{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:36:44Z","timestamp":1787506604268,"version":"build-2736575974"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T00:00:00Z","timestamp":1659657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>In haploidentical peripheral blood stem cell transplantation (haplo-PBSCT), the combination of anti-thymocyte globulin and post-transplant cyclophosphamide (ATG\/PTCy) has a synergistic impact in preventing graft-versus-host disease (GvHD). However, little is known about the long-term consequences of the new combination approach. Our goal is to evaluate the efficacy of ATG\/PTCy versus a standard ATG regimen by focusing at long-term outcomes in a more homogeneous group of patients. We retrospectively included 118 adult patients up to 60 years with acute leukemia who underwent haplo-PBSCT at our single institution, following the same myeloablative conditioning regimen. From 2010 to 2020, 78 patients received a modified combination of ATG (2.5 mg\/kg\/day, on days \u22123, \u22122, and \u22121) and PTCy (40 mg\/kg\/day on days +3 and +4) compared to 40 patients who had a standard ATG-based regimen (2.5 mg\/kg\/day from days \u22124 to \u22121) from 2008 to 2015. The median follow-up time for all patients was 5.36 years, respectively. The cumulative incidence (CI) of neutrophil and platelet engraftment, as well as CMV reactivation, did not differ statistically between the two groups. The CI of the acute GvHD of grades II\u2013IV and III\u2013IV and extensive chronic GvHD were considerably lower in the ATG\/PTCy (34.6%, 8.97%, and 13.63%) than in the ATG cohort (57.5%, 30%, and 38.23%) as validated by multivariable modeling. Additionally, compared to the ATG arm, the ATG\/PTCy was a hazard factor associated with a higher risk of relapse (HR = 2.23, p = 0.039). The probability of 5-year overall survival, disease-free survival, and GvHD-free relapse-free survival in the ATG\/PTCy group (53.34%, 49.77%, and 36.04%) was comparable with the ATG group (47.5%, 42.5%, and 22.5%), respectively. Our finding suggested that a modified ATG\/PTCy combination resulted in a lower risk of acute and chronic GvHD and a higher risk of relapse than the standard ATG-based protocol but had no effect on long-term outcomes. However, certain adjustments in the immunosuppression protocol are warranted to improve the outcome.<\/jats:p>","DOI":"10.3389\/fimmu.2022.921293","type":"journal-article","created":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T01:56:00Z","timestamp":1659664560000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":28,"title":["Modified combination of anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy) as compared with standard ATG protocol in haploidentical peripheral blood stem cell transplantation for acute leukemia"],"prefix":"10.3389","volume":"13","author":[{"given":"Maryam","family":"Barkhordar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Kasaeian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghasem","family":"Janbabai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein","family":"Kamranzadeh Fumani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar","family":"Tavakoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir Abbas","family":"Rashidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seied Asadollah","family":"Mousavi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ardeshir","family":"Ghavamzadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Vaezi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e91","DOI":"10.1016\/S2352-3026(15)00028-9","article-title":"One million haemopoietic stem-cell transplants: a retrospective observational study","volume":"2","author":"Gratwohl","year":"2015","journal-title":"Lancet Haematol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2015.11.001","article-title":"Haploidentical hematopoietic stem cell transplantation: a global overview comparing Asia, the European union, and the united states","volume":"22","author":"Apperley","year":"2016","journal-title":"Biol Blood Marrow Transpl"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2017.34","article-title":"Use of haploidentical stem cell transplantation continues to increase: the 2015 European society for blood and marrow transplant activity survey report","volume":"52","author":"Passweg","year":"2017","journal-title":"Bone Marrow Transpl"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-02-627786","article-title":"Haploidentical vs identical-sibling transplant for AML in remission: a multicenter, prospective study","volume":"125","author":"Wang","year":"2015","journal-title":"Blood"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2019.07.028","article-title":"Haploidentical transplantation with post-transplant cyclophosphamide versus unrelated donor hematopoietic stem cell transplantation: A systematic review and meta-analysis","volume":"25","author":"Arcuri","year":"2019","journal-title":"Biol Blood Marrow Transpl"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-05-2146","article-title":"Conditioning including antithymocyte globulin followed by unmanipulated HLA-mismatched\/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA identical sibling transplantation","volume":"107","author":"Lu","year":"2006","journal-title":"Blood"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.12.3456","article-title":"Durable engraftment of major histocompatibility complex-incompatible cells after nonmyeloablative conditioning with fludarabine, low-dose total body irradiation, and posttransplantation cyclophosphamide","volume":"98","author":"Luznik","year":"2001","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2016.01.004","article-title":"Haploidentical stem cell transplantation: antithymocyte globulin-based experience","volume":"53","author":"Chang","year":"2016","journal-title":"Semin Hematol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.148510","article-title":"Anti-thymocyte globulin as graft-versus-host disease prevention in the setting of allogeneic peripheral blood stem cell transplantation: a review from the acute leukemia working party of the European society for blood and marrow transplantation","volume":"102","author":"Baron","year":"2017","journal-title":"Haematologica"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.75.8177","article-title":"Prospective, randomized, double-blind, phase III clinical trial of anti-t-lymphocyte globulin to assess impact on chronic graft-versus-host disease-free survival in patients undergoing HLA-matched unrelated myeloablative hematopoietic cell transplantation","volume":"35","author":"Soiffer","year":"2017","journal-title":"J Clin Oncol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2016.05.020","article-title":"Impact of donor and recipient cytomegalovirus serostatus on outcomes of antithymocyte globulin-conditioned hematopoietic cell transplantation","volume":"22","author":"Kalra","year":"2016","journal-title":"Biol Blood Marrow Transpl"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1182\/blood2013-10-525873","article-title":"Donor CD4C Foxp3C regulatory T cells are necessary for posttransplantation cyclophosphamide-mediated protection against GVHD in mice","volume":"124","author":"Ganguly","year":"2014","journal-title":"Blood"},{"key":"B13","doi-asserted-by":"publisher","first-page":"211ra157","DOI":"10.1126\/scitranslmed.3006960","article-title":"Aldehyde dehydrogenase expression drives human regulatory T cell resistance to posttransplantation cyclophosphamide","volume":"5","author":"Kanakry","year":"2013","journal-title":"Sci Trans Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2016.01.005","article-title":"Haploidentical bone marrow and stem cell transplantation: experience with posttransplantation cyclophosphamide","volume":"53","author":"Robinson","year":"2016","journal-title":"Semin Hematol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2015.93","article-title":"Unmanipulated haploidentical bone marrow transplantation and post-transplant cyclophosphamide for hematologic malignanices following a myeloablative conditioning: an update","author":"Bacigalupo","year":"2015","journal-title":"Bone Marrow Transpl"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2015.04.025","article-title":"Post-transplantation cyclophosphamide and sirolimus after haploidentical hematopoietic stem cell transplantation using a treosulfan-based myeloablative conditioning and peripheral blood stem cells","volume":"21","author":"Cieri","year":"2015","journal-title":"Biol Blood Marrow Transpl"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31228","article-title":"Bone marrow versus mobilized peripheral blood stem cells in haploidentical transplants using posttransplantation cyclophosphamide","volume":"124","author":"Ruggeri","year":"2018","journal-title":"Cancer"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.72.8428","article-title":"Mobilized peripheral blood stem cells versus unstimulated bone marrow as a graft source for t-cell\u2013replete haploidentical donor transplantation using post-transplant cyclophosphamide","volume":"35","author":"Bashey","year":"2017","journal-title":"J Clin Oncol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1978","DOI":"10.1182\/blood.V130.Suppl_1.1978.1978","article-title":"Post-transplant cyclophosphamide (PTCy) with anti-thymocyte globulin (ATG) as GVHD prophylaxis is effective in haploidentical peripheral stem cell transplantation and without increasing risk of relapse","volume":"130","author":"Lin","year":"2017","journal-title":"Blood"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-020-0813-9","article-title":"Dual T-cell depletion with ATG and PTCy for peripheral blood reduced intensity conditioning allo-HSCT results in very low rates of GVHD","volume":"55","author":"Salas","year":"2020","journal-title":"Bone Marrow Transpl"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2000578","article-title":"Posttransplant cyclophosphamide and antithymocyte globulin versus posttransplant cyclophosphamide as graft-versus-Host disease prophylaxis for peripheral blood stem cell haploidentical transplants: Comparison of T cell and NK effector reconstitution","volume":"205","author":"Makanga","year":"2020","journal-title":"J Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-018-0382-3","article-title":"Low-dose anti-thymocyte globulin plus low-dose posttransplant cyclophosphamide as graft-versushost disease prophylaxis in haploidentical peripheral blood stem cell transplantation combined with unrelated cord blood for patients with hematologic malignancies: a prospective, phase II study","volume":"54","author":"Yang","year":"2019","journal-title":"Bone Marrow Transpl"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-020-01047-2","article-title":"Low dose anti-thymocyte globulin with low dose posttransplant cyclophosphamide (low dose ATG\/PTCy) can reduce the risk of graft-versus-host disease as compared with standard-dose anti-thymocyte globulin in haploidentical peripheral hematopoietic stem cell transplantation combined with unrelated cord blood","volume":"56","author":"Xu","year":"2021","journal-title":"Bone Marrow Transpl"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2018.07.008","article-title":"Reduced intensity conditioning and dual T lymphocyte suppression with antithymocyte globulin and post-transplant cyclophosphamide as graft-versus-host disease prophylaxis in haploidentical hematopoietic stem cell transplants for hematological malignancies","volume":"24","author":"Law","year":"2018","journal-title":"Biol Blood Marrow Transpl"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13045-019-0781-y","article-title":"Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients","volume":"12","author":"Wang","year":"2019","journal-title":"J Hematol Oncol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-020-0792-x","article-title":"Rabbit ATG\/ATLG in preventing graft-versus-host disease after allogeneic stem cell transplantation: consensus-based recommendations by an international expert panel","volume":"55","author":"Bonifazi","year":"2020","journal-title":"Bone Marrow Transpl"},{"key":"B27","doi-asserted-by":"publisher","first-page":"51","DOI":"10.18502\/ijhoscr.v15i1.5249","article-title":"Selection of suitable alternative donor in the absence of matched sibling donor: A retrospective single-center study to compare between haploidentical, 10\/10 and 9\/10 unrelated donor transplantation","volume":"15","author":"Barkhordar","year":"2021","journal-title":"Int J Hematol Oncol Stem Cell Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2015.305","article-title":"Definition of GvHD free, relapse-free survival for registry-based studies: an ALWP-EBMT analysis on patients with AML in remission","volume":"51","author":"Ruggeri","year":"2016","journal-title":"Bone Marrow Transpl"},{"key":"B29","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1097\/00007890-197410000-00001","article-title":"Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-a-matched sibling donors","volume":"18","author":"Glucksberg","year":"1974","journal-title":"Transplantation"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2005.09.004","article-title":"National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. diagnosis and staging working group report","volume":"11","author":"Filipovich","year":"2005","journal-title":"Biol Blood Marrow Transplant"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-01-552984","article-title":"Validation and refinement of the disease risk index for allogeneic stem cell transplantation","volume":"123","author":"Armand","year":"2014","journal-title":"Blood"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2020.05.001","article-title":"Risk factors for graft-versus-Host disease in haploidentical hematopoietic cell transplantation using post-transplant cyclophosphamide","volume":"26","author":"Im","year":"2020","journal-title":"Biol Blood Marrow Transpl"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24963","article-title":"Donor age determines outcome in acute leukemia patients over 40 undergoing haploidentical hematopoietic cell transplantation","volume":"93","author":"Canaani","year":"2018","journal-title":"Am J Hematol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-019-0726-7","article-title":"Thiotepa and antithymocyte globulin-based conditioning before haploidentical transplantation with post-transplant cyclophosphamide in high-risk hematological malignancies","volume":"55","author":"Peric","year":"2020","journal-title":"Bone Marrow Transpl"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1706640","article-title":"Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation","volume":"377","author":"Marty","year":"2017","journal-title":"N Engl J Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.921293\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T01:56:03Z","timestamp":1659664563000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.921293\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,5]]},"references-count":35,"alternative-id":["10.3389\/fimmu.2022.921293"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.921293","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,5]]},"article-number":"921293"}}