Pulmonary toxicity
Fludarabine
Fludarabine is a purine analog used mostly for refractory or relapsed hematologic malignancies including CLL. There is currently a black box warning regarding the use of fludarabine in combination with pentostatin in the treatment of patients with refractory CLL, as this has led to an unacceptably high incidence of fatal pulmonary toxicity. Currently the manufacturer does not recommend the combination of fludarabine and pentostatin due to this pulmonary toxicity.
Separately, fludarabine can cause interstitial pneumonitis. The largest series of 105 evaluated patients demonstrates an incidence rate of 8.6%. Pulmonary toxicity presents early into fludarabine therapy with signs and symptoms of dyspnea, fever, hypoxia and radiographic infiltrates. Treatment of fludarabine interstitial pneumonitis is to first ensure the patient does not have a concomitant infection, as fludarabine increases patient risk of bacterial and even some opportunistic infections, and then to discontinue fludarabine therapy and initiate corticosteroids, which will usually resolve symptoms.
Re-challenge with fludarabine is not recommended, as reoccurrence is likely.
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