CORRESPONDENCE

ACUTE TUMOR LYSIS SYNDROME AND ALKALI THERAPY

To the Editor: Hande and Garrow’ report a 6%

incidence of “clinical tumor lysis syndrome (CTIS)” following ther- apy in 102 patients with intermedi- ate and high-grade lymphomas. They believe that “with the use of hydration and allopurinol therapy, clinically significant metabolic complications from tumor lysis are rare.” This is probably true of pa- tients with non-Hodgkin’s lym- phoma of other than undifferenti- ated (Burkitt’s and non-Burldtt’s) and lymphoblastic histology. How- ever, in patients with Burkitt’s lym- phoma and lymphoblastic lym- phoma, renal failure from acUe tumor lysis syndrome continues to be a major clinical problem.2 The frequency of clinically significant tumor lysis syndrome (CTIS) and acute renal failure following ther- apy in three large series of patients with Burkitt’s lymphoma and lym- phoblastic lymphoma has ranged from 13% to 25%.““,”

The eligibility criteria used by Hande and Garrow regarding fluid therapy can not be considered ad- equate by current standards.“ Hydration should be judged ade- quate when the urine is maximally dilute with a urine flow rate of about 250 mIJh before initiating chemotherapy in patients with Burkitt’s and lymphoblastic lym- phoma who are at high risk of de- veloping tumor lysis syndrome.

Alkali therapy is stopped at the start of chemotherapy to decrease the risk of intrarenal precipitation of phosphate in alkaline urine dur- ing the period of phosphaturia as- sociated with acute tumor lysis. Continued alkali administration beyond the start of chemotherapy may have contributed to the hy- perphosphatemia and renal failure in several patients reported by Stapleton et al.” The risk of devel- oping severe hyperphosphatemia

following therapy in patients who are uniformly managed with ade- quate hydration and off alkali ther- apy is not known. In context, in- formation about urine flow rate, urine pH and specific gravity and alkali therapy in the hyperphos- phatemic patients reported by Hande and Garrow would be valu- able in assessing the efficacy of available therapy in preventing marked hyperphosphatemia.

Prasad Rao Koduri, MD Cook Cow@ Hospital

Chicago, Illinois

1. Hande KR, Garrow GC. Acute tumor lysis syndrome in patients with highgrade nontiodgkin’s lymphoma. Am J Med. 1993;94:133-139. 2. Stapleton FE, Strother DR, Roy S Ill, et al. Acute renal failure at onset of therapy for advanced stage BurkiWs lymphoma and B ceil acute lymphoblastic lymphoma. Pediatreics. 1988;82:863-869. 3. Tsokos GC, Balow JE, Spiegel RJ, et al. Renal and metabolic complications of undifferentiated and lymphoblastic lymphomas. Medicine. (Baltimore) 1981;60:218-229. 4. Colen LF, Balow JE, Magrath IT, et al. Acute tumor lysis syndrome: a review of 37 patients with Burkitt’s lymphoma. Am J Med. 1980;68:486-491. 5. Lange B, D’Angio G, Ross AJ Ill, et al. Oncologic emergencies. In: Pizro PA, Poplack DG, eds. Principles and Practice of Pediatric Oncology. Philadelphia: Lippincott; 1988;1988:816-817.

Manuscript submitted March 10, 1993 and accepted April 27, 1993.

To the Editor: I read with interest the article by

Hande and Garrow’ about the tu- mor lysis syndrome in patients with malignant lymphoma. I agree with the observation about the high prevalence of this complica- tion in patients with intermediate- and high-grade malignancy non- Hodgkin’s lymphoma; this has also been seen in patients with high tu- mor burden (indirectly measured by high levels of lactic dehydroge- nase), bulky disease, high levels of beta 2 microglobulin.” Also, I agree that early institution of treatment will be mandat.ory in such cases. Nevertheless, the use of strong measures such as hydration, use of allopurinol, and urine alkalization with sodium bicarbonate is not

enough to prevent the emergence of this syndrome; this was demon- strated in the same study: 42% of the patients had laboratory abnor- malities and 6% developed clinical ma.nifestation.3.

For this reason we began a prospective clinical trial between 1982 and 1983 to evaluate the use- fulness of low doses of methrotrex- ate (MTX) before intensive chemo- therapy for preventing the tumor lysis syndrome in patients with high-risk malignant lymphoma. The goal was to avoid the emer- gence of this syndrome and evalu- ate the significance in response and duration of survival.

Forty-six cases received low doses (50 mg) of MTX IV followed by leucovorin rescue: 21 mg/m’ every 6 hours for six doses started 24 hours later. One week later the patients received the second dose: 120 m&/m” followed by the same leucovorin rescue. The control group (62 patients) did not receive the preinduction doses of MTX. All cases were treated with hydration, allopurinol, and sodium bicarbon- ate. Six cases in the control group developed clinical and biochemi- cal manifestations of tumor lysis syndrome; 22 developed only lab- oratory features. Of the patients who received MTX, only 2 devel- oped biochemical abnormalities, and no clinical manifestations were observed.

The response to chemotherapy, duration of response, and survival were better in the patients who re- ceived MTX, compared to patients in the control grow.3 We believe that low doses of MTX can reduce the high tumor burden and thereby, when chemotherapy is started, the incidence of tumor lysis syndrome is also reduced.

Since 1983, low-dose MTX has been introduced in our treatment policy on patients with intermedi- ate- and high-grade malignancy, and approximately 850 cases have been treated. Only 4 patients de- veloped clinical tumor lysis syn-

April 1995 The American Journal of Medicinea Volume 98 417