Quantitative real-time polymerase chain reaction for monitoring minimal residual disease in patients with advanced indolent lymphomas treated with rituximab, fludarabine, mitoxantrone, and dexamethasone.
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.
Sarris
Andreas H
AH
Department of Lymphoma and Myeloma, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Jiang
Yunfang
Y
Tsimberidou
Apostolia M
AM
Thomaides
Athanasios
A
Rassidakis
George Z
GZ
Ford
Richard J
RJ
Medeiros
L Jeffrey
LJ
Cabanillas
Fernando
F
McLaughlin
Peter
P
D000199:Actins; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D004247:DNA / Q000032:analysis*; D003907:Dexamethasone / Q000008:administration & dosage; D006801:Humans; D008224:Lymphoma, Follicular / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D008942:Mitoxantrone / Q000008:administration & dosage; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D000069283:Rituximab; D014178:Translocation, Genetic; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
D000199:Actins; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D003907:Dexamethasone; D004247:DNA; D008942:Mitoxantrone; D014740:Vidarabine; C024352:fludarabine