Combined fludarabine and rituximab for low grade lymphoproliferative disorders

David G. Savage, Gwen Nichols, Neil S. Cohen, Charles S. Hesdorffer, Robert March, Mathew Lonberg, Thomas J. Garrett, Javier Ruiz, Michael Flamm, J. G. Mears, Andrea Troxel, Anna Parke, Michael Rock

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1 Scopus citations


Background: As both fludarabine and rituximab are active against low grade CD20+ lymphoproliferative disorders, it is logical to test the efficacy of these drugs in combination. Protocol & patients: This is a phase I-II trial of combined fludarabine and rituximab therapy: fludarabine 30 mg/m2 on days 1-4 and escalating doses of rituximab 125-375 mg/m2 on day 5. The regimen is given every 4 wks to a maximum of 8 cycles until complete remission (CR), relapse, or patient intolerance. Fifteen patients have enrolled ( 10 men, 5 women, age 26-80 yrs, median 56 yrs). Of 5 patients treated for chronic lymphocytic leukemia (CLL), all had Rai stages 1I-IV. Of 10 patients treated for low grade lymphoma (follicular, 5, small lymphocytic, 2, Waldenstrom's, 2, mantle cell, 1), all had Ann Arbor stage IV disease. Chemotherapy had previously been administered to 6 patients, of whom 3 had received at least 2 regimens. Results: Rituximab has been administered at a dose of 125 mg/m2 to 3 patients, 250 mg/m2 to 4 patients, and 375 mg/m2 to 8. A total of 79 cycles of treatment have been given. Fludarabine doses have been reduced or delayed in 6 instances. Two patients received only 1 treatment. A 59 year old man with advanced CLL and a prior episode of near-fatal pneumonia developed fever, pulmonary infiltrates, and septic shock and died one day after completing his first cycle; this was the sole infectious complication in the overall series. One patient with follicular lymphoma suffered anaphylaxis after the first 5 minutes of her first rituximab infusion. Non-hematopoietic toxicity has not exceeded grade I-II in any other patient. Grade II-III leukopenia has been noted in 2 patients and immune hemolytic anemia in a third. Of 11 évaluable patients, 6 have had a CR (median duration 3+ mos, range 2-10+ mos), one has had a partial response (PR) of 2 mos, one stable disease for 3 mos, and 2 showed progressive disease. Of the 6 patients with CR's, 3 were treated for CLL and 2 for follicular lymphoma. One patient with mantle cell lymphoma had a PR after 4 cycles of treatment, but then developed Burkitt's lymphoma. Responses have been seen at all dose levels of rituximab. Conclusions: Our preliminary data suggest that combined fludarabine/ rituximab therapy has excellent activity with acceptable toxicity in patients with low grade CD20+ lymphoproliferative disorders. We will continue to study this novel combination regimen.

Original languageEnglish (US)
Pages (from-to)247b
Issue number11 PART II
StatePublished - Dec 1 2000

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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