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Haplo transplant

Nina Müller, Katharina Landwehr, Kirsten Langeveld, Joanna Stenzel, Walter Pouwels, Menno A W G van der Hoorn, Erhard Seifried, Halvard Bonig
BACKGROUND AIMS: For patients needing allogeneic stem cell transplantation but lacking a major histocompatibility complex (MHC)-matched donor, haplo-identical (family) donors may be an alternative. Stringent T-cell depletion required in these cases to avoid lethal graft-versus-host disease (GVHD) can delay immune reconstitution, thus impairing defense against virus reactivation and attenuating graft-versus-leukemia (GVL) activity. Several groups reported that GVHD is caused by cells residing within the naive (CD45RA+ ) T-cell compartment and proposed use of CD45RA-depleted donor lymphocyte infusion (DLI) to accelerate immune reconstitution...
February 28, 2018: Cytotherapy
Jonathan Canaani, Myriam Labopin, Xiao-Jun Huang, William Arcese, Fabio Ciceri, Didier Blaise, Giuseppe Irrera, Lucia Lopez Corral, Benedetto Bruno, Stella Santarone, Maria Teresa Van Lint, Antonin Vitek, Jordi Esteve, Mohamad Mohty, Arnon Nagler
Acute myeloid leukemia (AML) patients harboring the FLT3-ITD mutation are considered a high risk patient subset preferentially allocated for allogeneic stem cell transplantation in first remission. Whether FLT3-ITD retains a prognostic role in haploidentical stem cell transplantation (haplo-SCT) is unknown. To analyze the prognostic impact of FLT3-ITD in haplo-SCT, we performed a retrospective analysis of the multicenter registry of the acute leukemia working party of the European Society for Blood and Marrow Transplantation...
March 2, 2018: American Journal of Hematology
Yu-Qian Sun, Ying-Jun Chang, Xiao-Jun Huang
Haploidentical stem cell transplantation (Haplo-SCT) is currently a suitable alternative worldwide for patients with hematological diseases, who lack human leukocyte antigen (HLA)-matched siblings or unrelated donors. Areas covered: This review summarizes the advancements in Haplo-SCT in recent years, primarily focusing on the global trends of haploidentical allograft, the comparison of outcomes between Haplo-SCT and other transplantation modalities, strategies for improving clinical outcomes, including donor selection, hematopoietic reconstitution promotion, and graft-versus-host disease, and relapse prevention/management, as well as the expanded indications of Haplo-SCT, such as severe aplastic anemia, myeloma and lymphoma...
March 6, 2018: Expert Review of Hematology
Simona Sestili, Myriam Labopin, Annalisa Ruggeri, Andrea Velardi, Fabio Ciceri, Johan Maertens, Lothar Kanz, Franco Aversa, Philippe Lewalle, Donald Bunjes, Mohamad Mohty, Arnon Nagler
BACKGROUND: T-cell-depleted, haploidentical transplantations (haplos) are commonly offered to patients who have high-risk, acute leukemia in the absence of a human leukocyte antigen (HLA) full-matched donor. METHODS: To determine the effect of transplantation period, the authors divided 308 adults with de novo, acute leukemia who underwent T-cell-depleted haplo from 2005 to 2015 into 2 groups, according the year in which they underwent transplantation (2005-2011 [n = 191] and 2012-2015 [n = 117])...
February 22, 2018: Cancer
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
Javid Gaziev, Antonella Isgrò, Pietro Sodani, Katia Paciaroni, Gioia De Angelis, Marco Marziali, Michela Ribersani, Cecilia Alfieri, Alessandro Lanti, Tiziana Galluccio, Gaspare Adorno, Marco Andreani
We examined outcomes of haploidentical hematopoietic cell transplantation (haplo-HCT) using T-cell receptor αβ+ (TCRαβ+ )/CD19+ -depleted grafts (TCR group, 14 patients) in children with hemoglobinopathies. Patients received a preparative regimen consisting of busulfan, thiotepa, cyclophosphamide, and antithymocyte globulin preceded by fludarabine, hydroxyurea, and azathioprine. The median follow-up among surviving patients was 3.9 years. The 5-year probabilities of overall survival (OS) and disease-free survival (DFS) were 84% and 69%, respectively...
February 13, 2018: Blood Advances
Xiaosu Zhao, Zhidong Wang, Guorui Ruan, Yanrong Liu, Yu Wang, Xiaohui Zhang, Lanping Xu, Xiaojun Huang, Yingjun Chang
In this study, using multiparameter flow cytometry (FCM), we investigate the impact of minimal residual disease prior to transplantation (pre-MRD) on the transplant outcomes of AML patients with fms-related tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) mutation. A total of 20 patients who received HLA-matched sibling donor transplantation (MSDT) and 63 patients who received unmanipulated haploidentical hematopoietic stem cell transplantation (haplo-HSCT) were enrolled. Patients were classified into four groups based on the status of pre-FCM: group 1 with positive pre-FCM before MSDT, group 2 with negative pre-FCM before MSDT, group 3 with positive pre-FCM before haplo-HSCT, and group 4 with positive pre-FCM before haplo-HSCT...
February 8, 2018: Annals of Hematology
Patrizia Chiusolo, Gesine Bug, Attilio Olivieri, Mats Brune, Nicola Mordini, Paolo Emilio Alessandrino, Alida Dominietto, Anna Maria Raiola, Carmen Di Grazia, Francesca Gualandi, Maria Teresa Van Lint, Felicetto Ferrara, Olimpia Finizio, Emanuele Angelucci, Andrea Bacigalupo
We are reporting a modified post-transplant cyclophosphamide (PT-CY) regimen, for unmanipulated haploidentical marrow transplants (HAPLO), in 150 patients with acute myeloid leukemia (AML). All patients received a myeloablative regimen, cyclosporine (CsA) on day 0, mycophenolate on day +1, and PT-CY 50 mg/kg, on days +3 and +5. The median age was 51 years (17-74), 51 patients (34%) had active disease at transplant, and the median follow up of surviving patients 903 days (150-1955). The cumulative incidence (CI) of engraftment, acute graft versus host disease (GVHD) grade II-IV and moderate/severe chronic GvHD was respectively 92%, 17% and 15%...
February 5, 2018: Biology of Blood and Marrow Transplantation
Akiyoshi Takami
Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) yields a high rate of curability for acute myeloid leukemia (AML), it is also associated with transplant-related morbidity and mortality (TRM). The risk and severity of TRM increase with the use of an alternative donor graft in the absence of an HLA-matched sibling donor (MSD). With the declining birthrate and aging of the population, the numbers of patients with an MSD are decreasing, and alternative donor transplants, including the post-transplant cyclophosphamide method using haplo-identical donors, are increasing...
January 27, 2018: International Journal of Hematology
Luo Rongmu, Zhang Xiaomei, Du Zhenlan, Wang Ya, Chen Wei, Si Yingjian, Gu Wenjing, Xing Guosheng, Wang Yang, Da Wanming
Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) is widely carried out in China, and transplantation related complications decreased gradually with the transplant technology improving, and the overall survival(OS) increased year by year. However, relapse after transplantation is still one of the main causes of death in patients with hematological malignancy. In order to reduce the recurrence after HSCT, we set a tumorablative conditioning regimen (TAC ) regimen; the aim is as much as possible to eliminate the malignant clone to reduce the recurrence without increasing the conditioning toxicity...
December 26, 2017: Oncotarget
Eric M Przybyszewski, Elizabeth C Verna, Steven J Lobritto, Mercedes Martinez, Jennifer M Vittorio, Alyson N Fox, Benjamin Samstein, Tomoaki Kato, Adam D Griesemer, Jean C Emond
BACKGROUND: Despite high survival in pediatric living donor liver transplantation (LDLT), only 10% of liver transplants in children in the United States are from living donors, reflecting reluctance to embrace this approach. In addition to optimal timing and graft quality, LDLT may offer immunologic benefit since most donors are haplo-identical parents. We sought to quantify the benefit of LDLT compared to deceased donor liver transplantation (DDLT) using granular clinical and immunologic outcomes over the long-term...
January 23, 2018: Transplantation
Ming Li, Michelle Bui, Omar S Akbari
The jewel wasp Nasonia vitripennis has emerged as an effective model system for the study of processes including sex determination, haplo-diploid sex determination, venom synthesis, and host-symbiont interactions, among others. A major limitation of working with this organism is the lack of effective protocols to perform directed genome modifications. An important part of genome modification is delivery of editing reagents, including CRISPR/Cas9 molecules, into embryos through microinjection. While microinjection is well established in many model organisms, this technique is particularly challenging to perform in N...
December 25, 2017: Journal of Visualized Experiments: JoVE
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
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 post-transplantation 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 the risk of relapse and improve immune reconstitution, but may increase the risk of GVHD. We conducted a prospective trial of NMA haplo BMT for patients with hematologic malignancies (median age, 61 years), evaluating the safety of early discontinuation of tacrolimus...
January 17, 2018: Biology of Blood and Marrow Transplantation
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
Ming-Rui Huo, Xu-Ying Pei, Dan Li, Ying-Jun Chang, Lan-Ping Xu, Xiao-Hui Zhang, Kai-Yan Liu, Xiao-Jun Huang
The impact of human leukocyte antigen (HLA) allele mismatch on transplant outcomes in haploidentical stem cell transplantation (haplo-SCT) has not been established. We retrospectively studied 595 patients with hematologic malignancy who received haplo-SCT. The impact of multiple HLA allele mismatches (HLA-A, -B, -C, -DRB1, and -DQB1) and each HLA allele mismatch on transplant outcomes was analyzed. Greater number of HLA allele disparity does not appear worsen outcome. As for each HLA locus, HLA-A mismatch correlated with decreased rate of platelet engraftment (HR 0...
January 15, 2018: Bone Marrow Transplantation
Jordan Gauthier, Xavier Poiré, Anne-Claire Gac, Mathieu Leclerc, Thierry Guillaume, Yves Chalandon, Stéphanie Nguyen, Edouard Forcade, Caroline Régny, Jacques-Olivier Bay, Ali Bazarbachi, Pierre-Simon Rohrlich, Anne Huynh, Jonathan Farhi, Tony Marchand, Jean-Valère Malfuson, Sylvain Pilorge, Hélène Labussière-Wallet, Cécile Renard, Luc-Matthieu Fornecker, Marie Detrait, Rémy Duléry, Jérémy Delage, Anne-Lise Ménard, Amandine Charbonnier, Brigitte Nelken, Charlotte Jubert, Felipe Suarez, Régis Peffault de la Tour, Yves Beguin, Hélène Schoemans, Didier Blaise, Ibrahim Yakoub-Agha
The question of the best donor type between haploidentical (HAPLO) and matched-related donors (MRD) for patients with advanced HL receiving an allogeneic hematopoietic cell transplantation (allo-HCT) is still debated. Given the lack of data comparing these two types of donor in the setting of non-myeloablative (NMA) or reduced-intensity (RIC) allo-HCT, we performed a multicentre retrospective study using graft-vs.-host disease-free relapse-free survival (GRFS) as our primary endpoint. We analysed the data of 151 consecutive HL patients who underwent NMA or RIC allo-HCT from a HAPLO (N  =  61) or MRD (N  =  90) between January 2011 and January 2016...
January 12, 2018: Bone Marrow Transplantation
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
D Atay, A Akcay, F Erbey, G Ozturk
Viral infections remain one of the most important complications following allogeneic HSCT. Few reports compare virus infection between different donor types in pediatric patients. We retrospectively analyzed viral infections and the outcome of one hundred and seventy-one pediatric patients (median 7.38 years) who underwent allogeneic HSCT from matched related donor (MRD, n = 71), 10 of 10 HLA allele-matched unrelated donors (MUD1; n = 29), 9 of 10 HLA allele-matched unrelated donors (MUD2; n = 40), and haploidentical donors (n = 31)...
January 3, 2018: Pediatric Transplantation
Jurjen Versluis, Myriam Labopin, Annalisa Ruggeri, Gerard Socie, Depei Wu, Liisa Volin, Didier Blaise, Noel Milpied, Charles Craddock, Ibrahim Yakoub-Agha, Johan Maertens, Per Ljungman, Anne Huynh, Mauricette Michallet, Eric Deconinck, Patrice Chevallier, Jakob Passweg, Fabio Ciceri, Mohamad Mohty, Jan J Cornelissen, Arnon Nagler
Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains the treatment of choice to consolidate remission in patients with poor-risk acute myeloid leukemia (AML). With increasing alternative donors available, the preferred donor or stem cell source is debated. We set out to study outcome in recipients of alloHSCT with poor-risk AML in first complete remission (CR1) by donor type. A total of 6545 adult patients with poor-risk AML in CR1 receiving an alloHSCT using matched related donor (MRD, n = 3511) or alternative donors, including 10/10 (n = 1959) or 9/10 matched unrelated donors (MUDs, n = 549), umbilical cord blood (UCB) grafts (n = 333), or haplo-identical (haplo) donors (n = 193) were compared...
February 28, 2017: Blood Advances
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