{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T10:42:26Z","timestamp":1772620946764,"version":"3.50.1"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Cladribine, a synthetic analog of deoxyadenosine, exhibits potent activity against hematological malignancies. While cladribine-containing regimens combined with allogeneic hematopoietic stem cell transplantation (allo-HSCT) have been proposed as a potential strategy to improve outcomes in relapsed or refractory (R\/R) acute myeloid leukemia (AML), additional clinical evidence is needed, particularly in pediatric populations. This single-center retrospective study aimed to describe the efficacy and safety of a cladribine-based conditioning regimen for allo-HSCT in children with R\/R AML.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Clinical data of 16 children with R\/R AML who underwent allo-HSCT following a cladribine-based conditioning regimen at our hospital from October 2020 to June 2024 were analyzed retrospectively. Key outcomes included hematopoietic reconstruction, regimen-related toxicity (RRT), cumulative incidence of graft-versus-host disease (GVHD), infection profiles, overall survival (OS), disease-free survival (DFS), relapse rate, and non-relapse mortality (NRM). Flow-cytometry minimal residual disease (MRD) results before HSCT were collected and analyzed as an additional key baseline index.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All 16 patients attained hematopoietic reconstruction, with pre-transplant flow-cytometry MRD negative in 13 cases (81.25%) and positive (MRD \u22650.01%) in three cases (18.75%). The median time of neutrophil and platelet engraftment was 12 (10\u201316) days and 15 (10\u201325) days, respectively. The incidence of I\/II grade RRT was 31.3% (oral cavity: three cases, liver: two cases), with no III\/IV grade RRT observed. The cumulative incidence of acute GVHD (aGVHD) was 50.0% (grade I\/II skin: five cases, grade IIIl: three cases). Among 15 evaluable patients, the cumulative incidence of chronic GVHD (cGVHD) was 26.7% (local skin: three cases, ocular keratoconjunctivitis sicca: one case). Post-transplant infections occurred in 31.3% of patients, predominantly viral pathogens: one case of BK virus-associated hemorrhagic cystitis, one case of BK virus combined with bacterial infection, and three cases of cytomegalovirus (CMV) DNAemia. The median follow-up time was 28.03 (11.67\u201355.34) months (follow-up cutoff: 30 June 2024). Using the Kaplan\u2013Meier method, the 1-year OS rate was 87.5% (95% CI: 65.2%\u221296.4%), and the 1-year DFS rate was 87.4% (95% CI: 64.9%\u221296.3%). The relapse rate and NRM were both 6.3% (95% CI: 0.8%\u221229.1%); the NRM case was confirmed as bronchiolitis obliterans syndrome (BOS) induced by pulmonary cGVHD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this small single-center retrospective series, the cladribine-based conditioning regimen was associated with favorable hematopoietic reconstruction, mild RRT, and promising survival outcomes in children with R\/R AML, even in partial patients with pre-transplant MRD positivity. However, due to the limited sample size, single-arm design, and lack of a control group, conclusions regarding superiority (e.g., improved OS or reduced relapse) cannot be drawn. Larger prospective multi-center studies are required to validate these preliminary findings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1747147","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T05:41:08Z","timestamp":1772602868000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of a new cladribine-based conditioning regimen for allogeneic hematopoietic stem cell transplantation in children with relapsed or refractory acute myeloid leukemia"],"prefix":"10.3389","volume":"13","author":[{"given":"Wen-ting","family":"Pei","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital)","place":["Jinan, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-lei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Information Technology, Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital)","place":["Jinan, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-ling","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital)","place":["Jinan, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1612702","DOI":"10.1155\/2022\/1612702","article-title":"The global burden of leukemia and its attributable factors in 204 countries and territories: findings from the global burden of disease 2019 study and projections to 2030","volume":"2022","author":"Du","year":"2022","journal-title":"J Oncol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1002\/cam4.3681","article-title":"Improved outcome of children with relapsed\/refractory acute myeloid leukemia by addition of cladribine to re-induction chemotherapy","volume":"10","author":"Ruan","year":"2021","journal-title":"Cancer Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/j.annonc.2020.02.018","article-title":"Acute myeloid leukaemia in adult patients: ESMO clinical practice guidelines for diagnosis, treatment and follow-up","volume":"31","author":"Heuser","year":"2020","journal-title":"Ann Oncol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/s41409-018-0286-2","article-title":"Post-remission strategies for the prevention of relapse following allogeneic hematopoietic cell transplantation for high-risk acute myeloid leukemia: expert review from the acute leukemia working party of the European society for blood and marrow transplantation","volume":"54","author":"Lee","year":"2019","journal-title":"Bone Marrow Transplant"},{"key":"B5","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1186\/s13045-021-01159-2","article-title":"The consensus from the Chinese Society of Hematology on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation: 2021 update","volume":"14","author":"Zhang","year":"2021"},{"key":"B6","doi-asserted-by":"publisher","first-page":"3488","DOI":"10.3390\/cells10123488","article-title":"Immunomodulatory effects associated with Cladribine treatment","volume":"10","author":"Fissolo","year":"2021","journal-title":"Cells."},{"key":"B7","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1080\/10428194.2020.1821009","article-title":"Comparison of salvage chemotherapy regimens and prognostic significance of minimal residual disease in relapsed\/refractory acute myeloid leukemia","volume":"62","author":"Mushtaq","year":"2021","journal-title":"Leuk Lymphoma."},{"key":"B8","doi-asserted-by":"publisher","first-page":"183","DOI":"10.3760\/cma.j.issn.0253-2727.2017.03.002","article-title":"The guidelines for diagnosis and treatment of acute myelogenous leukemia (relapse\/refractory) in China","volume":"38","year":"2017","journal-title":"Zhonghua Xue Ye Xue Za Zhi"},{"key":"B9","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/j.bbmt.2014.12.001","article-title":"National Institutes of health consensus development project on criteria for clinical trials in Chronic Graft-versus-Host Disease: I. The 2014 diagnosis and staging working group report","volume":"21","author":"Jagasia","year":"2015","journal-title":"Biol Blood Marrow Transpl."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1003908","DOI":"10.3389\/fonc.2022.1003908","article-title":"Total marrow irradiation (TMI): addressing an unmet need in hematopoietic cell transplantation - a single institution experience review","volume":"12","author":"Wong","year":"2022","journal-title":"Front Oncol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1182\/blood-2009-07-235358","article-title":"Diagnosis and management of acute leukemia in adults: recommendations from an international expert panel, on behalf of the European LenkemiaNet","volume":"115","author":"D\u00f6hner","year":"2010","journal-title":"Blood"},{"key":"B12","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.jtct.2021.02.031","article-title":"Myeloablative versus reduced-intensity conditioning for hematopoietic cell transplantation in acute myelogenous leukemia and myelodysplastic syndromes-long-term follow-up of the BMT CTN 0901 clinical trial","volume":"27","author":"Scott","year":"2021","journal-title":"Transplant Cell Ther"},{"key":"B13","doi-asserted-by":"publisher","first-page":"102037","DOI":"10.1016\/j.trim.2024.102037","article-title":"Efficacy and safety of cladribine in combination with busulfan and cyclophosphamide as an intensive conditioning regimen preceding allogeneic hematopoietic stem cell transplantation in relapsed or refractory acute myeloid leukemia","volume":"84","author":"Xiao","year":"2024","journal-title":"Transplant Immunol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1014306","DOI":"10.3389\/fphar.2023.1014306","article-title":"Safety and efficacy of a modified busulfan\/cyclophosphamide conditioning regimen incorporating cladribine for autologous hematopoietic stem cell transplantation in acute myeloid leukemia","volume":"14","author":"Shi","year":"2023","journal-title":"Front Pharmacol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.4149\/neo_2021_210426N573","article-title":"A novel intensive conditioning regimen for allogeneic hematopoietic stem cell transplantation in the treatment of relapsed\/refractory acute myeloid leukemia","volume":"68","author":"Sun","year":"2021","journal-title":"Neoplasma."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2123","DOI":"10.1002\/ijc.34419","article-title":"Cladribine- and decitabine-containing conditioning regimen has a low post-transplant relapse rate in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome","volume":"152","author":"Tong","year":"2023","journal-title":"Int J Cancer."},{"key":"B17","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jtct.2022.09.003","article-title":"Impact on outcome of minimal residual disease after hematopoietic stem cell transplantation with fludarabine, Amsacrine, and cytosine arabinosidebusulfan conditioning: a retrospective monocentric study","volume":"29","author":"Meur","year":"2023","journal-title":"Transplant Cell Ther."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2674","DOI":"10.1200\/JCO.2009.24.8997","article-title":"Cytogenetics of childhood acute myeloid leukemia: United Kingdom Medical Research Council treatment trials AML 10 and 12","volume":"28","author":"Harrison","year":"2010","journal-title":"J Clin Oncol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1186\/s12885-020-07043-5","article-title":"Allogeneic hematopoietic stem cell transplantation can improve the prognosis of high-risk pediatric t(8;21) acute myeloid leukemia in first remission based on MRD-guided treatment","volume":"20","author":"Hu","year":"2020","journal-title":"BMC Cancer."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1038\/s41409-025-02596-0","article-title":"Allogeneic stem cell transplantation in de novo core-binding factor acute myeloid leukemia in active disease: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation","volume":"60","author":"Tarantino","year":"2025","journal-title":"Bone Marrow Transplant"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1747147\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T05:41:12Z","timestamp":1772602872000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1747147\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,4]]},"references-count":20,"alternative-id":["10.3389\/fmed.2026.1747147"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1747147","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,4]]},"article-number":"1747147"}}