{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:32:52Z","timestamp":1787725972659,"version":"build-2784847793"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T00:00:00Z","timestamp":1665014400000},"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. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for various hematologic disorders. Alternative donor strategies such as mismatched unrelated donors (MMUD) offer the option of HSCT to patients lacking a human leukocyte antigen (HLA)-matched donor. We conducted a systematic review and meta-analysis to evaluate outcomes after MMUD-HSCT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A literature search was performed on PubMed, Cochrane Library, and ClinicalTrials.gov from the inception date through April 6, 2022. After screening 2477 manuscripts, 19 studies were included. Data was extracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Pooled analysis was done using the meta-package by Schwarzer et\u00a0al. Proportions with 95% confidence intervals (CI) were computed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 3336 patients from 19 studies were included. The median age was <jats:italic>52.1<\/jats:italic> years, and 53% of recipients were males. The graft source was bone marrow in 19% and peripheral blood stem cells in 81% of recipients. The median time to transplant from hematologic diagnosis was 10 (1-247) months. Hematologic diagnoses included myeloid (82.9%), lymphoid (41.1%), and other disorders (3%). The reduced intensity and myeloablative conditioning were used in 65.6% and 32% of recipients, respectively. <jats:italic>In-vivo<\/jats:italic> T-cell depletion was performed in 56.7% of the patients. Most patients had one (87.9%) or two (11.4%) antigen HLA-mismatch. The pooled 1-year overall survival (OS) was 63.9% (95% CI 0.57-0.71, n=1426\/2706), and the pooled 3-year OS was 42.1% (95% CI 0.34.2-0.50, n=907\/2355). The pooled progression-free survival was 46.6% (95% CI 0.39-0.55, n=1295\/3253) after a median follow-up of 1.8 (range 1-6) years. The pooled relapse rate was 26.8% (95% CI 0.22-0.32, n=972\/3253) after a median follow-up of 2.25 (1-3) years. The pooled incidence of acute (grade II-IV) graft-versus-host disease (GVHD) and chronic GVHD was 36.4% (95% CI 0.31-0.42, n=1131\/3030) and 41.2% (95% CI 0.35-0.48, n=1337\/3228), respectively. The pooled non-relapse mortality was 22.6% (95% CI 0.17-0.29, n=888\/3196) after a median follow-up of 2.6 (1-5) years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>MMUD-HSCT has demonstrated favorable outcomes with an acceptable toxicity profile. It represents a promising option in patients lacking an HLA-matched or haploidentical donor and may expand HSCT access to underrepresented racial and ethnic populations.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2022.1005042","type":"journal-article","created":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T07:01:21Z","timestamp":1665039681000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Outcomes with mismatched unrelated donor allogeneic hematopoietic stem cell transplantation in adults: A systematic review and meta-analysis"],"prefix":"10.3389","volume":"12","author":[{"given":"Muhammad Umair","family":"Mushtaq","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moazzam","family":"Shahzad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezza","family":"Tariq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qamar","family":"Iqbal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibgha Gull","family":"Chaudhary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad U.","family":"Zafar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iqra","family":"Anwar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nausheen","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajat","family":"Bansal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anurag K.","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil H.","family":"Abhyankar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie S.","family":"Callander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiman","family":"Hematti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph P.","family":"McGuirk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,6]]},"reference":[{"key":"B1","volume-title":"Current use and outcome of hematopoietic stem cell transplantation: CIBMTR US summary slides","author":"Phelan","year":"2020"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.2009.01291.x","article-title":"A short history of HLA","volume":"74","author":"Thorsby","year":"2009","journal-title":"Tissue Antigens"},{"key":"B3","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1056\/nejm199303043280901","article-title":"Analysis of 462 transplantations from unrelated donors facilitated by the national marrow donor program","volume":"328","author":"Kernan","year":"1993","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsa1311707","article-title":"HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry","volume":"371","author":"Gragert","year":"2014","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2021.279189","article-title":"One and a half million hematopoietic stem cell transplants: continuous and differential improvement in worldwide access with the use of non-identical family donors","volume":"107","author":"Niederwieser","year":"2022","journal-title":"Haematologica"},{"key":"B6","unstructured":"How does a patient\u2019s ethnic background affect matching?"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2011.11.004","article-title":"Back to the future: mismatched unrelated donor, haploidentical related donor, or unrelated umbilical cord blood transplantation","volume":"18","author":"Anasetti","year":"2012","journal-title":"Biol Blood Marrow Transplant"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2011.214","article-title":"Racial disparities in hematopoietic cell transplantation in the united states","volume":"47","author":"Majhail","year":"2012","journal-title":"Bone Marrow Transplant"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1182\/hematology.2021000259","article-title":"Increasing access to allotransplants in the united states: the impact of race, geography, and socioeconomics","volume":"2021","author":"Hong","year":"2021","journal-title":"Hematology"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2015.09.012","article-title":"On modeling human leukocyte antigen-identical sibling match probability for allogeneic hematopoietic cell transplantation: Estimating the need for an unrelated donor source","volume":"22","author":"Besse","year":"2016","journal-title":"Biol Blood Marrow Transplant"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2014.10.015","article-title":"Impact of HLA mismatch direction on the outcome of unrelated bone marrow transplantation: a retrospective analysis from the Japan society for hematopoietic cell transplantation","volume":"21","author":"Kanda","year":"2015","journal-title":"Biol Blood Marrow Transplant"},{"key":"B12","doi-asserted-by":"publisher","first-page":"999.e1","DOI":"10.1016\/j.jtct.2021.09.008","article-title":"Post-transplantation cyclophosphamide for graft-versus- host disease prophylaxis in multiple myeloma patients who underwent allogeneic hematopoietic cell transplantation: First comparison by donor type. A study from the chronic malignancies working party of the European society for blood and marrow transplantation","volume":"27","author":"Sahebi","year":"2021","journal-title":"Transplant Cell Ther"},{"key":"B13","first-page":"55","article-title":"The national marrow donor program: improving access to hematopoietic cell transplantation","author":"Walker","year":"2011","journal-title":"Clin Transpl"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1182\/hematology.2021000258","article-title":"Transplantation ftBSoBM, blood tWNf, transplantation m. increasing access to allogeneic hematopoietic cell transplant: an international perspective","volume":"2021","author":"Rocha","year":"2021","journal-title":"Hematology"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b2700","article-title":"The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration","volume":"339","author":"Liberati","year":"2009","journal-title":"BMJ"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1200\/jco.20.01086","article-title":"Phase II trial of costimulation blockade with abatacept for prevention of acute GVHD","volume":"39","author":"Watkins","year":"2021","journal-title":"J Clin Oncol"},{"key":"B17","article-title":"Meta: An r package for meta-analysis","volume":"7","author":"Schwarzer","year":"2007","journal-title":"R News"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(86)90046-2","article-title":"Meta-analysis in clinical trials","volume":"7","author":"DerSimonian","year":"1986","journal-title":"Controlled Clin Trials"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2016.11.009","article-title":"Impact of human leukocyte antigen allele mismatch in unrelated bone marrow transplantation with reduced-intensity conditioning regimen","volume":"23","author":"Yokoyama","year":"2017","journal-title":"Biol Blood Marrow Transplant"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021004192","article-title":"Posttransplant cyclophosphamide as GVHD prophylaxis for peripheral blood stem cell HLA-mismatched unrelated donor transplant","volume":"5","author":"Al Malki","year":"2021","journal-title":"Blood Adv"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2014.10.030","article-title":"Allogeneic hematopoietic cell transplantation outcomes in acute myeloid leukemia: similar outcomes regardless of donor type","volume":"21","author":"Warlick","year":"2015","journal-title":"Biol Blood Marrow Transplant"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-01-265413","article-title":"HLA-mismatched unrelated donors are a viable alternate graft source for allogeneic transplantation following alemtuzumab-based reduced-intensity conditioning","volume":"115","author":"Mead","year":"2010","journal-title":"Blood"},{"key":"B23","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/s13045-021-01086-2","article-title":"Allogeneic hematopoietic cell transplantation with cord blood versus mismatched unrelated donor with post-transplant cyclophosphamide in acute myeloid leukemia","volume":"14","author":"Dholaria","year":"2021","journal-title":"J Hematol Oncol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/bmt.2014.259","article-title":"Alternative donors extend transplantation for patients with lymphoma who lack an HLA matched donor","volume":"50","author":"Bachanova","year":"2015","journal-title":"Bone Marrow Transplant"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2018.08.026","article-title":"HLA-mismatched donors in patients with myelodysplastic syndrome: An EBMT registry analysis","volume":"25","author":"Robin","year":"2019","journal-title":"Biol Blood Marrow Transplant"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.187450","article-title":"Haploidentical versus unrelated allogeneic stem cell transplantation for relapsed\/refractory acute myeloid leukemia: A report on 1578 patients from the acute leukemia working party of the EBMT","volume":"104","author":"Brissot","year":"2019","journal-title":"Haematologica"},{"key":"B27","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s13045-016-0314-x","article-title":"Matched and mismatched unrelated donor compared to autologous stem cell transplantation for acute myeloid leukemia in first complete remission: A retrospective, propensity score-weighted analysis from the ALWP of the EBMT","volume":"9","author":"Saraceni","year":"2016","journal-title":"J Hematol Oncol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2014.11.675","article-title":"Comparison of unrelated cord blood and peripheral blood stem cell transplantation in adults with myelodysplastic syndrome after reduced-intensity conditioning regimen: a collaborative study from eurocord (Cord blood committee of cellular therapy & immunobiology working party of EBMT) and chronic malignancies working party","volume":"21","author":"Robin","year":"2015","journal-title":"Biol Blood Marrow Transplant"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020005338","article-title":"Sirolimus with CSP and MMF as GVHD prophylaxis for allogeneic transplantation with HLA antigen-mismatched donors","volume":"136","author":"Kornblit","year":"2020","journal-title":"Blood"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2021.08.013","article-title":"Nonmyeloablative, HLA-mismatched unrelated peripheral blood transplantation with high-dose post-transplantation cyclophosphamide","volume":"27","author":"Rappazzo","year":"2021","journal-title":"Transplant Cell Ther"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.03502","article-title":"National marrow donor program\u2013sponsored multicenter, phase II trial of HLA-mismatched unrelated donor bone marrow transplantation using post-transplant cyclophosphamide","volume":"39","author":"Shaw","year":"2021","journal-title":"J Clin Oncol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2003.03.129","article-title":"Matched and mismatched allogeneic stem-cell transplantation from unrelated donors using combined graft-versus-host disease prophylaxis including rabbit anti-T lymphocyte globulin","volume":"21","author":"Finke","year":"2003","journal-title":"J Clin Oncol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1097\/tp.0000000000002932","article-title":"Long-term outcome of allogeneic hematopoietic stem cell transplantation from unrelated donor using Tacrolimus\/Sirolimus-based GvHD prophylaxis: Impact of HLA mismatch","volume":"104","author":"Al Malki","year":"2020","journal-title":"Transplantation"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2015.05.028","article-title":"HLA mismatch is associated with worse outcomes after unrelated donor reduced-intensity conditioning hematopoietic cell transplantation: An analysis from the center for international blood and marrow transplant research","volume":"21","author":"Verneris","year":"2015","journal-title":"Biol Blood Marrow Transplant"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2016002766","article-title":"Prospective study of nonmyeloablative, HLA-mismatched unrelated BMT with high-dose posttransplantation cyclophosphamide","volume":"1","author":"Kasamon","year":"2017","journal-title":"Blood Adv"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-022-01577-x","article-title":"Post-transplant cyclophosphamide in one-antigen mismatched unrelated donor transplantation versus haploidentical transplantation in acute myeloid leukemia: a study from the acute leukemia working party of the EBMT","volume":"57","author":"Battipaglia","year":"2022","journal-title":"Bone Marrow Transplant"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1200\/jco.20.03502","article-title":"National marrow donor program-sponsored multicenter, phase II trial of HLA-mismatched unrelated donor bone marrow transplantation using post-transplant cyclophosphamide","volume":"39","author":"Shaw","year":"2021","journal-title":"J Clin Oncol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-09-381699","article-title":"Outcomes after matched unrelated donor versus identical sibling hematopoietic cell transplantation in adults with acute myelogenous leukemia","volume":"119","author":"Saber","year":"2012","journal-title":"Blood"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2011.05.001","article-title":"Improved survival after allogeneic hematopoietic stem cell transplantation in recent years. a single-center study","volume":"17","author":"Remberger","year":"2011","journal-title":"Biol Blood Marrow Transplant"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.2520","article-title":"Comparison of patient-reported outcomes in 5-year survivors who received bone marrow vs peripheral blood unrelated donor transplantation: Long-term follow-up of a randomized clinical trial","volume":"2","author":"Lee","year":"2016","journal-title":"JAMA Oncol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2020.07.035","article-title":"Differences in graft-versus-Host disease characteristics between haploidentical transplantation using post-transplantation cyclophosphamide and matched unrelated donor transplantation using calcineurin inhibitors","volume":"26","author":"Solh","year":"2020","journal-title":"Biol Blood Marrow Transplant"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-03-0803","article-title":"Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-c mismatching is associated with a strong adverse effect on transplantation outcome","volume":"104","author":"Flomenberg","year":"2004","journal-title":"Blood"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(10)70127-3","article-title":"Effect of graft source on unrelated donor haemopoietic stem-cell transplantation in adults with acute leukaemia: a retrospective analysis","volume":"11","author":"Eapen","year":"2010","journal-title":"Lancet Oncol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.135699","article-title":"Peripheral blood stem cell graft compared to bone marrow after reduced intensity conditioning regimens for acute leukemia: a report from the ALWP of the EBMT","volume":"101","author":"Bipin","year":"2016","journal-title":"Haematologica"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1702349","article-title":"A comparative study of peripheral blood stem cell vs bone marrow transplantation from unrelated donors (MUD): a single center study","volume":"25","author":"Fauser","year":"2000","journal-title":"Bone Marrow Transplant"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-097386","article-title":"High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation","volume":"110","author":"Lee","year":"2007","journal-title":"Blood"},{"key":"B47","doi-asserted-by":"publisher","first-page":"776.e1","DOI":"10.1016\/j.jtct.2021.05.023","article-title":"Posttransplantation cyclophosphamide- and sirolimus-based graft-Versus-Host-Disease prophylaxis in allogeneic stem cell transplant","volume":"27","author":"Greco","year":"2021","journal-title":"Transplant Cell Ther"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021011281","article-title":"HLA-haploidentical vs matched unrelated donor transplants with posttransplant cyclophosphamide-based prophylaxis","volume":"138","author":"Gooptu","year":"2021","journal-title":"Blood"},{"key":"B49","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/leu.2010.219","article-title":"Unrelated cord blood transplantation in adults with myelodysplasia or secondary acute myeloblastic leukemia: a survey on behalf of eurocord and CLWP of EBMT","volume":"25","author":"Robin","year":"2011","journal-title":"Leukemia"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1003.e1","DOI":"10.1016\/j.jtct.2021.09.003","article-title":"Bone marrow versus peripheral blood grafts for haploidentical hematopoietic cell transplantation with post-transplantation cyclophosphamide","volume":"27","author":"Mehta","year":"2021","journal-title":"Transplant Cell Ther"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.1005042\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T07:01:25Z","timestamp":1665039685000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.1005042\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,6]]},"references-count":50,"alternative-id":["10.3389\/fonc.2022.1005042"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2022.1005042","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,6]]},"article-number":"1005042"}}