSN (online)	1613-4133
ISSN	1613-4125
DOI	10.1002/mnfr.201801064
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Article ; Online: Induction of autophagy restores the loss of sevoflurane cardiac preconditioning seen with prolonged ischemic insult.

Shiomi, Mayumi / Miyamae, Masami / Takemura, Genzou / Kaneda, Kazuhiro / Inamura, Yoshitaka / Onishi, Anna / Koshinuma, Shizuka / Momota, Yoshihiro / Minami, Toshiaki / Figueredo, Vincent M

European journal of pharmacology

2014 Volume 724, Page(s) 58–66

Abstract: Sevoflurane preconditioning against myocardial ischemia-reperfusion injury is lost if the ischemic insult is too long. Emerging evidence suggests that induction of autophagy may also confer cardioprotection against ischemia-reperfusion injury. We ... ...

Abstract	Sevoflurane preconditioning against myocardial ischemia-reperfusion injury is lost if the ischemic insult is too long. Emerging evidence suggests that induction of autophagy may also confer cardioprotection against ischemia-reperfusion injury. We examined whether induction of autophagy prolongs sevoflurane preconditioning protection during a longer ischemic insult. Isolated guinea pigs hearts were subjected to 30 or 45 min ischemia, followed by 120 min reperfusion (control). Anesthetic preconditioning was elicited with 2% sevoflurane for 10 min prior to ischemia (SEVO-30, SEVO-45). Chloramphenicol (autophagy upregulator, 300 µM) was administered starting 20 min before ischemia and throughout reperfusion in SEVO-45 (SEVO-45+CAP). To inhibit autophagy, 3-methyladenine (10 μM) was administered during sevoflurane administration in SEVO-45+CAP. Infarct size was determined by triphenyltetrazolium chloride stain. Tissue samples were obtained before ischemia to determine autophagy-related protein (microtubule-associated protein light chain I and II: LC3-I, II), Akt and glycogen synthase kinase 3β (GSK3β) expression using Western blot analysis. The effect of autophagy on calcium-induced mitochondrial permeability transition pore (MPTP) opening in isolated calcein-loaded mitochondria was assessed. Electron microscopy was used to detect autophagosomes. Infarct size was significantly reduced in SEVO-30, but not in SEVO-45. Chloramphenicol restored sevoflurane preconditioning lost by 45 min ischemia. There were more abundant autophagozomes and LC3-II expression was significantly increased in SEVO-45+CAP. Induction of autophagy before ischemia enhanced GSK3β phosphorylation and inhibition of calcium-induced MPTP opening. These effects were abolished by 3-methyladenine. Pre-ischemic induction of autophagy restores sevoflurane preconditioning lost by longer ischemic insult. This effect is associated with enhanced inhibition of MPTP by autophagy.
MeSH term(s)	Adenine/analogs & derivatives ; Adenine/pharmacology ; Anesthetics, Inhalation/pharmacology ; Animals ; Autophagy ; Cardiotonic Agents/pharmacology ; Chloramphenicol/pharmacology ; Glycogen Synthase Kinase 3/metabolism ; Glycogen Synthase Kinase 3 beta ; Guinea Pigs ; Heart/drug effects ; Heart/physiology ; In Vitro Techniques ; Ischemic Preconditioning, Myocardial ; Male ; Methyl Ethers/pharmacology ; Microscopy, Electron, Transmission ; Microtubule-Associated Proteins/metabolism ; Mitochondria, Heart ; Mitochondrial Membrane Transport Proteins ; Myocardial Infarction/metabolism ; Myocardial Infarction/pathology ; Myocardium/metabolism ; Myocardium/ultrastructure ; Proto-Oncogene Proteins c-akt/metabolism
Chemical Substances	Anesthetics, Inhalation ; Cardiotonic Agents ; Methyl Ethers ; Microtubule-Associated Proteins ; Mitochondrial Membrane Transport Proteins ; mitochondrial permeability transition pore ; sevoflurane (38LVP0K73A) ; 3-methyladenine (5142-23-4) ; Chloramphenicol (66974FR9Q1) ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Glycogen Synthase Kinase 3 (EC 2.7.11.26) ; Adenine (JAC85A2161)
Language	English
Publishing date	2014-02-05
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80121-5
ISSN	1879-0712 ; 0014-2999
ISSN (online)	1879-0712
ISSN	0014-2999
DOI	10.1016/j.ejphar.2013.12.027
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Article ; Online: Outcomes of pediatric patients with therapy-related myeloid neoplasms.

Sharma, Akshay / Huang, Sujuan / Li, Ying / Brooke, Russell J / Ahmed, Ibrahim / Allewelt, Heather B / Amrolia, Persis / Bertaina, Alice / Bhatt, Neel S / Bierings, Marc B / Bies, Joshua / Brisset, Claire / Brondon, Jennifer E / Dahlberg, Ann / Dalle, Jean-Hugues / Eissa, Hesham / Fahd, Mony / Gassas, Adam / Gloude, Nicholas J /

Goebel, W Scott / Goeckerman, Erika S / Harris, Katherine / Ho, Richard / Hudspeth, Michelle P / Huo, Jeffrey S / Jacobsohn, David / Kasow, Kimberly A / Katsanis, Emmanuel / Kaviany, Saara / Keating, Amy K / Kernan, Nancy A / Ktena, Yiouli P / Lauhan, Colette R / López-Hernandez, Gerardo / Martin, Paul L / Myers, Kasiani C / Naik, Swati / Olaya-Vargas, Alberto / Onishi, Toshihiro / Radhi, Mohamed / Ramachandran, Shanti / Ramos, Kristie / Rangarajan, Hemalatha G / Roehrs, Philip A / Sampson, Megan E / Shaw, Peter J / Skiles, Jodi L / Somers, Katherine / Symons, Heather J / de Tersant, Marie / Uber, Allison N / Versluys, Birgitta / Cheng, Cheng / Triplett, Brandon M

Bone marrow transplantation

2021 Volume 56, Issue 12, Page(s) 2997–3007

Abstract: Long-term outcomes after allogeneic hematopoietic cell transplantation (HCT) for therapy-related myeloid neoplasms (tMNs) are dismal. There are few multicenter studies defining prognostic factors in pediatric patients with tMNs. We have accumulated the ... ...

Abstract	Long-term outcomes after allogeneic hematopoietic cell transplantation (HCT) for therapy-related myeloid neoplasms (tMNs) are dismal. There are few multicenter studies defining prognostic factors in pediatric patients with tMNs. We have accumulated the largest cohort of pediatric patients who have undergone HCT for a tMN to perform a multivariate analysis defining factors predictive of long-term survival. Sixty-eight percent of the 401 patients underwent HCT using a myeloablative conditioning (MAC) regimen, but there were no statistically significant differences in the overall survival (OS), event-free survival (EFS), or cumulative incidence of relapse and non-relapse mortality based on the conditioning intensity. Among the recipients of MAC regimens, 38.4% of deaths were from treatment-related causes, especially acute graft versus host disease (GVHD) and end-organ failure, as compared to only 20.9% of deaths in the reduced-intensity conditioning (RIC) cohort. Exposure to total body irradiation (TBI) during conditioning and experiencing grade III/IV acute GVHD was associated with worse OS. In addition, a diagnosis of therapy-related myelodysplastic syndrome and having a structurally complex karyotype at tMN diagnosis were associated with worse EFS. Reduced-toxicity (but not reduced-intensity) regimens might help to decrease relapse while limiting mortality associated with TBI-based HCT conditioning in pediatric patients with tMNs.
MeSH term(s)	Child ; Graft vs Host Disease/etiology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Leukemia, Myeloid, Acute/complications ; Neoplasm Recurrence, Local ; Retrospective Studies ; Transplantation Conditioning/adverse effects
Language	English
Publishing date	2021-09-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632854-4
ISSN	1476-5365 ; 0268-3369 ; 0951-3078
ISSN (online)	1476-5365
ISSN	0268-3369 ; 0951-3078
DOI	10.1038/s41409-021-01448-x
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