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post transplantation cyclophosphamide

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https://www.readbyqxmd.com/read/29147612/low-dose-post-transplant-cyclophosphamide-can-mitigate-gvhd-and-enhance-the-g-csf-atg-induced-gvhd-protective-activity-and-improve-haploidentical-transplant-outcomes
#1
Yu Wang, Ying-Jun Chang, Lu Chen, Lan-Ping Xu, Zhi-Lei Bian, Xiao-Hui Zhang, Chen-Hua Yan, Kai-Yan Liu, Xiao-Jun Huang
Use of high-dose, post-transplant cyclophosphamide (PTCy) results in low rates of graft-versus-host-disease (GVHD) and favorable immune reconstitution, although with higher rates of relapse and somewhat high rates of graft failure. We hypothesized that permissible dose reduction of PTCy might be feasible. The current study attempts to establish a murine model and focus on regulatory T cells (Tregs) to clarify the immunological mechanisms for GVHD prevention by low-dose PTCy. In addition, a prospective, clinical cohort study in haploidentical, T-cell replete transplantation is initiated to support the rational...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29136299/malignancy-in-renal-transplant-recipients-exposed-to-cyclophosphamide-prior-to-transplantation-for-the-treatment-of-native-glomerular-disease
#2
M R Jorgenson, J L Descourouez, T Singh, Brad C Astor, Sarah E Panzer
STUDY OBJECTIVE: To evaluate the risk of post-transplantation malignancy in renal transplant recipients exposed to pre-transplantation cyclophosphamide for treatment of glomerular nephropathy (GN). DESIGN: Retrospective cohort study. SETTING: Tertiary academic medical center. PATIENTS: Six hundred adult renal transplant recipients transplanted between 1993 and 2014; 54 patients were exposed to pre-transplantation cyclophosphamide for treatment of GN (GN-CYC group), and 546 patients with polycystic kidney disease were not exposed to pre-transplantation cyclophosphamide (PKD group)...
November 14, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/29132903/progressive-multifocal-leukoencephalopathy-in-patients-receiving-rituximab-and-cyclophosphamide-after-haplo-identical-t-cell-replete-transplantation-and-review-of-the-literature
#3
REVIEW
R Salem, R Massoud, S S Kanj, M Hamdan, R Salman, A Bazarbachi, J El-Cheikh
John Cunningham virus (JCV) reactivation, occurring mainly in immunocompromised patients, leads to progressive multifocal leukoencephalopathy, an uncommon but lethal disease. JCV reactivation after T-cell replete haploidentical stem cell transplantation, in the pre-cyclophosphamide era, is poorly represented in the literature. We therefore describe two cases of acute myeloid leukemia who developed JCV reactivation after receiving cyclophosphamide and rituximab post haploidentical stem cell transplantation, and review the literature, aiming to a better understanding of the disease course and its risk factors...
November 10, 2017: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/29127275/allogeneic-stem-cell-transplantation-in-fully-mhc-matched-mauritian-cynomolgus-macaques-recapitulates-diverse-human-clinical-outcomes
#4
Benjamin J Burwitz, Helen L Wu, Shaheed Abdulhaqq, Christine Shriver-Munsch, Tonya Swanson, Alfred W Legasse, Katherine B Hammond, Stephanie L Junell, Jason S Reed, Benjamin N Bimber, Justin M Greene, Gabriela M Webb, Mina Northrup, Wolfram Laub, Paul Kievit, Rhonda MacAllister, Michael K Axthelm, Rebecca Ducore, Anne Lewis, Lois M A Colgin, Theodore Hobbs, Lauren D Martin, Betsy Ferguson, Charles R Thomas, Angela Panoskaltsis-Mortari, Gabrielle Meyers, Jeffrey J Stanton, Richard T Maziarz, Jonah B Sacha
Allogeneic hematopoietic stem cell transplantation (HSCT) is a critically important therapy for hematological malignancies, inborn errors of metabolism, and immunodeficiency disorders, yet complications such as graft-vs.-host disease (GvHD) limit survival. Development of anti-GvHD therapies that do not adversely affect susceptibility to infection or graft-vs.-tumor immunity are hampered by the lack of a physiologically relevant, preclinical model of allogeneic HSCT. Here we show a spectrum of diverse clinical HSCT outcomes including primary and secondary graft failure, lethal GvHD, and stable, disease-free full donor engraftment using reduced intensity conditioning and mobilized peripheral blood HSCT in unrelated, fully MHC-matched Mauritian-origin cynomolgus macaques...
November 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29100905/post-transplant-cyclophosphamide-ptcy-as-sole-gvhd-prophylaxis-is-feasible-in-patients-undergoing-peripheral-blood-stem-cell-transplantation-for-severe-aplastic-anaemia-using-matched-sibling-donors
#5
Biju George, Nisham Pn, Anup J Devasia, Uday Kulkarni, Anu Korula, Kavitha M Lakshmi, Aby Abraham, Alok Srivastava, Vikram Mathews
High-dose cyclophosphamide (PTCY) following allogeneic hematopoietic cell transplantation (HSCT) has been shown to be effective in preventing graft-versus-host disease (GVHD) following HLA-matched bone marrow transplantation. We performed a phase II study of PTCY given at 50 mg/kg IV on days 3 and 4 as sole GVHD prophylaxis following HSCT for severe aplastic anemia (SAA) receiving G-CSF-mobilized peripheral blood stem cell (PBSC) grafts from HLA-matched related donors following conditioning with fludarabine, cyclophosphamide and single dose Total Body Irradiation (TBI)...
October 31, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29061531/outcomes-of-unrelated-donor-stem-cell-transplant-with-post-transplant-cyclophosphamide-for-graft-versus-host-disease-prophylaxis-in-patients-with-severe-sickle-cell-disease
#6
Hemalatha G Rangarajan, Rolla Abu-Arja, Vinita Pai, Gregory M T Guilcher, Sandeep Soni
Unrelated donor (URD) hematopoietic cell transplants (HCT) in children with sickle cell disease (SCD) is associated with a high incidence of rejection and graft versus host disease. We report on first four patients with severe SCD who underwent URD HCT using a novel myeloablative and immunosuppressive regimen comprising of busulfan, fludarabine and anti-thymocyte globulin with a single dose of post-transplant cyclophosphamide along with tacrolimus and mycophenolate mofetil for graft versus host disease prophylaxis...
October 20, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29052026/high-dose-chemotherapy-and-autologous-peripheral-blood-stem-cell-transplantation-with-bcvac-regimen-followed-by-maintenance-chemotherapy-for-children-with-very-high-risk-acute-lymphoblastic-leukemia
#7
Che Ry Hong, Hyoung Jin Kang, Kyung Duk Park, Hee Young Shin, Hyo Seop Ahn
Allogeneic hematopoietic stem cell transplantation (HSCT) is the recommended treatment for children with very high risk acute lymphoblastic leukemia (ALL), but it requires adequate institutional infrastructure, experience, and expertise, especially for alternative donor HSCT. We review our experience with high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplantation (APBSCT), followed by post-APBSCT maintenance chemotherapy for children with very high risk ALL. Between August 1997 and November 2012, our institute was not successful with HLA-haploidentical HSCT...
October 20, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29045503/maintenance-therapy-following-induction-chemoimmunotherapy-in-patients-with-diffuse-large-b-cell-lymphoma-current-perspective
#8
N M Reddy, C Thieblemont
Background: Maintenance therapy has proven efficacy in indolent non-Hodgkin lymphoma (NHL), yet its role in diffuse large B-cell lymphoma (DLBCL) is an area of ongoing investigation. While DLBCL is potentially curable, >30% of patients relapse following front-line therapy and have a poor prognosis, especially those with refractory disease. Maintenance therapy holds promise to maintain response post-induction. Patients and methods: Keyword searches were carried out in PubMed and congress abstracts of 'diffuse large B-cell lymphoma' and 'maintenance' and focused on phase II/III studies of maintenance following front-line induction...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29035393/donor-lymphocyte-infusion-following-haploidentical-hematopoietic-cell-transplantation-with-peripheral-blood-stem-cell-grafts-and-ptcy
#9
S R Goldsmith, M Slade, J F DiPersio, P Westervelt, M A Schroeder, F Gao, R Romee
Donor-lymphocyte infusion (DLI) for relapse following haploidentical hematopoietic cell transplantation (haploHCT) with post-transplant cyclophosphamide (PTCy) has been described in recipients of bone marrow grafts, but not recipients of G-CSF mobilized peripheral blood (PB) grafts. We retrospectively identified patients who underwent DLI following PB-haploHCT with PTCy for relapse, or loss of chimerism (LOC). Twelve patients (57%) received DLI for hematologic relapse/persistent disease, seven (33%) for extramedullary relapse and two (10%) for LOC...
October 16, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29035392/long-term-outcome-of-mixed-chimerism-after-stem-cell-transplantation-for-thalassemia-major-conditioned-with-busulfan-and-cyclophosphamide
#10
N A Fouzia, E S Edison, K M Lakshmi, A Korula, S R Velayudhan, P Balasubramanian, A Abraham, A Viswabandya, B George, V Mathews, A Srivastava
Mixed chimerism (MC) occurs frequently after allogeneic hematopoietic stem cell transplantation (HSCT) for thalassemia major (TM) and may be associated with rejection. We report the outcome of MC in 132 TM patients conditioned with Busulphan/Cyclophosphamide, who had successful engraftment and had ⩾1 year follow-up. Chimerism was first assessed at day +28, then every 3-9 months or more frequently if there was MC. If rejection was suspected, immunosuppression was stopped and donor-lymphocyte infusion (DLI) was given if there was no response...
October 16, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29024804/impact-of-hla-disparity-in-haploidentical-bone-marrow-transplantation-followed-by-high-dose-cyclophosphamide
#11
Anna Maria Raiola, Antonio Risitano, Nicoletta Sacchi, Livia Giannoni, Alessio Signori, Sara Aquino, Stefania Bregante, Carmen Di Grazia, Alida Dominietto, Simona Geroldi, Anna Ghiso, Francesca Gualandi, Teresa Lamparelli, Elisabetta Tedone, Maria Teresa Van Lint, Riccardo Varaldo, Adalberto Ibatici, Carlo Marani, Serena Marotta, Fabio Guolo, Daniele Avenoso, Lucia Garbarino, Fabrizio Pane, Andrea Bacigalupo, Emanuele Angelucci
We studied the impact of HLA mismatching on the outcome of 318 consecutive patients who received an unmanipulated haploidentical bone marrow transplant, followed by post-transplant cyclophosphamide (PTCy). The number of HLA-mismatched antigens was tested for its impact on overall survival (OS) and nonrelapse mortality (NRM), whereas HLA mismatches in the graft-versus-host (GVH) direction were tested for prediction of graft-versus-host disease (GVHD and relapse. Finally, we studied whether graft rejection correlated with the number of HLA mismatched antigens in host-versus-graft (HVG) direction...
October 9, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29024803/graft-derived-reconstitution-of-mucosal-associated-invariant-t-cells-after-allogeneic-hematopoietic-cell-transplantation
#12
Abir Bhattacharyya, Laïla-Aïcha Hanafi, Alyssa Sheih, Jonathan L Golob, Sujatha Srinivasan, Michael J Boeckh, Steven A Pergam, Sajid Mahmood, Kelsey K Baker, Ted A Gooley, Filippo Milano, David N Fredricks, Stanley R Riddell, Cameron J Turtle
Mucosal-associated invariant T (MAIT) cells express a semi-invariant Vα7.2(+) TCR that recognizes ligands from distinct bacterial and fungal species. In neonates, MAIT cells proliferate coincident with gastrointestinal (GI) bacterial colonization. In contrast, under noninflammatory conditions adult MAIT cells remain quiescent because of acquired regulation of TCR signaling. Effects of inflammation and the altered GI microbiota after allogeneic hematopoietic cell transplantation (HCT) on MAIT cell reconstitution have not been described...
October 9, 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
#13
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/28983949/improved-prognosis-with-additional-medium-dose-vp16-to-cy-tbi-in-allogeneic-transplantation-for-high-risk-all-in-adults
#14
Yasuyuki Arai, Tadakazu Kondo, Akio Shigematsu, Junji Tanaka, Kazuteru Ohashi, Takahiro Fukuda, Michihiro Hidaka, Naoki Kobayashi, Koji Iwato, Toru Sakura, Makoto Onizuka, Yukiyasu Ozawa, Tetsuya Eto, Mineo Kurokawa, Kaoru Kahata, Naoyuki Uchida, Yoshiko Atsuta, Shuichi Mizuta, Shinichi Kako
Allogeneic hematopoietic stem cell transplantation (HSCT) with the conventional cyclophosphamide and total body irradiation (CY/TBI) regimen is an essential therapeutic strategy for acute lymphoblastic leukemia (ALL) in adults. Medium-dose etoposide (VP16, 30 - 40 mg/kg) can be added to intensify this CY/TBI regimen and reduce relapse; however, differences in prognosis between the VP16/CY/TBI and CY/TBI regimens have not yet been fully analyzed. We conducted a retrospective cohort study using a Japanese transplant registry database to compare the prognosis between the VP16/CY/TBI (VP16, total 30-40 mg/kg) (N=376) and CY/TBI (N=1178) regimens in adult patients with ALL transplanted at complete remission (CR) between January 1, 2000 and December 31, 2014...
October 6, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28978857/hla-haploidentical-transplantation-with-post-transplant-cyclophosphamide
#15
Junichi Sugita
Recently, post-transplant cyclophosphamide (PTCy) -based HLA-haploidentical stem cell transplantation (PTCy-haploSCT) has been increasingly performed. The mechanism of GVHD prevention by PTCy is selective depletion of proliferating alloreactive T cells, while preserving non-alloreactive T cells. Several studies have reported that the incidence of non-relapse mortality, relapse, disease-free survival, and overall survival after PTCy-haploSCT are equivalent to those after HLA-matched SCT. Furthermore, the incidence of GVHD, especially chronic GVHD, after PTCy-haploSCT was lower than that of HLA-matched SCT...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28969012/similar-outcomes-after-haploidentical-transplantation-with-post-transplant-cyclophosphamide-versus-hla-matched-transplantation-a-meta-analysis-of-case-control-studies
#16
Zhenyang Gu, Li Wang, Lei Yuan, Wenrong Huang, Meng Li, Lixun Guan, Qingyi Wang, Zhe Gao, Shasha Zhao, Lan Luo, Feiyan Wang, Nan Yang, Daihong Liu, Jon C Aster, Chunji Gao
BACKGROUND: Outcomes of haploidentical hematopoietic cell transplantation (haplo-HCT) with post-transplant cyclophosphamide (PT-Cy) have greatly improved. It remains unknown whether haplo-HCT with PT-Cy was associated with poor outcomes when compared with HLA-matched HCT. To address this issue, we performed a meta-analysis to compare outcomes of haplo-HCT with PT-Cy with those of HLA-matched HCT. METHODS: A systematic search for case-control studies were performed in PubMed, Embase and Cochrane Library databases...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28961309/phase-ii-study-of-bortezomib-cyclophosphamide-and-dexamethasone-as-induction-therapy-in-multiple-myeloma-dsmm-xi-trial
#17
Hermann Einsele, Monika Engelhardt, Christoph Tapprich, Jürgen Müller, Peter Liebisch, Christian Langer, Martin Kropff, Lars O Mügge, Wolfram Jung, Hans-Heinrich Wolf, Bernd Metzner, Christina Hart, Martin Gramatzki, Bernd Hertenstein, Michael Pfreundschuh, Wolf Rösler, Thomas Fischer, Georg Maschmeyer, Lothar Kanz, Georg Hess, Elke Jäger, Martin Bentz, Heinz A Dürk, Hans Salwender, Holger Hebart, Christian Straka, Stefan Knop
We assessed the safety and efficacy of bortezomib, cyclophosphamide and dexamethasone (VCD) induction therapy in previously untreated multiple myeloma patients. A total of 414 patients received three 21-day cycles of VCD prior to autologous stem-cell transplantation (ASCT). Most common grade ≥3 adverse events were leucopenia (31·4%) and thrombocytopenia (6·8%). The overall response rate (ORR) by investigator-based assessment was 85·4%. Most patients (74%) underwent successful central laboratory-based molecular cytogenetic analysis...
September 29, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28939451/hla-haploidentical-stem-cell-transplant-with-pretransplant-immunosuppression-for-patients-with-sickle-cell-disease
#18
Anna B Pawlowska, Jerry C Cheng, Nicole A Karras, Weili Sun, Leo D Wang, Alison D Bell, Lisa Gutierrez, Joseph Rosenthal
Allogeneic stem cell transplantation (HCT) is curative in patients with severe sickle cell disease (SCD), but a significant number of patients lack an HLA-identical sibling or matched unrelated donor. Mismatched related (haploidentical) HCT with post-transplant cyclophosphamide (PTCY) allows expansion of the donor pool but is complicated by high rates of graft failure. In this report we describe a favorable haploidentical HCT approach in a limited cohort of SCD patients with significant comorbidities. To reduce the risk of graft failure we administered the conditioning regimen of rabbit antithymocyte globulin, busulfan, and fludarabine preceded with 2 courses of pretransplant immunosuppressive therapy (PTIS) with fludarabine and dexamethasone...
September 20, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28918304/haploidentical-transplantation-for-older-patients-with-acute-myeloid-leukemia-and-myelodysplastic-syndrome
#19
Stefan O Ciurea, Mithun V Shah, Rima M Saliba, Sameh Gaballa, Piyanuch Kongtim, Gabriela Rondon, Julianne Chen, Whitney Wallis, Kai Cao, Marina Konopleva, Naval Daver, Jorge Cortes, Farhad Ravandi, Amin Alousi, Sairah Ahmed, Uday Popat, Simrit Parmar, Qaiser Bashir, Oran Betul, Chitra Hosing, Elizabeth J Shpall, Katayoun Rezvani, Issa F Khouri, Partow Kebriaei, Richard E Champlin
Allogeneic stem cell transplantation with HLA-matched donors is increasingly used for older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). It remains unclear if haploidentical stem cell transplantation (haploSCT) is a suitable option for older patients with this disease. We analyzed 43 patients with AML/MDS (median age, 61 years) who underwent a haploSCT at our institution. All patients received a fludarabine-melphalan-based reduced-intensity conditioning regimen and post-transplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis...
September 14, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28898706/profiles-of-pro-inflammatory-cytokines-in-allogenic-stem-cell-transplantation-with-post-transplant-cyclophosphamide
#20
O V Pirogova, I S Moiseev, E A Surkova, S V Lapin, S N Bondarenko, A D Kulagin, B V Afanasyev
Large number of studies was published about predictive value of cytokines for graft-versus-host disease (GVHD) after allogeneic stem cell transplantation. Recently, there has been a growing interest in GVHD prophylaxis with post-transplant cyclophosphamide (PTCy). Clinical data on the dynamics of proinflammatory cytokines with this prophylaxis is lacking. In this study, we have measured the levels of IL-17, IL-6, IL-8, IFN-γ and TNF-α in plasma on days -7, 0, +7, +14 and after engraftment in 20 patients with acute GVHD and 40 matched control patients with PTCy-based prophylaxis...
September 9, 2017: Cytokine
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