Case Presentation:

We are reporting a patient who presented with acute renal failure secondary to intrathecal methotrexate administration for treatment of acute lymphoblastic leukemia (ALL). This occurred despite normal renal function prior to methotrexate (MTX) initiation and vigorous hydration with urinary alkalinization during treatment.

Discussion:

A 47 year–old Hispanic gentleman presented to our hospital complaining of generalized fatigue and lower extremity rash. Laboratory data disclosed a complete blood cell count with a WBC of 1.6, PLT < 61,000, HCT 40.9%, HGB 14.4 g/dl. Serum urea was 14 mg/dl, serum creatinine .9 mg/dL, sodium 134 mmol/L and bicarbonate 27 mmol/L. Bone marrow biopsy showed a hypercellular bone marrow (90%) and left shift with increased blast cells (nearly 100%) compatible with ALL. Our patient received his second course of cyclophosphamide, vincristine, doxorubicin and dexamethasone and intrathecal methotrexate. The following day creatinine increased to 2.5mg/dl, serum uric acid level was 10.6 mg/dL, methotrexate level was 23.56 mM. Thus confirming our suspicion of tumor lysis syndrome. He was treated with intravenous hydration, alkalinization of the urine, and supportive therapy with intensive leucovorin for 12 days. The patients renal function slowly improved, creatinine returned to baseline and methotrexate and uric acid level returned to normal.

Conclusions:

This is the 2nd case report that illustrates a previously unrecognized potential complication of intrathecal methotrexate—acute tumor lysis syndrome. Despite normal baseline creatinine clearance and adherence to standard precaution to prevent renal toxicity with hydration and alkalinization, severe renal toxicity may occur secondary to tymor lysis syndrome. Development of acute renal failure during methotrexate therapy is a medical emergency, since more than 90% MTX is cleared by the kidneys, renal failure contributes to the sustained toxic levels of MTX. If not treated early and aggressively, methotrexate can damage the ability of normal cells to synthesize DNA leading to cell death and resulting in renal, hepatic, and central nervous system toxicity. As this case illustrates, even with intrathecal methotrexate toxicity, treatment with pharmacologically guided leucovorin rescue along with continuation of hydration and alkalinization will facilitate restoration of renal function and decrease the risk of impending systemic toxicity.