The

n e w e ng l a n d j o u r na l

of

m e dic i n e

somepositive acute lymphoid leukemia. Full de- Charles L. Sawyers, M.D.

tails of these studies have not yet been reported, Howard Hughes Medical Institute
but 28% of the patients had pleural effusions Los Angeles, CA 90095
csawyers@mednet.ucla.edu
while receiving dasatinib at doses of less than
140 mg per day, with treatment administered Moshe Talpaz, M.D.
twice daily. A randomized study now under way University of Michigan
comparing once- with twice-daily treatment with Ann Arbor, MI 48109
dasatinib at a dose of 100 or 140 mg daily could Eric Bleickardt, M.D.
determine whether the dose of this agent and the Bristol-Myers Squibb
schedule affect the incidence of pleural effusion. Wallingford, CT 06492

Genomic Diagnosis of Burkitts Lymphoma

To the Editor: In the article by Dave et al. (June
8 issue)1 concerning the molecular diagnosis of
Burkitts lymphoma, almost half the patients with
Burkitts lymphoma were children. The data in
the companion article by Hummel et al.2 were not
stratified according to age. If the patients are
separated into adults and children, are the results
similar? Can the same method be applied to patients with immunodeficiency?
Bryan T. Lin, M.D., Ph.D.
EncinoTarzana Regional Medical Center
Tarzana, CA 91356
btltarzana@hotmail.com
1. Dave SS, Fu K, Wright GW, et al. Molecular diagnosis of

Burkitts lymphoma. N Engl J Med 2006;354:2431-42.

2. Hummel M, Bentink S, Berger H, et al. A biologic definition
of Burkitts lymphoma from transcriptional and genomic profiling. N Engl J Med 2006;354:2419-30.

Drs. Dave and Staudt Reply: The tumors from

children and adults with Burkitts lymphoma were
indistinguishable on the basis of the expression
of the predictor genes. There was also no difference in outcome between children and adults who
received intensive therapies. However, all nine
Burkitts lymphomadiscrepant cases (i.e., cases
of Burkitts lymphoma identified on the basis of
gene expression but not standard diagnostic methods) were in adults. Thus, cases in adults may be
more variable with regard to morphologic characteristics and other diagnostic criteria than in
cases in children, perhaps reflecting the influence
of additional genomic abnormalities in adults.
Although our study did not examine tumors
from Burkitts lymphoma associated with immu-

1064

n engl j med 355;10

nodeficiency, it seems to be likely that this type

of Burkitts lymphoma would share the geneexpression hallmarks of sporadic Burkitts lymphoma, but this possibility requires a separate
study. The turnaround time for a diagnosis based
on DNA microarray could be about 48 hours,
which is similar to that for conventional methods
used in the diagnosis of Burkitts lymphoma. We
agree with Dr. Lin that correctly distinguishing
Burkitts lymphoma from diffuse large B-cell
lymphoma is critical, since it dictates the optimal
treatment for each patient.
Sandeep S. Dave, M.D.
Louis M. Staudt, M.D., Ph.D.
National Cancer Institute
Bethesda, MD 20892
lstaudt@mail.nih.gov

Dr. Hummel and colleagues Reply: In our

study, 24 of 44 cases of molecular Burkitts lymphoma (mBL), 1 of 128 non-mBL cases, and 6 of
48 intermediate cases arose in children (<18 years
of age). When age and clinical stage were included in the multivariate model, molecular diagnosis was not a significant independent prognostic
factor for survival. The results of a univariate comparison of survival among children and adults
with mBL who were treated with acute lymphoblastic leukemia (ALL)like chemotherapy (14 children and 7 adults) or with chemotherapy regimens
based on cyclophosphamide, doxorubicin, vincristine, and prednisone (2 children and 1 adult) were
not meaningful, owing to the small number of
cases. Whether it is possible to apply the mBL

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correspondence

signature to patients with immunodeficiency will Reiner Siebert, M.D.

Christian-Albrechts-Universitt zu Kiel
require further investigation.
25105 Kiel, Germany
Michael Hummel, Ph.D.
for the Molecular Mechanisms in Malignant
Harald Stein, M.D.
Lymphomas Network Project of the Deutsche
Charit Campus Benjamin Franklin
D-12200 Berlin, Germany
Krebshilfe
Harald.Stein@charite.de

Vitamins C and E and the Prevention of Preeclampsia

To the Editor: The report by Rumbold et al. on
the Australian Collaborative Trial of Supplements
(ACTS) and the accompanying editorial by Jeyabalan and Caritis (April 27 issue)1,2 overlooked a
key reason for the lack of effect of vitamin C on
the prevention of preeclampsia. Ascorbate administration is based on the hypothesis that different
intakes will produce different concentrations and
hence outcomes. Because plasma ascorbate concentrations were not reported, we estimated them
from known data. On the basis of data from
young women who were not pregnant,3 the placebo and treatment groups in the study by Rumbold
et al. probably had similar plasma and tissue ascorbate concentrations. The timeconcentration curve
for vitamin C is sigmoidal, with plasma concentrations nearing a plateau of 70 to 80 M at an
intake of 200 mg per day.3,4 Doses of 1 g per day
have little effect on plasma or intracellular ascorbate concentrations. Corrections for estimated increased ascorbate needs in pregnancy5 do not
change the conclusion that the concentrations in
women in the control group were near saturation.
An appropriate study would measure the effect
of ascorbate supplementation in women who
were shown to have low plasma ascorbate concentrations at entry. Such subjects exist: among
women between the ages of 19 and 30 years in
the United States, the lowest 10th percentile receive only 40 mg of vitamin C per day.5 Plasma
measurements and attention to the pharmacokinetics of vitamin C are required before a conclusion can be made regarding whether supplementation has benefit.
Sebastian J. Padayatty, M.D., Ph.D.
Mark Levine, M.D.
National Institutes of Health
Bethesda, MD 20892

n engl j med 355;10

1. Rumbold AR, Crowther CA, Haslam RR, Dekker GA, Robin-

son JS. Vitamins C and E and the risks of preeclampsia and

perinatal complications. N Engl J Med 2006;354:1796-806.
2. Jeyabalan A, Caritis SN. Antioxidants and the prevention
of preeclampsia unresolved issues. N Engl J Med 2006;354:
1841-3.
3. Levine M, Wang Y, Padayatty SJ, Morrow J. A new recommended dietary allowance of vitamin C for healthy young women.
Proc Natl Acad Sci U S A 2001;98:9842-6.
4. Levine M, Conry-Cantilena C, Wang Y, et al. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended
dietary allowance. Proc Natl Acad Sci U S A 1996;93:3704-9.
5. Food and Nutrition Board, Panel on Dietary Antioxidants
and Related Compounds. Dietary reference intakes for vitamin C,
vitamin E, selenium, and carotenoids. Washington, DC: National
Academy Press, 2000:95-185, 432-7.

To the Editor: Rumbold et al. concluded that

vitamin C and E supplementation in nulliparous
women did not prevent preeclampsia findings
that concurred with those of our trial in high-risk
women.1 Our study suggested possible harmful
effects of these antioxidants in women with clinical risk factors, including an increased frequency
of infants with low birth weight (the principal
neonatal end point) and an increased use of medication (antihypertensive agents, corticosteroids,
and magnesium sulfate). Rumbold et al. also reported an increased requirement for antihypertensive treatment. In exploratory analysis, we found
an earlier onset of both preeclampsia and delivery among women who received such supplementation.
Variable definitions make comparisons between studies difficult.2 We used the definition
of preeclampsia proteinuric hypertension
adopted by the International Society for the Study
of Hypertension in Pregnancy (ISSHP).3 Rumbold et al. used a less specific definition of hypertension and one or more of the following: proteinuria, renal insufficiency, liver disease, neurologic

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