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Article ; Online: Sir Michael Anthony Epstein (1921-2024).

Ambinder, Richard F / Xian, Rena R

2024 Volume 384, Issue 6693, Page(s) 274

Abstract: Codiscoverer of the Epstein-Barr virus. ...

Abstract	Codiscoverer of the Epstein-Barr virus.
MeSH term(s)	Humans ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections
Language	English
Publishing date	2024-04-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.adp2961
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Article ; Online: Cell-Free Circulating Tumor DNA and Epstein-Barr Virus DNA for Early Diagnosis of Epstein-Barr Virus-Associated Cancers.

Xian, Rena R / Ambinder, Richard F

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2023 Volume 41, Issue 26, Page(s) 4290–4292

MeSH term(s)	Humans ; Herpesvirus 4, Human/genetics ; Epstein-Barr Virus Infections/complications ; Epstein-Barr Virus Infections/diagnosis ; Epstein-Barr Virus Infections/pathology ; Circulating Tumor DNA ; Early Detection of Cancer ; Neoplasms/diagnosis ; Neoplasms/genetics ; DNA ; DNA, Viral
Chemical Substances	Circulating Tumor DNA ; DNA (9007-49-2) ; DNA, Viral
Language	English
Publishing date	2023-07-21
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.23.00687
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Article ; Online: Significance of lymph node fine needle aspiration for the diagnosis of HIV-associated lymphoma in a low-resource setting.

Vogt, Samantha L / Maloma, Lucia / Xian, Rena R / Ambinder, Richard F / Philip, Vinitha / Patel, Moosa / Martinson, Neil A / Omar, Tanvier

AIDS (London, England)

2022 Volume 36, Issue 10, Page(s) 1393–1398

Abstract: Objective: Fine needle aspiration (FNA) is an early step in the work-up of lymphadenopathy in people with HIV (PWH). We set out to characterize the FNA cytology in PWH and report on the time to lymphoma diagnosis through the FNA clinics in the public ... ...

Abstract	Objective: Fine needle aspiration (FNA) is an early step in the work-up of lymphadenopathy in people with HIV (PWH). We set out to characterize the FNA cytology in PWH and report on the time to lymphoma diagnosis through the FNA clinics in the public healthcare system in Johannesburg, South Africa. Design: Retrospective review of laboratory database. Methods: A retrospective chart review of patients undergoing FNA through the department of cytopathology at the National Health Laboratory Service (NHLS) was undertaken. Results of FNAs performed between March and May 2018 were reviewed. Medical record chart abstraction included general demographics, HIV status, site and results of FNA, prior history of malignancy and other laboratory data. Results: Five hundred and thirty-nine lymph node FNAs were performed on PWH. Pathological findings included tuberculosis 47% (252), inadequate sampling 14% (75), reactive adenopathy 13% (71), benign disease 12% (63), suspicious for lymphoproliferative neoplasm 8% (45), other malignancy 4% (21) and inflammation 2% ( n = 12). Only 53% (24) of lymphomas were confirmed by biopsy. Those not confirmed had a high mortality (57%) and loss to follow-up rate (29%) over the following year. The median diagnostic interval exceeded 8 weeks from time of FNA to lymphoma diagnosis. Conclusion: FNA is an important screening modality in this high HIV and tuberculosis (TB) burden region. Patients with cytology suggestive for lymphoma, but without biopsy confirmation, have a high mortality rate suggesting undiagnosed lymphoma. A better understanding of the barriers to appropriate diagnostic triage for lymphoma is needed.
MeSH term(s)	Biopsy, Fine-Needle ; HIV Infections/complications ; HIV Infections/pathology ; Humans ; Lymph Nodes/pathology ; Lymphoma/diagnosis ; Lymphoma/pathology ; Neoplasms ; Retrospective Studies ; South Africa ; Tuberculosis/pathology
Language	English
Publishing date	2022-04-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	639076-6
ISSN	1473-5571 ; 0269-9370 ; 1350-2840
ISSN (online)	1473-5571
ISSN	0269-9370 ; 1350-2840
DOI	10.1097/QAD.0000000000003261
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Article: Nelfinavir inhibition of Kaposi's sarcoma-associated herpesvirus protein expression and capsid assembly.

Li, Maggie / Smith, Barbara J / Lee, Jaeyeun / Petr, Jennifer / Anders, Nicole M / Wiseman, Robyn / Rudek, Michelle A / Ambinder, Richard F / Desai, Prashant J

Infectious agents and cancer

2024 Volume 19, Issue 1, Page(s) 7

Abstract: Background: Antiviral therapies that target herpesviruses are clinically important. Nelfinavir is a protease inhibitor that targets the human immunodeficiency virus (HIV) aspartyl protease. Previous studies demonstrated that this drug could also inhibit ...

Abstract	Background: Antiviral therapies that target herpesviruses are clinically important. Nelfinavir is a protease inhibitor that targets the human immunodeficiency virus (HIV) aspartyl protease. Previous studies demonstrated that this drug could also inhibit Kaposi's sarcoma-associated herpesvirus (KSHV) production. Our laboratory demonstrated nelfinavir can effectively inhibit herpes simplex virus type 1 (HSV-1) replication. For HSV-1 we were able to determine that virus capsids were assembled and exited the nucleus but did not mature in the cytoplasm indicating the drug inhibited secondary envelopment of virions. Methods: For KSHV, we recently derived a tractable cell culture system that allowed us to analyze the virus replication cycle in greater detail. We used this system to further define the stage at which nelfinavir inhibits KSHV replication. Results: We discovered that nelfinavir inhibits KSHV extracellular virus production. This was seen when the drug was incubated with the cells for 3 days and when we pulsed the cells with the drug for 1-5 min. When KSHV infected cells exposed to the drug were examined using ultrastructural methods there was an absence of mature capsids in the nucleus indicating a defect in capsid assembly. Because nelfinavir influences the integrated stress response (ISR), we examined the expression of viral proteins in the presence of the drug. We observed that the expression of many were significantly changed in the presence of drug. The accumulation of the capsid triplex protein, ORF26, was markedly reduced. This is an essential protein required for herpesvirus capsid assembly. Conclusions: Our studies confirm that nelfinavir inhibits KSHV virion production by disrupting virus assembly and maturation. This is likely because of the effect of nelfinavir on the ISR and thus protein synthesis and accumulation of the essential triplex capsid protein, ORF26. Of interest is that inhibition requires only a short exposure to drug. The source of infectious virus in saliva has not been defined in detail but may well be lymphocytes or other cells in the oral mucosa. Thus, it might be that a "swish and spit" exposure rather than systemic administration would prevent virion production.
Language	English
Publishing date	2024-03-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2251117-9
ISSN	1750-9378
ISSN	1750-9378
DOI	10.1186/s13027-024-00566-7
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Article ; Online: Alternative donor BMT with posttransplant cyclophosphamide as initial therapy for acquired severe aplastic anemia.

DeZern, Amy E / Zahurak, Marianna / Symons, Heather J / Cooke, Kenneth R / Huff, Carol Ann / Jain, Tania / Swinnen, Lode J / Imus, Philip H / Wagner-Johnston, Nina D / Ambinder, Richard F / Levis, Mark / Luznik, Leo / Bolaños-Meade, Javier / Fuchs, Ephraim J / Jones, Richard J / Brodsky, Robert A

Blood

2024 Volume 141, Issue 25, Page(s) 3031–3038

Abstract: Severe aplastic anemia (SAA) is a marrow failure disorder with high morbidity and mortality. It is treated with bone marrow transplantation (BMT) for those with fully matched donors, or immunosuppressive therapy (IST) for those who lack such a donor, ... ...

Abstract	Severe aplastic anemia (SAA) is a marrow failure disorder with high morbidity and mortality. It is treated with bone marrow transplantation (BMT) for those with fully matched donors, or immunosuppressive therapy (IST) for those who lack such a donor, which is often the case for underrepresented minorities. We conducted a prospective phase 2 trial of reduced-intensity conditioning HLA-haploidentical BMT and posttransplantation cyclophosphamide (PTCy)-based graft-versus-host (GVHD) prophylaxis as initial therapy for patients with SAA. The median patient age was 25 years (range, 3-63 years), and the median follow-up time was 40.9 months (95% confidence interval [CI], 29.4-55.7). More than 35% of enrollment was from underrepresented racial/ethnic groups. The cumulative incidence of grade 2 or 4 acute GVHD on day 100 was 7% (95% CI, not applicable [NA]-17), and chronic GVHD at 2 years was 4% (95% CI, NA-11). The overall survival of 27 patients was 92% (95% CI, 83-100) at 1, 2, and 3 years. The first 7 patients received lower dose total body irradiation (200 vs 400 cGy), but these patients were more likely to have graft failure (3 of 7) compared with 0 of 20 patients in the higher dose group (P = .01; Fisher exact test). HLA-haploidentical BMT with PTCy using 400 cGy total body irradiation resulted in 100% overall survival with minimal GVHD in 20 consecutive patients. Not only does this approach avoid any adverse ramifications of IST and its low failure-free survival, but the use of haploidentical donors also expands access to BMT across all populations. This trial was registered at www.clinicaltrials.gov as NCT02833805.
MeSH term(s)	Humans ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Bone Marrow Transplantation/adverse effects ; Anemia, Aplastic ; Prospective Studies ; Graft vs Host Disease/etiology ; Graft vs Host Disease/prevention & control ; Cyclophosphamide/therapeutic use
Chemical Substances	Cyclophosphamide (8N3DW7272P)
Language	English
Publishing date	2024-03-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2023020435
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Article ; Online: The same but different: autologous hematopoietic stem cell transplantation for patients with lymphoma and HIV infection.

Ambinder, R F

Bone marrow transplantation

2009 Volume 44, Issue 1, Page(s) 1–5

Abstract: In an earlier era, high-dose therapies were thought to be contraindicated in HIV-infected patients. Patients with HIV fared somewhat better with reduced-dose lymphoma therapies and salvage of relapsed patients was rarely possible. With more than a decade ...

Abstract	In an earlier era, high-dose therapies were thought to be contraindicated in HIV-infected patients. Patients with HIV fared somewhat better with reduced-dose lymphoma therapies and salvage of relapsed patients was rarely possible. With more than a decade of effective antiretroviral therapy, full-dose lymphoma therapies have become standard, and high-dose therapy with autologous hematopoietic stem cell rescue for those who fail frontline therapy or who are judged to have very high risk disease has been pursued with very encouraging results. Transplant-related mortality is less than 5%. With prophylaxis for pneumocystis and herpesvirus infections, deaths due to opportunistic infections are distinctly unusual. Most deaths have been associated with veno-occlusive disease or lymphoma progression. There is no need for quarantine of patients or special isolation procedures. Most patients with responsive lymphoma remain lymphoma free several years after high-dose therapy. CD4(+) cell count and HIV load seem not to be adversely affected in the long term. Much like diabetes, HIV infection should be regarded as a problem that requires special attention during high-dose therapy rather than a contraindication to high-dose therapy in patients with lymphoma who would otherwise be judged transplant candidates.
MeSH term(s)	HIV Infections/complications ; HIV Infections/immunology ; HIV Infections/mortality ; HIV Infections/therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma/complications ; Lymphoma/immunology ; Lymphoma/mortality ; Lymphoma/therapy ; Transplantation, Autologous
Language	English
Publishing date	2009-05-18
Publishing country	England
Document type	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/bmt.2009.105
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Article ; Online: Short Communication: Persistence of HIV After Allogeneic Bone Marrow Transplant in a Dually Infected Individual.

Capoferri, Adam A / Redd, Andrew D / Gocke, Christopher D / Clark, Laura R / Ambinder, Richard F / Durand, Christine M

AIDS research and human retroviruses

2021 Volume 38, Issue 1, Page(s) 33–36

Abstract: Allogeneic bone marrow transplant (alloBMT) with continuous antiretroviral therapy alone has not been shown to completely eradicate HIV, possibly due to HIV persistence in rare residual host cells or infection of donor cells. Within a trial of alloBMT in ...

Abstract	Allogeneic bone marrow transplant (alloBMT) with continuous antiretroviral therapy alone has not been shown to completely eradicate HIV, possibly due to HIV persistence in rare residual host cells or infection of donor cells. Within a trial of alloBMT in individuals with hematological malignancies and HIV (ClinicalTrials.gov, NCT01836068), we measured HIV reservoirs longitudinally using a quantitative viral outgrowth assay. We sequenced the reverse transcriptase region of
MeSH term(s)	Anti-Retroviral Agents/therapeutic use ; Bone Marrow Transplantation ; CD4-Positive T-Lymphocytes ; HIV Infections/complications ; HIV Infections/drug therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Phylogeny ; Viral Load
Chemical Substances	Anti-Retroviral Agents
Language	English
Publishing date	2021-07-05
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639130-8
ISSN	1931-8405 ; 0889-2229
ISSN (online)	1931-8405
ISSN	0889-2229
DOI	10.1089/AID.2021.0047
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Article ; Online: Brief Report: Rebound HIV Viremia With Meningoencephalitis After Antiretroviral Therapy Interruption After Allogeneic Bone Marrow Transplant.

Capoferri, Adam A / Redd, Andrew D / Gocke, Christopher D / Clark, Laura R / Quinn, Thomas C / Ambinder, Richard F / Durand, Christine M

Journal of acquired immune deficiency syndromes (1999)

2021 Volume 89, Issue 3, Page(s) 297–302

Abstract: Background: Allogeneic bone marrow transplant (alloBMT) in people living with HIV can lead to the undetectable levels of HIV reservoirs in blood, even using highly sensitive assays. However, with antiretroviral therapy (ART) interruption, rebound of HIV ...

Abstract	Background: Allogeneic bone marrow transplant (alloBMT) in people living with HIV can lead to the undetectable levels of HIV reservoirs in blood, even using highly sensitive assays. However, with antiretroviral therapy (ART) interruption, rebound of HIV viremia occurs. The source of this rebound viremia is of interest in HIV cure strategies. Methods: Within a trial of alloBMT in individuals with hematologic malignancies and HIV (ClinicalTrials.gov, NCT01836068), one recipient self-interrupted ART after achieving >99.5% host cell replacement in peripheral blood by day 147 and developed severe acute retroviral syndrome with meningoencephalitis at 156 days post alloBMT. We isolated replication-competent HIV using a quantitative viral outgrowth assay at 100 and 25 days before alloBMT and from the same time points before alloBMT for HIV DNA and cell-associated RNA from peripheral blood mononuclear cells and resting memory CD4+ T cells. We isolated HIV RNA in plasma and cerebrospinal fluid (CSF) at viral rebound. We sequenced the RT-region of pol and performed neighbor-joining phylogenetic reconstruction. Results: Phylogenetic analysis revealed an identical viral sequence at both pre-alloBMT time points accounting for 9 of 34 sequences (26%) of the sampled HIV reservoir. This sequence population grouped with viral rebound sequences from plasma and CSF with high sequence homology. Discussion: Despite >99.5% replacement of host cells in peripheral blood, ART interruption led to HIV viral rebound in plasma and CSF. Furthermore, the rebound virus matched replication-competent virus from resting memory CD4+ T cells before alloBMT. This case underscores that HIV-infected recipient cells can persist after alloBMT and that latent replication-competent virus can reestablish infection.
MeSH term(s)	Anti-Retroviral Agents/therapeutic use ; CD4-Positive T-Lymphocytes ; HIV Infections/complications ; HIV Infections/drug therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukocytes, Mononuclear ; Meningoencephalitis/drug therapy ; Phylogeny ; Viral Load ; Viremia/drug therapy ; Virus Replication
Chemical Substances	Anti-Retroviral Agents
Language	English
Publishing date	2021-11-09
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	645053-2
ISSN	1944-7884 ; 1077-9450 ; 0897-5965 ; 0894-9255 ; 1525-4135
ISSN (online)	1944-7884 ; 1077-9450
ISSN	0897-5965 ; 0894-9255 ; 1525-4135
DOI	10.1097/QAI.0000000000002862
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Article ; Online: Survival after autologous versus allogeneic transplantation in patients with relapsed and refractory Hodgkin lymphoma.

Fakhri, Bita / Yilmaz, Elif / Gao, Feng / Ambinder, Richard F / Jones, Richard / Bartlett, Nancy L / Cashen, Amanda / Wagner-Johnston, Nina

Leukemia & lymphoma

2021 Volume 62, Issue 10, Page(s) 2408–2415

Abstract: For relapsed Hodgkin lymphoma, salvage chemotherapy followed by auto-HCT is the standard of care. It is important to identify subpopulations who could benefit from allo-HCT. This retrospective analysis included 277 patients with rrHL who underwent first ... ...

Abstract	For relapsed Hodgkin lymphoma, salvage chemotherapy followed by auto-HCT is the standard of care. It is important to identify subpopulations who could benefit from allo-HCT. This retrospective analysis included 277 patients with rrHL who underwent first transplant with auto-HCT or allo-HCT between 2007-2017. Patients in the auto-HCT cohort (
MeSH term(s)	Hematopoietic Stem Cell Transplantation ; Hodgkin Disease/therapy ; Humans ; Neoplasm Recurrence, Local ; Retrospective Studies ; Transplantation, Homologous
Language	English
Publishing date	2021-05-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2021.1927016
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Article: Treatment of HIV-Associated Lymphomas: The Latest Approaches for Optimizing Outcomes.

Hunter, Natasha B / Vogt, Samantha / Ambinder, Richard F

Oncology (Williston Park, N.Y.)

2017 Volume 31, Issue 12, Page(s) 872–7, 884

Abstract: Treatment outcomes for patients with HIV-related lymphoma have improved since the advent of combination antiretroviral therapy. Standard regimens, including intensive regimens, are being used with encouraging results in patients with diffuse large B-cell ...

Abstract	Treatment outcomes for patients with HIV-related lymphoma have improved since the advent of combination antiretroviral therapy. Standard regimens, including intensive regimens, are being used with encouraging results in patients with diffuse large B-cell lymphoma, Burkitt lymphoma, Hodgkin lymphoma, and primary central nervous system lymphoma. Approaches to salvage therapy also parallel those used in patients without HIV infection, including autologous and allogeneic hematopoietic stem cell transplant. Drug interactions with particular antiretrovirals warrant close attention. At a population level, outcomes in patients with HIV infection and lymphoma remain inferior to outcomes achieved in the general population-but a great deal of progress has been made.
MeSH term(s)	Antibodies, Monoclonal, Murine-Derived/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Burkitt Lymphoma/drug therapy ; Cyclophosphamide/therapeutic use ; Doxorubicin/therapeutic use ; Etoposide/therapeutic use ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma, AIDS-Related/therapy ; Lymphoma, Large B-Cell, Diffuse/drug therapy ; Plasmablastic Lymphoma/drug therapy ; Prednisone/therapeutic use ; Vincristine/therapeutic use
Chemical Substances	Antibodies, Monoclonal, Murine-Derived ; R-CHOP protocol ; Vincristine (5J49Q6B70F) ; Etoposide (6PLQ3CP4P3) ; Doxorubicin (80168379AG) ; Cyclophosphamide (8N3DW7272P) ; Prednisone (VB0R961HZT)
Language	English
Publishing date	2017--15
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1067950-9
ISSN	0890-9091
ISSN	0890-9091
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