{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:59:59Z","timestamp":1790171999003,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp;amp; Cancer"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Relapsed and refractory (R\/R) T\u2010cell acute lymphoblastic leukemia\/lymphoma (T\u2010ALL\/T\u2010LL) remains a therapeutic challenge. Allogeneic hematopoietic stem cell transplantation (HSCT) after achieving complete remission (CR) offers the only chance of cure, but effective modalities to achieve CR are limited. Activation of mTOR and PI3K pathways has been well described in T\u2010ALL and monotherapy with mTOR inhibitors has shown efficacy signals used in relapsed disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multisite Phase 1 study evaluated the safety, tolerability, and anti\u2010leukemic activity of everolimus with NEC chemotherapy (nelarabine, etoposide, and cyclophosphamide) among children and young adults with relapsed\/refractory T\u2010ALL\/T\u2010LL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eight patients were enrolled to two dose levels (DLs) on this study and no dose\u2010limiting toxicities were reported. Most adverse events related to therapy were expected and hematological. DL2 (\n                      <jats:italic>n<\/jats:italic>\n                      = 5) of everolimus at 5 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      \/day was the highest dose tested. The overall response rate (complete response + complete response with incomplete platelet recovery + partial response) was 75% (6\/8) with 100% (5\/5) responses in the T\u2010ALL cohort and 33% (1\/3) responses in T\u2010LL cohort. All six patients who obtained a PR or greater proceeded to receive HSCT as consolidation therapy. Two of the six patients transplanted are alive today with two deaths related to progressive disease and two related to veno\u2010occlusive disease post transplantation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study demonstrates safety with a combination of everolimus and NEC chemotherapy. Given the observed tolerability and efficacy of everolimus with NEC in this small cohort of patients, this combination should be further evaluated in larger phase 2\/3 clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov identifier: NCT03328104<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/1545-5017.70662","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T13:37:25Z","timestamp":1789047445000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ENCERT: A Multisite Phase 1 Trial Using Everolimus in Combination With Nelarabine, Cyclophosphamide, and Etoposide in Relapsed T\u2010Cell Lymphoblastic Leukemia\/Lymphoma"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3763-3253","authenticated-orcid":false,"given":"Himalee S.","family":"Sabnis","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology\/Bone Marrow Transplantation Department of Pediatrics, Emory University  Atlanta Georgia USA"},{"name":"Aflac Cancer and Blood Disorders Center Children's Healthcare of Atlanta  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8906-5836","authenticated-orcid":false,"given":"Melinda","family":"Pauly","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology\/Bone Marrow Transplantation Department of Pediatrics, Emory University  Atlanta Georgia USA"},{"name":"Aflac Cancer and Blood Disorders Center Children's Healthcare of Atlanta  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7063-512X","authenticated-orcid":false,"given":"Eric S.","family":"Schafer","sequence":"additional","affiliation":[{"name":"Texas Children's Cancer and Hematology Center and Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8589-1804","authenticated-orcid":false,"given":"Robin E.","family":"Norris","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Ginn","sequence":"additional","affiliation":[{"name":"Children's Mercy Hospital  Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsz","family":"Yeung","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology\/Bone Marrow 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