L-Asparaginase monotherapy for EBV-positive T/NK lymphoproliferative diseases: A pilot Study.

We investigated the effects of L-asparaginase (L-asp) on Epstein-Barr virus (EBV)-positive T/NK lymphoproliferative diseases (EBV-T/ NK-LPDs). Seven doses of L-asp (6,000 U/m2) were administered intravenously, with one dose administered on every alternate day. Five consecutive patients were enrolled. Three patients completed the treatment. The clinical symptoms resolved in 1 patient who started the administration 8 months after the onset, being the earliest among the 5 patients. Her EBV-DNA level in whole blood markedly decreased to 0.08 times of that before treatment, and the level in plasma became undetectable. In the other 2 patients whose administration was started 3 and 3.5 years after the onset, however, a remarkable improvement was not detected. Treatment was discontinued in 2 patients because of disease progression or idiopathic dystonia. The mRNA levels of asparagine synthetase in EBV-infected cells were examined. The level from the patient who responded to L-asp treatment was low, but it did not correlate with the effects in the other patients. Liver dysfunction (grades 2 and 3) was observed in 2 patients and neutropenia (grade 3) was noted in 1 patient. In conclusion, the effect of L-asp as monotherapy in EBV-T/NK-LPDs is limited, and early treatment initiation might be effective.