Correspondence

Listeriosis after 2-Chlorodeoxyadenosine Treatment

N Engl J Med 1993; 328:813-814March 18, 1993

Article

To the Editor:

Infections caused by Listeria monocytogenes have been described in patients with chronic lymphocytic leukemia (CLL). Cases have also occurred after treatment with prednisone combined with the purine analogue fludarabine1. We have been conducting a phase I trial of another purine analogue, 2-chlorodeoxyadenosine, given intravenously as a one-hour bolus dose for five days. This drug is effective in patients with CLL refractory to fludarabine2. We describe here a patient with CLL in whom listeriosis developed after treatment with 2-chlorodeoxyadenosine.

A 68-year-old woman with an eight-year history of CLL had been treated during the previous six years with a variety of chemotherapy regimens containing alkylating agents and prednisone. In October 1991, treatment for progressive disease was begun with monthly cycles of fludarabine; corticosteroids were not administered. After initial improvement, the disease progressed. Fludarabine was discontinued after 10 cycles. Five weeks later, in November 1992, 2-chlorodeoxyadenosine was started in a dose of 15 mg per square meter of body-surface area per day and was given for five days. At that time the white-cell count was 23,600 per cubic millimeter, the absolute neutrophil count 3304 per cubic millimeter, and the lymphocyte count 18,172 per cubic millimeter. Nineteen days after 2-chlorodeoxyadenosine administration, fever developed (temperature, 39.4 °C), with fatigue and anorexia. The lymphadenopathy had decreased markedly. The white-cell count at this time was 30,400 per cubic millimeter, and the absolute neutrophil count 1216 per cubic millimeter. Bacterial cultures of blood and spinal fluid grew L. monocytogenes. The patient was treated with intravenous ampicillin and gentamicin. Subsequent cultures of her blood, spinal fluid, and urine showed no growth. Her fever resolved. She was discharged after 17 days and received antibiotic therapy for 2 more weeks.

Infections due to L. monocytogenes occur in adults with impaired immune function. We are unaware of other cases occurring after therapy with 2-chlorodeoxyadenosine. Our patient had received fludarabine until five weeks before 2-chlorodeoxyadenosine administration, but the risk of listeriosis seems to be associated only with the combined use of fludarabine and corticosteroids1. Thus, our patient's susceptibility to listeria infection may have been due to treatment with 2-chlorodeoxyadenosine alone or to the sequential use of fludarabine and 2-chlorodeoxyadenosine.

With the wider use of new purine analogues that have profound immunomodulatory effects, physicians must be vigilant for unusual opportunistic infections.

Ricardo T. Spielberger, M.D.
Wendy Stock, M.D.
Richard A. Larson, M.D.
University of Chicago, Chicago, IL 60637

2 References

1. 1

   Anaissie E, Kontoyiannis DP, Kantarjian H, Elting L, Robertson LE, Keating M. Listeriosis in patients with chronic lymphocytic leukemia who were treated with fludarabine and prednisone. Ann Intern Med 1992;117:466-469
   Web of Science | Medline

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   Juliusson G, Elmhorn-Rosenborg A, Liliemark J. Response to 2-chlorodeoxyadenosine in patients with B-cell chronic lymphocytic leukemia resistant to fludarabine. N Engl J Med 1992;327:1056-1061
   Full Text | Web of Science | Medline

Citing Articles (8)

Citing Articles

1. 1

   Terry J. Hamblin. (2001) Achieving Optimal Outcomes in Chronic Lymphocytic Leukaemia. Drugs 61:5, 593-611
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2. 2

   S Tsiodras, G Samonis, M J Keating, D P Kontoyiannis. (2000) Infection and immunity in chronic lymphocytic leukemia.. Mayo Clinic Proceedings 75:10, 1039-1054
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3. 3

   Nelson Kalil, Bruce D. Cheson. (2000) Management of Chronic Lymphocytic Leukaemia. Drugs & Aging 16:1, 9-27
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4. 4

   John C. Byrd, Jeffrey B. Hargis, Kent E. Kester, Duane R. Hospenthal, Sarah W. Knutson, Louis F. Diehl. (1995) Opportunistic pulmonary infections with fludarabine in previously treated patients with low-grade lymphoid malignancies: A role for pneumocystis carinii pneumonia prophylaxis. American Journal of Hematology 49:2, 135-142
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5. 5

   (1994) 2-Chlorodeoxyadenosine Therapy in Chronic Lymphocytic Leukemia. New England Journal of Medicine 330:25, 1828-1830
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6. 6

   Corrado Girmenia, Francesca Romana Mauro, Siavash Rahimi. (1994) Late listeriosis after fludarabine plus prednisone treatment. British Journal of Haematology 87:2, 407-408
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7. 7

   &NA;. (1993) Chlorodeoxyadenosine. Reactions Weekly &NA;:446, 7
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8. 8

   B. D. Cheson. (1993) Purine Analogs in Lymphoproliferative Disorders. Leukemia & Lymphoma 11:s2, 153-159
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