Correspondence

Tumor Lysis Syndrome after Treatment of Chronic Lymphocytic Leukemia with Cladribine

N Engl J Med 1994; 330:1090April 14, 1994

Article

To the Editor:

In the November 18 issue of the Journal, Dann et al.1 reported a case of tumor lysis syndrome after treatment with 2-chlorodeoxyadenosine (cladribine) in a patient with refractory chronic lymphocytic leukemia. We would like to report another case of tumor lysis syndrome resulting from treatment with 2-chlorodeoxyadenosine.

A 59-year-old man presented to the Mayo Clinic for a second opinion concerning therapy for his chronic myelogenous leukemia in chronic phase, which had been diagnosed approximately 18 months earlier. The patient could not tolerate hydroxyurea, had dose-limiting thrombocytopenia when treated with busulfan, and did not want to try interferon alfa. He was therefore enrolled in a phase 1 experimental protocol using 2-chlorodeoxyadenosine. He was not taking allopurinol because of a history of a dermatologic reaction. Physical examination revealed a spleen palpable 10 cm below the left costal margin. The initial white-cell count was 138,200 per cubic millimeter. The bone marrow-biopsy specimen contained 5 percent blasts, a finding consistent with chronic myelogenous leukemia in chronic phase. Cytogenetic studies revealed the Philadelphia chromosome. The initial electrolyte, creatinine, and uric acid concentrations were normal. The protocol called for the patient to receive an infusion of 12 mg of 2-chlorodeoxyadenosine per square meter of body-surface area over a period of two hours for five days. On the morning after the second infusion, the patient had a temperature of 38.7 °C, was nauseated, and generally felt unwell. The 2-chlorodeoxyadenosine was discontinued. A laboratory evaluation revealed a serum potassium concentration of 5.5 mmol per liter, a serum bicarbonate concentration of 19 mmol per liter, a uric acid concentration of 22.0 mg per deciliter, and a creatinine concentration of 1.9 mg per deciliter; the white-cell count had decreased to 69,800 per cubic millimeter. The patient was treated with intravenous hydration, alkalinization of the urine, and cautious reinstatement of allopurinol. Within 72 hours, all metabolic measures normalized. The white-cell count reached a nadir of 2300 per cubic millimeter eight days after 2-chlorodeoxyadenosine was initiated.

This case is a second example of tumor lysis syndrome resulting from 2-chlorodeoxyadenosine. The use of this relatively new chemotherapeutic agent requires close monitoring of renal function and serum uric acid concentrations and the prophylactic use of allopurinol.

Michael C. Trendle, M.D.
Ayalew Tefferi, M.D.
Mayo Clinic, Rochester, MN 55905

1 References

1. 1

   Dann EJ, Gillis S, Polliack A, Okon E, Rund D, Rachmilewitz EA. Tumor lysis syndrome following treatment with 2-chlorodeoxyadenosine for refractory chronic lymphocytic leukemia. N Engl J Med 1993;329:1547-1548
   Full Text | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: A rapid decline in the white-cell count following treatment with 2-chlorodeoxyadenosine in two patients with chronic myelogenous leukemia in blast crisis was reported by Carson et al. 10 years ago,1 although full-blown tumor lysis syndrome was not described in these patients. The patient described by Drs. Trendle and Tefferi seems to have been given considerably higher doses of 2-chlorodeoxyadenosine, in terms of both peak levels and total dose, than those given to the patients of Carson et al. (12 mg per square meter of body-surface area per day over a 2-hour period vs. 0.1 to 0.15 mg per kilogram of body weight per day over a 24-hour period). In previous phase 1 trials, doses of 2-chlorodeoxyadenosine exceeding 0.5 mg per kilogram per day were associated with nephrotoxicity2. It is possible that the acute renal failure documented by Trendle and Tefferi in their patient may have resulted from nephrotoxicity and not from tumor lysis syndrome itself.

Nonetheless, we fully concur that in patients being treated with this new drug, especially if innovative dosing regimens are being used or if there is evidence of a large tumor burden, very close monitoring of renal, biochemical, and hematologic variables is essential.

Eldad J. Dann, M.D.
Eliezer A. Rachmilewitz, M.D.
Deborah Rund, M.D.
Hadassah University Hospital, il-91120 Jerusalem, Israel

2 References

1. 1

   Carson DA, Wasson DB, Beutler E. Antileukemic and immunosuppressive activity of 2-chloro-2'-deoxyadenosine. Proc Natl Acad Sci U S A 1984;81:2232-2236
   CrossRef | Web of Science | Medline

2. 2

   Saven A, Piro LD. 2-Chlorodeoxyadenosine: a new nucleoside agent effective in the treatment of lymphoid malignancies. Leuk Lymphoma 1993;10:Suppl:43-49
   CrossRef | Medline

Citing Articles (5)

Citing Articles

1. 1

   Elvira Rampello, Tiziana Fricia, Mariano Malaguarnera. (2006) The management of tumor lysis syndrome. Nature Clinical Practice Oncology 3:8, 438-447
   CrossRef

2. 2

   Margit Hummel, Dieter Buchheidt, Sebastian Reiter, Jorg Bergmann, Katja Adam, Rudiger Hehlmann. (2005) Recurrent chemotherapy-induced tumor lysis syndrome (TLS) with renal failure in a patient with chronic lymphocytic leukemia - successful treatment and prevention of TLS with low-dose rasburicase. European Journal of Haematology 75:6, 518-521
   CrossRef

3. 3

   Kashif Hussain, Joseph J. Mazza, Lawrence H. Clouse. (2003) Tumor lysis syndrome (TLS) following fludarabine therapy for chronic lymphocytic leukemia (CLL): Case report and review of the literature. American Journal of Hematology 72:3, 212-215
   CrossRef

4. 4

   H. H. Sewani, J. T. Rabatin. (2002) Acute Tumor Lysis Syndrome in a Patient With Mixed Small Cell and Non-Small Cell Tumor. Mayo Clinic Proceedings 77:7, 722-728
   CrossRef

5. 5

   &NA;. (1994) Cladribine. Reactions Weekly &NA;:499, 5
   CrossRef