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Blood, 15 January 2001, Vol. 97, No. 2, pp. 393-398
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Raised blast glutathione levels are associated with an increased
risk of relapse in childhood acute lymphocytic leukemia
Pamela R. Kearns,
Rob Pieters,
M. M. Antoinette Rottier,
Andrew D. J. Pearson, and
Andrew G. Hall
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.
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 < .0001). There was a significant correlation between
presenting white cell count (WBC) and glutathione level (Spearman rank
correlation coefficient,  = 0.45, P = .001). A high
DNA index correlated with low glutathione levels (Mann-Whitney test,
P = .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 = .018), and
the overall survival rate was significantly reduced (log-rank test
statistic, 4.38; P = .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.
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