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Leo luznik

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https://www.readbyqxmd.com/read/29452245/haploidentical-bone-marrow-transplantation-with-post-transplant-cyclophosphamide-using-non-first-degree-related-donors
#1
Hany Elmariah, Yvette L Kasamon, Marianna Zahurak, Karen W Macfarlane, Noah Tucker, Gary L Rosner, Javier Bolaños-Meade, Ephraim J Fuchs, Nina Wagner-Johnston, Lode J Swinnen, Carol Ann Huff, William H Matsui, Douglas E Gladstone, Shannon R McCurdy, Ivan Borrello, Christian B Gocke, Satish Shanbhag, Kenneth R Cooke, Syed Abbas Ali, Robert A Brodsky, Amy E DeZern, Leo Luznik, Richard J Jones, Richard F Ambinder
Outcomes of nonmyeloablative (NMA) haploidentical (haplo) blood or marrow transplant (BMT) with post-transplantation cyclophosphamide (PTCy) using non-first-degree relatives are unknown. We evaluated 33 consecutive adult patients (median age 56 years) with hematologic malignancies who underwent NMA haplo T-cell replete BMT with PTCy at Johns Hopkins using second- or third-degree related donors. Donors consisted of 10 nieces (30%), 9 nephews (27%), 7 first cousins (21%), 5 grandchildren (15%), and 2 uncles (6%)...
February 13, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29353109/shortened-duration-tacrolimus-after-nonmyeloablative-hla-haploidentical-bmt
#2
Yvette L Kasamon, Ephraim J Fuchs, Marianna Zahurak, Gary L Rosner, Heather J Symons, Douglas E Gladstone, Carol Ann Huff, Lode J Swinnen, Robert A Brodsky, William H Matsui, Ivan Borrello, Satish Shanbhag, Kenneth R Cooke, Richard F Ambinder, Leo Luznik, Javier Bolaños-Meade, Richard J Jones
With posttransplantation cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis, nonmyeloablative HLA-haploidentical (NMA haplo) and HLA-matched blood or marrow transplantation (BMT) have comparable outcomes. Early discontinuation of immunosuppression may reduce relapse, as well as improve immune reconstitution, but may increase GVHD. We conducted a prospective trial of NMA haplo BMT for patients with hematologic malignancies (median age, 61), evaluating the safety of early discontinuation of tacrolimus...
January 15, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29335625/the-european-society-for-blood-and-marrow-transplantation-ebmt-consensus-guidelines-for-the-detection-and-treatment-of-donor-specific-anti-hla-antibodies-dsa-in-haploidentical-hematopoietic-cell-transplantation
#3
REVIEW
Stefan O Ciurea, Kai Cao, Marcelo Fernadez-Vina, Piyanuch Kongtim, Monzr Al Malki, Ephraim Fuchs, Leo Luznik, Xiao-Jun Huang, Fabio Ciceri, Franco Locatelli, Franco Aversa, Luca Castagna, Andrea Bacigalupo, Massimo Martelli, Didier Blaise, Rupert Handgretinger, Denis-Claude Roy, Paul O'Donnell, Asad Bashey, Hillard M Lazarus, Karen Ballen, Bipin N Savani, Mohamad Mohty, Arnon Nagler
Haploidentical donors are now increasingly considered for transplantation in the absence of HLA-matched donors or when an urgent transplant is needed. Donor-specific anti-HLA antibodies (DSA) have been recently recognized as an important barrier against successful engraftment of donor cells, which can affect transplant survival. DSA appear more prevalent in this type of transplant due to higher likelihood of alloimmunization of multiparous females against offspring's HLA antigens, and the degree of mismatch...
January 15, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29325830/blood-and-marrow-transplant-clinical-trials-network-report-on-development-of-novel-endpoints-and-selection-of-promising-approaches-for-graft-versus-host-disease-prevention-trials
#4
Marcelo C Pasquini, Brent Logan, Richard J Jones, Amin M Alousi, Frederick R Appelbaum, Javier Bolaños-Meade, Mary E D Flowers, Sergio Giralt, Mary M Horowitz, David Jacobsohn, John Koreth, John E Levine, Leo Luznik, Richard Maziarz, Adam Mendizabal, Steven Pavletic, Miguel-Angel Perales, David Porter, Ran Reshef, Daniel Weisdorf, Joseph H Antin
Graft versus host disease (GVHD) is a common complication after hematopoietic cell transplantation (HCT) and associated with significant morbidity and mortality. Preventing GVHD without chronic therapy or increasing relapse is a desired goal. Here, we report a benchmark analysis to evaluate the performance of six GVHD prevention strategies tested at single institutions compared to a large multicenter outcomes database as a control. Each intervention was compared to the control for the incidence of acute and chronic GVHD and overall survival and against novel composite endpoints: acute and chronic GVHD, relapse-free survival (GRFS) and chronic GVHD, relapse-free survival (CRFS)...
January 8, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29296707/cyclophosphamide-improves-engraftment-in-patients-with-scd-and-severe-organ-damage-who-undergo-haploidentical-pbsct
#5
Courtney D Fitzhugh, Matthew M Hsieh, Tiffani Taylor, Wynona Coles, Katherine Roskom, Delon Wilson, Elizabeth Wright, Neal Jeffries, Christopher J Gamper, Jonathan Powell, Leo Luznik, John F Tisdale
Peripheral blood stem cell transplantation (PBSCT) offers a curative option for sickle cell disease (SCD). Although HLA-matched sibling transplantation is promising, the vast majority of patients lack such a donor. We sought to develop a novel nonmyeloablative HLA-haploidentical PBSCT approach that could safely be used for patients with severe organ damage. Based on findings in our preclinical model, we developed a phase 1/2 trial using alemtuzumab, 400 cGy total body irradiation, and escalating doses of posttransplant cyclophosphamide (PT-Cy): 0 mg/kg in cohort 1, 50 mg/kg in cohort 2, and 100 mg/kg in cohort 3...
April 25, 2017: Blood Advances
https://www.readbyqxmd.com/read/29283908/have-haploidentical-transplants-replaced-umbilical-cord-transplants-for-acute-leukemias
#6
Jia Hau Liu, Christopher G Kanakry, Leo Luznik
PURPOSE OF REVIEW: Haploidentical stem cell transplantation (Haplo SCT) and umbilical cord blood stem cell transplantation (UCB SCT) have emerged over the past two to three decades as viable sources of alternative donor SCT when a human leukocyte antigen matched donor is not available. However, which of these two donor types is optimal for patients with leukemia in need of allografting is unknown. RECENT FINDINGS: For patients with acute leukemia, results of UCB SCT have been improved by the use of double umbilical cord units and emerging ex-vivo expansion technologies...
March 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29242852/prospective-study-of-nonmyeloablative-hla-mismatched-unrelated-bmt-with-high-dose-posttransplantation-cyclophosphamide
#7
Yvette L Kasamon, Richard F Ambinder, Ephraim J Fuchs, Marianna Zahurak, Gary L Rosner, Javier Bolaños-Meade, Mark J Levis, Douglas E Gladstone, Carol Ann Huff, Lode J Swinnen, William H Matsui, Ivan Borrello, Robert A Brodsky, Richard J Jones, Leo Luznik
Allogeneic blood or marrow transplantation (BMT) candidates may lack HLA-matched, related haploidentical, and unrelated umbilical cord options. Barriers to partially HLA-mismatched, unrelated donor (mMUD) BMT include excess graft-versus-host disease (GVHD), graft failure, and death. We prospectively studied nonmyeloablative (NMA) mMUD BMT with high-dose posttransplantation cyclophosphamide (PTCy) for patients with hematologic malignancies. Three transplants were performed with busulfan/fludarabine conditioning, with subsequent change to fludarabine/Cy/total body irradiation (flu/Cy/TBI)...
2017: Blood Advances
https://www.readbyqxmd.com/read/29197680/increased-co-expression-of-pd-1-tigit-and-klrg-1-on-tumor-reactive-cd8-t-cells-during-relapse-after-allo-sct
#8
Tim J A Hutten, Wieger J Norde, Rob Woestenenk, Ruo Chen Wang, Frans Maas, Michel Kester, J H Frederik Falkenburg, Sofia Berglund, Leo Luznik, Joop H Jansen, Nicolaas Schaap, Harry Dolstra, Willemijn Hobo
Allogeneic stem cell transplantation (allo-SCT) can be a curative treatment for patients with a hematological malignancy due to allo-reactive T cell responses recognizing minor histocompatibility antigens (MiHA). Yet, tumor immune escape mechanisms can cause failure of T cell immunity, leading to relapse. Tumor cells display low expression of co-stimulatory molecules and can up-regulate co-inhibitory molecules that, upon ligation with their counter receptors on the tumor-reactive T cells, inhibit T cell functionality...
November 29, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29122773/notching-up-b-cell-pathology-in-chronic-gvhd
#9
Vedran Radojcic, Leo Luznik
No abstract text is available yet for this article.
November 9, 2017: Blood
https://www.readbyqxmd.com/read/29055682/grade-ii-acute-graft-versus-host-disease-and-higher-nucleated-cell-graft-dose-improve-progression-free-survival-after-hla-haploidentical-transplant-with-post-transplant-cyclophosphamide
#10
Shannon R McCurdy, Christopher G Kanakry, Hua-Ling Tsai, Yvette L Kasamon, Margaret M Showel, Javier Bolaños-Meade, Carol Ann Huff, Ivan Borrello, William H Matsui, Robert A Brodsky, Richard F Ambinder, Maria P Bettinotti, Ephraim J Fuchs, Gary L Rosner, Richard J Jones, Leo Luznik
Compared with standard graft-versus-host disease (GVHD) prophylaxis platforms, post-transplantation cyclophosphamide (PTCy) after T cell-replete HLA-haploidentical (haplo) bone marrow transplantation (BMT) reduces the risk of grades III to IV acute (a) and chronic (c) GVHD but maintains similar rates of grade II aGVHD. Given that mild GVHD has been associated with reduced treatment failure in HLA-matched BMT, we evaluated the risk factors for and effects of GVHD on survival in 340 adults with hematologic malignancies who engrafted after nonmyeloablative haplo-BMT with PTCy, mycophenolate mofetil, and tacrolimus...
October 18, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28986344/nk-cell-recovery-after-haploidentical-hsct-with-post-transplant-cyclophosphamide-dynamics-and-clinical-implications
#11
Antonio Russo, Giacomo Oliveira, Sofia Berglund, Raffaella Greco, Valentina Gambacorta, Nicoletta Cieri, Cristina Toffalori, Laura Zito, Francesca Lorentino, Simona Piemontese, Mara Morelli, Fabio Giglio, Andrea Assanelli, Maria Teresa Lupo Stanghellini, Chiara Bonini, Jacopo Peccatori, Fabio Ciceri, Leo Luznik, Luca Vago
The use of post-transplant cyclophosphamide (PT-Cy) as GvHD prophylaxis has revolutionized haploidentical HSCT, allowing safe infusion of unmanipulated T cell-replete grafts. PT-Cy selectively eliminates proliferating alloreactive T cells, but whether and how it affects NK cells and their alloreactivity is largely unknown. Here we characterized NK cell dynamics in 17 patients who received unmanipulated haploidentical grafts, containing high numbers of mature NK cells, according to PT-Cy-based protocols in two independent centers...
October 6, 2017: Blood
https://www.readbyqxmd.com/read/28754545/major-histocompatibility-mismatch-and-donor-choice-for-second-allogeneic-bone-marrow-transplantation
#12
Philip H Imus, Amanda L Blackford, Maria Bettinotti, Brian Iglehart, August Dietrich, Noah Tucker, Heather Symons, Kenneth R Cooke, Leo Luznik, Ephraim J Fuchs, Robert A Brodsky, William H Matsui, Carol Ann Huff, Douglas Gladstone, Richard F Ambinder, Ivan M Borrello, Lode J Swinnen, Richard J Jones, Javier Bolaños-Meade
Large alternative donor pools provide the potential for selecting a different donor for a second allogeneic (allo) bone or marrow transplant (BMT). As HLA disparity may contribute to the graft-versus-tumor effect, utilizing new mismatched haplotype donors may potentially improve the antitumor activity for relapsed hematologic malignancies despite a previous alloBMT. Data from patients who received a second alloBMT for relapsed hematologic malignancies at Johns Hopkins were analyzed. Outcomes were compared between patients who received a second allograft with the same MHC composition and those who received an allograft with a new mismatched haplotype...
July 25, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28711728/allogeneic-blood-or-marrow-transplantation-with-post-transplantation-cyclophosphamide-as-graft-versus-host-disease-prophylaxis-in-multiple-myeloma
#13
Nilanjan Ghosh, Xiaobu Ye, Hua-Ling Tsai, Javier Bolaños-Meade, Ephraim J Fuchs, Leo Luznik, Lode J Swinnen, Douglas E Gladstone, Richard F Ambinder, Ravi Varadhan, Satish Shanbhag, Robert A Brodsky, Ivan M Borrello, Richard J Jones, William Matsui, Carol Ann Huff
Allogeneic blood or marrow transplantation (alloBMT) may lead to long-term disease control in patients with multiple myeloma (MM). However, historically, the use of alloBMT in MM has been limited by its high nonrelapse mortality (NRM) rates, primarily from graft-versus-host disease (GVHD). We previously demonstrated that post-transplantation cyclophosphamide (PTCy) decreases the toxicities of both acute and chronic GVHD after alloBMT. Here, we examine the impact of PTCy in patients with MM undergoing alloBMT at Johns Hopkins Hospital...
November 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28254742/pirfenidone-ameliorates-murine-chronic-gvhd-through-inhibition-of-macrophage-infiltration-and-tgf-%C3%AE-production
#14
Jing Du, Katelyn Paz, Ryan Flynn, Ante Vulic, Tara M Robinson, Katie E Lineburg, Kylie A Alexander, Jingjing Meng, Sabita Roy, Angela Panoskaltsis-Mortari, Michael Loschi, Geoffrey R Hill, Jonathan S Serody, Ivan Maillard, David Miklos, John Koreth, Corey S Cutler, Joseph H Antin, Jerome Ritz, Kelli P MacDonald, Timothy W Schacker, Leo Luznik, Bruce R Blazar
Allogeneic hematopoietic stem cell transplantation is hampered by chronic graft-versus-host disease (cGVHD), resulting in multiorgan fibrosis and diminished function. Fibrosis in lung and skin leads to progressive bronchiolitis obliterans (BO) and scleroderma, respectively, for which new treatments are needed. We evaluated pirfenidone, a Food and Drug Administration (FDA)-approved drug for idiopathic pulmonary fibrosis, for its therapeutic effect in cGVHD mouse models with distinct pathophysiology. In a full major histocompatibility complex (MHC)-mismatched, multiorgan system model with BO, donor T-cell responses that support pathogenic antibody production are required for cGVHD development...
May 4, 2017: Blood
https://www.readbyqxmd.com/read/28126963/plasma-derived-proteomic-biomarkers-in-human-leukocyte-antigen-haploidentical-or-human-leukocyte-antigen-matched-bone-marrow-transplantation-using-post-transplantation-cyclophosphamide
#15
Christopher G Kanakry, Giorgos Bakoyannis, Susan M Perkins, Shannon R McCurdy, Ante Vulic, Edus H Warren, Etienne Daguindau, Taylor Olmsted, Christen Mumaw, Andrea M H Towlerton, Kenneth R Cooke, Paul V O'Donnell, Heather J Symons, Sophie Paczesny, Leo Luznik
Recent studies have suggested that plasma-derived proteins may be potential biomarkers relevant for graft-versus-host disease and/or non-relapse mortality occurring after allogeneic blood or marrow transplantation. However, none of these putative biomarkers have been assessed in patients treated either with human leukocyte antigen-haploidentical blood or marrow transplantation or with post-transplantation cyclophosphamide, which has been repeatedly associated with low rates of severe acute graft-versus-host disease, chronic graft-versus-host disease, and non-relapse mortality...
May 2017: Haematologica
https://www.readbyqxmd.com/read/28062216/post-transplantation-cyclophosphamide-after-bone-marrow-transplantation-is-not-associated-with-an-increased-risk-of-donor-derived-malignancy
#16
Robbie G Majzner, Huzefa Mogri, Ravi Varadhan, Patrick Brown, Kenneth R Cooke, Javier Bolaños-Meade, Lode Swinnen, Jennifer Kanakry, Leo Luznik, Richard J Jones, Ephraim Fuchs, Rich Ambinder, Yvette Kasamon, Heather J Symons
Post-transplantation cyclophosphamide (PTCy) can be used for graft-versus-host disease (GVHD) prophylaxis alone or in combination with other agents and is associated with excellent rates of engraftment and acute and chronic GVHD, as well as absence of post-transplantation lymphoproliferative disease. No study has previously evaluated the risk for developing donor-derived malignancy (DDM) in patients who receive PTCy. Giving chemotherapy in the immediate post-transplantation period carries with it a theoretic risk of disturbing the graft at a time of increased hematopoietic stress and causing or accelerating the development of malignancy...
April 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28049637/low-immunosuppressive-burden-after-hla-matched-related-or-unrelated-bmt-using-posttransplantation-cyclophosphamide
#17
Christopher G Kanakry, Javier Bolaños-Meade, Yvette L Kasamon, Marianna Zahurak, Nadira Durakovic, Terry Furlong, Marco Mielcarek, Marta Medeot, Ivana Gojo, B Douglas Smith, Jennifer A Kanakry, Ivan M Borrello, Robert A Brodsky, Douglas E Gladstone, Carol Ann Huff, William H Matsui, Lode J Swinnen, Kenneth R Cooke, Richard F Ambinder, Ephraim J Fuchs, Marcos J de Lima, Borje S Andersson, Ravi Varadhan, Paul V O'Donnell, Richard J Jones, Leo Luznik
The intensive and prolonged immunosuppressive therapy required to prevent or treat graft-versus-host disease (GVHD) after allogeneic blood or marrow transplantation (alloBMT) puts patients at substantial risk for life-threatening infections, organ toxicity, and disease relapse. Posttransplantation cyclophosphamide (PTCy) can function as single-agent GVHD prophylaxis after myeloablative, HLA-matched related (MRD), or HLA-matched unrelated (MUD) donor T-cell-replete bone marrow allografting, obviating the need for additional prophylactic immunosuppression...
March 9, 2017: Blood
https://www.readbyqxmd.com/read/27888014/nonmyeloablative-haploidentical-bone-marrow-transplantation-with-post-transplantation-cyclophosphamide-for-pediatric-and-young-adult-patients-with-high-risk-hematologic-malignancies
#18
Orly R Klein, Jessica Buddenbaum, Noah Tucker, Allen R Chen, Christopher J Gamper, David Loeb, Elias Zambidis, Nicolas J Llosa, Jeffrey S Huo, Nancy Robey, Mary Jo Holuba, Yvette L Kasamon, Shannon R McCurdy, Richard Ambinder, Javier Bolaños-Meade, Leo Luznik, Ephraim J Fuchs, Richard J Jones, Kenneth R Cooke, Heather J Symons
Lower-intensity conditioning regimens for haploidentical blood or marrow transplantation (BMT) are safe and efficacious for adult patients with hematologic malignancies. We report data for pediatric/young adult patients with high-risk hematologic malignancies (n = 40) treated with nonmyeloablative haploidentical BMT with post-transplantation cyclophosphamide from 2003 to 2015. Patients received a preparative regimen of fludarabine, cyclophosphamide, and total body irradiation. Post-transplantation immunosuppression consisted of cyclophosphamide, mycophenolate mofetil, and tacrolimus...
February 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27861294/induction-of-major-histocompatibility-complex-mismatched-mouse-lung-allograft-acceptance-with-combined-donor-bone-marrow-lung-transplant-using-a-12-hour-nonmyeloablative-conditioning-regimen
#19
Jeffrey M Dodd-O, Sudipto Ganguly, Ante Vulic, Angela Panoskaltsis-Mortari, John F McDyer, Leo Luznik
BACKGROUND: Despite broad and intense conventional immunosuppression, long-term survival after lung transplantation lags behind that for other solid organ transplants, primarily because of allograft rejection. Therefore, new strategies to promote lung allograft acceptance are urgently needed. The purpose of the present study was to induce allograft tolerance with a protocol compatible with deceased donor organ utilization. METHODS: Using the major histocompatibility complex-mismatched mouse orthotopic lung transplant model, we investigated a conditioning regimen consisting of pretransplant T cell depletion, low-dose total body irradiation and posttransplant (donor) bone marrow, and splenocyte infusion followed by posttransplantation cyclophosphamide...
December 2016: Transplantation
https://www.readbyqxmd.com/read/27846611/comparable-composite-endpoints-after-hla-matched-and-hla-haploidentical-transplantation-with-post-transplantation-cyclophosphamide
#20
Shannon R McCurdy, Yvette L Kasamon, Christopher G Kanakry, Javier Bolaños-Meade, Hua-Ling Tsai, Margaret M Showel, Jennifer A Kanakry, Heather J Symons, Ivana Gojo, B Douglas Smith, Maria P Bettinotti, William H Matsui, Amy E Dezern, Carol Ann Huff, Ivan Borrello, Keith W Pratz, Douglas E Gladstone, Lode J Swinnen, Robert A Brodsky, Mark J Levis, Richard F Ambinder, Ephraim J Fuchs, Gary L Rosner, Richard J Jones, Leo Luznik
Composite endpoints that not only encompass mortality and relapse, but other critical post-transplant events such as graft-versus-host disease, are being increasingly utilized to quantify survival without significant morbidity after allogeneic blood or marrow transplantation. High-dose, post-transplantation cyclophosphamide reduces severe graft-versus-host disease with allogeneic marrow transplantation, making composite endpoints after this management particularly interesting. We retrospectively analyzed 684 adults with hematologic malignancies who received T-cell-replete bone marrow grafts and cyclophosphamide after myeloablative HLA-matched related (n=192) or unrelated (n=120), or non-myeloablative HLA-haploidentical (n=372) donor transplantation...
February 2017: Haematologica
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