{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:14:24Z","timestamp":1790208864178,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,8,21]],"date-time":"2022-08-21T00:00:00Z","timestamp":1661040000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Children with relapse of T\u2010cell acute lymphoblastic leukemia (T\u2010ALL) or lymphoblastic lymphoma (T\u2010LBL) have a dismal prognosis, largely due to difficulty attaining second remission. We hypothesized that adding etoposide and cyclophosphamide to the nucleoside analog nelarabine could improve response rates over single\u2010agent nelarabine for relapsed T\u2010ALL and T\u2010LBL. This phase I dose\u2010escalation trial's primary objective was to evaluate the dose and safety of nelarabine given in combination with etoposide at 100\u00a0mg\/m<jats:sup>2<\/jats:sup>\/day and cyclophosphamide at 330\u2013400\u00a0mg\/m<jats:sup>2<\/jats:sup>\/day, each for 5 consecutive days in children with either T\u2010ALL (13 patients) or T\u2010LBL (10 patients). Twenty\u2010three patients were treated at three dose levels; 21 were evaluable for dose\u2010limiting toxicities (DLT) and response. The recommended phase II doses (RP2D) for this regimen, when given daily \u00d75 every 3\u00a0weeks, were nelarabine 650\u00a0mg\/m<jats:sup>2<\/jats:sup>\/day, etoposide 100\u00a0mg\/m<jats:sup>2<\/jats:sup>\/day, and cyclophosphamide 400\u00a0mg\/m<jats:sup>2<\/jats:sup>\/day. DLTs included peripheral motor and sensory neuropathies. An expansion cohort to evaluate responses at the RP2D was terminated early due to slow accrual. The overall best response rate was 38% (8\/21), with 33% (4\/12) responses in the T\u2010ALL cohort and 44% (4\/9) responses in the T\u2010LBL cohort. These response rates are comparable to those seen with single\u2010agent nelarabine in this setting. These data suggest that the addition of cyclophosphamide and etoposide to nelarabine does not increase the incidence of neurologic toxicities or the response rate beyond that obtained with single\u2010agent nelarabine in children with first relapse of T\u2010ALL and T\u2010LBL.<\/jats:p>","DOI":"10.1002\/pbc.29901","type":"journal-article","created":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T04:23:43Z","timestamp":1661142223000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Nelarabine, etoposide, and cyclophosphamide in relapsed pediatric T\u2010acute lymphoblastic leukemia and T\u2010lymphoblastic lymphoma (study T2008\u2010002 NECTAR)"],"prefix":"10.1002","volume":"69","author":[{"given":"James A.","family":"Whitlock","sequence":"first","affiliation":[{"name":"Division of Haematology\/Oncology Department of Paediatrics The Hospital for Sick Children University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jemily","family":"Malvar","sequence":"additional","affiliation":[{"name":"Division of Hematology Oncology and Blood and Marrow Transplantation Department of Pediatrics Keck School of Medicine of the University of Southern California  Los Angeles California USA"},{"name":"The Saban Research Institute Children's Hospital Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"Dalla\u2010Pozza","sequence":"additional","affiliation":[{"name":"The Children's Hospital at Westmead  Westmead New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Goldberg","sequence":"additional","affiliation":[{"name":"University of Miami Miller School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis B.","family":"Silverman","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber Cancer Institute\/Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Ziegler","sequence":"additional","affiliation":[{"name":"Kids Cancer Centre Sydney Children's Hospital  Randwick New South Wales Australia"},{"name":"School of Women's and Children's Health University of New South Wales  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9285-6898","authenticated-orcid":false,"given":"Andishe","family":"Attarbaschi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology St. Anna Children's Hospital Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick A.","family":"Brown","sequence":"additional","affiliation":[{"name":"Johns Hopkins University\/Sidney Kimmel Cancer Center  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca A.","family":"Gardner","sequence":"additional","affiliation":[{"name":"Seattle Children's Hospital  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1582-2862","authenticated-orcid":false,"given":"Paul S.","family":"Gaynon","sequence":"additional","affiliation":[{"name":"Children's Center for Cancer and Blood Disease Children's Hospital of Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Hutchinson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hematology and Oncology C.S. Mott Children's Hospital University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2781-5627","authenticated-orcid":false,"given":"Van T.","family":"Huynh","sequence":"additional","affiliation":[{"name":"Children's Hospital Orange County  Orange California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sima","family":"Jeha","sequence":"additional","affiliation":[{"name":"Department of Oncology St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh","family":"Marcus","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research U.S. Food and Drug Administration  White Oak Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7990-1802","authenticated-orcid":false,"given":"Yoav","family":"Messinger","sequence":"additional","affiliation":[{"name":"Children's Hospital and Clinics of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirk R.","family":"Schultz","sequence":"additional","affiliation":[{"name":"BC Children's Hospital and Research Institute  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeannette","family":"Cassar","sequence":"additional","affiliation":[{"name":"Children's Oncology Group  Monrovia California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7976-3654","authenticated-orcid":false,"given":"Franco","family":"Locatelli","sequence":"additional","affiliation":[{"name":"Ospedale Bambino Ges\u00f9 University of Pavia  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1353-9166","authenticated-orcid":false,"given":"C. 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