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Article ; Online: Increased donor inhibitory KIR are associated with reduced GVHD and improved survival following HLA-matched unrelated donor HCT in paediatric acute leukaemia.

Krieger, Elizabeth / Qayyum, Rehan / Toor, Amir

2024

Abstract: Killer immunoglobulin-like receptor (KIR) and KIR-ligand (KIRL) interactions play an important role in natural killer cell-mediated effects after haematopoietic stem cell transplantation (HCT). Previous work has shown that accounting for known KIR-KIRL ... ...

Abstract	Killer immunoglobulin-like receptor (KIR) and KIR-ligand (KIRL) interactions play an important role in natural killer cell-mediated effects after haematopoietic stem cell transplantation (HCT). Previous work has shown that accounting for known KIR-KIRL interactions may identify donors with optimal NK cell-mediated alloreactivity in the adult transplant setting. Paediatric acute leukaemia patients were retrospectively analysed, and KIR-KIRL combinations and maximal inhibitory KIR ligand (IM-KIR) scores were determined. Clinical outcomes were examined using a series of graphs depicting clinical events and endpoints. The graph methodology demonstrated that prognostic variables significant in the occurrence of specific clinical endpoints remained significant for relevant downstream events. KIR-KIRL combinations were significantly predictive for reduced grade 3-4 aGVHD likelihood, in patients transplanted with increased inhibitory KIR gene content and IM-KIR = 5 scores. Improvements were also observed in associated outcomes for both ALL and AML patients, including relapse-free survival, GRFS and overall survival. This study demonstrates that NK cell KIR HLA interactions may be relevant to the paediatric acute leukaemia transplant setting. Reduction in aGVHD suggests KIR effects may extend beyond NK cells. Moving forward clinical trials utilizing donors with a higher iKIR should be considered for URD HCT in paediatric recipients with acute leukaemia to optimize clinical outcomes.
Language	English
Publishing date	2024-03-05
Publishing country	England
Document type	Journal Article
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.19356
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Article ; Online: Correction: Increased donor inhibitory KIR with known HLA interactions provide protection from relapse following HLA matched unrelated donor HCT for AML.

Krieger, Elizabeth / Qayyum, Rehan / Keating, Armand / Toor, Amir

Bone marrow transplantation

2021 Volume 56, Issue 11, Page(s) 2871

Language	English
Publishing date	2021-10-15
Publishing country	England
Document type	Published Erratum
ZDB-ID	632854-4
ISSN	1476-5365 ; 0268-3369 ; 0951-3078
ISSN (online)	1476-5365
ISSN	0268-3369 ; 0951-3078
DOI	10.1038/s41409-021-01488-3
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Zs.A 2168: Show issues

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Article ; Online: Engraftment syndrome after allogeneic stem cell transplantation: a systematic review and meta-analysis.

ElGohary, Ghada / Toor, Amir A / Gergis, Usama

Bone marrow transplantation

2022 Volume 58, Issue 1, Page(s) 1–9

Abstract: Engraftment syndrome (ES) is associated with neutrophil recovery after stem cell transplantation (SCT). It is associated with autologous and allogeneic SCT. However, a literature review has shown that allogeneic SCT (allo-SCT) is associated with ES ... ...

Abstract	Engraftment syndrome (ES) is associated with neutrophil recovery after stem cell transplantation (SCT). It is associated with autologous and allogeneic SCT. However, a literature review has shown that allogeneic SCT (allo-SCT) is associated with ES without conclusive data on risk factors or effects on outcomes. This meta-analysis was undertaken to estimate the cumulative incidence of ES following allo-SCT, and to evaluate the risk factors and outcomes among patients with ES following allo-SCT. Current literature was searched using electronic databases, and manually. Studies with ES after allo-SCT were selected, and a meta-analysis of proportion was performed using the Freeman-Tukey Double Arcsine transformation, random-effects model to calculate the cumulative incidence of ES. Donor type, source of haematopoetic stem cells, graft vs. host disease (GvHD) prophylaxes, and conditioning regimens' intensity were evaluated for risk factors for ES. Association of acute GvHD (aGvHD), chronic GvHD (cGvHD), relapse, nonrelapse mortality (NRM), and overall survival (OS) between the ES and no ES groups were assessed using the odds ratio (OR). Eighteen studies were included comprising 3620 patients receiving allo-SCT and 774 of them had developed ES with a cumulative incidence of 35.4%. The odds of aGvHD (OR 2.5, p < 0.001), cGvHD (OR 4.5, p = 0.021), and NRM (OR 1.8, p = 0.01) were higher among patients who developed ES. The odds of relapse were significantly less (OR = 0.679, p = 0.011) among the ES group. OS (OR = 0.72, p < 0.001) was reduced in the ES group. Myeloablative conditioning was found to be a significant risk factor for ES development. In conclusion, ES after allo-SCT is common with higher odds of developing aGvHD, cGvHD, and NRM and lower odds of OS.
MeSH term(s)	Humans ; Hematopoietic Stem Cell Transplantation/adverse effects ; Hematologic Diseases/complications ; Graft vs Host Disease/etiology ; Stem Cell Transplantation/adverse effects ; Recurrence ; Transplantation Conditioning/adverse effects ; Retrospective Studies
Language	English
Publishing date	2022-10-25
Publishing country	England
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Review
ZDB-ID	632854-4
ISSN	1476-5365 ; 0268-3369 ; 0951-3078
ISSN (online)	1476-5365
ISSN	0268-3369 ; 0951-3078
DOI	10.1038/s41409-022-01849-6
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Article: Recombinant activated factor VII in a patient with intracranial hemorrhage and severe thrombocytopenia.

Ansari, Amir M / Khorasanchi, Adam / Faghihimehr, Armaghan / Toor, Amir

Clinical case reports

2021 Volume 9, Issue 10, Page(s) e04788

Abstract: Hemorrhage in patients with hematologic malignancies is often difficult to manage as many of these patients also have coagulopathy and thrombocytopenia of varying severity. Recombinant factor VIIa is a FDA-approved agent for management of bleeding in ... ...

Abstract	Hemorrhage in patients with hematologic malignancies is often difficult to manage as many of these patients also have coagulopathy and thrombocytopenia of varying severity. Recombinant factor VIIa is a FDA-approved agent for management of bleeding in hemophilia patients with inhibitors. Use of recombinant FVIIa has also been used as a last resort in various clinical settings such as trauma, alveolar hemorrhage, gastrointestinal bleeding, and intracranial hemorrhage for control of bleeding with variable outcomes. This paper presents a case of recombinant FVIIa administration in a patient with multiple myeloma and profound transfusion refractory thrombocytopenia suffering from traumatic subdural hematoma.
Language	English
Publishing date	2021-10-10
Publishing country	England
Document type	Case Reports
ZDB-ID	2740234-4
ISSN	2050-0904
ISSN	2050-0904
DOI	10.1002/ccr3.4788
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Article ; Online: Cell-free next-generation sequencing impacts diagnosis and antimicrobial therapy in immunocompromised hosts: A retrospective study.

Vissichelli, Nicole C / Morales, Megan K / Kolipakkam, Bharadhwaj / Bryson, Alexandra / Sabo, Roy T / Toor, Amir A

Transplant infectious disease : an official journal of the Transplantation Society

2023 Volume 25, Issue 1, Page(s) e13954

Abstract: Background: Cell-free next-generation sequencing (cfNGS) may have a unique role in the diagnosis of infectious complications in immunocompromised hosts. The rapid turnaround time and non-invasive nature make it a promising supplement to standard of care. ...

Abstract	Background: Cell-free next-generation sequencing (cfNGS) may have a unique role in the diagnosis of infectious complications in immunocompromised hosts. The rapid turnaround time and non-invasive nature make it a promising supplement to standard of care. Methods: This retrospective, observational single-center study at a tertiary care medical center in Virginia investigated the use of cfNGS in clinical practice. Patients over age 18 years with cfNGS performed for any indication were included. The primary outcome was detection of bacteria and/or fungi on cfNGS. The secondary outcomes were concordance, and abundance of fungal and bacterial organism concentration detected over time from symptom onset, and clinical impact. Results: Thirty-six patients (92% immunosuppressed) were identified and included. Twenty-one (58%) tests detected one to five organisms (14/21 bacteria, 8/21 fungi, and 6/21 viruses). The clinical impact of cfNGS was positive in 52.8% of cases, negative in 2.8%, and negligible in 44.4%. Positive tests prompted therapy changes in 12 of 21 patients; six of 20 bacteria and seven of eight fungi identified were considered clinically pathogenic. Three bacteria identifications and six fungi identifications prompted targeted treatment. When fungal species were not identified by cNFGS, antifungal de-escalation occurred in seven patients. Conclusion: cfNGS assisted in critical management changes, including initiation of treatment for identified organisms and antimicrobial de-escalation. Its non-invasive nature and rapid turnaround time make this an important adjunct to standard of care testing that may assist in providing earlier, targeted therapy, especially when opportunistic pathogens remain high on the differential diagnosis.
MeSH term(s)	Humans ; Adolescent ; Retrospective Studies ; Fungi/genetics ; Antifungal Agents ; Bacteria/genetics ; Immunocompromised Host ; High-Throughput Nucleotide Sequencing ; Sensitivity and Specificity
Chemical Substances	Antifungal Agents
Language	English
Publishing date	2023-01-11
Publishing country	Denmark
Document type	Observational Study ; Journal Article
ZDB-ID	1476094-0
ISSN	1399-3062 ; 1398-2273
ISSN (online)	1399-3062
ISSN	1398-2273
DOI	10.1111/tid.13954
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Zs.A 5100: Show issues

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Article ; Online: DNA Methylation Research in Autologous Hematopoietic Stem Cell Transplant Population.

Mohanraj, Lathika / Lapato, Dana M / Toor, Amir / Swift-Scanlan, Theresa

Biological research for nursing

2022 Volume 25, Issue 2, Page(s) 220–226

Abstract: Despite increased sophistication in DNA methylation (DNAm) measurement and methods, conducting studies in specific populations such as the hematopoietic stem cell transplant (HCT) population, presents unique challenges and study design considerations. In ...

Abstract	Despite increased sophistication in DNA methylation (DNAm) measurement and methods, conducting studies in specific populations such as the hematopoietic stem cell transplant (HCT) population, presents unique challenges and study design considerations. In this article, we explain the motivation for investigating DNAm in the HCT population, highlighting important study design features and key findings in a longitudinal prospective pilot study of DNAm in 32 patients undergoing autologous HCT in Central Virginia, USA. We also discuss limitations and challenges to generating robust results. We observed that HCT does not prevent high-quality DNA from being extracted from whole blood for DNAm research and that longitudinal prospective studies that span pre- and 2-months post-HCT are feasible. Critically, we did not observe significant impacts of cancer diagnosis, time since transplant, age, or chromosomal sex on overall DNAm data dimensionality. These observations demonstrate that while extreme care is required to ensure generalizable, accurate, and interpretable results, researchers should not avoid HCT-DNAm research simply for fear that the transplant procedure or presence of a cancer diagnosis will prevent meaningful conclusions from being drawn. DNAm is an attractive biomarker that is understudied in patients undergoing HCT and needs to expand to improve precise prediction of HCT outcomes.
MeSH term(s)	Humans ; Hematopoietic Stem Cell Transplantation/methods ; Prospective Studies ; DNA Methylation ; Pilot Projects ; Neoplasms
Language	English
Publishing date	2022-10-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2145107-2
ISSN	1552-4175 ; 1099-8004
ISSN (online)	1552-4175
ISSN	1099-8004
DOI	10.1177/10998004221132251
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Zs.A 5946: Show issues

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Article ; Online: Increased donor inhibitory KIR with known HLA interactions provide protection from relapse following HLA matched unrelated donor HCT for AML.

Krieger, Elizabeth / Qayyum, Rehan / Keating, Armand / Toor, Amir

Bone marrow transplantation

2021 Volume 56, Issue 11, Page(s) 2714–2722

Abstract: Killer immunoglobulin-like receptor (KIR) and KIR-ligand (KIRL) interactions play an important role in natural killer cell-mediated graft versus leukemia effect (GVL) after hematopoietic cell transplant (HCT) for AML. Accounting for known KIR-KIRL ... ...

Abstract	Killer immunoglobulin-like receptor (KIR) and KIR-ligand (KIRL) interactions play an important role in natural killer cell-mediated graft versus leukemia effect (GVL) after hematopoietic cell transplant (HCT) for AML. Accounting for known KIR-KIRL interactions may identify donors with optimal NK cell-mediated alloreactivity and GVL. A retrospective study of 2359 donor-recipient pairs (DRP) who underwent unrelated donor (URD) HCT for AML was performed. KIR-KIRL combinations were determined and associations with clinical outcomes examined. Relapse risk was reduced in DRP with both higher inhibitory KIR-KIRL (iKIR) and missing KIRL (mKIR) scores, with HR 0.86 (P = 0.01) & HR 0.84 (P = 0.02) respectively. The iKIR and mKIR score components were summed to give a maximal inhibitory KIR ligand (IM-KIR) score for each donor, which if it was 5, as opposed to <5, was also associated with a lower relapse risk, SHR 0.8 (P = 0.004). All IM = 5 donors possess KIR Haplotype B/x. Transplant-related mortality was increased among those with IM-KIR = 5, HR, 1.32 (P = 0.01). In a subset analysis of those transplanted with 8/8 HLA-matched DRP, anti-thymocyte globulin recipients with IM-KIR = 5, had a lower relapse rate HR, 0.61 (p = 0.001). This study demonstrates that HLA-matched unrelated donors with the highest inhibitory KIR content confer relapse protection, albeit with increased TRM. These donors all have KIR haplotype B. Clinical trials utilizing donors with a higher iKIR content in conjunction with novel strategies to reduce TRM should be considered for URD HCT in recipients with AML to optimize clinical outcomes.
MeSH term(s)	Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute/therapy ; Receptors, KIR ; Recurrence ; Retrospective Studies ; Unrelated Donors
Chemical Substances	Receptors, KIR
Language	English
Publishing date	2021-07-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	632854-4
ISSN	1476-5365 ; 0268-3369 ; 0951-3078
ISSN (online)	1476-5365
ISSN	0268-3369 ; 0951-3078
DOI	10.1038/s41409-021-01393-9
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Zs.A 2168: Show issues

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Article ; Online: Transient left ventricular dysfunction following chimeric antigen receptor T-cell-mediated encephalopathy: A form of stress cardiomyopathy.

Khorasanchi, Adam / Ansari, Amir M / Bottinor, Wendy / Simmons, Gary / Abbate, Antonio / Toor, Amir A

EJHaem

2021 Volume 3, Issue 1, Page(s) 231–234

Abstract: Chimeric antigen receptor (CAR) T-cell therapy represents a new strategy in treating lymphoid malignancies, such as relapsed-refractory diffuse large B-cell lymphoma (DLBCL). Several toxicities including cytokine release syndrome (CRS), neurotoxicity, ... ...

Abstract	Chimeric antigen receptor (CAR) T-cell therapy represents a new strategy in treating lymphoid malignancies, such as relapsed-refractory diffuse large B-cell lymphoma (DLBCL). Several toxicities including cytokine release syndrome (CRS), neurotoxicity, and cardiovascular toxicity have been linked to CAR T-cell therapy. Transient impairment in left ventricular systolic function is described after CAR-T, however, the mechanism remains poorly understood. This paper reports the clinical presentation and outcome of two patients with relapsed-refractory DLBCL who experienced encephalopathy and CRS following CAR T-cell therapy and developed transient left ventricular dysfunction consistent with stress cardiomyopathy.
Language	English
Publishing date	2021-12-14
Publishing country	United States
Document type	Case Reports
ISSN	2688-6146
ISSN (online)	2688-6146
DOI	10.1002/jha2.369
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Article ; Online: Defining and Grading Infections in Clinical Trials Involving Hematopoietic Cell Transplantation: A Report From the BMT CTN Infectious Disease Technical Committee.

Shahid, Zainab / Etra, Aaron M / Levine, John E / Riches, Marcie L / Baluch, Aliyah / Hill, Joshua A / Nakamura, Ryo / Toor, Amir A / Ustun, Celalettin / Young, Jo-Anne H / Perales, Miguel-Angel / Epstein, David J / Murthy, Hemant S

Transplantation and cellular therapy

2024

Abstract: The Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) was established in 2001 to conduct large multi-institutional clinical trials addressing important issues towards improving the outcomes of HCT and other cellular therapies. Trials ... ...

Abstract	The Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) was established in 2001 to conduct large multi-institutional clinical trials addressing important issues towards improving the outcomes of HCT and other cellular therapies. Trials conducted by the network investigating new advances in HCT and cellular therapy not only assess efficacy but require careful capturing and severity assessment of adverse events and toxicities. Adverse infectious events in cancer clinical trials are typically graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE). However, there are limitations to this framework as it relates to HCT given the associated immunodeficiency and delayed immune reconstitution. The BMT-CTN Infection Grading System is a monitoring tool developed by the BMT CTN to capture and monitor infectious complications and differs from the CTCAE by its classification of infections based on their potential impact on morbidity and mortality for HCT recipients. Here we offer a report from the BMT CTN Infectious Disease Technical Committee regarding the rationale, development, and revising of BMT-CTN Infection Grading System and future directions as it applies to future clinical trials involving HCT and cellular therapy recipients.
Language	English
Publishing date	2024-03-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	3062231-1
ISSN	2666-6367
ISSN (online)	2666-6367
DOI	10.1016/j.jtct.2024.03.001
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Zs.A 5082: Show issues

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Article ; Online: DNA Methylation Changes in Autologous Hematopoietic Stem Cell Transplant Patients.

Mohanraj, Lathika / Wolf, Hope / Silvey, Scott / Liu, Jinze / Toor, Amir / Swift-Scanlan, Theresa

Biological research for nursing

2022 Volume 25, Issue 2, Page(s) 310–325

Abstract: Background: Blood cancers may be potentially cured with hematopoietic stem cell transplantation (HCT); however, standard pre-assessments for transplant eligibility do not capture all contributing factors for transplant outcomes. Epigenetic biomarkers ... ...

Abstract	Background: Blood cancers may be potentially cured with hematopoietic stem cell transplantation (HCT); however, standard pre-assessments for transplant eligibility do not capture all contributing factors for transplant outcomes. Epigenetic biomarkers predict outcomes in various diseases. This pilot study aims to explore epigenetic changes (epigenetic age and differentially methylated genes) in patients before and after autologous HCT, that can serve as potential biomarkers to better predict HCT outcomes. Methods: This study used a prospective longitudinal study design to compare genome wide DNA methylation changes in 36 autologous HCT eligible patients recruited from the Cellular Immunotherapies and Transplant clinic at a designated National Cancer Center. Results: Genome-wide DNA methylation, measured by the Illumina Infinium Human Methylation 850K BeadChip, showed a significant difference in DNA methylation patterns post-HCT compared to pre-HCT. Compared to baseline levels of DNA methylation pre-HCT, 3358 CpG sites were hypo-methylated and 3687 were hyper-methylated. Identified differentially methylated positions overlapped with genes involved in hematopoiesis, blood cancers, inflammation and immune responses. Enrichment analyses showed significant alterations in biological processes such as immune response and cell structure organization, however no significant pathways were noted. Though participants had an advanced epigenetic age compared to chronologic age before and after HCT, both epigenetic age and accelerated age decreased post-HCT. Conclusion: Epigenetic changes, both in epigenetic age and differentially methylated genes were observed in autologous HCT recipients, and should be explored as biomarkers to predict transplant outcomes after autologous HCT in larger, longitudinal studies.
MeSH term(s)	Humans ; DNA Methylation/genetics ; Longitudinal Studies ; Prospective Studies ; Pilot Projects ; Hematopoietic Stem Cell Transplantation ; Hematologic Neoplasms/genetics
Language	English
Publishing date	2022-11-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2145107-2
ISSN	1552-4175 ; 1099-8004
ISSN (online)	1552-4175
ISSN	1099-8004
DOI	10.1177/10998004221135628
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