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  1. Article ; Online: This CAR won't start: predicting nonresponse in ALL.

    Webster, Jonathan A / Luznik, Leo

    Blood advances

    2023  Volume 7, Issue 15, Page(s) 4215–4217

    MeSH term(s) Child ; Humans ; Epigenome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; T-Lymphocytes
    Language English
    Publishing date 2023-08-08
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2023009776
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    Zs.A 7153: Show issues Location:
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  2. Article ; Online: Relapse after allogeneic transplantation with post-transplant cyclophosphamide: Shattering myths and evolving insight.

    McCurdy, Shannon R / Luznik, Leo

    Blood reviews

    2023  Volume 62, Page(s) 101093

    Abstract: Early studies in allogeneic blood or marrow transplantation (alloBMT) demonstrated that HLA-mismatching was protective again relapse. However, benefits in relapse reduction were outweighed by a high risk of graft-versus-host disease (GVHD) when using ... ...

    Abstract Early studies in allogeneic blood or marrow transplantation (alloBMT) demonstrated that HLA-mismatching was protective again relapse. However, benefits in relapse reduction were outweighed by a high risk of graft-versus-host disease (GVHD) when using conventional pharmacological immunosuppression. Post-transplant cyclophosphamide(PTCy)-based platforms abated the risk of GVHD thereby overcoming the negative effects of HLA-mismatching on survival. However, since its inception, PTCy has been shadowed by a reputation for a greater risk of relapse when compared with traditional GVHD prophylaxis. Specifically, whether PTCy reduces the anti-tumor efficacy of HLA-mismatched alloBMT by killing alloreactive T cells has been the subject of debate since the early 2000's. Here we review the many studies demonstrating the potent graft-versus-malignancy (GVM) properties of alloBMT with PTCy. We discuss the laboratory data from PTCy platforms supporting that T regulatory cells may be a major mechanism of prevention of GVHD and that natural killer (NK) cells may be early effectors of GVM. Finally, we propose potential paths to optimize GVM through selecting for class II mismatching and augmenting NK cell activity.
    MeSH term(s) Humans ; Cyclophosphamide/pharmacology ; Cyclophosphamide/therapeutic use ; Transplantation, Homologous ; Graft vs Host Disease/etiology ; Graft vs Host Disease/prevention & control ; Recurrence ; Immune Tolerance ; Hematopoietic Stem Cell Transplantation/adverse effects
    Chemical Substances Cyclophosphamide (8N3DW7272P)
    Language English
    Publishing date 2023-04-28
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 639015-8
    ISSN 1532-1681 ; 0268-960X
    ISSN (online) 1532-1681
    ISSN 0268-960X
    DOI 10.1016/j.blre.2023.101093
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2207: Show issues Location:
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  3. Article ; Online: PTCy and "The Story of the Three Bears".

    Radojcic, Vedran / Luznik, Leo

    Bone marrow transplantation

    2020  Volume 56, Issue 4, Page(s) 765–766

    MeSH term(s) Animals ; Cyclophosphamide ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Transplantation Conditioning ; Ursidae
    Chemical Substances Cyclophosphamide (8N3DW7272P)
    Language English
    Publishing date 2020-11-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 632854-4
    ISSN 1476-5365 ; 0268-3369 ; 0951-3078
    ISSN (online) 1476-5365
    ISSN 0268-3369 ; 0951-3078
    DOI 10.1038/s41409-020-01123-7
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    Zs.A 2168: Show issues Location:
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  4. Article ; Online: How I prevent GVHD in high-risk patients: posttransplant cyclophosphamide and beyond.

    Rimando, Joseph / McCurdy, Shannon R / Luznik, Leo

    Blood

    2022  Volume 141, Issue 1, Page(s) 49–59

    Abstract: Advances in conditioning, graft-versus-host disease (GVHD) prophylaxis and antimicrobial prophylaxis have improved the safety of allogeneic hematopoietic cell transplantation (HCT), leading to a substantial increase in the number of patients transplanted ...

    Abstract Advances in conditioning, graft-versus-host disease (GVHD) prophylaxis and antimicrobial prophylaxis have improved the safety of allogeneic hematopoietic cell transplantation (HCT), leading to a substantial increase in the number of patients transplanted each year. This influx of patients along with progress in remission-inducing and posttransplant maintenance strategies for hematologic malignancies has led to new GVHD risk factors and high-risk groups: HLA-mismatched related (haplo) and unrelated (MMUD) donors; older recipient age; posttransplant maintenance; prior checkpoint inhibitor and autologous HCT exposure; and patients with benign hematologic disorders. Along with the changing transplant population, the field of HCT has dramatically shifted in the past decade because of the widespread adoption of posttransplantation cyclophosphamide (PTCy), which has increased the use of HLA-mismatched related donors to levels comparable to HLA-matched related donors. Its success has led investigators to explore PTCy's utility for HLA-matched HCT, where we predict it will be embraced as well. Additionally, combinations of promising new agents for GVHD prophylaxis such as abatacept and JAK inhibitors with PTCy inspire hope for an even safer transplant platform. Using 3 illustrative cases, we review our current approach to transplantation of patients at high risk of GVHD using our modern armamentarium.
    MeSH term(s) Humans ; Graft vs Host Disease/etiology ; Graft vs Host Disease/prevention & control ; Graft vs Host Disease/drug therapy ; Cyclophosphamide/therapeutic use ; Hematopoietic Stem Cell Transplantation/adverse effects ; Hematologic Neoplasms/drug therapy ; Tissue Donors ; Unrelated Donors ; Transplantation Conditioning/adverse effects ; Retrospective Studies
    Chemical Substances Cyclophosphamide (8N3DW7272P)
    Language English
    Publishing date 2022-04-11
    Publishing country United States
    Document type Review ; Journal Article
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2021015129
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: PTCY keeps on giving!

    Radojcic, Vedran / Luznik, Leo

    Blood

    2019  Volume 134, Issue 11, Page(s) 848–849

    MeSH term(s) Antilymphocyte Serum ; Cyclophosphamide ; Graft vs Host Disease ; Humans ; Unrelated Donors
    Chemical Substances Antilymphocyte Serum ; Cyclophosphamide (8N3DW7272P)
    Language English
    Publishing date 2019-09-12
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2019002284
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  6. Article ; Online: Mechanism of action of posttransplantation cyclophosphamide: more than meets the eye.

    Radojcic, Vedran / Luznik, Leo

    The Journal of clinical investigation

    2019  Volume 129, Issue 6, Page(s) 2189–2191

    Abstract: For high-risk and refractory hematological malignancies, allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only available curative therapy, with benefits derived from the antigenic disparity between recipient cancer and the incoming ... ...

    Abstract For high-risk and refractory hematological malignancies, allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only available curative therapy, with benefits derived from the antigenic disparity between recipient cancer and the incoming immune system. This immunologic mismatch can also lead to lethal graft-versus-host disease (GVHD), and immunosuppression strategies, including high-dose posttransplantation cyclophosphamide (PTCy), have been developed to allow for safe alloHSCT delivery. In this issue of JCI, Wachsmuth et al. present the results of preclinical studies designed to evaluate the mechanisms that underlie efficacy of PTCy after alloHSCT. The results of this study challenge previous reports indicating that alloreactive T cell elimination and thymic clonal deletion are primary mediators of PTCy efficacy and provide strong evidence to support FoxP3+CD4+ Tregs as important effectors of PTCy benefits.
    MeSH term(s) Cyclophosphamide ; Graft vs Host Disease ; Hematologic Neoplasms ; Hematopoietic Stem Cell Transplantation ; Humans
    Chemical Substances Cyclophosphamide (8N3DW7272P)
    Language English
    Publishing date 2019-05-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI128710
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    Ua VI Zs.184: Show issues Location:
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  7. Article: Treatment of AML Relapse After Allo-HCT.

    Webster, Jonathan A / Luznik, Leo / Gojo, Ivana

    Frontiers in oncology

    2021  Volume 11, Page(s) 812207

    Abstract: With advances in allogeneic hematopoietic stem cell transplant (allo-HCT), disease relapse has replaced transplant-related mortality as the primary cause of treatment failure for patients with acute myeloid leukemia (AML). The efficacy of allo-HCT in AML ...

    Abstract With advances in allogeneic hematopoietic stem cell transplant (allo-HCT), disease relapse has replaced transplant-related mortality as the primary cause of treatment failure for patients with acute myeloid leukemia (AML). The efficacy of allo-HCT in AML is a consequence of a graft-versus-leukemia (GVL) effect that is mediated by T lymphocytes, and unique mechanisms of immune evasion underlying post-allo-HCT AML relapses have recently been characterized. Relapsed AML following allo-HCT presents a particularly vexing clinical challenge because transplant-related toxicities, such as graft-versus-host (GVHD) and infections, increase the risk of treatment-related morbidity and mortality. In general, the prognosis of relapsed AML following allo-HCT is poor with most patients failing to achieve a subsequent remission and 2-year survival consistently <15%. The two factors that have been found to predict a better prognosis are a longer duration of post-transplant remission prior to relapse and a lower disease burden at the time of relapse. When considered in combination with a patient's age; co-morbidities; and performance status, these factors can help to inform the appropriate therapy for the treatment of post-transplant relapse. This review discusses the options for the treatment of post-transplant AML relapse with a focus on the options to achieve a subsequent remission and consolidation with cellular immunotherapy, such as a second transplant or donor lymphocyte infusion (DLI). While intensive reinduction therapy and less intensive approaches with hypomethylating agents have long represented the two primary options for the initial treatment of post-transplant relapse, molecularly targeted therapies and immunotherapy are emerging as potential alternative options to achieve remission. Herein, we highlight response and survival outcomes achieved specifically in the post-transplant setting using each of these approaches and discuss how some therapies may overcome the immunologic mechanisms that have been implicated in post-transplant relapse. As long-term survival in post-transplant relapse necessarily involves consolidation with cellular immunotherapy, we present data on the efficacy and toxicity of both DLI and second allo-HCT including when such therapies are integrated with reinduction. Finally, we provide our general approach to the treatment of post-transplant relapse, integrating both novel therapies and our improved understanding of the mechanisms underlying post-transplant relapse.
    Language English
    Publishing date 2021-12-16
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2021.812207
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  8. Article ; Online: Teaching a Young Dog New Tricks: Modifications to the Post-Transplantation Cyclophosphamide Haploidentical Transplantation Platform.

    Kanakry, Christopher G / Luznik, Leo

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation

    2018  Volume 24, Issue 6, Page(s) 1108–1110

    MeSH term(s) Animals ; Bone Marrow ; Bone Marrow Transplantation ; Cyclophosphamide ; Dogs ; Leukemia, Myeloid, Acute ; Transplantation, Haploidentical
    Chemical Substances Cyclophosphamide (8N3DW7272P)
    Language English
    Publishing date 2018-04-10
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1474865-4
    ISSN 1523-6536 ; 1083-8791
    ISSN (online) 1523-6536
    ISSN 1083-8791
    DOI 10.1016/j.bbmt.2018.04.004
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  9. Article ; Online: Notching up B-cell pathology in chronic GVHD.

    Radojcic, Vedran / Luznik, Leo

    Blood

    2017  Volume 130, Issue 19, Page(s) 2053–2054

    MeSH term(s) B-Lymphocytes ; Chronic Disease ; Graft vs Host Disease ; Humans
    Language English
    Publishing date 2017-11-09
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood-2017-09-805366
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  10. Article ; Online: For Whom the Bell Tolls: Programmed Death 1 as a Marker of Post-Transplantation Mortality.

    Robinson, Tara M / Luznik, Leo

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation

    2016  Volume 22, Issue 12, Page(s) 2115–2116

    Language English
    Publishing date 2016-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1474865-4
    ISSN 1523-6536 ; 1083-8791
    ISSN (online) 1523-6536
    ISSN 1083-8791
    DOI 10.1016/j.bbmt.2016.09.009
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