{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T16:36:17Z","timestamp":1765038977049},"reference-count":47,"publisher":"American Society of Hematology","issue":"2","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A preliminary study has linked raised blast glutathione levels with chemoresistance in acute myeloid and lymphoblastic leukemia in adults and children. In this study, therefore, the relationship between leukemic blast glutathione levels and prognosis in childhood acute lymphoblastic leukemia (ALL) was investigated. A total of 77 childhood ALL samples were analyzed, 62 at initial presentation and 15 at relapse. A 20-fold interindividual variation in glutathione levels at presentation (median, 6.54 nmol\/mg protein; range, 1.37 to 27.9) was demonstrated. The median level in T-lineage ALL was 2.3-fold higher than in B-lineage ALL (Mann-Whitney test,P\u2009&amp;lt;\u2009.0001). There was a significant correlation between presenting white cell count (WBC) and glutathione level (Spearman rank correlation coefficient, \u03c1\u2009=\u20090.45, P\u2009=\u2009.001). A high DNA index correlated with low glutathione levels (Mann-Whitney test,P\u2009=\u2009.013). There was no significant relationship between glutathione levels and in vitro drug sensitivity. Patients with glutathione levels above the median had a significantly greater risk of relapse (log-rank test statistic, 5.55; P\u2009=\u2009.018), and the overall survival rate was significantly reduced (log-rank test statistic, 4.38; P\u2009=\u2009.04). Multivariate analysis demonstrated that glutathione concentration was of independent prognostic value when assessed in conjunction with age, gender, WBC, and immunophenotype. The association of elevated blast glutathione levels with an increased risk of relapse suggests that glutathione-depleting agents may be of therapeutic value in patients who present with a high WBC.<\/jats:p>","DOI":"10.1182\/blood.v97.2.393","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:47Z","timestamp":1027774007000},"page":"393-398","update-policy":"http:\/\/dx.doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":33,"title":["Raised blast glutathione levels are associated with an increased risk of relapse in childhood acute lymphocytic leukemia"],"prefix":"10.1182","volume":"97","author":[{"given":"Pamela R.","family":"Kearns","sequence":"first","affiliation":[{"name":"From the Department of Paediatric Oncology, University of Newcastle, and the Medical School, Newcastle Upon Tyne, United Kingdom; Sophia Children's Hospital, University Hospital, Rotterdam, and the University Hospital VU, Amsterdam, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rob","family":"Pieters","sequence":"additional","affiliation":[{"name":"From the Department of Paediatric Oncology, University of Newcastle, and the Medical School, Newcastle Upon Tyne, United Kingdom; Sophia Children's Hospital, University Hospital, Rotterdam, and the University Hospital VU, Amsterdam, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. M. Antoinette","family":"Rottier","sequence":"additional","affiliation":[{"name":"From the Department of Paediatric Oncology, University of Newcastle, and the Medical School, Newcastle Upon Tyne, United Kingdom; Sophia Children's Hospital, University Hospital, Rotterdam, and the University Hospital VU, Amsterdam, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew D. J.","family":"Pearson","sequence":"additional","affiliation":[{"name":"From the Department of Paediatric Oncology, University of Newcastle, and the Medical School, Newcastle Upon Tyne, United Kingdom; Sophia Children's Hospital, University Hospital, Rotterdam, and the University Hospital VU, Amsterdam, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew G.","family":"Hall","sequence":"additional","affiliation":[{"name":"From the Department of Paediatric Oncology, University of Newcastle, and the Medical School, Newcastle Upon Tyne, United Kingdom; Sophia Children's Hospital, University Hospital, Rotterdam, and the University Hospital VU, Amsterdam, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"key":"2020012417534128500_B1","first-page":"275","article-title":"The United Kingdom Medical Research Council trials for the treatment of childhood acute lymphoblastic leukaemia.","volume":"5","author":"Saha","year":"1998","journal-title":"Int J Paediatr Haematol Oncol."},{"key":"2020012417534128500_B2","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1200\/JCO.1994.12.4.740","article-title":"Treatment of childhood acute lymphoblastic leukaemia: results of Dana-Farber Cancer Institute\/Children's Hospital Acute Lymphoblastic Leukemia Consortium Protocol 85-01.","volume":"12","author":"Schorin","year":"1994","journal-title":"J Clin Oncol."},{"key":"2020012417534128500_B3","doi-asserted-by":"crossref","first-page":"3122","DOI":"10.1182\/blood.V84.9.3122.3122","article-title":"Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients: results and conclusions of the multicenter trial ALL-BFM 86.","volume":"84","author":"Reiter","year":"1994","journal-title":"Blood."},{"key":"2020012417534128500_B4","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.1200\/JCO.1995.13.10.2490","article-title":"Cognitive sequelae of treatment in childhood acute lymphoblastic leukemia: cranial radiation requires an accomplice.","volume":"13","author":"Waber","year":"1995","journal-title":"J Clin Oncol."},{"key":"2020012417534128500_B5","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1200\/JCO.1995.13.10.2503","article-title":"Pubertal growth in young adult survivors of childhood leukemia.","volume":"13","author":"Didcock","year":"1995","journal-title":"J Clin Oncol."},{"key":"2020012417534128500_B6","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1038\/bjc.1996.145","article-title":"Risk factors for intellectual and educational sequelae of cranial irradiation in childhood acute lymphoblastic leukaemia.","volume":"73","author":"Smibert","year":"1996","journal-title":"Br J Cancer."},{"key":"2020012417534128500_B7","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1136\/adc.71.5.457","article-title":"Anthracyclines: cardiotoxicity and its prevention.","volume":"71","author":"Hale","year":"1994","journal-title":"Arch Dis Child."},{"key":"2020012417534128500_B8","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1136\/bmj.304.6832.951","article-title":"Epipodophyllotoxins, alkylating agents, and radiation and risk of secondary leukaemia after childhood cancer.","volume":"304","author":"Hawkins","year":"1992","journal-title":"BMJ."},{"key":"2020012417534128500_B9","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1046\/j.1365-2141.1998.00818.x","article-title":"Critical study of prognostic factors in childhood acute lymphoblastic leukaemia: differences in outcome are poorly explained by the most significant prognostic variables. 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