Quantitative real-time polymerase chain reaction for monitoring minimal residual disease in patients with advanced indolent lymphomas treated with rituximab, fludarabine, mitoxantrone, and dexamethasone

Semin Oncol. 2002 Feb;29(1 Suppl 2):48-55.

Abstract

Fludarabine and rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA) are active against indolent lymphomas. We have previously shown the safety and efficacy of the combination of FND (fludarabine/mitoxantrone/dexamethasone) in relapsed and subsequently untreated patients with stage IV indolent lymphomas. Currently, we treat patients with stage IV indolent lymphomas who are previously untreated, younger than 60 years, human immunodeficiency virus-negative, and have adequate organ and marrow function with FND and random assignment to concurrent or delayed administration of rituximab. We have developed a quantitative real-time polymerase chain reaction assay for t(14;18). With 1 microg of DNA, this assay detects 0.6 copies in 55% of reactions, as expected for the Poisson distribution. When 1microg of DNA was analyzed in duplicate, cells with the t(14;18) were detected in peripheral blood of 22% of 152 volunteer blood donors. Quantitation showed that numbers of t(14;18) cells were higher than the statistical upper normal limit (mean of all volunteer values plus standard deviations) in 2% of volunteer blood donors. By contrast, 36% of blood or marrow specimens from follicular lymphoma patients were positive, and the number of cells with t(14;18) was higher than the normal upper limit in 26%. The presence of cells with t(14;18) and their numbers are prospectively quantitated in blood and marrow of patients treated with FND plus rituximab to determine their clinical significance both at presentation and during therapy.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chromosomes, Human, Pair 14
  • Chromosomes, Human, Pair 18
  • DNA / analysis*
  • Dexamethasone / administration & dosage
  • Humans
  • Lymphoma, Follicular / diagnosis
  • Lymphoma, Follicular / drug therapy
  • Lymphoma, Follicular / genetics
  • Lymphoma, Non-Hodgkin / diagnosis
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / genetics
  • Mitoxantrone / administration & dosage
  • Neoplasm, Residual / diagnosis*
  • Neoplasm, Residual / genetics
  • Polymerase Chain Reaction*
  • Rituximab
  • Translocation, Genetic
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives

Substances

  • Actins
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Rituximab
  • Dexamethasone
  • DNA
  • Mitoxantrone
  • Vidarabine
  • fludarabine