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https://www.readbyqxmd.com/read/29355721/selecting-the-best-donor-for-haploidentical-transplant-impact-of-hla-kir-genotyping-and-other-clinical-variables
#1
Scott R Solomon, Michael A Aubrey, Xu Zhang, Allison Piluso, Brian M Freed, Stacey Brown, Katelin C Jackson, Lawrence E Morris, H Kent Holland, Melhem M Solh, Asad Bashey
The use of post-transplant cyclophosphamide (PTCy)-based haploidentical (haplo) transplant is increasing worldwide. However, as multiple potential haplo donors are usually available, data-driven guidance is clearly needed to help transplant centers prioritize donors. To that end, we retrospectively analyzed 208 consecutive donor-recipient pairs receiving PTCy-based haplo transplant at a single institution. Median recipient and donor age was 52 (19-75) and 38 (15-73) years, PBSC was the stem cell source in 66%, and myeloablative conditioning was used in 41%...
January 17, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29339270/proceedings-from-the-fourth-haploidentical-stem-cell-transplantation-symposium-haplo2016-san-diego-california-december-1-2016
#2
REVIEW
Monzr Al Malki, Richard Jones, Qing Ma, Dean Lee, Yair Reisner, Jeffrey S Miller, Peter Lang, Suradej Hongeng, Parameswaran Hari, Samuel Strober, Jianhua Yu, Richard Maziarz, Domenico Mavilio, Denis-Claude Roy, Chiara Bonini, Richard E Champlin, Ephraim J Fuchs, Stefan O Ciurea
The resurgence of haploidentical stem cell transplantation (HaploSCT) over the last decade is one of the most important advances in the field of hematopoietic stem cell transplantation (HSCT). The modified platforms of T cell depletion either ex vivo (CD34+ selection, 'mega-dose' of purified CD34+ cells, or selective depletion of T-cells) or newer platforms of in vivo depletion of T cells, with either post-transplant high-dose cyclophosphamide (PTCy) or intensified immune suppression, have contributed to better outcomes, with survival that is similar to HLA-match donor transplantation...
January 12, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29338540/efficacy-and-safety-of-frontline-rituximab-cyclophosphamide-doxorubicin-and-prednisone-plus-bortezomib-vr-cap-or-vincristine-r-chop-in-a-subset-of-newly-diagnosed-mantle-cell-lymphoma-patients-medically-eligible-for-transplantation-in-the-randomized-phase-3
#3
Johannes Drach, Huiqiang Huang, Olga Samoilova, Andrew Belch, Charles Farber, André Bosly, Jan Novak, Jan Zaucha, Angela Dascalescu, Udomsak Bunworasate, Zvenyslava Masliak, Kateryna Vilchevskaya, Tadeusz Robak, Lixia Pei, Brendan Rooney, Helgi van de Velde, Franco Cavalli
This post-hoc subanalysis of the LYM-3002 phase 3 study assessed the efficacy and safety of substituting vincristine in rituximab, cyclophosphamide, doxorubicin and prednisone (R-CHOP; n = 42) for bortezomib (VR-CAP; n = 38) in a subgroup of 80 mantle cell lymphoma (MCL) patients aged <60 years who did not receive stem cell transplantation (SCT) despite medical eligibility. Complete response (CR)/unconfirmed CR (CRu) rates were 67 vs. 39% (odds ratio 3.69 [95% CI(confidence interval): 1.31, 10...
January 17, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29338084/importance-of-b-cells-to-development-of-tregs-and-prolongation-of-tissue-allograft-survival-in-recipients-receiving-autologous-bone-marrow-transplantation
#4
Reginald M Gorczynski, Kaveh Farrokhi, Christopher Gorczynski, Hassan Sadozai, Fang Zhu, Ismat Khatri
We previously showed that congenic bone marrow transplantation (BMTx) post myeloablation augmented tissue allograft survival in association with increased Tregs of both host and bone marrow donor origin. Regulatory B cells (Bregs) can also modulate T cell immunity and B cells may be implicated in the development of Tregs. Accordingly, we explored the effect of B cell depletion in vivo on augmented graft survival post BMTx. C57BL/6 mice received BALB/c skin allografts followed 7d later by myeloablation using cyclophosphamide and busulphan...
January 16, 2018: Immunology
https://www.readbyqxmd.com/read/29337223/sequential-conditioning-with-thiotepa-in-t-cell-replete-hematopoietic-stem-cell-transplantation-for-the-treatment-of-refractory-hematological-malignancies-comparison-with-matched-related-haplo-mismatched-and-unrelated-donors
#5
Rémy Duléry, Anne-Lise Ménard, Sylvain Chantepie, Jean El Cheikh, Sylvie François, Jérémy Delage, Federica Giannotti, Annalisa Ruggeri, Eolia Brissot, Giorgia Battipaglia, Florent Malard, Ramdane Belhocine, Simona Sestili, Anne Vekhoff, François Delhommeau, Oumédaly Reman, Ollivier Legrand, Myriam Labopin, Marie-Thérèse Rubio, Mohamad Mohty
The results of conventional allogeneic stem cell transplantation (SCT) in refractory hematological malignancies are poor. Sequential strategies have shown promising results in refractory acute myeloid leukemia (AML), but have not been validated in a haploidentical (Haplo) setting. We developed a new sequential approach combining chemotherapy with broad anti-tumor activity (thiotepa 10 mg/kg, etoposide 400 mg/m2, cyclophosphamide 1600 mg/m2 from Day-15 to -10), followed after 3 days of rest by reduced-intensity conditioning regimen (fludarabine 150 mg/m2, intravenous busulfan 6...
January 11, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29330396/comparable-survival-using-a-cmv-matched-or-a-mismatched-donor-for-cmv-patients-undergoing-t-replete-haplo-hsct-with-pt-cy-for-acute-leukemia-a-study-of-behalf-of-the-infectious-diseases-and-acute-leukemia-working-parties-of-the-ebmt
#6
Simone Cesaro, Roberto Crocchiolo, Gloria Tridello, Nina Knelange, Maria Teresa Van Lint, Yener Koc, Fabio Ciceri, Zafer Gülbas, Johanna Tischer, Boris Afanasyev, Benedetto Bruno, Luca Castagna, Didier Blaise, Mohamad Mohty, Giuseppe Irrera, J L Diez-Martin, Luca Pierelli, Pietro Pioltelli, Mutlu Arat, Mario Delia, Franca Fagioli, Gerhard Ehninger, Mahmoud Aljurf, Angelo Michele Carella, Hakan Ozdogu, Malgorzata Mikulska, Per Ljungman, Arnon Nagler, Jan Styczynski
The role of donor CMV serostatus in the setting of non T-cell depleted haplo-HSCT with post-transplant cyclophosphamide (PT-Cy) has not been specifically addressed so far. Here we analyzed the impact of the donor CMV serological status on the outcome of 983 CMV seropositive (CMV+), acute leukemia patients receiving a first, non T-cell depleted haplo-HSCT registered in the EBMT database. The 1-year NRM was 21.3% (95% CI: 18.4-24.8) and 18.8% (95% CI: 13.8-25.5) in the CMV D+/R+ and D-/R+ pairs, respectively (p = 0...
January 12, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29330393/haploidentical-bone-marrow-transplantation-with-post-transplant-cyclophosphamide-for-patients-with-x-linked-adrenoleukodystrophy-a-suitable-choice-in-an-urgent-situation
#7
Juliana Folloni Fernandes, Carmem Bonfim, Fábio Rodrigues Kerbauy, Morgani Rodrigues, Iracema Esteves, Nathalia Halley Silva, Alessandra Prandini Azambuja, Luiz Fernando Mantovani, José Mauro Kutner, Gisele Loth, Cilmara Cristina Kuwahara, Clarissa Bueno, Andrea Tiemi Kondo, Andreza Alice Feitosa Ribeiro, Fernando Kok, Nelson Hamerschlak
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only treatment that enhances survival and stabilizes neurologic symptoms in X-linked adrenoleukodystrophy (X-ALD) with cerebral involvement, a severe demyelinating disease of childhood. Patients with X-ALD who lack a well-matched HLA donor need a rapid alternative. Haploidentical HSCT using post transplant cyclophosphamide (PT/Cy) has been performed in patients with malignant and nonmalignant diseases showing similar outcomes compared to other alternative sources...
January 12, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29330390/freezing-the-graft-is-not-necessary-for-autotransplants-for-plasma-cell-myeloma-and-lymphomas
#8
Amado Kardduss-Urueta, Robert Peter Gale, César H Gutierrez-Aguirre, Miguel Angel Herrera-Rojas, Iván Murrieta-Álvarez, Rosendo Perez-Fontalvo, Guillermo J Ruiz-Delgado, Giovanni Ruiz-Rojas, Gregorio Jaimovich, Leonardo Feldman, Nancy Labastida-Mercado, Alicia Endara, Martín Castro, Samantha Galindo-Becerra, María Angélica Cardona-Molina, David Gomez-Almaguer, Guillermo J Ruiz-Argüelles
We studied rates of granulocyte and platelets recovery in 359 consecutive subjects receiving blood cell infusions in the context of autotransplants for plasma cell myeloma (N = 216) and lymphomas (N = 143). Blood cells were mobilised with filgrastim given for 4-5 days and collected after a median of 2 (range, 1-2) apheresis. Apheresis products were stored at 4° C for a median of 3 days (range, 2-6 days). Most subjects received carmustine, etoposide, cytarabine and melphalan (BEAM), cyclophosphamide, carmustine and etoposide (CBV) or high-dose melphalan...
January 12, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29298160/myeloablative-autologous-stem-cell-transplantation-for-severe-scleroderma
#9
RANDOMIZED CONTROLLED TRIAL
Keith M Sullivan, Ellen A Goldmuntz, Lynette Keyes-Elstein, Peter A McSweeney, Ashley Pinckney, Beverly Welch, Maureen D Mayes, Richard A Nash, Leslie J Crofford, Barry Eggleston, Sharon Castina, Linda M Griffith, Julia S Goldstein, Dennis Wallace, Oana Craciunescu, Dinesh Khanna, Rodney J Folz, Jonathan Goldin, E William St Clair, James R Seibold, Kristine Phillips, Shin Mineishi, Robert W Simms, Karen Ballen, Mark H Wener, George E Georges, Shelly Heimfeld, Chitra Hosing, Stephen Forman, Suzanne Kafaja, Richard M Silver, Leroy Griffing, Jan Storek, Sharon LeClercq, Richard Brasington, Mary E Csuka, Christopher Bredeson, Carolyn Keever-Taylor, Robyn T Domsic, M Bashar Kahaleh, Thomas Medsger, Daniel E Furst
BACKGROUND: Despite current therapies, diffuse cutaneous systemic sclerosis (scleroderma) often has a devastating outcome. We compared myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation with immunosuppression by means of 12 monthly infusions of cyclophosphamide in patients with scleroderma. METHODS: We randomly assigned adults (18 to 69 years of age) with severe scleroderma to undergo myeloablative autologous stem-cell transplantation (36 participants) or to receive cyclophosphamide (39 participants)...
January 4, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29283908/have-haploidentical-transplants-replaced-umbilical-cord-transplants-for-acute-leukemias
#10
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...
December 27, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29247781/kir-ligand-mismatch-in-donor-vs-recipient-direction-provides-better-graft-versus-tumor-effect-in-patients-with-hematological-malignancies-undergoing-allogeneic-t-replete-haploidentical-transplantation-followed-by-post-transplant-cyclophosphamide
#11
Anne Wanquet, Stephania Bramanti, Samia Harbi, Sabine Fürst, Faezeh Legrand, Catherine Faucher, Angela Granata, Boris Calmels, Claude Lemarie, Christophe Picard, Christian Chabannon, Pierre-Jean Weiller, Luca Castagna, Didier Blaise, Raynier Devillier
We evaluated the impact of unidirectional donor vs. recipient killer-cell immunoglobulin-like receptor (KIR)-ligand mismatch (KIR-Lmm) on the outcomes of T-replete Haplo-SCT with post-transplant cyclophosphamide (PT-Cy) in a cohort of 144 patients treated for various hematological diseases. We separately analyzed 81 patients in complete remission (CR group) and 63 with active disease (no CR group) at the time of Haplo-SCT. One-third of patients in each group had KIR-Lmm. In the no CR group, KIR-Lmm was associated with a significantly lower incidence of relapse (hazard ratio (HR) = 0...
December 13, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29237963/analysis-of-factors-affecting-initial-cyclosporine-level-and-its-impact-on-post-transplant-outcomes-in-acute-leukemia
#12
Alok Gupta, Sachin Punatar, Jayant Gawande, Libin Mathew, Sadhana Kannan, Navin Khattry
BACKGROUND: Trough cyclosporine (CsA) blood level can influence incidence of graft-versus-host disease (GVHD) and relapse in patients with acute leukemia undergoing allogeneic hematopoietic stem cell transplant (HSCT). We sought to determine factors affecting initial trough CsA level (CsA-1) and its impact on transplant outcome in acute leukemia. MATERIALS AND METHODS: Seventy-seven patients underwent HSCT for acute leukemia between January 2008 and March 2013 and were included...
October 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/29197681/t-cell-replete-haploidentical-transplantation-with-post-transplant-cyclophosphamide-for-hodgkin-lymphoma-relapsed-after-autologous-transplant-reduced-incidence-of-relapse-and-of-chronic-gvhd-compared-to-hla-identical-related-donors
#13
Jacopo Mariotti, Raynier Devillier, Stefania Bramanti, Barbara Sarina, Sabine Furst, Angela Granata, Catherine Faucher, Samia Harbi, Lucio Morabito, Christian Chabannon, Carmelo Carlo-Stella, Reda Bouabdallah, Armando Santoro, Didier Blaise, Luca Castagna
Allogeneic hematopoietic stem cell transplant (SCT) represents a potential curative strategy for patients with Hodgkin lymphoma (HL) relapsing after autologous transplant (ASCT), but the incidence of disease relapse is still high. We performed a retrospective study on 64 patients with HL relapsing after ASCT in order to compare the outcome after HLA identical (HLAid-SCT, n=34) or haploidentical SCT with post-transplant cyclophosphamide (PT-Cy) (Haplo-SCT, n=30). All patients engrafted with a median time for neutrophil and platelet engraftment significantly shorter after HLAid compared with Haplo-SCT (14 vs 19 days and 11 vs 23 days, p<0...
November 29, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29191665/augmenting-total-body-irradiation-with-a-cranial-boost-before-stem-cell-transplantation-protects-against-post-transplant-cns-relapse-in-acute-lymphoblastic-leukemia
#14
Robert W Gao, Kathryn E Dusenbery, Qing Cao, Angela R Smith, Jianling Yuan
PURPOSE: The purpose of this study was to determine the effect of a pre-transplant cranial boost (CB) on post-transplant central nervous system (CNS) relapse and survival in acute lymphoblastic leukemia (ALL) patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) using a total body irradiation (TBI)-containing preparation regimen. METHODS AND MATERIALS: Two hundred thirteen ALL patients were treated consecutively at our institution with allogeneic HSCT...
November 27, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29191663/the-impact-of-single-dose-plerixafor-as-an-adjunct-to-g-csf-based-peripheral-blood-stem-cell-mobilisation-on-the-graft-composition-and-outcome-for-t-replete-haploidentical-pbsc-transplantation-with-post-transplantation-cyclophosphamide-a-comparative-study
#15
Sarita Rani Jaiswal, Prakash Bhakuni, Aby Joy, Nisha Murli, Priyanka Bharadwaj, Shamsur Zaman, Nedunchezian Murugayan, Suparno Chakrabarti
We conducted a prospective study on T and NK cell subset composition of the graft and the transplant outcomes inT-replete haploidentical transplantationwithsingle dose of subcutaneous Plerixafor(Px)added to G-CSF based mobilisation in allogeneic donors to collect 10 x 106/kg CD34+HSC at single apheresis. 26 donors received G-CSF+Px and 25 donors received G-CSF alone for mobilisation. Despite a significantly lower peripheral blood (PB) CD34+HSC on day 4 in the G-CSF+Px group [33(6-47) cells/µl vs 81(50-168) cells/µl in G-CSF group, p=0...
November 27, 2017: Biology of Blood and Marrow Transplantation
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
#16
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
#17
Margaret R Jorgenson, Jillian L Descourouez, Tripti Singh, Brad C Astor, Sarah E Panzer
STUDY OBJECTIVE: To evaluate the risk of posttransplantation malignancy in renal transplant recipients exposed to pretransplantation cyclophosphamide for the treatment of glomerular nephropathy (GN). DESIGN: Retrospective cohort study. SETTING: Tertiary academic medical center. PATIENTS: Six hundred adult renal transplant recipients were transplanted between 1993 and 2014; 54 patients were exposed to pretransplantation cyclophosphamide for treatment of GN (GN-CYC group), and 546 patients with polycystic kidney disease were not exposed to pretransplantation 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
#18
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 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
#19
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
#20
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
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